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Miklowitz DJ, Gitlin MJ. Practical Psychosocial Management for Patients With Bipolar Disorder. Am J Psychother 2025; 78:81-87. [PMID: 39582312 DOI: 10.1176/appi.psychotherapy.20240028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2024]
Abstract
The broad acceptance of evidence-based psychosocial interventions as adjuncts to pharmacotherapy for bipolar disorder has been inhibited by the extensive training, supervision, and fidelity requirements of these approaches. Interventions that emphasize evidence-based strategies drawn from these modalities-rather than the full manualized protocols-may broaden the availability of psychotherapy for patients with bipolar disorder. In this article, psychosocial risk factors relevant to the course of bipolar disorder (stressful life events that disrupt social rhythms, lack of social support, family criticism and conflict, and lack of illness awareness or literacy) are reviewed, along with evidence-based psychosocial interventions (e.g., interpersonal and social rhythm therapy, cognitive-behavioral therapy, family-focused therapy, and group psychoeducation) to address these risk factors. The results of a component network meta-analysis of randomized psychotherapy trials in bipolar disorder are discussed. Manualized psychoeducation protocols-especially those that encourage active skill practice and mood monitoring in a family or group format-were found to be more effective, compared with individual psychoeducation or routine care, in reducing 1-year recurrence rates. Cognitive restructuring, regulation of daily and nightly routines, and communication skills training were core components associated with stabilization of depressive symptoms. The authors describe a novel psychoeducational approach-practical psychosocial management (PPM)-that integrates these core strategies into the personalized care of patients with bipolar disorder to reduce recurrences and enhance mood stability. PPM is designed to be implemented, without time-intensive training and oversight, by physician or nonphysician clinicians. Evaluating the efficacy and coverage of PPM will require implementation trials in community settings.
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Affiliation(s)
- David J Miklowitz
- Department of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles
| | - Michael J Gitlin
- Department of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles
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Sultan AA, Goldstein BI, Blanco C, Kennedy KG, Conway KP, He JP, Merikangas K. Correlates of cannabis use and cannabis use disorder among adolescents with major depressive disorder and bipolar disorder in the National Comorbidity Survey-Adolescent Supplement (NCS-A). J Affect Disord 2025; 371:268-278. [PMID: 39299588 DOI: 10.1016/j.jad.2024.09.114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Revised: 09/13/2024] [Accepted: 09/16/2024] [Indexed: 09/22/2024]
Abstract
BACKGROUND Despite evidence regarding prevalence and correlates of cannabis use (CU) and cannabis use disorder (CUD) in major depressive disorder (MDD) and bipolar disorder (BD) in adults, little is known about this topic among adolescents. METHODS Data are from the 2001-2004 National Comorbidity Survey-Adolescent Supplement, an in-person, cross-sectional epidemiologic survey of mental disorders. Participants included adolescents, ages 13-18 years, with MDD (n = 354 with CU, n = 70 with CUD, n = 688 with no CU), BD (n = 79 with CU, n = 32 with CUD, n = 184 with no CU), or adolescents without mood disorders (n = 1413 with CU, n = 333 with CUD, n = 6970 with no CU). Analyses examined prevalence and correlates of CU and CUD within MDD and BD groups. RESULTS CU was most prevalent in adolescents with MDD followed by adolescents with BD then controls. CUD was most prevalent in adolescents with BD followed by adolescents with MDD then controls. In covariate-adjusted ordinal logistic regression models, within MDD and BD, CU and CUD groups had significantly higher odds of lifetime suicidal ideation/attempts, as well as other significant indicators of clinical severity. LIMITATIONS Based on changes in cannabis acceptance, potency, and availability in the two decades since this study was conducted, present findings may underestimate adverse cannabis associations. CONCLUSION CU and CUD are both associated with adverse clinical characteristics in a community-based sample of adolescents with MDD and BD. Evidence that risks of cannabis use extend across the spectrum of use is important for adolescents with MDD and BD, in whom cannabis-related consequences tend to be more severe.
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Affiliation(s)
- Alysha A Sultan
- Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Benjamin I Goldstein
- Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Carlos Blanco
- Genetic Epidemiology Research Branch, National Institute of Mental Health, Bethesda, MD, United States of America
| | - Kody G Kennedy
- Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Kevin P Conway
- Genetic Epidemiology Research Branch, National Institute of Mental Health, Bethesda, MD, United States of America
| | - Jian-Ping He
- Genetic Epidemiology Research Branch, National Institute of Mental Health, Bethesda, MD, United States of America
| | - Kathleen Merikangas
- Genetic Epidemiology Research Branch, National Institute of Mental Health, Bethesda, MD, United States of America.
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Llamocca EN, Fristad MA, Brock G, Steelesmith DL, Felix AS, Fontanella CA. Associations between minimally adequate treatment and clinical outcomes among Medicaid-enrolled youth with bipolar disorder. J Psychiatr Res 2025; 182:497-505. [PMID: 39899945 DOI: 10.1016/j.jpsychires.2025.01.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 10/06/2024] [Accepted: 01/09/2025] [Indexed: 02/05/2025]
Abstract
OBJECTIVE To investigate associations between minimally adequate treatment and clinical outcomes among youth with bipolar disorder. METHODS This study utilized a retrospective cohort of publicly-insured (Medicaid) youth aged 10-18 years with a new bipolar disorder episode between 2009 and 2013 from 15 geographically diverse states. Four minimally adequate treatment measures were evaluated during a 180-day treatment period: 1) Minimally Adequate Pharmacotherapy: medication (mood stabilizer and/or atypical antipsychotic) possession ratio ≥80%; 2) Minimally Adequate Psychotherapy: ≥8 psychotherapy visits; 3) Minimally Adequate Pharmacotherapy and Psychotherapy, and 4) Recommended Pharmacotherapy with No Antidepressant Monotherapy: no antidepressant prescription without a mood stabilizer and/or atypical antipsychotic. Cox proportional hazards models examined associations between minimally adequate care and time to four clinical outcomes: bipolar disorder-related psychiatric hospitalization or emergency room (ER) visits, deliberate self-harm, and all-cause mortality. We estimated average treatment effects (ATE) using propensity score weighting with stabilized ATE weights to control for confounding. RESULTS Hazard of hospitalization was increased among youth receiving minimally adequate psychotherapy (HR = 1.23 [95% CI: 1.04-1.44]) and both minimally adequate pharmacotherapy and psychotherapy (HR = 1.48 [95% CI: 1.12-1.96]) and decreased among youth receiving no antidepressant monotherapy (HR = 0.74 [95% CI: 0.62-0.88]). Hazard of ER visits was increased among youth receiving minimally adequate pharmacotherapy (HR = 1.38 [95% CI: 1.14-1.68]), minimally adequate psychotherapy (HR = 1.35 [95% CI: 1.13-1.61]), and both minimally adequate pharmacotherapy and psychotherapy (HR = 1.66 [95% CI: 1.24-2.24]). CONCLUSIONS Further research is needed to understand why receipt of minimally adequate care is positively associated with increased mental healthcare utilization among youth with new bipolar disorder episodes.
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Affiliation(s)
- Elyse N Llamocca
- Center for Suicide Prevention and Research, Abigail Wexner Research Institute, Nationwide Children's Hospital, Big Lots Behavioral Health Pavilion, 444 Butterfly Gardens Drive, Suite 2B, Columbus, OH, 43215, USA.
| | - Mary A Fristad
- Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH, USA; Big Lots Behavioral Health Services and Division of Child and Family Psychiatry, Nationwide Children's Hospital, 444 Butterfly Gardens Drive #3207, Columbus, OH, 43215, USA.
| | - Guy Brock
- Department of Biomedical Informatics, The Ohio State University, 320-N Lincoln Tower, Columbus, OH, 43210, USA.
| | - Danielle L Steelesmith
- Center for Suicide Prevention and Research, Abigail Wexner Research Institute, Nationwide Children's Hospital, Big Lots Behavioral Health Pavilion, 444 Butterfly Gardens Drive, Suite 2B, Columbus, OH, 43215, USA.
| | - Ashley S Felix
- Division of Epidemiology, The Ohio State University, 1841 Neil Ave, 346 Cunz Hall, Columbus, OH, 43210, USA.
| | - Cynthia A Fontanella
- Center for Suicide Prevention and Research, Abigail Wexner Research Institute, Nationwide Children's Hospital, Big Lots Behavioral Health Pavilion, 444 Butterfly Gardens Drive, Suite 2B, Columbus, OH, 43215, USA; Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH, USA.
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Sood K, Buddhavarapu M, Bansal LR, Schaefer D, Parikh P. Utilizing long-acting injectables to address noncompliance among adolescents diagnosed with bipolar disorder. Bipolar Disord 2024; 26:831-834. [PMID: 39218699 DOI: 10.1111/bdi.13493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Affiliation(s)
- Kanuja Sood
- Department of Psychiatry, SGT University, Gurugram, India
| | - Mahiya Buddhavarapu
- Bachelors of Science, Department of Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Lajpat Rai Bansal
- Department of Psychiatry, Maharja Agrasen Medical College, Hospital and Research Institute, Haryana, India
| | | | - Parinda Parikh
- Department of Psychiatry, Weill-Cornell Medical College, New York, New York, USA
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Farrow JE, DelBello MP, Patino LR, Blom TJ, Welge JA. A Double-Blind, Placebo-Controlled Study of Adjunctive Topiramate in Adolescents With Co-Occurring Bipolar and Cannabis Use Disorders. JAACAP OPEN 2024; 2:290-300. [PMID: 39697396 PMCID: PMC11650694 DOI: 10.1016/j.jaacop.2024.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Accepted: 08/19/2024] [Indexed: 12/20/2024]
Abstract
Objective To evaluate the efficacy of adjunctive topiramate (TPM) for the treatment of cannabis use disorder in adolescents with bipolar I disorder. Method We conducted a 16-week, double-blind, randomized, placebo-controlled investigation of quetiapine plus TPM (median dose = 208 mg) vs quetiapine plus placebo in adolescents with bipolar I and cannabis use disorder. All subjects participated in a Motivational Interview and Compliance Enhancement Therapy. The primary outcome measure was change in weekly cannabis use over a 16-week treatment period using the Timeline Followback. The secondary outcome measure was the baseline-to-endpoint total score change in the Young Mania Rating Scale (YMRS). Results A total of 75 participants completed at least 1 post-baseline assessment (TPM = 38, placebo = 37). There was a significant time-by-treatment effect over the 16-week treatment period, with baseline-adjusted treatment differences in favor of the TPM group over time (p < .001). Although there was no difference in baseline-to-endpoint YMRS total score change between groups (p = .342), there was as significant decline in YMRS total score within both groups (p < .0001). There was a significant positive effect for alcohol use (p < .001) and nicotine use (p = .033) in the TPM group. More participants in the TPM group experienced appetite decrease (p = .032) and excitement (p = .025). Participants in the placebo group experienced greater weight gain (p = .010). Conclusion Treatment with TPM adjunctive to quetiapine and a Motivational Interview and Compliance Enhancement Therapy is associated with a greater decrease in cannabis use and less weight gain. TPM is a well-tolerated and efficacious treatment for cannabis use disorder in adolescents with bipolar I disorder. Clinical trial registration information Efficacy Study of Quetiapine Plus Topiramate for Reducing Cannabis Consumption and Bipolar Mania; https://clinicaltrials.gov/; NCT00393978. Diversity & Inclusion Statement We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science.
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Affiliation(s)
- Jenni E. Farrow
- University of Cincinnati College of Medicine, Cincinnati, Ohio
| | | | - Luis R. Patino
- University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Thomas J. Blom
- University of Cincinnati College of Medicine, Cincinnati, Ohio
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Klein CC, Modi AC, Welge JA, Fornari VM, Kurtz B, Blom TJ, Higdon C, Correll CU, DelBello MP. Adherence Rates and Barriers to Second-Generation Antipsychotic Medication Use in Youth with Bipolar Spectrum Disorders Who Have Overweight/Obesity. J Child Adolesc Psychopharmacol 2024; 34:353-358. [PMID: 38770645 DOI: 10.1089/cap.2024.0011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/22/2024]
Abstract
Objective: Youth with bipolar spectrum disorders (BSD) are frequently prescribed second-generation antipsychotics (SGAs). Nonadherence to treatment often results in increased mood symptoms and diminished quality of life. We examined SGA adherence rates and adherence barriers among youth who have overweight/obesity and are diagnosed with BSD enrolled in a multisite pragmatic clinical trial. Methods: SGA adherence and adherence barriers at baseline via patient- and caregiver report was assessed. Adherence was defined as taking ≥70% of prescribed SGA doses in the past week. The weighted Kappa statistic was used to measure child-caregiver agreement about adherence rates, barriers, and caregiver assistance. Regression analyses were used to examine associations of caregiver assistance, age, sex, race, insurance status, dosing frequency, and number of concomitant medications with adherence. Barriers to adherence were analyzed separately for youth and their caregivers, using logistic regression to assess associations between informant-reported barriers and informant-reported adherence. Results: Participants included 1485 patients and/or caregivers. At baseline, 88.6% of patients self-reported as adherent; 92.0% of caregivers reported their child was adherent. Concordance between patients and caregivers was moderate (k = 0.42). Approximately, 50% of the sample reported no adherence barriers. Frequently endorsed barriers included forgetting, side effects, being embarrassed to take medications, and preferring to do something else. Concordance between informants regarding adherence barriers was weak (k = 0.05-0.36). Patients and caregivers who did not endorse adherence barriers reported higher adherence than those who endorsed barriers. Male sex and having once daily dosing of medications were associated with lower adherence. Discussion: One-week patient- and caregiver-reported adherence was high in this sample. Half of the sample reported adherence barriers. Most commonly endorsed barriers were forgetting, side effects, being embarrassed, and preferring to do something else. Caregivers and patients have unique perspectives regarding adherence barriers. Understanding and addressing treatment barriers in clinical practice may facilitate adherence.
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Affiliation(s)
- Christina C Klein
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Avani C Modi
- Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital and Medical Center, Cincinnati, Ohio, USA
| | - Jeffrey A Welge
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Victor M Fornari
- Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, USA
- Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA
| | - Brian Kurtz
- Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital and Medical Center, Cincinnati, Ohio, USA
| | - Thomas J Blom
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Claudine Higdon
- Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, USA
- Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA
| | - Christoph U Correll
- Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, USA
- Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA
- Department of Child and Adolescent Psychiatry, Charité - Universitätsmedizin Berlin, Berlin, Germany
- German Center for Mental Health (DZPG), Berlin, Germany
| | - Melissa P DelBello
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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Vahapoğlu B, Aksoy Poyraz C, Özdemir A. Psychosocial Impairment in Older Patients With Bipolar I Disorder. J Psychiatr Pract 2024; 30:147-156. [PMID: 38526403 DOI: 10.1097/pra.0000000000000767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/26/2024]
Abstract
BACKGROUND The goal of this study was to assess psychosocial functioning in older patients with bipolar I disorder compared with healthy subjects and to identify the psychopathological factors associated with poor functioning in patients. METHODS We recruited 68 euthymic patients with bipolar I disorder from the outpatient unit and 89 healthy controls who were older than 50 years of age. In addition to clinical variables, we used other standardized measures, including the Young Mania Rating Scale, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the Functional Assessment Short Test, and the Montreal Cognitive Assessment. RESULTS Older patients with bipolar I disorder had poorer psychosocial functioning in general and in the domains of occupation, autonomy, and cognition than the healthy controls on the basis of previously defined Functional Assessment Short Test cutoff scores. We found that 35.3% (95% CI: 23%-47%) of the patients did not have clinically significant functional impairment, 38.2% (95% CI: 26%-50%) had mild impairment, and 26.5% (95% CI: 16%-37%) had moderate impairment. Depressive symptoms and impaired cognition were associated with poor overall functioning. CONCLUSIONS The level of psychosocial functioning was heterogeneous among the patients. Subsyndromal depressive symptoms, even at low levels, and impaired cognition predicted poor functioning in euthymic middle-aged and older patients with bipolar I disorder.
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Affiliation(s)
- Berkay Vahapoğlu
- VAHAPOĞLU and ÖZDEMIR: Bakirköy Mazhar Osman Bakirköy Mental Health and Neurological Diseases Education and Research Hospital, Istanbul, Turkey; POYRAZ: Department of Psychiatry, İstanbul University-Cerrahpaşa Medical School, Istanbul, Turkey
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Forthun LF, Sajatovic M, Levin JB, DelBello MP, Appling D, Broadnax MD, Fuentes-Casiano E, Cooley R, Blixen CE, Modi AC. Modification of an Intervention to Improve Adherence in Adolescents and Young Adults With Bipolar Disorder. JAACAP OPEN 2023; 1:80-92. [PMID: 38143721 PMCID: PMC10745282 DOI: 10.1016/j.jaacop.2023.04.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/26/2023]
Abstract
Objective Managing bipolar disorder (BD) is particularly challenging for adolescents and young adults (AYAs) ages 16 to 21. Few interventions exist that address self-management in AYAs with BD. Thus, this study aimed to modify the customized adherence enhancement behavioral intervention for AYAs through an iterative, patient-centered process. Method The Obesity-Related Behavioral Intervention Trials (ORBIT) model was used for intervention development. In phase 1a, adherence barriers and facilitators were identified to refine intervention content. Phase 1b occurred following curriculum modification to ensure that the modified intervention was relevant and usable by the target population. Data were collected via focus groups and interviews with AYAs with BD, parents, and providers. Transcripts were analyzed using directed content analysis. Results Phase 1a included focus groups/interviews with AYAs (n = 10), parents (n = 4), and providers (n = 9) who described the difficulties and successes in managing BD symptoms, improving adherence, and transitioning care from caregivers. Phase 1b included an advisory board composed of 8 phase 1a participants who provided feedback on modified session activities, module delivery, and curriculum. Phase 1b involved usability testing with new participants (n = 8), revealing the need for modifiable language based on developmental level, more engaging visual images, and confirmation that topics were salient to AYAs with BD. Conclusion Though sample sizes were small and not representative of the population of AYAs with BD, the ORBIT methodology informed the adaptation of the customized adherence enhancement intervention to improve adherence in AYAs with BD. Important next steps are to conduct a pilot randomized clinical trial of customized adherence enhancement for AYAs.
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Affiliation(s)
- Larry F Forthun
- Dr. Forthun is with the University of Florida, Gainesville, Florida. Drs. Sajatovic, Levin, and Blixen, Mss. Broadnax and Fuentes-Casiano, and Mr. Appling are with Case Western Reserve University School of Medicine, Cleveland, Ohio, and University Hospitals of Cleveland Medical Center, Cleveland, Ohio. Dr. DelBello and Ms. Cooley are with the University of Cincinnati College of Medicine, Cincinnati, Ohio. Dr. Modi is with Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Martha Sajatovic
- Dr. Forthun is with the University of Florida, Gainesville, Florida. Drs. Sajatovic, Levin, and Blixen, Mss. Broadnax and Fuentes-Casiano, and Mr. Appling are with Case Western Reserve University School of Medicine, Cleveland, Ohio, and University Hospitals of Cleveland Medical Center, Cleveland, Ohio. Dr. DelBello and Ms. Cooley are with the University of Cincinnati College of Medicine, Cincinnati, Ohio. Dr. Modi is with Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Jennifer B Levin
- Dr. Forthun is with the University of Florida, Gainesville, Florida. Drs. Sajatovic, Levin, and Blixen, Mss. Broadnax and Fuentes-Casiano, and Mr. Appling are with Case Western Reserve University School of Medicine, Cleveland, Ohio, and University Hospitals of Cleveland Medical Center, Cleveland, Ohio. Dr. DelBello and Ms. Cooley are with the University of Cincinnati College of Medicine, Cincinnati, Ohio. Dr. Modi is with Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Melissa P DelBello
- Dr. Forthun is with the University of Florida, Gainesville, Florida. Drs. Sajatovic, Levin, and Blixen, Mss. Broadnax and Fuentes-Casiano, and Mr. Appling are with Case Western Reserve University School of Medicine, Cleveland, Ohio, and University Hospitals of Cleveland Medical Center, Cleveland, Ohio. Dr. DelBello and Ms. Cooley are with the University of Cincinnati College of Medicine, Cincinnati, Ohio. Dr. Modi is with Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Deionte Appling
- Dr. Forthun is with the University of Florida, Gainesville, Florida. Drs. Sajatovic, Levin, and Blixen, Mss. Broadnax and Fuentes-Casiano, and Mr. Appling are with Case Western Reserve University School of Medicine, Cleveland, Ohio, and University Hospitals of Cleveland Medical Center, Cleveland, Ohio. Dr. DelBello and Ms. Cooley are with the University of Cincinnati College of Medicine, Cincinnati, Ohio. Dr. Modi is with Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Michaela D Broadnax
- Dr. Forthun is with the University of Florida, Gainesville, Florida. Drs. Sajatovic, Levin, and Blixen, Mss. Broadnax and Fuentes-Casiano, and Mr. Appling are with Case Western Reserve University School of Medicine, Cleveland, Ohio, and University Hospitals of Cleveland Medical Center, Cleveland, Ohio. Dr. DelBello and Ms. Cooley are with the University of Cincinnati College of Medicine, Cincinnati, Ohio. Dr. Modi is with Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Edna Fuentes-Casiano
- Dr. Forthun is with the University of Florida, Gainesville, Florida. Drs. Sajatovic, Levin, and Blixen, Mss. Broadnax and Fuentes-Casiano, and Mr. Appling are with Case Western Reserve University School of Medicine, Cleveland, Ohio, and University Hospitals of Cleveland Medical Center, Cleveland, Ohio. Dr. DelBello and Ms. Cooley are with the University of Cincinnati College of Medicine, Cincinnati, Ohio. Dr. Modi is with Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Raechel Cooley
- Dr. Forthun is with the University of Florida, Gainesville, Florida. Drs. Sajatovic, Levin, and Blixen, Mss. Broadnax and Fuentes-Casiano, and Mr. Appling are with Case Western Reserve University School of Medicine, Cleveland, Ohio, and University Hospitals of Cleveland Medical Center, Cleveland, Ohio. Dr. DelBello and Ms. Cooley are with the University of Cincinnati College of Medicine, Cincinnati, Ohio. Dr. Modi is with Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Carol E Blixen
- Dr. Forthun is with the University of Florida, Gainesville, Florida. Drs. Sajatovic, Levin, and Blixen, Mss. Broadnax and Fuentes-Casiano, and Mr. Appling are with Case Western Reserve University School of Medicine, Cleveland, Ohio, and University Hospitals of Cleveland Medical Center, Cleveland, Ohio. Dr. DelBello and Ms. Cooley are with the University of Cincinnati College of Medicine, Cincinnati, Ohio. Dr. Modi is with Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Avani C Modi
- Dr. Forthun is with the University of Florida, Gainesville, Florida. Drs. Sajatovic, Levin, and Blixen, Mss. Broadnax and Fuentes-Casiano, and Mr. Appling are with Case Western Reserve University School of Medicine, Cleveland, Ohio, and University Hospitals of Cleveland Medical Center, Cleveland, Ohio. Dr. DelBello and Ms. Cooley are with the University of Cincinnati College of Medicine, Cincinnati, Ohio. Dr. Modi is with Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
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Elhosary MY, Merranko JA, Goldstein TR, Hafeman DM, Goldstein BI, Gill MK, Hower H, Axelson DA, Hunt JI, Yen S, Diler RS, Ryan ND, Keller MB, Weinstock LM, Strober M, Birmaher B. Examining Factors Associated With Medication Adherence in Youth With Bipolar Disorder. JAACAP OPEN 2023; 1:105-115. [PMID: 39381188 PMCID: PMC11460791 DOI: 10.1016/j.jaacop.2023.06.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/10/2024]
Abstract
Objective To assess medication adherence and factors associated with poor adherence in youth with bipolar disorder (BD) followed from adolescence through young adulthood. Method Participants with BD recruited through the Course and Outcome of Bipolar Youth (COBY) study were included in this study if they were prescribed psychotropic medications and had at least 3 follow-up assessments of medication adherence (N= 179, ages 12-36). Medication adherence had been evaluated for a median of 8 years using a questionnaire derived from the Coronary Artery Risk Development in Young Adults (CARDIA) study. For the longitudinal evaluation, adherence was measured as the percentage of follow-up assessments in which the participants did not endorse any of the nonadherence items included in the questionnaire. Concurrent and future predictors of poor adherence were assessed using both univariate and multivariate longitudinal analyses. Results Among the participants, 51% reported poor adherence in more than 50% of their follow-up assessments. Younger age, family conflicts, polypharmacy, lower functioning, greater severity of mood symptoms, and comorbid disorders were associated with poor adherence in the univariate analyses. In the multivariate analyses, comorbid ADHD was the single most influential factor associated with concurrent and future poor adherence in all age groups. Participants' most reported reasons for poor adherence were forgetfulness (56%), negative attitudes toward medication treatment (10.5%), and disturbed daily routine (7%). Conclusions Poor medication adherence is a significant problem in youth with BD with the most influential factor being the presence of comorbid ADHD. Thus, it is important to identify and appropriately treat comorbid ADHD to improve medication adherence and patients' prognosis. Providers should also recommend tools to enhance consistent medication intake and address patients' concerns and negative beliefs about their illness and treatment.
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Affiliation(s)
- Mohamed Y Elhosary
- UPMC Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - John A Merranko
- UPMC Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Tina R Goldstein
- UPMC Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Danella M Hafeman
- UPMC Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Benjamin I Goldstein
- Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, University of Toronto Faculty of Medicine, Toronto, Ontario, Canada
| | - Mary Kay Gill
- UPMC Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Heather Hower
- Warren Alpert Medical School of Brown University, Providence, Rhode Island
| | - David A Axelson
- Nationwide Children's Hospital, and The Ohio State College of Medicine, Columbus, Ohio
| | - Jeffrey I Hunt
- Warren Alpert Medical School of Brown University, Providence, Rhode Island
| | - Shirley Yen
- Warren Alpert Medical School of Brown University, Providence, Rhode Island
- Massachusetts Mental Health Center and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Rasim Somer Diler
- UPMC Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Neal D Ryan
- UPMC Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Martin B Keller
- Warren Alpert Medical School of Brown University, Providence, Rhode Island
- Miller School of Medicine at the University of Miami, Miami, FL
| | - Lauren M Weinstock
- Warren Alpert Medical School of Brown University, Providence, Rhode Island
| | - Michael Strober
- David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California
| | - Boris Birmaher
- UPMC Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
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Sultan AA, Mio M, Dimick MK, Zou Y, Karthikeyan S, Kolla N, Lanctot K, Zack M, Goldstein BI. Association of cannabis use with neurocognition in adolescents with bipolar disorder. J Psychopharmacol 2023; 37:920-927. [PMID: 37497695 DOI: 10.1177/02698811231187128] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/28/2023]
Abstract
BACKGROUND Bipolar disorder (BD) and cannabis use are each associated with neurocognitive deficits in adolescents. However, little is known regarding the association of neurocognition with cannabis use among adolescents with BD. Therefore, we examined this topic in a sample of adolescents with BD and healthy control (HC) adolescents. METHODS Participants included 121 adolescents (n = 32 with BD and lifetime cannabis use (BDCB+), n = 31 with BD and no lifetime cannabis use (BDCB-), n = 58 HC with no lifetime cannabis use), aged 14-20 years. Five neurocognitive subtests of the computerized CANTAB battery were assessed. Groups were compared using an analysis of covariance (ANCOVA) covarying for age, sex, and intelligence quotient. RESULTS The three groups differed significantly on tests of visuospatial working memory (F = 4.41, p = 0.014, η p 2 = 0 . 07 ) and sustained attention (F = 5.15, p = 0.007, η p 2 = 0 . 08 ). Post hoc analyses revealed working memory scores were significantly worse in BDCB+ versus HC (p = 0.04, d = 0.59), and sustained attention was significantly worse in BDCB- versus HC (p = 0.006, d = 0.70). CONCLUSION These preliminary findings suggest that cannabis use among adolescents with BD is associated with working memory deficits. Future studies in larger samples are warranted to evaluate causation versus predisposition to cannabis use, and to evaluate duration, quantity, and potency of cannabis on neurocognition among adolescents with BD.
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Affiliation(s)
- Alysha A Sultan
- Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Megan Mio
- Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Mikaela K Dimick
- Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Yi Zou
- Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | | | - Nathan Kolla
- Centre for Addiction and Mental Health, Toronto, ON, Canada
- Department of Medicine, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Krista Lanctot
- Department of Medicine, University of Toronto, Toronto, ON, Canada
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
- Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | - Martin Zack
- Centre for Addiction and Mental Health, Toronto, ON, Canada
- Department of Medicine, University of Toronto, Toronto, ON, Canada
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
| | - Benjamin I Goldstein
- Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Department of Medicine, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
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11
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Sesso G, Masi G. Pharmacological strategies for the management of the antisocial personality disorder. Expert Rev Clin Pharmacol 2023; 16:181-194. [PMID: 36787887 DOI: 10.1080/17512433.2023.2181159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 02/09/2023] [Indexed: 02/16/2023]
Abstract
INTRODUCTION Antisocial personality disorder (AsPD) is a pervasive pattern of violation of others' rights, related to the concept of psychopathy. AsPD is stable over time from adolescence, with evidence of conduct disorder (CD) before 15 years. DSM-5 included a specifier 'with limited prosocial emotions' (LPE), which characterizes adolescents with higher developmental vulnerability to develop AsPD. Despite being relatively frequent with considerable societal impact, AsPD is a difficult-to-treat condition with high comorbidity rates and poor evidence for effective pharmacological interventions. AREAS COVERED We conducted a narrative review and searched PubMed up to September 2022. We included RCTs and naturalistic studies evaluating pharmacological interventions on AsPD in adults, including those with comorbid substance use disorder or psychopathic traits. Evidence in youths with CD, callous-unemotional (CU) traits and aggression were also reviewed, exploring the role of CU traits as moderators of response. EXPERT OPINION Psychosocial interventions are the first option, with possible improvement of CU traits, beyond behavioral and affective symptoms, particularly if implemented early during development. Limited information, based on low-quality studies, supports the pharmacological options. Second-generation antipsychotics, lithium, anti-epileptic drugs, and stimulants are first-line medications, according to different target symptoms. Developmental pathways including ADHD suggest a specific role of psychostimulants.
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Affiliation(s)
- Gianluca Sesso
- Social and Affective Neuroscience Group, Molecular Mind Lab, IMT School for Advanced Studies Lucca, Lucca, Italy
- Department of Child and Adolescent Psychiatry and Psychopharmacology, IRCCS Stella Maris Foundation, Pisa, Italy
| | - Gabriele Masi
- Department of Child and Adolescent Psychiatry and Psychopharmacology, IRCCS Stella Maris Foundation, Pisa, Italy
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12
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Lei D, Li W, Qin K, Ai Y, Tallman MJ, Patino LR, Welge JA, Blom TJ, Klein CC, Fleck DE, Gong Q, Adler CM, Strawn JR, Sweeney JA, DelBello MP. Effects of short-term quetiapine and lithium therapy for acute manic or mixed episodes on the limbic system and emotion regulation circuitry in youth with bipolar disorder. Neuropsychopharmacology 2023; 48:615-622. [PMID: 36229596 PMCID: PMC9938175 DOI: 10.1038/s41386-022-01463-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 09/11/2022] [Accepted: 09/14/2022] [Indexed: 01/07/2023]
Abstract
Disruptions in the limbic system, and in emotion regulation circuitry that supports affect modulation, have been reported during acute manic episodes of bipolar disorder (BD). The impact of pharmacological treatment on these deficits, especially in youth, remains poorly characterized. 107 youths with acute manic or mixed episodes of bipolar I disorder and 60 group-matched healthy controls were recruited. Youth with bipolar disorder were randomized to double-blind treatment with quetiapine or lithium and assessed weekly. Task-based fMRI studies were performed using an identical pairs continuous performance task (CPT-IP) at pre-treatment baseline and post-treatment weeks one and six. Region of interest analyses focused on the limbic system and ventral PFC - basal ganglia - thalamocortical loop structures known to be involved in emotion regulation. Changes in regional activation were compared between the two treatment groups, and pretreatment regional activation was used to predict treatment outcome. Mania treatment scores improved more rapidly in the quetiapine than lithium treated group, as did significant normalization of neural activation toward that of healthy individuals in left amygdala (p = 0.007), right putamen (p < 0.001), and right globus pallidus (p = 0.003). Activation changes in the right putamen were correlated with reduction of mania symptoms. The limbic and emotion regulation system activation at baseline and week one predicted treatment outcome in youth with bipolar disorder with significant accuracy (up to 87.5%). Our findings document more rapid functional brain changes associated with quetiapine than lithium treatment in youth with bipolar disorder, with most notable changes in the limbic system and emotion regulation circuitry. Pretreatment alterations in these regions predicted treatment response. These findings advance understanding of regional brain alterations in youth with bipolar disorder, and show that fMRI data can predict treatment outcome before it can be determined clinically, highlighting the potential utility of fMRI biomarkers for early prediction of treatment outcomes in bipolar disorder.Clinical Trials Registration: Name: Multimodal Neuroimaging of Treatment Effects in Adolescent Mania. URL: https://clinicaltrials.gov/ . Registration number: NCT00893581.
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Affiliation(s)
- Du Lei
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, 45219, OH, USA.
| | - Wenbin Li
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, 45219, OH, USA
- Huaxi MR Research Center (HMRRC), Department of Radiology, The Center for Medical Imaging, West China Hospital of Sichuan University, Chengdu, 610041, PR China
- Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, PR China
| | - Kun Qin
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, 45219, OH, USA
- Huaxi MR Research Center (HMRRC), Department of Radiology, The Center for Medical Imaging, West China Hospital of Sichuan University, Chengdu, 610041, PR China
| | - Yuan Ai
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, 45219, OH, USA
- Huaxi MR Research Center (HMRRC), Department of Radiology, The Center for Medical Imaging, West China Hospital of Sichuan University, Chengdu, 610041, PR China
| | - Maxwell J Tallman
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, 45219, OH, USA
| | - L Rodrigo Patino
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, 45219, OH, USA
| | - Jeffrey A Welge
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, 45219, OH, USA
| | - Thomas J Blom
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, 45219, OH, USA
| | - Christina C Klein
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, 45219, OH, USA
| | - David E Fleck
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, 45219, OH, USA
| | - Qiyong Gong
- Huaxi MR Research Center (HMRRC), Department of Radiology, The Center for Medical Imaging, West China Hospital of Sichuan University, Chengdu, 610041, PR China
| | - Caleb M Adler
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, 45219, OH, USA
| | - Jeffrey R Strawn
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, 45219, OH, USA
| | - John A Sweeney
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, 45219, OH, USA
- Huaxi MR Research Center (HMRRC), Department of Radiology, The Center for Medical Imaging, West China Hospital of Sichuan University, Chengdu, 610041, PR China
| | - Melissa P DelBello
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, 45219, OH, USA
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13
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Parental Factors Associated with Child or Adolescent Medication Adherence: A Systematic Review. Healthcare (Basel) 2023; 11:healthcare11040501. [PMID: 36833035 PMCID: PMC9957533 DOI: 10.3390/healthcare11040501] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 02/01/2023] [Accepted: 02/02/2023] [Indexed: 02/11/2023] Open
Abstract
Medication adherence, especially among children and adolescents with psychiatric disorders, is often seen as a major treatment challenge. The purpose of this study is to systematically review studies addressing specific aspects of parental factors that are positively or negatively associated with medication adherence among children and adolescents with psychiatric disorders. A systematic literature search of English language publications, from inception through December 2021, was conducted from PubMed, Scopus, and MEDLINE databases. This review has complied with Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines. A total of 23 studies (77,188 participants) met inclusion criteria. Nonadherence rates ranged between 8% to 69%. Parents' socioeconomic background, family living status and functioning, parents' perception and attitude towards the importance of medication taking in treating psychiatric disorders, and parents' mental health status are significant parental characteristics associated with medication adherence in children and adolescents with psychiatric disorders. In conclusion, by identifying specific parental characteristics related to the medication adherence of children and adolescents with psychiatric disorders, targeted interventions on parents could be developed to guide parents in improving their child's medication adherence.
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14
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Benatti B, Girone N, Conti D, Cocchi M, Achilli F, Leo S, Putti G, Bosi M, Dell’Osso B. The Role of Lifestyle on Adherence to Treatment in a Sample of Patients with Unipolar and Bipolar Depression. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:ijerph20031994. [PMID: 36767361 PMCID: PMC9915922 DOI: 10.3390/ijerph20031994] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 01/18/2023] [Accepted: 01/19/2023] [Indexed: 06/01/2023]
Abstract
Introduction: Poor adherence to treatment is currently stated to be one of the causes of depression relapse and recurrence. The aim of the present study is to assess potential differences in terms of clinical and lifestyle features related to adherence to treatment in a sample of patients with unipolar and bipolar depression. Methods: One hundred and eight patients with a diagnosis of unipolar or bipolar depressive episode were recruited from January 2021 to October 2022. Adherence to psychopharmacological treatment was assessed using the clinician rating scale. Descriptive and association analyses were performed to compare subgroups based on adherence to treatment. Results: Lower levels of adherence to treatment were associated with fewer years of education, work impairment, manic prevalent polarity lifetime, and greater comorbidity with alcohol and drug abuse. The majority of patients with positive adherence did not report any hospitalization and involuntary commitment lifetime. Conclusions: Patients with a positive treatment adherence showed significant differences in terms of lifestyle and clinical features compared to non-adherent patients. Our results may help to identify patients more likely to have poor medication adherence, which seem to lead to a worse disease course and quality of life.
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Affiliation(s)
- Beatrice Benatti
- Department of Mental Health, Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, 20122 Milan, Italy
- “Aldo Ravelli” Center for Neurotechnology and Brain Therapeutic, University of Milan, 20122 Milan, Italy
| | - Nicolaja Girone
- Department of Mental Health, Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, 20122 Milan, Italy
| | - Dario Conti
- Department of Mental Health, Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, 20122 Milan, Italy
| | - Maddalena Cocchi
- Department of Mental Health, Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, 20122 Milan, Italy
| | - Francesco Achilli
- Department of Mental Health, Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, 20122 Milan, Italy
| | - Silvia Leo
- Department of Mental Health, Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, 20122 Milan, Italy
| | - Gianmarco Putti
- Department of Mental Health, Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, 20122 Milan, Italy
| | - Monica Bosi
- Department of Mental Health, Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, 20122 Milan, Italy
| | - Bernardo Dell’Osso
- Department of Mental Health, Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, 20122 Milan, Italy
- “Aldo Ravelli” Center for Neurotechnology and Brain Therapeutic, University of Milan, 20122 Milan, Italy
- Department of Psychiatry and Behavioral Sciences, Bipolar Disorders Clinic, Stanford University, Stanford, CA 94305, USA
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15
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Sesso G, Brancati GE, Masi G. Comorbidities in Youth with Bipolar Disorder: Clinical Features and Pharmacological Management. Curr Neuropharmacol 2023; 21:911-934. [PMID: 35794777 PMCID: PMC10227908 DOI: 10.2174/1570159x20666220706104117] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 04/14/2022] [Accepted: 06/13/2022] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Bipolar Disorder (BD) is a highly comorbid condition, and rates of cooccurring disorders are even higher in youth. Comorbid disorders strongly affect clinical presentation, natural course, prognosis, and treatment. METHODS This review focuses on the clinical and treatment implications of the comorbidity between BD and Attention-Deficit/Hyperactivity Disorder, disruptive behavior disorders (Oppositional Defiant Disorder and/or Conduct Disorder), alcohol and substance use disorders, Autism Spectrum Disorder, anxiety disorders, Obsessive-Compulsive Disorder, and eating disorders. RESULTS These associations define specific conditions which are not simply a sum of different clinical pictures, but occur as distinct and complex combinations with specific developmental pathways over time and selective therapeutic requirements. Pharmacological treatments can improve these clinical pictures by addressing the comorbid conditions, though the same treatments may also worsen BD by inducing manic or depressive switches. CONCLUSION The timely identification of BD comorbidities may have relevant clinical implications in terms of symptomatology, course, treatment and outcome. Specific studies addressing the pharmacological management of BD and comorbidities are still scarce, and information is particularly lacking in children and adolescents; for this reason, the present review also included studies conducted on adult samples. Developmentally-sensitive controlled clinical trials are thus warranted to improve the prognosis of these highly complex patients, requiring timely and finely personalized therapies.
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Affiliation(s)
- Gianluca Sesso
- IRCCS Stella Maris, Scientific Institute of Child Neurology and Psychiat., Calambrone (Pisa), Italy
| | | | - Gabriele Masi
- IRCCS Stella Maris, Scientific Institute of Child Neurology and Psychiat., Calambrone (Pisa), Italy
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16
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Grover S, Avasthi A, Chakravarty R, Dan A, Chakraborty K, Neogi R, Desouza A, Nayak O, Praharaj S, Menon V, Deep R, Bathla M, Subramanyam AA, Nebhinani N, Ghosh P, Lakdawala B, Bhattacharya R. Prevalence and association of comorbid substance dependence on the course and outcome of bipolar disorder: Findings from the bipolar disorder course and outcome study from India (BiD-CoIN study). Indian J Psychiatry 2022; 64:449-456. [PMID: 36458086 PMCID: PMC9707659 DOI: 10.4103/indianjpsychiatry.indianjpsychiatry_665_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 06/16/2022] [Accepted: 07/27/2022] [Indexed: 11/05/2022] Open
Abstract
AIM To evaluate the prevalence of substance use disorder (SUD) and its association with the course and outcome of bipolar disorder (BD). MATERIALS AND METHODS A total of 773 patients with BD were recruited from 14 centers in different parts of India, and they were evaluated for the prevalence of comorbid substance dependence, course and outcome, subjective cognitive functioning, and disability. RESULTS About one-fourth (22.9%) of the participants had one or more substance dependence. In terms of specific substance of abuse, 136 (17.6%) had nicotine dependence, 80 (10.3%) patients had alcohol dependence, 13 (1.7%) had cannabis dependence, and nine (1.2%) had opioid dependence. Compared to those without comorbid substance dependence, those with a dual diagnosis (i.e., using at least one substance in a dependent pattern) were less educated, more often males, more often currently single, more often employed, had a lower number of depressive episodes per year of illness, had a higher number of manic and mixed episodes per year of illness in the first 5 years of illness, had a higher level of disability, and more often had a history of hospitalization and a history of receiving electroconvulsive therapy (ECT); also, a higher proportion of them had manic predominant polarity, more often had recurrent mania course, and were more often receiving a combination of lithium and valproate. CONCLUSION About one-fourth of BD patients have comorbid SUDs, and presence of SUD has a negative impact on the course and outcome of BD.
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Affiliation(s)
- Sandeep Grover
- Department of Psychiatry, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ajit Avasthi
- Department of Psychiatry, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Rahul Chakravarty
- Department of Psychiatry, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Amitava Dan
- Department of Psychiatry, Burdwan Medical College and Hospital, Burdwan, West Bengal, India
| | - Kaustav Chakraborty
- Department of Psychiatry, College of Medicine and J.N.M. Hospital WBUHS, Kalyani, Kolkata, West Bengal, India
| | - Rajarshi Neogi
- Department of Psychiatry, R. G. Kar Medical College and Hospital, Kolkata, West Bengal, India
| | - Avinash Desouza
- Department of Psychiatry, Lokmanya Tilak Municipal General Hospital (SION Hospital), Mumbai, Maharashtra, India
| | - Omkar Nayak
- Department of Psychiatry, Lokmanya Tilak Municipal General Hospital (SION Hospital), Mumbai, Maharashtra, India
| | - Samir Praharaj
- Department of Psychiatry, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Vikas Menon
- Department of Psychiatry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Raman Deep
- Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India
| | - Manish Bathla
- Department of Psychiatry, Maharishi Markandeshwar Institute of Medical Sciences and Research, Mullana, Ambala, Haryana, India
| | - Alka A Subramanyam
- Department of Psychiatry, Topiwala National Medical College (Nair Hospital), Mumbai, Maharashtra, India
| | - Naresh Nebhinani
- Department of Psychiatry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Prosenjit Ghosh
- Department of Psychiatry, Silchar Medical College, Silchar, Assam, India
| | - Bhavesh Lakdawala
- Department of Psychiatry, Ahmedabad Municipal Corporation Medical Education Trust Medical College, Ahmedabad, Gujarat, India
| | - Ranjan Bhattacharya
- Department of Psychiatry, Murshidabad Medical College and Hospital, Murshidabad, West Bengal, India
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Diaz Maldonado A, Simon A, Barry C, Hassler C, Lenjalley A, Giacobi C, Moro MR, Lachal J. Adolescent attendance at transcultural psychotherapy: a retrospective cohort study. Eur Child Adolesc Psychiatry 2022; 31:1-8. [PMID: 33751239 DOI: 10.1007/s00787-021-01760-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 03/11/2021] [Indexed: 11/27/2022]
Abstract
Migrant adolescents in therapy for psychological problems are at risk of poor attendance or even of dropping out. Transcultural psychotherapy has been developed in France to take cultural diversity into account in psychological treatment and to deal with the specific difficulties encountered in the psychotherapeutic treatment of this population. This study aims to assess adolescents' attendance rates to this form of psychotherapy and to explore the association of these rates with demographic, cultural, and clinical variables. We conducted a retrospective clinical cohort study of 148 adolescents aged from 11 to 20 years treated between 2008 and 2018 at two transcultural psychotherapy centers in Paris. Statistical analyses tested demographic, cultural, and clinical hypotheses. The main result was the high attendance rate at transcultural psychotherapy sessions among adolescents (77.8%). Attendance rates were not associated with age, gender, family size, generation of migration, or cultural area of origin, but were significantly linked to support in therapy, specifically, the presence at the first transcultural psychotherapy session of the first-line therapist, an interpreter, or both. Transcultural psychotherapy appears to be an effective method for addressing the complex symptoms experienced by migrant adolescents. Better attendance at sessions is statistically significantly associated with factors favoring a therapeutic alliance, specifically, the presence of the first-line therapist or an interpreter in TPT sessions and the existence of support from a social worker. The holistic approach of transcultural psychotherapy to adolescent care may explain the high attendance rates observed.
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Affiliation(s)
- Andrea Diaz Maldonado
- AP-HP, Cochin Hospital, Maison de Solenn, 75014, Paris, France
- Université de Paris, PCPP, 92100, Boulogne-Billancourt, France
| | - Amalini Simon
- AP-HP, Cochin Hospital, Maison de Solenn, 75014, Paris, France
- Université de Paris, PCPP, 92100, Boulogne-Billancourt, France
- Fac. de Médecine - Univ. Paris-Sud, Fac. de Médecine - UVSQ, CESP, INSERM, Université Paris-Saclay, 94807, Villejuif, France
- Assistance publique-Hôpitaux de Paris (AP-HP), Université de Paris 13, Hôpital Avicenne, service de psychopathologie, 3413, 93009, Bobigny cedex, EA, France
| | - Caroline Barry
- Fac. de Médecine - Univ. Paris-Sud, Fac. de Médecine - UVSQ, CESP, INSERM, Université Paris-Saclay, 94807, Villejuif, France
| | - Christine Hassler
- Fac. de Médecine - Univ. Paris-Sud, Fac. de Médecine - UVSQ, CESP, INSERM, Université Paris-Saclay, 94807, Villejuif, France
| | - Adrien Lenjalley
- Centre Hospitalier de Niort, Unité Pour Adolescent, 79000, Niort, France
| | - Carole Giacobi
- Groupe Hospitalier Littoral Atlantique, Service de pédopsychiatrie, 17019, La Rochelle, France
| | - Marie Rose Moro
- AP-HP, Cochin Hospital, Maison de Solenn, 75014, Paris, France
- Université de Paris, PCPP, 92100, Boulogne-Billancourt, France
- Fac. de Médecine - Univ. Paris-Sud, Fac. de Médecine - UVSQ, CESP, INSERM, Université Paris-Saclay, 94807, Villejuif, France
| | - Jonathan Lachal
- Fac. de Médecine - Univ. Paris-Sud, Fac. de Médecine - UVSQ, CESP, INSERM, Université Paris-Saclay, 94807, Villejuif, France.
- CHU de Clermont-Ferrand, Service de Psychiatrie de L'Enfant Et de L'Adolescent, 63000, Clermont-Ferrand, France.
- Université Clermont Auvergne, 63000, Clermont-Ferrand, France.
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18
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Wozniak J, DiSalvo M, Farrell A, Joshi G, Uchida M, Faraone SV, Cook E, Biederman J. Long term outcomes of pediatric Bipolar-I disorder: A prospective follow-up analysis attending to full syndomatic, subsyndromal and functional types of remission. J Psychiatr Res 2022; 151:667-675. [PMID: 35667335 PMCID: PMC10043808 DOI: 10.1016/j.jpsychires.2022.04.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 12/24/2021] [Accepted: 04/07/2022] [Indexed: 10/18/2022]
Abstract
OBJECTIVE To examine patterns of remission of pediatric bipolar I (BP-I) disorder attending to syndromatic, symptomatic, and functional outcomes from childhood to adolescent and young adult years. METHODS We analyzed data from a six-year prospective follow-up study of youths aged 6-17 years with BP-I disorder. Subjects were comprehensively assessed at baseline and subsequently at four, five, and six years thereafter. Assessments included structured diagnostic interviews and measures of psychosocial and educational functioning. Patterns of remission were calculated attending to whether syndromatic, symptomatic, and functional remission were achieved. RESULTS Kaplan-Meier failure functions revealed that the probability of functional recovery from pediatric BP-I disorder was very low. Of the 88 youths assessed, only 6% (N = 5) of the sample were euthymic with normal functioning during the year prior to their last follow-up assessment (average follow-up time = 5.8 ± 1.8 years). CONCLUSIONS These results provide compelling evidence of the high level of persistence of pediatric BP-I disorder. Symptomatic and functional remission were uncommon and most subjects continued to demonstrate high morbidity into late adolescence and early adulthood.
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Affiliation(s)
- Janet Wozniak
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
| | - Maura DiSalvo
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA
| | - Abigail Farrell
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA
| | - Gagan Joshi
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA
| | - Mai Uchida
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA
| | - Stephen V Faraone
- Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA
| | - Emmaline Cook
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA
| | - Joseph Biederman
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA
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A retrospective cohort study of the change in inflammatory parameters in childhood schizophrenia and bipolar disorder from childhood to adulthood. JOURNAL OF SURGERY AND MEDICINE 2022. [DOI: 10.28982/josam.1109124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Background/Aim: The etiologies of childhood schizophrenia and bipolar disorder have not yet been clarified. In cases in which the symptoms of mood are not dominant and psychotic symptoms are more dominant, it may be difficult to distinguish between childhood schizophrenia and bipolar disorder diagnoses. Follow-up studies concerning this subject have indicated that approximately half of the adolescents diagnosed with bipolar disorder were first (and incorrectly) diagnosed with schizophrenia. Therefore, strong markers are still needed to be used in the differential diagnosis at the time of the first application. An increase in the number of studies on the neuroinflammatory process in pediatric schizophrenia and bipolar illness have started to appear in the literature. The neutrophil–lymphocyte, thrombocyte–lymphocyte, and thrombocyte–neutrophil ratio (NLR, TLR, and TNR, respectively) levels in patients with childhood schizophrenia and childhood bipolar disorder at the time of admission and five years later were evaluated to determine whether inflammatory markers changed over time.
Methods: Twelve patients diagnosed with childhood schizophrenia and 14 patients diagnosed with childhood bipolar disorder were included in the study. Active infections, medical, neurological, endocrine, and metabolic illnesses, mental retardation, further concomitant psychiatric diagnoses, and intoxication were all exclusion factors. Hemograms from the same patients who satisfied the inclusion criteria when they originally applied and again at the fifth year follow-up were evaluated. Age, gender, neutrophil, lymphocyte, leukocyte, and thrombocyte values were recorded. NLR was calculated by dividing the neutrophil count by lymphocyte count. TLR value was calculated by dividing the thrombocyte count by lymphocyte count. TNR value was calculated by dividing the thrombocyte count by neutrophil count. Bipolar disorder and schizophrenia status were compared using NLR, TLR, and TNR parameters both at the time of initial diagnosis and at the fifth year of follow-up.
Results: When the initial admission hemograms of patients with childhood schizophrenia or childhood bipolar disorder were examined, no statistically significant differences between the two groups in terms of NLR (P = 0.150) and TLR (P = 0.440) were found. TNR was significantly higher in childhood bipolar disorder patients than in childhood schizophrenia (P = 0.015). At the fifth year follow-up, the hemograms of individuals diagnosed with either childhood schizophrenia or childhood bipolar disorder were compared, and no statistically significant differences between the two groups in NLR, (P = 0.572),TLR (P = 0.758), and TNR (P = 0.328) were found.
Conclusion: It was concluded that NLR and TLR levels did not change significantly over time in either disease and could not be used for the differential diagnosis of either disease. TNR may be considered for differential diagnoses in childhood schizophrenia and bipolar disease, particularly at the time of the first episode after confirmation of this study's findings with future studies.
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Llamocca EN, Fristad MA, Bridge JA, Brock G, Steelesmith DL, Axelson DA, Fontanella CA. Correlates of deliberate self-harm among youth with bipolar disorder. J Affect Disord 2022; 302:376-384. [PMID: 35066010 PMCID: PMC8957063 DOI: 10.1016/j.jad.2022.01.085] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 12/15/2021] [Accepted: 01/19/2022] [Indexed: 11/15/2022]
Abstract
OBJECTIVE Youth with bipolar disorder (BD) are at high risk for deliberate self-harm (DSH) and suicide. However, research regarding factors associated with DSH, a key suicide risk factor, among youth with BD is limited. In a population-based sample of youth with BD, we therefore investigated associations between demographic, clinical, and service utilization factors and DSH incidence and compared suicide, unintentional injury, and all-cause mortality to the general population. METHOD We analyzed a retrospective cohort of youth aged 5 to 19 years with a new BD episode between 2010 and 2017 (n = 25,244) using Ohio Medicaid claims and death certificate data. Cox proportional hazards models examined associations between different factors and DSH. Mortality rates were compared to the general population using standardized mortality ratios. RESULTS During follow-up, 1,517 (6.0%) youth had at least one DSH event. Older index age, female sex, comorbid psychiatric/medical conditions, prior DSH/suicidal ideation, and prior ER mental healthcare were associated with increased DSH risk. Prior DSH was most strongly associated with increased DSH risk for 3 months after a new BD episode. Being non-Hispanic Black (vs. White, non-Hispanic) and prior psychiatric hospitalization were associated with decreased DSH hazard. DSH risk was highest for 3 months after a new BD episode. Suicide, unintentional injury, and all-cause mortality rates were elevated in youth with BD. LIMITATIONS May not generalize to other states or non-Medicaid populations; claims data cannot distinguish suicidal intent of self-harm CONCLUSION: Early intervention following a new BD episode, particularly among high-risk groups, is key to prevent DSH.
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Affiliation(s)
- Elyse N Llamocca
- Division of Epidemiology, The Ohio State University, Columbus, OH, USA; Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH, USA
| | - Mary A Fristad
- Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH, USA; Big Lots Behavioral Health Services and Division of Child and Family Psychiatry, Nationwide Children's Hospital, Columbus, OH, USA
| | - Jeffrey A Bridge
- Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH, USA; Department of Pediatrics, The Ohio State University, Columbus, OH, USA; Center for Suicide Prevention and Research, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA
| | - Guy Brock
- Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA
| | - Danielle L Steelesmith
- Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH, USA
| | - David A Axelson
- Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH, USA; Department of Psychiatry, Nationwide Children's Hospital, Columbus, OH, USA
| | - Cynthia A Fontanella
- Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH, USA.
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Diler RS, Merranko JA, Hafeman D, Goldstein TR, Goldstein BI, Hower H, Gill MK, Axelson DA, Ryan N, Strober M, Keller MB, Yen S, Hunt JI, Weinstock LM, Iyengar S, Birmaher BB. Higher socioeconomic status and less parental psychopathology improve prognosis in youths with bipolar disorder. J Affect Disord 2022; 302:185-193. [PMID: 35033593 PMCID: PMC8857063 DOI: 10.1016/j.jad.2022.01.058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Revised: 12/19/2021] [Accepted: 01/11/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND To identify prospectively ascertained individual and family factors that are associated with improvement in Bipolar Disorder (BD) among youths who initially presented with poor course. METHODS 82 youths with BD with persistent poor mood symptomatology ("predominantly ill course") were compared to 70 youths with BD who at intake had poor course, but showed improvement during the follow-up ("ill with improving course"), (ages 12.3 ± 3.3, vs. 11.7 ± 3.3 years old, at intake). Improvement was measured by the percentage of time euthymic during a mean follow-up of 12.8 years. Youths and parents were interviewed to assess psychopathology, functioning, treatment, and familial functioning and psychopathology. RESULTS Compared to the ill group, since intake, the improving group showed significantly lower subthreshold depression and hypo/mania, Attention Deficit Hyperactivity Disorder, and Disruptive Behavior Disorders. Parental Socioeconomic Status (SES) remained unchanged over time in the ill group, but progressively increased in the improving group. Importantly, the change in SES predated the improvement in the mood trajectory. The most influential variables that predicted improvement were higher SES, and absence of parental BD and Substance Use Disorder (SUD). Parental SUD also negatively affected the parental SES, which was directly associated with worse mood course. LIMITATIONS Predominantly self-reported White samples may limit generalizability; other factors potentially associated with outcome (e.g., treatment adherence), were not ascertained. CONCLUSIONS In addition to treating mood/comorbid psychopathology in symptomatic BD youths, to improve their prognosis, it is crucial to address their parent's BD and SUD and promote parental education/employment.
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Affiliation(s)
- Rasim S Diler
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh School of Medicine, 3811 O'Hara St., Pittsburgh, PA 15213, United States of America.
| | - John A Merranko
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh School of Medicine, 3811 O'Hara St., Pittsburgh, PA 15213, United States of America
| | - Danella Hafeman
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh School of Medicine, 3811 O'Hara St., Pittsburgh, PA 15213, United States of America
| | - Tina R Goldstein
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh School of Medicine, 3811 O'Hara St., Pittsburgh, PA 15213, United States of America
| | - Benjamin I Goldstein
- Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto Faculty of Medicine, 2075 Bayview Ave., FG-53, Toronto, ON M4N-3M5, Canada
| | - Heather Hower
- Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Box G-BH, Providence, RI 02912, United States of America; Department of Health Services, Policy, and Practice, Brown University School of Public Health, 121 South Main Street, Providence, RI 02903, United States of America; Department of Psychiatry, University of California San Diego, 4510 Executive Drive, Suite 315, San Diego, CA 92121, United States of America
| | - Mary Kay Gill
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh School of Medicine, 3811 O'Hara St., Pittsburgh, PA 15213, United States of America
| | - David A Axelson
- Department of Psychiatry, Nationwide Children's Hospital, Ohio State College of Medicine, 700 Children's Drive, Columbus, OH 43205, United States of America
| | - Neal Ryan
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh School of Medicine, 3811 O'Hara St., Pittsburgh, PA 15213, United States of America
| | - Michael Strober
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States of America
| | - Martin B Keller
- Department of Psychiatry, University of California San Diego, 4510 Executive Drive, Suite 315, San Diego, CA 92121, United States of America; Department of Psychiatry, University of Miami, 1120 NW 14th St., Miami, FL 33136, United States of America
| | - Shirley Yen
- Departments of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, United States of America
| | - Jeffrey I Hunt
- Department of Health Services, Policy, and Practice, Brown University School of Public Health, 121 South Main Street, Providence, RI 02903, United States of America; Department of Psychiatry, Bradley Hospital, 1011 Veterans Memorial Parkway, East Providence, RI 02915, United States of America
| | - Lauren M Weinstock
- Department of Psychiatry, University of California San Diego, 4510 Executive Drive, Suite 315, San Diego, CA 92121, United States of America
| | - Satish Iyengar
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh School of Medicine, 3811 O'Hara St., Pittsburgh, PA 15213, United States of America
| | - Boris B Birmaher
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh School of Medicine, 3811 O'Hara St., Pittsburgh, PA 15213, United States of America
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22
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McVoy M, Delbello M, Levin J, Modi AC, Forthun LF, Briggs F, Appling D, Broadnax M, Conroy C, Cooley R, Eapen G, Sajatovic M. A customized adherence enhancement program for adolescents and young adults with suboptimal adherence and bipolar disorder: Trial design and methodological report. Contemp Clin Trials 2022; 115:106729. [PMID: 35278693 PMCID: PMC9022043 DOI: 10.1016/j.cct.2022.106729] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 02/15/2022] [Accepted: 03/05/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND The onset of bipolar disorder (BD) is common during late adolescence and young adulthood (AYA). Suboptimal medication adherence is a critical yet modifiable risk factor for negative outcomes among AYAs with BD. METHODS This research used an iterative process (e.g., focus groups, advisory board, cognitive interviews) to modify an existing adherence intervention to address suboptimal adherence in AYAs with BD. The modified version of Customized Adherence Enhancement for Adolescents and Young Adults (CAE-AYA) will be compared to an Enhanced Treatment as Usual condition (ETAU) in 40 AYAs intervention using a 6-month prospective, randomized controlled trial (RCT) in a high-risk group of 16-21 year old AYAs with BD with demonstrated non-adherence to their prescribed BD medications. CONCLUSIONS This report describes the methodology and design of the ImprovinG adhereNce In adolescenTs with bipolar disordEr (IGNITE) study. If successful, the CAE-AYA approach has the potential to advance care for vulnerable youth with BD.
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Affiliation(s)
- Molly McVoy
- Department of Psychiatry, University Hospitals Cleveland Medical Center, Cleveland, OH, United States of America; Case Western Reserve University School of Medicine, Cleveland, OH, United States of America; Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center, Cleveland, OH, United States of America.
| | - Melissa Delbello
- University of Cincinnati, College of Medicine, Cincinnati, OH, United States of America
| | - Jennifer Levin
- Department of Psychiatry, University Hospitals Cleveland Medical Center, Cleveland, OH, United States of America; Case Western Reserve University School of Medicine, Cleveland, OH, United States of America; Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center, Cleveland, OH, United States of America
| | - Avani C Modi
- Division of Behavioral Medicine and Clinical Psychology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of America; University of Cincinnati, College of Medicine, Cincinnati, OH, United States of America
| | - Larry F Forthun
- Department of Family, Youth and Community Sciences, University of Florida, Gainesville, FL, United States of America
| | - Farren Briggs
- Case Western Reserve University School of Medicine, Cleveland, OH, United States of America; Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center, Cleveland, OH, United States of America
| | - Deionte Appling
- Case Western Reserve University School of Medicine, Cleveland, OH, United States of America
| | - Michaela Broadnax
- Case Western Reserve University School of Medicine, Cleveland, OH, United States of America
| | - Carla Conroy
- Case Western Reserve University School of Medicine, Cleveland, OH, United States of America
| | - Raechel Cooley
- University of Cincinnati, College of Medicine, Cincinnati, OH, United States of America
| | - George Eapen
- Department of Psychiatry, University Hospitals Cleveland Medical Center, Cleveland, OH, United States of America
| | - Martha Sajatovic
- Department of Psychiatry, University Hospitals Cleveland Medical Center, Cleveland, OH, United States of America; Department of Neurology, University Hospitals Cleveland Medical Center, Cleveland, OH, United States of America; Case Western Reserve University School of Medicine, Cleveland, OH, United States of America; Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center, Cleveland, OH, United States of America
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Menculini G, Steardo L, Verdolini N, Cirimbilli F, Moretti P, Tortorella A. Substance use disorders in bipolar disorders: Clinical correlates and treatment response to mood stabilizers. J Affect Disord 2022; 300:326-333. [PMID: 34990627 DOI: 10.1016/j.jad.2022.01.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 11/06/2021] [Accepted: 01/01/2022] [Indexed: 12/17/2022]
Abstract
BACKGROUND Substance use disorders (SUD) in bipolar disorders (BD) present relevant impact on psychopathological features and illness course. The present study was aimed at analyzing the clinical correlates of this comorbidity. METHODS In- and outpatients suffering from BD were recruited. Socio-demographic and clinical characteristics were collected. Subjects underwent a psychopathological assessment evaluating affective temperaments and impulsiveness. The appraisal of treatment response to mood stabilizers was conducted with the Alda Scale. Bivariate analyses were used to compare subjects suffering from BD with (SUD-BD) or without comorbid SUD (nSUD-BD) (p<0.05). A logistic regression model was performed to identify specific correlates of SUD in BD. RESULTS Among the 161 included subjects, 63 (39.1%) were diagnosed with comorbid SUD. SUD-BD subjects showed younger age at onset (p = 0.003) and higher prevalence of BD type I diagnosis (BDI) (p<0.001). Furthermore, lifetime mixed features (p<0.001), psychotic symptoms (p<0.001), suicide attempts (p = 0.002), aggression (p = 0.003), antidepressant-induced manic switch (p = 0.003), and poor treatment response (p<0.001) were more frequent in the SUD-BD subgroup. At the logistic regression, SUD revealed a positive association with BD type I diagnosis (Odds Ratio (OR) 4.77, 95% CI 1.66-13.71, p = 0.004) and mixed features (OR 2.54, 95% CI 1.17-5.53, p = 0.019). LIMITATIONS The cross-sectional study design and the relatively small sample size may limit the generalizability of the findings. The retrospective evaluation of comorbid SUD could have biased the outcome assessment. CONCLUSIONS Subjects with BD and SUD are characterized by higher clinical severity and require careful assessment of treatment response.
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Affiliation(s)
| | - Luca Steardo
- Psychiatric Unit, Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Norma Verdolini
- Department of Psychiatry, University of Perugia, Perugia, Italy; Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain
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Coffman BA, Torrence N, Murphy T, Bebko G, Graur S, Chase HW, Salisbury DF, Phillips ML. Trait sensation seeking is associated with heightened beta-band oscillatory dynamics over left ventrolateral prefrontal cortex during reward expectancy. J Affect Disord 2021; 292:67-74. [PMID: 34102550 DOI: 10.1016/j.jad.2021.05.029] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 05/14/2021] [Accepted: 05/21/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Sensation Seeking, the proclivity toward novel and stimulating experiences, is associated with greater left ventrolateral prefrontal cortex (vlPFC) activity during uncertain reward expectancy. Here, we examined relationships between sensation seeking and vlPFC oscillatory dynamics using electroencephalography (EEG). METHODS In 26 adolescents/young adults (16 female; 22.3 ± 1.7yrs), EEG was measured during uncertain reward expectancy. Event-related spectral perturbations (ERSP) from 15-80 Hz (beta/gamma bands) were compared as a function of uncertain reward expected value and assessed for relationships with feedback-related negativity (FRN) response to outcome feedback and response tendency measures of risk for BD. RESULTS Event-related synchronization (ERS) between 15-25 Hz (beta) over left vlPFC was sensitive to the expected value of uncertain reward (rho=0.46; p = 0.048), and correlated with sensation seeking (r = 0.49, p < 0.01) and feedback-related negativity (FRN), where greater beta ERS was related to larger FRN (r = -0.39, p = 0.047). FRN was also related to behavioral inhibition (r = 0.49, p < 0.01). LIMITATIONS It is unknown whether results may extrapolate to clinical populations, given the healthy sample used here. Further, although we have confidence that the beta-band signal we measure in this study arises from left prefrontal cortex, we largely infer a left vlPFC source. CONCLUSIONS These findings highlight the role of left vlPFC in evaluation of immediate rewards. We now provide a link between reward expectancy-related left vlPFC activity and the well-characterized FRN, with a known role in attentive processing. These findings can guide treatment development for mania/hypomania at-risk individuals, including transcranial alternating current stimulation.
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Affiliation(s)
- Brian A Coffman
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
| | - Natasha Torrence
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
| | - Timothy Murphy
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
| | - Genna Bebko
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
| | - Simona Graur
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
| | - Henry W Chase
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
| | - Dean F Salisbury
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
| | - Mary L Phillips
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
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25
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Both C, Mechler K, Niemeyer L, Jennen-Steinmetz C, Hohmann S, Schumm L, Dittmann RW, Häge A. Medication Adherence in Adolescents with Psychiatric Disorders. ZEITSCHRIFT FUR KINDER-UND JUGENDPSYCHIATRIE UND PSYCHOTHERAPIE 2021; 49:295-306. [PMID: 34240621 DOI: 10.1024/1422-4917/a000813] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Objective: This study investigates whether adolescents' adherence to psychotropic medication is associated with demographic and socioeconomic factors, and to what extent parents' assessments of their offspring's attitudes toward treatment correspond with the adolescents' self-report. Methods: This study is part of the multicenter SEMA study (Subjective Experience and Medication Adherence in Adolescents with Psychiatric Disorders). Adolescents' subjective attitudes toward medication and their adherence were assessed using the patient and parent versions of the QATT (Questionnaire on Attitudes Toward Treatment) and the MARS (Medication Adherence Rating Scale). Furthermore, we collected socioeconomic and demographic data. Results: Of the n = 75 adolescents included in the study, n = 45 (60 %) were classified as completely adherent. Patients receiving monotherapy were more often completely adherent than those receiving a combination of different medications. There was no statistically significant association between adherence and demographic or socioeconomic factors. Consensus between adolescents and their parents regarding adolescents' attitudes toward treatment ranged from slight (κ = 0.157) to fair (κ = 0.205). Conclusion: Incomplete medication adherence in adolescents with psychiatric disorders is a common phenomenon and still poorly understood. Demographic and socioeconomic factors do not seem to be relevant in this respect. However, adolescents' subjective attitudes towards medication, which parents are presumably unable to adequately assess, warrant more careful consideration in future research.
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Affiliation(s)
- Clara Both
- Research Group of Pediatric Psychopharmacology, Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Konstantin Mechler
- Research Group of Pediatric Psychopharmacology, Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Larissa Niemeyer
- Research Group of Pediatric Psychopharmacology, Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Christine Jennen-Steinmetz
- Department of Biostatistics, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Sarah Hohmann
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Lucca Schumm
- Department of Child and Adolescent Psychiatry and Psychotherapy, Centre for Mental Health, Klinikum Stuttgart, Germany
| | - Ralf W Dittmann
- Research Group of Pediatric Psychopharmacology, Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Alexander Häge
- Research Group of Pediatric Psychopharmacology, Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
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Post RM, Grunze H. The Challenges of Children with Bipolar Disorder. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:601. [PMID: 34207966 PMCID: PMC8230664 DOI: 10.3390/medicina57060601] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/08/2021] [Accepted: 06/09/2021] [Indexed: 02/05/2023]
Abstract
Childhood onset bipolar disorder (CO-BD) presents a panoply of difficulties associated with early recognition and treatment. CO-BD is associated with a variety of precursors and comorbidities that have been inadequately studied, so treatment remains obscure. The earlier the onset, the longer is the delay to first treatment, and both early onset and treatment delay are associated with more depressive episodes and a poor prognosis in adulthood. Ultra-rapid and ultradian cycling, consistent with a diagnosis of BP-NOS, are highly prevalent in the youngest children and take long periods of time and complex treatment regimens to achieve euthymia. Lithium and atypical antipsychotics are effective in mania, but treatment of depression remains obscure, with the exception of lurasidone, for children ages 10-17. Treatment of the common comorbid anxiety disorders, oppositional defiant disorders, pathological habits, and substance abuse are all poorly studied and are off-label. Cognitive dysfunction after a first manic hospitalization improves over the next year only on the condition that no further episodes occur. Yet comprehensive expert treatment after an initial manic hospitalization results in many fewer relapses than traditional treatment as usual, emphasizing the need for combined pharmacological, psychosocial, and psycho-educational approaches to this difficult and highly recurrent illness.
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Affiliation(s)
- Robert M. Post
- School of Medicine, George Washington University, Washington, DC 20052, USA
- Bipolar Collaborative Network, 5415 W. Cedar Lane, Suite 201-B, Bethesda, MD 20814, USA
| | - Heinz Grunze
- Psychiatrie Schwäbisch Hall, Campus ZfPG, 74523 Schwäbisch Hall, Germany;
- Campus Nuremberg-Nord, Paracelsus Medical University, 90419 Nuremberg, Germany
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Halac E, Ciray RO, Turan S, Tuncturk M, Agac N, Elmas FN, Rosson S, Ermis C. Impaired theory of mind and emotion recognition in pediatric bipolar disorder: A systematic review and meta-analysis. J Psychiatr Res 2021; 138:246-255. [PMID: 33866053 DOI: 10.1016/j.jpsychires.2021.04.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 03/16/2021] [Accepted: 04/05/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND Social cognition is impaired in patients with severe mental disorders. We aimed to investigate impairments in social cognition in youth with pediatric bipolar disorder (PBD) through a systematic review of the literature and the meta-analysis. METHOD Following the PRISMA guidelines, we searched in PubMed, Scopus, and Cochrane CENTRAL for studies reporting on the theory of mind (ToM) and emotion recognition (ER) abilities of patients with PBD compared to healthy controls (HC). We conducted a random-effects model meta-analysis for the contrast between PBD and HC. Subgroup and meta-regression analyses were conducted for demographic and clinical variables as appropriate. RESULTS A total of thirteen studies involving 429 patients with PBD and 394 HC were included. Patients with PBD had significantly poorer social cognitive abilities (Hedges' g for ER, g = -0.74, CI = -0.91, -0.57; and for ToM, g = -0.98, CI = -1.41 to -0.55). Subgroup analysis also revealed significant impairment in ER for patients in a euthymic state (g = -0.75). Age, gender, sample size, the severity of mood symptoms, estimated IQ, the frequencies of bipolar-I disorder, attention-deficit hyperactivity disorder, medications, study quality and euthymia did not moderate the difference in meta-regression. Heterogeneity was low in all analyses and there was no evidence for publication bias. CONCLUSION The results of this meta-analysis supported the notion that PBD is associated with a deficit in social cognitive abilities at a medium to a large level. Impairments in social cognition could be an illness-related trait of PBD. Meta-regression results did not find a moderator of the deficits in social cognition.
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Affiliation(s)
- Eren Halac
- Dokuz Eylul University Faculty of Medicine, Department of Child and Adolescent Psychiatry, Izmir, Turkey.
| | | | - Serkan Turan
- Uludağ University Faculty of Medicine, Department of Child and Adolescent Psychiatry, Bursa, Turkey
| | - Mustafa Tuncturk
- İstanbul Bakirkoy Prof. Dr. Mazhar Osman Research and Training Hospital for Psychiatric and Neurological Diseases, Department of Child and Adolescent Psychiatry, Istanbul, Turkey
| | - Nilay Agac
- Dokuz Eylul University Faculty of Medicine, Department of Child and Adolescent Psychiatry, Izmir, Turkey
| | - Fatma Nur Elmas
- İstanbul Marmara University Faculty of Medicine, Department of Child and Adolescent Psychiatry, Istanbul, Turkey
| | - Stella Rosson
- ULSS 3 Serenissima, Psychiatric Unit, Venezia, Italy; University of Padova, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, Padova, Italy
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Fournier JC, Bertocci M, Ladouceur CD, Bonar L, Monk K, Abdul-Waalee H, Versace A, Santos JPL, Iyengar S, Birmaher B, Phillips ML. Neural function during emotion regulation and future depressive symptoms in youth at risk for affective disorders. Neuropsychopharmacology 2021; 46:1340-1347. [PMID: 33782511 PMCID: PMC8134479 DOI: 10.1038/s41386-021-01001-w] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 02/04/2021] [Accepted: 03/10/2021] [Indexed: 02/01/2023]
Abstract
Affective disorders (AD, including bipolar disorder, BD, and major depressive disorder) are severe recurrent illnesses. Identifying neural markers of processes underlying AD development in at-risk youth can provide objective, "early-warning" signs that may predate onset or worsening of symptoms. Using data (n = 34) from the Bipolar Offspring Study, we examined relationships between neural response in regions supporting executive function, and those supporting self-monitoring, during an emotional n-back task (focusing on the 2-back face distractor versus the 0-back no-face control conditions) and future depressive and hypo/manic symptoms across two groups of youth at familial risk for AD: Offspring of parents with BD (n = 15, age = 14.15) and offspring of parents with non-BD psychopathology (n = 19, age = 13.62). Participants were scanned and assessed twice, approximately 4 years apart. Across groups, less deactivation in the mid-cingulate cortex during emotional regulation (Rate Ratio = 3.07(95% CI:1.09-8.66), χ2(1) = 4.48, p = 0.03) at Time-1, and increases in functional connectivity from Time-1 to 2 (Rate Ratio = 1.45(95% CI:1.15-1.84), χ2(1) = 8.69, p = 0.003) between regions that showed deactivation during emotional regulation and the right caudate, predicted higher depression severity at Time-2. Both effects were robust to sensitivity analyses controlling for clinical characteristics. Decreases in deactivation between Times 1 and 2 in the right putamen tail were associated with increases in hypo/mania at Time-2, but this effect was not robust to sensitivity analyses. Our findings reflect neural mechanisms of risk for worsening affective symptoms, particularly depression, in youth across a range of familial risk for affective disorders. They may serve as potential objective, early-warning signs of AD in youth.
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Affiliation(s)
- Jay C. Fournier
- grid.21925.3d0000 0004 1936 9000University of Pittsburgh School of Medicine, Pittsburgh, PA USA
| | - Michele Bertocci
- grid.21925.3d0000 0004 1936 9000University of Pittsburgh School of Medicine, Pittsburgh, PA USA
| | - Cecile D. Ladouceur
- grid.21925.3d0000 0004 1936 9000University of Pittsburgh School of Medicine, Pittsburgh, PA USA
| | - Lisa Bonar
- grid.21925.3d0000 0004 1936 9000University of Pittsburgh School of Medicine, Pittsburgh, PA USA
| | - Kelly Monk
- grid.21925.3d0000 0004 1936 9000University of Pittsburgh School of Medicine, Pittsburgh, PA USA
| | - Halimah Abdul-Waalee
- grid.21925.3d0000 0004 1936 9000University of Pittsburgh School of Medicine, Pittsburgh, PA USA
| | - Amelia Versace
- grid.21925.3d0000 0004 1936 9000University of Pittsburgh School of Medicine, Pittsburgh, PA USA
| | - João Paulo Lima Santos
- grid.21925.3d0000 0004 1936 9000University of Pittsburgh School of Medicine, Pittsburgh, PA USA
| | - Satish Iyengar
- grid.21925.3d0000 0004 1936 9000University of Pittsburgh, Pittsburgh, PA USA
| | - Boris Birmaher
- grid.21925.3d0000 0004 1936 9000University of Pittsburgh School of Medicine, Pittsburgh, PA USA
| | - Mary L. Phillips
- grid.21925.3d0000 0004 1936 9000University of Pittsburgh School of Medicine, Pittsburgh, PA USA
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Liu X, Ma X, Wang W, Zhang J, Sun X, Luo X, Zhang Y. The functional impairment of different subtypes and occupational states in euthymic patients with bipolar disorder. BMC Psychiatry 2021; 21:240. [PMID: 33957876 PMCID: PMC8103625 DOI: 10.1186/s12888-021-03242-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 04/26/2021] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND The aim was to explore the associations between clinical symptoms, demographic variables, social and neurocognitive functioning in euthymic patients with bipolar disorder (BD) stratified by subgroups of DSM-IV BD (type I (BD-I) and type II (BD-II)) and occupational status (employed/unemployed), and to highlight the significance of occupational status when assessing social and neurocognitive functioning in euthymic BD patients. METHODS A total of 81 euthymic BD patients were participated in the study. The severity of the depressive and manic/hypomanic symptoms was measured using the 17-item Hamilton Depression Rating Scale (HDRS-17) and the Young Mania Rating Scale (YMRS), respectively. Social functioning and neurocognitive functioning were evaluated by the Functioning Assessment Short Test (FAST) and neurocognitive measures, respectively. RESULTS Employed BD patients displayed greater social functioning (autonomy, occupational functioning, interpersonal relationship domain) and better verbal learning performance and speed of processing than unemployed BD patients. The correlation between neurocognitive functioning and social functioning was stronger in the employed group than in the unemployed group. There were no significant differences in neurocognitive and social functioning between the BD-I and BD-II groups, and the correlation between neurocognitive functioning and social functioning was similar between the BD-I and BD-II groups. CONCLUSION Employed BD patients may present greater occupational functioning and interpersonal relationships, as well as better verbal learning performance and speed of processing.
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Affiliation(s)
- Xinyu Liu
- Henan Key Laboratory of Neurorestoratology, the first Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
- Unit of Bipolar Disorder, Tianjin Anding Hospital, 13 Liulin Road, Hexi District, Tianjin, 300222, China
| | | | - Wenchen Wang
- Unit of Bipolar Disorder, Tianjin Anding Hospital, 13 Liulin Road, Hexi District, Tianjin, 300222, China
| | - Jian Zhang
- Unit of Bipolar Disorder, Tianjin Anding Hospital, 13 Liulin Road, Hexi District, Tianjin, 300222, China
| | - Xia Sun
- Unit of Bipolar Disorder, Tianjin Anding Hospital, 13 Liulin Road, Hexi District, Tianjin, 300222, China
| | - Xingguang Luo
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
| | - Yong Zhang
- Henan Key Laboratory of Neurorestoratology, the first Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
- Unit of Bipolar Disorder, Tianjin Anding Hospital, 13 Liulin Road, Hexi District, Tianjin, 300222, China.
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Khafif TC, Rotenberg LDS, Nascimento C, Beraldi GH, Lafer B. Emotion regulation in pediatric bipolar disorder: A meta-analysis of published studies. J Affect Disord 2021; 285:86-96. [PMID: 33639359 DOI: 10.1016/j.jad.2021.02.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 01/14/2021] [Accepted: 02/01/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Emotion regulation is a relatively recent topic in psychiatry, and has only recently begun to be tested across Pediatric Bipolar Disorder (PBD). To date, no meta-analysis has investigated the presence of emotion regulation deficits in PBD patients. OBJECTIVES The aim of this study is to understand where the literature stands on this topic, as well as how different researchers are measuring and grasping the concept of emotion regulation in pediatric bipolar disorders. METHODS A systematic search of trials using the terms ("Pediatric Bipolar Disorder") AND ("Emotion Regulation" OR "Affect Regulation" OR "Mood Lability" OR "Mood Instability" OR "Irritability") was conducted using PubMed, Google Scholar, ResearchGate, Web of Science and Psych Info databases. Of the initial 366 articles identified, 8 met eligibility criteria for the meta-analysis and were included in this study. RESULTS There is a statistically significant difference in Accuracy in Emotion Regulation tasks, with a tendency for lower accuracy in PBD patients; however, both groups did not differ statistically regarding Response Time. CONCLUSION Our data suggests that PBD patients do present emotion regulation deficits, particularly regarding facial emotion recognition and affective language interference tasks mediated by cognitive assignments. These results have important implications in developing novel psychotherapeutic interventions for this population.
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Affiliation(s)
- Tatiana Cohab Khafif
- Bipolar Disorder Program (PROMAN), Department of Psychiatry, University of São Paulo Medical School, Rua Dr. Ovídio Pires de Campos, 785, São Paulo, Brazil.
| | - Luisa de Siqueira Rotenberg
- Bipolar Disorder Program (PROMAN), Department of Psychiatry, University of São Paulo Medical School, Rua Dr. Ovídio Pires de Campos, 785, São Paulo, Brazil
| | - Camila Nascimento
- Bipolar Disorder Program (PROMAN), Department of Psychiatry, University of São Paulo Medical School, Rua Dr. Ovídio Pires de Campos, 785, São Paulo, Brazil
| | - Gabriel Henrique Beraldi
- Bipolar Disorder Program (PROMAN), Department of Psychiatry, University of São Paulo Medical School, Rua Dr. Ovídio Pires de Campos, 785, São Paulo, Brazil
| | - Beny Lafer
- Bipolar Disorder Program (PROMAN), Department of Psychiatry, University of São Paulo Medical School, Rua Dr. Ovídio Pires de Campos, 785, São Paulo, Brazil
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MacPherson HA, Wolff J, Nestor B, Frazier E, Massing-Schaffer M, Graves H, Esposito-Smythers C, Spirito A. Parental Monitoring Predicts Depressive Symptom and Suicidal Ideation Outcomes in Adolescents Being Treated for Co-Occurring Substance Use and Psychiatric Disorders. J Affect Disord 2021; 284:190-198. [PMID: 33607509 PMCID: PMC7926270 DOI: 10.1016/j.jad.2021.02.021] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 01/30/2021] [Accepted: 02/03/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Comorbidity of substance use disorders (SUDs) with mood disorders and other psychiatric conditions is common. Parenting processes and family functioning are impaired in adolescents with SUDs and mood disorders, and parent/family factors predict intervention response. However, limited research has examined the relationship between parent/family factors and mood symptom treatment response in adolescents with comorbid SUDs and psychiatric conditions. METHOD This study examined the predictive effects of parenting processes and family functioning on depressive symptoms and suicidal ideation (SI) in a randomized controlled trial of integrated cognitive-behavioral therapy vs. treatment as usual for 111 adolescents with comorbid SUDs and psychiatric disorders. Measures of parenting processes, family functioning, depressive symptoms, and SI were completed at baseline and 3-, 6-, and 12-month follow-ups. Exploratory analyses involved mixed-effects regression models. RESULTS Across treatment conditions, depressive symptoms and SI improved over 12 months. Family functioning domains of family roles (d=0.47) and affective involvement (d=0.39) significantly improved across treatment conditions over 12 months. Higher baseline parental monitoring predicted improved trajectory of depressive symptoms (d=0.44) and SI (d=0.46). There were no significant predictive effects for baseline family functioning or other parenting processes (listening, limit setting). LIMITATIONS Limitations include the modest sample, attrition over follow-up, and generalizability to samples with higher rates of mood disorders and/or uncomplicated mood disorders. CONCLUSIONS Parental monitoring may be an important prognostic indicator of depressive symptoms and SI in adolescents with co-occurring SUDs and psychiatric conditions, and therefore may be useful to assess and target in treatment, in addition to family functioning.
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Affiliation(s)
- Heather A. MacPherson
- Department of Psychiatry and Human Behavior, Warren Alpert
Medical School of Brown University, Providence, RI, USA,Emma Pendleton Bradley Hospital, East Providence, RI,
USA,Corresponding Author: Heather A. MacPherson, 1011
Veterans Memorial Parkway, East Providence, RI 02915, Phone: (401) 432-1162,
Fax: (401) 432-1607,
| | - Jennifer Wolff
- Department of Psychiatry and Human Behavior, Warren Alpert
Medical School of Brown University, Providence, RI, USA,Rhode Island Hospital, Providence, RI, USA
| | - Bridget Nestor
- Department of Psychiatry and Human Behavior, Warren Alpert
Medical School of Brown University, Providence, RI, USA
| | - Elisabeth Frazier
- Department of Psychiatry and Human Behavior, Warren Alpert
Medical School of Brown University, Providence, RI, USA,Emma Pendleton Bradley Hospital, East Providence, RI,
USA
| | - Maya Massing-Schaffer
- Department of Psychiatry and Human Behavior, Warren Alpert
Medical School of Brown University, Providence, RI, USA
| | - Hannah Graves
- Department of Psychiatry and Human Behavior, Warren Alpert
Medical School of Brown University, Providence, RI, USA
| | | | - Anthony Spirito
- Department of Psychiatry and Human Behavior, Warren Alpert
Medical School of Brown University, Providence, RI, USA
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Cirone C, Secci I, Favole I, Ricci F, Amianto F, Davico C, Vitiello B. What Do We Know about the Long-Term Course of Early Onset Bipolar Disorder? A Review of the Current Evidence. Brain Sci 2021; 11:brainsci11030341. [PMID: 33800274 PMCID: PMC8001096 DOI: 10.3390/brainsci11030341] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 03/02/2021] [Accepted: 03/02/2021] [Indexed: 11/29/2022] Open
Abstract
Aim: Early onset of psychopathology is often an index of a more severe clinical course and worse prognosis. This review examined the course of bipolar disorder (BD) with onset in childhood and adolescence, with a focus on persistence of symptoms, severity of illness, comorbidity, and functional impairment. Methods: The databases of PubMed, Embase, and PsycInfo were systematically searched for publications since 1990 reporting on long-term (12 months or longer) assessments of patients with early onset BD. Results: Forty-two relevant publications were identified, which reported on data derived from 15 different patient cohorts, including 7 prospective research psychopathology studies, 4 medical record reviews, 2 follow-ups of clinical trial samples, 1 managed care database, and 1 nationwide registry, for a total of 10,187 patients. The length of follow-ups ranged from 1.0 to 15 years. Diagnostic stability of BD ranged from 73% to 100% over ten years. Recovery rate from an index episode was 81.5–100% and recurrence rate was 35–67%. Suicide attempt cumulative prevalence in five years was 18–20%. Earlier age at the first episode predicted a more severe clinical course. Conclusions: Early onset BD persists over time through adolescence, with homotypic diagnostic continuity over the years, but heterogeneity in the severity of the clinical course. Whether early identification and treatment improves distal prognosis remains to be further investigated.
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Affiliation(s)
- Carlotta Cirone
- Child and Adolescent Neuropsychiatry—Department of Public Health and Pediatric Sciences, Universita’ degli Studi di Torino, 10126 Turin, Italy; (C.C.); (I.S.); (I.F.); (F.R.); (B.V.)
| | - Ilaria Secci
- Child and Adolescent Neuropsychiatry—Department of Public Health and Pediatric Sciences, Universita’ degli Studi di Torino, 10126 Turin, Italy; (C.C.); (I.S.); (I.F.); (F.R.); (B.V.)
| | - Irene Favole
- Child and Adolescent Neuropsychiatry—Department of Public Health and Pediatric Sciences, Universita’ degli Studi di Torino, 10126 Turin, Italy; (C.C.); (I.S.); (I.F.); (F.R.); (B.V.)
| | - Federica Ricci
- Child and Adolescent Neuropsychiatry—Department of Public Health and Pediatric Sciences, Universita’ degli Studi di Torino, 10126 Turin, Italy; (C.C.); (I.S.); (I.F.); (F.R.); (B.V.)
| | - Federico Amianto
- Child and Adolescent Neuropsychiatry—Department of Neurosciences, Universita’ degli Studi di Torino, 10126 Turin, Italy;
| | - Chiara Davico
- Child and Adolescent Neuropsychiatry—Department of Public Health and Pediatric Sciences, Universita’ degli Studi di Torino, 10126 Turin, Italy; (C.C.); (I.S.); (I.F.); (F.R.); (B.V.)
- Correspondence:
| | - Benedetto Vitiello
- Child and Adolescent Neuropsychiatry—Department of Public Health and Pediatric Sciences, Universita’ degli Studi di Torino, 10126 Turin, Italy; (C.C.); (I.S.); (I.F.); (F.R.); (B.V.)
- Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
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Sanchez M, Lytle S, Neudecker M, McVoy M. Medication Adherence in Pediatric Patients with Bipolar Disorder: A Systematic Review. J Child Adolesc Psychopharmacol 2021; 31:86-94. [PMID: 33465006 DOI: 10.1089/cap.2020.0098] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Objectives: Pediatric bipolar disorder is a severe disabling condition affecting 1%-3% of youth worldwide. Both acute and maintenance treatment with medications are mainstays of treatment. It is well established in adult literature that adherence to medications improves outcomes and many adult studies have examined factors impacting adherence. This systematic review set out to identify the current state of research examining adherence to medications and characteristics influencing adherence in pediatric bipolar disorder. Methods: We performed a systematic literature review in the Medline, PsycINFO, CINAHL, EMBASE, Wiley Clinical Trials, and Cochrane databases. New research regarding characteristics and measurement of adherence to psychotropic medication for bipolar disorder (I, II, or not otherwise specified) in patients ≤18 years old were included for review. Exclusion criteria included no bipolar diagnosis, inclusion of patients >18 years old, no pharmacologic treatment, and lack of adherence measurements. Results: Initial search generated 439 articles after duplicate removal. One hundred thirty-three full-text articles were reviewed, 16 underwent additional review and 6 were selected for final inclusion. The majority of articles were excluded for patients >18 years old. Included articles were extremely heterogeneous for multiple measures, including methodology, determination of adherence, adherence rates, and characteristics influencing adherence. Of medications evaluated, 6/6 studies included mood stabilizers, 4/6 antidepressants, 3/6 antipsychotics, and 2/6 psychostimulants. Three out of six articles included patients <12 years old. Some significant factors affecting adherence included polypharmacy, comorbid psychiatric diagnoses, socioeconomic status, sex, family history and functioning, side effects, race, stability of bipolar diagnosis, and number of follow-up visits attended. Conclusions: Pediatric-specific information on medication adherence in bipolar disorder is very limited. Information on patient characteristics that may influence adherence rates is critical to target interventions to improve adherence. No articles reported on interventions to improve adherence. Given the different psychosocial situations of pediatric patients versus adults, it is likely that targets for improving adherence differ in pediatric patients.
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Affiliation(s)
- Matthew Sanchez
- Department of Child and Adolescent Psychiatry, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.,Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Sarah Lytle
- Department of Child and Adolescent Psychiatry, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.,Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Mandy Neudecker
- Rainbow Babies and Children's Hospital, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Molly McVoy
- Department of Child and Adolescent Psychiatry, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.,Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.,Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
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34
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Saunders H, Osuch E, Anderson K, Martin J, Kunnilathu A, John-Baptiste A. Factors associated with initiation of community-based therapy for emerging adults with mood and anxiety disorders. Early Interv Psychiatry 2021; 15:123-132. [PMID: 31975541 DOI: 10.1111/eip.12920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Revised: 11/05/2019] [Accepted: 12/14/2019] [Indexed: 11/29/2022]
Abstract
AIM The First Episode Mood and Anxiety Program (FEMAP) is a community-based early intervention program that has been shown to improve health outcomes for emerging adults (EAs) with mood and anxiety disorders. However, not all EAs who are admitted to the program initiate treatment. Our aim was to identify factors that distinguish those who initiated treatment from those who did not. METHODS FEMAP administered questionnaires to EAs upon first contact with the program, collecting information on a range of socioeconomic, patient and condition-related factors. We compared EAs who initiated treatment in the program (n = 318, 87.4%) to those who did not (n = 46, 12.6%). To examine factors associated with treatment initiation, we specified a parsimonious logistic regression model, using the method of purposeful selection to choose from a range of candidate variables. RESULTS Anxiety Sensitivity Index - Revised (ASI-R), binge drinking and cannabis use were included in the final logistic regression model. Each one-point increment in the ASI-R score was associated with a 1% increase in the odds of treatment initiation (OR = 1.014; 95% CI [1.003, 1.026]). No other variable was significantly associated with treatment initiation. CONCLUSIONS Our study provides insight on the differences between EAs with mood and anxiety disorders who initiated targeted treatment services and those who did not. Anxiety sensitivity was significantly associated with treatment initiation at FEMAP. Our findings suggest that it may be anxiety sensitivity, rather than depression or functional impairment per se that drive treatment initiation among EAs.
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Affiliation(s)
- Hailey Saunders
- Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
| | - Elizabeth Osuch
- Department of Psychiatry, Schulich School of Medicine and Dentistry, Western University, First Episode Mood and Anxiety Program (FEMAP), London Health Sciences Centre, Lawson Health Research Institute, London, ON, Canada
| | - Kelly Anderson
- Department of Epidemiology and Biostatistics, Department of Psychiatry, Schulich School of Medicine and Dentistry, Lawson Health Research Institute, London, ON, Canada
| | - Janet Martin
- Department of Anesthesia and Perioperative Medicine, Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Centre for Medical Evidence, Decision Integrity and Clinical Impact (MEDICI Centre), London, ON, Canada
| | - Abraham Kunnilathu
- Department of Anesthesia and Perioperative Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
| | - Ava John-Baptiste
- Department of Anesthesia and Perioperative Medicine,Department of Epidemiology and Biostatistics, Schulich Interfaculty Program in Public Health, Schulich School of Medicine and Dentistry, Western University, Centre for Medical Evidence, Decision Integrity and Clinical Impact (MEDICI Centre), Lawson Health Research Institute, London, ON, Canada
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35
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Weintraub MJ, Schneck CD, Walshaw PD, Chang KD, Sullivan AE, Singh MK, Miklowitz DJ. Longitudinal trajectories of mood symptoms and global functioning in youth at high risk for bipolar disorder. J Affect Disord 2020; 277:394-401. [PMID: 32861841 PMCID: PMC7572604 DOI: 10.1016/j.jad.2020.08.018] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 05/26/2020] [Accepted: 08/08/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND Little is known about the longitudinal course of mood symptoms and functioning in youth who are at high risk for bipolar disorder (BD). Identifying distinct course trajectories and predictors of those trajectories may help refine treatment approaches. METHODS This study examined the longitudinal course of mood symptoms and functioning ratings in 126 youth at high risk for BD based on family history and early mood symptoms. Participants were enrolled in a randomized trial of family-focused therapy and followed longitudinally (mean 2.0 years, SD = 53.6 weeks). RESULTS Using latent class growth analyses (LCGA), we observed three mood trajectories. All youth started the study with active mood symptoms. Following the index mood episode, participants were classified as having a "significantly improving course" (n = 41, 32.5% of sample), a "moderately symptomatic course" (n = 21, 16.7%), or a "predominantly symptomatic course" (n = 64, 50.8%) at follow-up. More severe depression, anxiety, and suicidality at the study's baseline were associated with a poorer course of illness. LCGA also revealed three trajectories of global functioning that closely corresponded to symptom trajectories; however, fewer youth exhibited functional recovery than exhibited symptomatic recovery. LIMITATIONS Mood trajectories were assessed within the context of a treatment trial. Ratings of mood and functioning were based on retrospective recall. CONCLUSIONS This study suggests considerable heterogeneity in the course trajectories of youth at high risk for BD, with a significant proportion (32.5%) showing long-term remission of symptoms. Treatments that enhance psychosocial functioning may be just as important as those that ameliorate symptoms in youth at risk for BD.
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Affiliation(s)
- Marc J Weintraub
- Semel Institute of Neuroscience and Human Behavior, University of California, 760 Westwood Plaza, A7-370, Los Angeles 90095, CA, USA.
| | | | - Patricia D Walshaw
- Semel Institute of Neuroscience and Human Behavior, University of California, 760 Westwood Plaza, A7-370, Los Angeles 90095, CA, USA
| | | | - Aimee E Sullivan
- School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | | | - David J Miklowitz
- Semel Institute of Neuroscience and Human Behavior, University of California, 760 Westwood Plaza, A7-370, Los Angeles 90095, CA, USA
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36
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Nery FG, Wilson AR, Schneider MR, Strawn JR, Patino LR, McNamara RK, Adler CM, Strakowski SM, DelBello MP. Medication exposure and predictors of first mood episode in offspring of parents with bipolar disorder: a prospective study. ACTA ACUST UNITED AC 2020; 42:481-488. [PMID: 32401870 PMCID: PMC7524417 DOI: 10.1590/1516-4446-2019-0802] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 03/01/2020] [Indexed: 12/14/2022]
Abstract
OBJECTIVES To prospectively investigate whether baseline clinical characteristics and medication exposure predict development of major depressive disorder or bipolar disorder in offspring of parents with bipolar disorder. METHODS Youth aged 9-20 years with at least one biological parent with bipolar disorder and no prior history of mood or psychotic episodes (n=93) were prospectively evaluated and treated naturalistically during the study. Participants were divided into two groups: converters, defined as those who met DSM-IV criteria for a mood episode during follow-up (n=19); or non-converters (n=74). Logistic regression models were used to investigate associations between baseline clinical variables and medication exposure during follow-up and risk of developing a first mood episode (conversion). RESULTS Multivariate regression analyses showed that baseline anxiety disorders and subsyndromal mood disorders were associated with increased risk of conversion during follow-up. Adding medication exposure to the multivariate model showed that exposure to antidepressants during follow-up was associated with increased risk of conversion. CONCLUSIONS Caution should be used when treating bipolar offspring with anxiety and/or emerging depressive symptoms using antidepressant agents, given the increased risk of developing a major mood disorder.
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Affiliation(s)
- Fabiano G Nery
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Anna R Wilson
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | | | - Jeffrey R Strawn
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Luis R Patino
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Robert K McNamara
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Caleb M Adler
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Stephen M Strakowski
- Department of Psychiatry, Dell Medical School, University of Texas at Austin, Austin, TX, USA
| | - Melissa P DelBello
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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37
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Birmaher B, Merranko JA, Gill MK, Hafeman D, Goldstein T, Goldstein B, Hower H, Strober M, Axelson D, Ryan N, Yen S, Diler R, Iyengar S, Kattan MW, Weinstock L, Keller M. Predicting Personalized Risk of Mood Recurrences in Youths and Young Adults With Bipolar Spectrum Disorder. J Am Acad Child Adolesc Psychiatry 2020; 59:1156-1164. [PMID: 31978620 PMCID: PMC7371512 DOI: 10.1016/j.jaac.2019.12.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 12/04/2019] [Accepted: 01/14/2020] [Indexed: 12/14/2022]
Abstract
OBJECTIVE With each recurrence the prognosis of bipolar disorder (BD) worsens, indicating the need to identify the factors associated with increased recurrence risk. The course of BD is heterogenous and although risk factors for recurrence for the group as a whole have been reported in the literature, identification of risk factors for a specific individual are crucial for developing personalized treatments. METHOD A total of 363 recovered BD youths/young adults from the Course and Outcome of Bipolar Youth (COBY) study were included. Participants were evaluated on average every 7 months for a median of 12.5 years and interviewed with standard instruments. Risk factors of recurrence from the literature were used to build a risk calculator (RC) to predict recurrence risk at different time intervals. RESULTS Approximately 80% of participants had at least one syndromal recurrence and 60% had ≥2 recurrences, particularly depressions. The 6-month and 1-, 2-, 3-, and 5-year RC showed an accuracy between 72% and 82% for predicting any mood recurrences, and up to 80% for depression and 89% for hypo/mania (sensitivity/specificity both 0.74). The most influential recurrence risk factors were shorter recovery lengths, younger age at assessment, earlier mood onset, and more severe prior depression. Although important, other factors associated with recurrence risk, such as interepisodic subsyndromal mood symptoms and comorbidities, did not influence the RC score beyond factors noted above. CONCLUSION The RC provides a useful tool for predicting an individual's recurrence risk of depression and/or hypo/mania in BD youths and for developing personalized interventions and informing research. Replication studies are warranted.
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Affiliation(s)
- Boris Birmaher
- Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
| | - John A. Merranko
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Mary Kay Gill
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Danella Hafeman
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Tina Goldstein
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Benjamin Goldstein
- Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto Faculty of Medicine, Ontario, Canada
| | - Heather Hower
- Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University; Butler Hospital, Providence, Rhode Island
| | - Michael Strober
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California
| | - David Axelson
- Department of Psychiatry, Nationwide Children’s Hospital and The Ohio State College of Medicine, Columbus, Ohio
| | - Neal Ryan
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Shirley Yen
- Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University; Butler Hospital, Providence, Rhode Island
| | - Rasim Diler
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Satish Iyengar
- Department of Statistics, University of Pittsburgh, 2717 Cathedral of Learning, Pittsburgh, PA
| | | | - Lauren Weinstock
- Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University; Butler Hospital, Providence, Rhode Island
| | - Martin Keller
- Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University; Butler Hospital, Providence, Rhode Island
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Post RM, Rowe M, Kaplin DB, Findling R. Preliminary evaluation of the utility of parental ratings in a Child Network. Psychiatry Res 2020; 290:112908. [PMID: 32480114 DOI: 10.1016/j.psychres.2020.112908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 03/02/2020] [Accepted: 03/05/2020] [Indexed: 10/24/2022]
Abstract
INTRODUCTION Children in the US have a high incidence of psychiatric disorders, but the symptoms of these illnesses are often poorly recognized and treated. We thus created a Child Network for parents of children aged 2-12 to rate their child on a weekly basis on a secure website so that longitudinal ratings could be easily visualized. METHODS After giving informed consent, parents filled out: a one-time questionnaire and a 97 item Child Checklist; and then rated the severity of depression, anxiety, ADHD, oppositional behavior, and mania each week. The new Checklist ratings were correlated with the 23 previous validated in adults (the M-3), and symptom burden was compared with diagnoses received in the community. RESULTS The 23 item M-3 ratings were highly correlated with the more extensive Child Checklist. Symptom severity also corresponded to diagnoses received in the community. An example of the longitudinal weekly ratings of a child with a dysphoric mania is also presented. CONCLUSIONS The convergence of scores on the adult and child portions of the Child Checklist and the ease of visualization of symptoms and response to treatment suggest the utility of the ratings in the Child Network.
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Affiliation(s)
- Robert M Post
- Clinical Professor of Psychiatry, George Washington University School of Medicine, Bipolar Collaborative Network, 5415 W. Cedar Lane, Suite 201-B, Bethesda, MD 20814, USA.
| | - Michael Rowe
- Bipolar Collaborative Network, 5415 W. Cedar Lane, Suite 201-B, Bethesda, MD 20814, USA
| | - Dana B Kaplin
- Sr. Clinical Research Program Manager, Clinical Trials Group, Department of Radiation Oncology and Molecular Radiation Sciences, 1550 Orleans Street, CRBll, 4M53, Baltimore, MD 21287, USA
| | - Robert Findling
- Chair, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
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Clinical correlates of socioeconomic status in adolescent bipolar disorder. Compr Psychiatry 2020; 101:152186. [PMID: 32504872 DOI: 10.1016/j.comppsych.2020.152186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 04/21/2020] [Accepted: 05/22/2020] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Lower socioeconomic status (SES) is associated with symptomatic severity, comorbidity, and functional impairment in adults with bipolar disorder (BD). Little is known about clinical correlates of SES in adolescents with BD. METHODS Participants included 195 adolescents, 13-20 years old, with BD type I, II or not otherwise specified (NOS). Diagnoses were determined by standardized semi-structured interviews. Based on the Hollingshead scale, participants were divided into "low" (SES 1-3) and the "high" (SES 4-5) SES groups. Demographic and clinical correlates of SES were evaluated in univariate analyses; significant variables were evaluated in a logistic regression model. RESULTS Compared to participants in the high SES group (n = 150), participants in the low SES group (n = 45) were significantly younger, less likely to be of Caucasian race and living with natural parents. In the logistic regression model, controlling for age and race, the low SES group had higher risk of police contact or arrest (OR = 2.41, 95% CI:1.14-5.11, p = 0.022), less treatment with stimulants(OR = 0.20 95% CI: 0.06-0.67, p = 0.009), and more post-traumatic stress disorder (PTSD) (OR = 4.08, 95% CI:1.33-12.46, p = 0.014) compared to the high SES group. In sensitivity analyses that further controlled for intact family, the finding of higher rates of police contact or arrest was no longer significant. LIMITATIONS Cross-sectional design; higher-skewed SES sample. CONCLUSIONS Lower SES in adolescent BD is associated with higher legal risk, increased PTSD, and under-treatment of attention-deficit/hyperactivity disorder (ADHD). Future studies are needed to evaluate the inter-relationships of these correlates, using prospective designs that can evaluate the direction of these associations. Further studies incorporating neurobiological markers are also needed to explore mechanisms underlying SES-related differences in BD.
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Klein CC, Topalian AG, Starr B, Welge J, Blom T, Starr C, Deetz I, Turner H, Sage J, Utecht J, Fornari V, Patino Duran L, Higdon C, Sutton JJ, Sorter MT, Correll CU, DelBello MP. The Importance of Second-Generation Antipsychotic-Related Weight Gain and Adherence Barriers in Youth with Bipolar Disorders: Patient, Parent, and Provider Perspectives. J Child Adolesc Psychopharmacol 2020; 30:376-380. [PMID: 32423240 DOI: 10.1089/cap.2019.0184] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Objectives: The objective of this research was to understand physician, patient, and parent perspectives on barriers to second-generation antipsychotic (SGA) medication adherence in youth with bipolar spectrum disorders, and attitudes toward treatment of SGA-related weight gain. Methods: Patients diagnosed with bipolar disorder before age 18, parents of children diagnosed before 18, and clinicians with experience prescribing SGAs for these patients completed surveys regarding SGA-related side effects, adherence barriers, and acceptability of weight management strategies. Results: Patients (n = 225), parents (n = 128), and clinicians (n = 54) reported weight gain as the most concerning SGA-related side effect (45.6%, 38.9%, and 70.4%, respectively). Weight gain was also the top adherence barrier for patients (35.9%), but was ranked fourth (41.8%) by parents. Patients (61.5%) were more likely "definitely" willing to co-initiate another medication to manage weight gain upon SGA initiation than parents (20.1%) or clinicians (1.9%). Conversely, parents (54.9%) and clinicians (84.9%) were "definitely" willing to accept/prescribe a second medication aiming to reverse weight gain of ≥10 lbs., and patients (61.1%) were willing to add another medication to reverse any weight gain. Conclusion: SGA-related weight gain impairs medication adherence in young patients with bipolar disorder. Many young patients would start pharmacologic treatment to mitigate SGA-related weight gain at treatment initiation, parents and clinicians are more hesitant. This research informs patient-centered perspectives on SGA adherence barriers and strategies to minimize potential side effects, which may improve adherence in this vulnerable patient population.
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Affiliation(s)
- Christina C Klein
- Division of Bipolar Disorders Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Alique G Topalian
- Division of Bipolar Disorders Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Brian Starr
- Division of Bipolar Disorders Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Jeffrey Welge
- Division of Bipolar Disorders Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Thomas Blom
- Division of Bipolar Disorders Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Cindy Starr
- Mayfield Brain and Spine, Cincinnati, Ohio, USA
| | - Ingrid Deetz
- Depression and Bipolar Support Alliance, Chicago, Illinois, USA
| | - Heather Turner
- National Alliance on Mental Illness, Southwest Ohio, Cincinnati, Ohio, USA
| | - Jessica Sage
- Division of Child and Adolescent Psychiatry, Cincinnati, Ohio, USA
| | - Jenna Utecht
- Division of Bipolar Disorders Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Victor Fornari
- Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra, Hempstead, New York, USA
- Department of Psychiatry, The Zucker Hillside Hospital and Zucker School of Medicine at Hofstra, Hempstead, New York, USA
| | - Luis Patino Duran
- Division of Bipolar Disorders Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Claudine Higdon
- Department of Psychiatry, The Zucker Hillside Hospital and Zucker School of Medicine at Hofstra, Hempstead, New York, USA
| | - John J Sutton
- Cincinnati Children's Hospital and Medical Center, Cincinnati, Ohio, USA
| | - Michael T Sorter
- Division of Child and Adolescent Psychiatry, Cincinnati, Ohio, USA
| | - Christoph U Correll
- Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra, Hempstead, New York, USA
- Department of Psychiatry, The Zucker Hillside Hospital and Zucker School of Medicine at Hofstra, Hempstead, New York, USA
- Department of Child and Adolescent Psychiatry, Psychosomatic Medicine and Psychotherapy, Charité Universitätsmedizin, Berlin, Germany
| | - Melissa P DelBello
- Division of Bipolar Disorders Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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Saito E, Eng S, Grosso C, Ozinci Z, Van Meter A. Pro Re Nata Medication Use in Acute Care Adolescent Psychiatric Unit. J Child Adolesc Psychopharmacol 2020; 30:250-260. [PMID: 31800304 DOI: 10.1089/cap.2019.0131] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Objective: Evidence to support the use of pro re nata (PRN) medication is limited, and the details of PRN use (indication, frequency of administration, patient characteristics) are rarely reported, particularly in youth populations. The goal of this study was to report on the pattern of PRN use over 6 years in an acute care psychiatric unit for adolescents. Methods: A retrospective chart review of patients' records from November 2012 to October 2018 was conducted. Variables extracted from electronic medical records included age, gender, race/ethnicity, clinical rating scores at admission (on a subset of patients), length of stay, psychotropic and nonpsychotropic PRN medication administration, timing of administration, discharge diagnosis, and discharge medication. Results: Records from 2961 individuals with a total 3937 admissions were analyzed. A total of 62% of admissions had at least one PRN medication administration. Severity of symptoms, as indicated by higher scores on clinical rating scales at admission, longer length of stay, and readmission were related to high PRN use. Patients with bipolar spectrum disorders received more psychotropic and nonpsychotropic PRN medications than other patients. Patients who were high psychotropic PRN users were also high nonpsychotropic PRN users. Conclusion: Despite the lack of clear evidence in support of the efficacy of PRN medications, they commonly used to control symptoms in acute care inpatient settings. Youth with severe symptoms utilized not only psychotropic PRN medication but also nonpsychotropic PRN more frequently, suggesting a possible role of systemic disorder among youth with serious mental illness. More research is necessary to examine the efficacy of PRN medications for managing targeted symptoms.
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Affiliation(s)
- Ema Saito
- Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, New York, USA.,Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA
| | - Stephanie Eng
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA
| | - Christine Grosso
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA
| | - Zeynep Ozinci
- Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, New York, USA
| | - Anna Van Meter
- Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, New York, USA.,Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA.,Feinstein Institutes of Medical Research, Glen Oaks, New York, USA
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Yapıcı Eser H, Taşkıran AS, Ertınmaz B, Mutluer T, Kılıç Ö, Özcan Morey A, Necef I, Yalçınay İnan M, Öngür D. Anxiety disorders comorbidity in pediatric bipolar disorder: a meta-analysis and meta-regression study. Acta Psychiatr Scand 2020; 141:327-339. [PMID: 31899546 DOI: 10.1111/acps.13146] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/26/2019] [Indexed: 01/18/2023]
Abstract
OBJECTIVE Anxiety disorders (AD) are known for its comorbidity and negative impact on the course of adult bipolar disorder (BD). However, there is limited research on AD comorbidity in pediatric BD (PBD). Here, we aimed to conduct a meta-analysis and meta-regression study about the comorbidity and covariates of AD and PBD. METHOD We systematically searched relevant articles published until May 2019, as defined in PRISMA guidelines. Variables for associated features and prevalence of AD were extracted. RESULTS Thirty-seven articles represented data for the analysis. Lifetime any AD comorbidity was 44.7%; panic disorder (PD) was 12.7%; generalized anxiety disorder (GAD) was 27.4%; social phobia was 20.1%; separation anxiety disorder (SAD) was 26.1%; and obsessive-compulsive disorder (OCD) was 16.7%. Childhood-onset studies reported higher GAD and SAD comorbidity, while adolescent-onset studies reported higher PD, OCD, and social phobia. Age of onset, gender, comorbidity of ADHD, substance use, oppositional defiant disorder and conduct disorder affected each anxiety disorders' comorbidity with PBD differently. CONCLUSION Anxiety disorders are highly comorbid with PBD. Early-onset PBD increases the risk of AD. Biopsychosocial aspects of this comorbidity and its course needs to be evaluated further.
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Affiliation(s)
- H Yapıcı Eser
- School of Medicine, Department of Psychiatry, Koç University, İstanbul, Turkey.,Research Center for Translational Medicine, Koç University, İstanbul, Turkey
| | - A S Taşkıran
- School of Medicine, Department of Psychiatry, Koç University, İstanbul, Turkey.,Child Mind Institute, New York, NY, USA
| | - B Ertınmaz
- School of Medicine, Koç University, İstanbul, Turkey
| | - T Mutluer
- School of Medicine, Department of Psychiatry, Koç University, İstanbul, Turkey
| | - Ö Kılıç
- Koç University Hospital, İstanbul, Turkey
| | | | - I Necef
- Koç University Hospital, İstanbul, Turkey
| | | | - D Öngür
- Harvard Medical School, Boston, MA, USA.,McLean Hospital, Belmont, MA, USA
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Goldstein TR, Krantz ML, Fersch-Podrat RK, Hotkowski NJ, Merranko J, Sobel L, Axelson D, Birmaher B, Douaihy A. A brief motivational intervention for enhancing medication adherence for adolescents with bipolar disorder: A pilot randomized trial. J Affect Disord 2020; 265:1-9. [PMID: 31957686 PMCID: PMC8713513 DOI: 10.1016/j.jad.2020.01.015] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Revised: 12/30/2019] [Accepted: 01/03/2020] [Indexed: 11/17/2022]
Abstract
BACKGROUND Youth with bipolar disorder (BP) exhibit poor medication adherence, contributing to affective recurrence. Brief Motivational Interventions (BMIs) improve adherence among adolescents with chronic conditions. METHODS In an open pilot series, we developed a 3-session BMI for BP adolescents targeting medication adherence and conducted a pilot randomized trial comparing Standard Care (SC) versus SC+BMI. Participants include 43 adolescents with BP prescribed psychotropic medications. We assessed medication adherence objectively via bluetooth-enabled electronic pillbox (MedTracker). A blinded evaluator assessed mood symptoms at intake, 3- and 6-months. RESULTS The BMI was well-received. Average objective medication adherence increased with time in SC+BMI, but decreased in SC-Alone (p < 0.0001). Adolescents' baseline self-rated expectation of improvement with treatment moderated the effect of treatment on improvement in adherence over time (p = 0.003). Across groups, poor adherence predicted increased likelihood of depression and hypo/mania symptoms in the subsequent two weeks; medication adherence mediated the effect of the BMI on the likelihood of depressive symptoms (p = 0.007). LIMITATIONS Electronic pillbox use (across groups) may enhance adherence, resulting in overestimates compared with naturalistic conditions. This pilot randomized trial may have been underpowered to detect some group differences. CONCLUSIONS A BMI offers promise as a disseminable adjunctive intervention for improving medication adherence for adolescents with BP. Future studies with larger samples can establish efficacy. NCT03203720.
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Affiliation(s)
- Tina R. Goldstein
- Western Psychiatric Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Megan L. Krantz
- Western Psychiatric Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | | | - Nina J. Hotkowski
- Western Psychiatric Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - John Merranko
- Western Psychiatric Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Loren Sobel
- Western Psychiatric Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - David Axelson
- Nationwide Children’s Hospital, The Ohio State University, Columbus, Ohio
| | - Boris Birmaher
- Western Psychiatric Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Antoine Douaihy
- Western Psychiatric Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
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Weintraub MJ, Schneck CD, Axelson DA, Birmaher B, Kowatch RA, Miklowitz DJ. Classifying Mood Symptom Trajectories in Adolescents With Bipolar Disorder. J Am Acad Child Adolesc Psychiatry 2020; 59:381-390. [PMID: 31150753 PMCID: PMC6881540 DOI: 10.1016/j.jaac.2019.04.028] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Revised: 03/08/2019] [Accepted: 04/23/2019] [Indexed: 11/17/2022]
Abstract
OBJECTIVE The Course and Outcome of Bipolar Youth study found that children and adolescents with bipolar spectrum disorders followed 1 of 4 distinct mood trajectories over 8 years of follow-up, with as many as 25% of participants showing a predominantly euthymic course. We evaluated whether similar patterns of illness course are observed in adolescents with bipolar I and II disorder who participated in a 2-year clinical trial. METHOD A total of 144 adolescents with bipolar I or II disorder, identified shortly after a mood episode, were assessed over a 2-year period. Participants were randomly assigned to one of 2 psychosocial family treatments during the first 9 months of the study, and pharmacotherapy was provided throughout the 2 years. Using latent class growth analyses, we classified participants into distinct courses of illness based on mood ratings collected over the 2 years. We examined demographic and illness variables as predictors of these course classifications. RESULTS Latent class growth analyses indicated four mood trajectories: "predominantly euthymic" (29.9% of sample), "ill with significantly improving course" (11.1%), "moderately euthymic" (26.4%), and "ill with moderately improving course" (32.6%). Adolescents in these classes were euthymic 77.7%, 53.6%, 44.1%, and 18.6% of the weeks of follow-up, respectively. Psychosocial treatment condition and baseline medication exposure were not associated with trajectories. However, youth with more severe baseline depressive symptoms, suicidality, lower quality of life scores, and minority race/ethnicity had more symptomatic courses of illness over time. CONCLUSION A substantial proportion (25%-30%) of youth with bipolar I or II disorder maintain euthymic states over extended periods of follow-up. Identifying youth who are more and less likely to remain stable over time may help guide psychosocial and pharmacological treatments after an illness episode. CLINICAL TRIAL REGISTRATION INFORMATION Effectiveness of Family-Focused Treatment Plus Pharmacotherapy for Bipolar Disorder in Adolescents; https://clinicaltrials.gov/; NCT00332098.
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Affiliation(s)
- Marc J Weintraub
- Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles.
| | | | - David A Axelson
- Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus
| | | | - Robert A Kowatch
- Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus
| | - David J Miklowitz
- Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles
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Preuss UW, Hesselbrock MN, Hesselbrock VM. A Prospective Comparison of Bipolar I and II Subjects With and Without Comorbid Alcohol Dependence From the COGA Dataset. Front Psychiatry 2020; 11:522228. [PMID: 33408647 PMCID: PMC7779525 DOI: 10.3389/fpsyt.2020.522228] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Accepted: 10/15/2020] [Indexed: 11/21/2022] Open
Abstract
Objective: Comorbidity of alcohol use disorders in bipolar subjects is high as indicated by epidemiological and clinical studies. Though a more severe course of bipolar disorder in subjects with comorbid alcohol dependence has been reported, fewer studies considered the longitudinal course of alcohol dependence in bipolar subjects and the prospective course of comorbid bipolar II subjects. Beside baseline analysis, longitudinal data of the COGA (Collaborative Study on Genetics in Alcoholism) were used to evaluate the course of bipolar I and II disordered subjects with and without comorbid alcohol dependence over more than 5 years of follow-up. Methods: Characteristics of bipolar disorder, alcohol dependence and comorbid psychiatric disorders were assessed using semi-structured interviews (SSAGA) at baseline and at a 5-year follow-up. Two hundred twenty-eight bipolar I and II patients were subdivided into groups with and without comorbid alcohol dependence. Results: Of the 152 bipolar I and 76 bipolar II patients, 172 (75, 4%) had a comorbid diagnosis of alcohol dependence. Bipolar I patients with alcohol dependence, in particular women, had a more severe course of bipolar disorder, worse social functioning and more suicidal behavior than all other groups of subjects during the 5-year follow-up. In contrast, alcohol dependence improved significantly in both comorbid bipolar I and II individuals during this time. Conclusions: A 5-year prospective evaluation of bipolar patients with and without alcohol dependence confirmed previous investigations suggesting a more severe course of bipolar disorder in comorbid bipolar I individuals, whereas bipolar II individuals were less severely impaired by comorbid alcohol use disorder. While severity of alcohol dependence improved during this time in comorbid alcohol-dependent bipolar I patients, the unfavorable outcome for these individuals might be due to the higher comorbidity with personality and other substance use disorders which, together with alcohol dependence, eventually lead to poorer symptomatic and functional clinical outcomes.
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Affiliation(s)
- Ulrich W Preuss
- Vitos Hospital Psychiatry and Psychotherapy, Herborn, Germany.,Department of Psychiatry, Psychotherapy and Psychosomatics, Martin Luther-University Halle-Wittenberg, Halle, Germany
| | - M N Hesselbrock
- Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, United States
| | - V M Hesselbrock
- Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, United States
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Faedda GL, Baldessarini RJ, Marangoni C, Bechdolf A, Berk M, Birmaher B, Conus P, DelBello MP, Duffy AC, Hillegers MHJ, Pfennig A, Post RM, Preisig M, Ratheesh A, Salvatore P, Tohen M, Vázquez GH, Vieta E, Yatham LN, Youngstrom EA, Van Meter A, Correll CU. An International Society of Bipolar Disorders task force report: Precursors and prodromes of bipolar disorder. Bipolar Disord 2019; 21:720-740. [PMID: 31479581 DOI: 10.1111/bdi.12831] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVES To clarify the clinical features preceding the onset of bipolar disorder (BD) has become a public health priority for the prevention of high morbidity and mortality. BD remains frequently under- or misdiagnosed, and under- or mistreated, often for years. METHODS We assessed the predictive value of precursors and prodromes of BD. We assessed precursors of first-lifetime manic or hypomanic episodes with/without mixed features in retrospective and prospective studies. The task force evaluated and summarized separately assessments of familial risk, premorbid personality traits, retrospective, and prospective studies. RESULTS Cyclothymic features, a family history of BD, retrospectively reported attenuated manic symptoms, prospectively identified subthreshold symptoms of hypomania, recurrence of depression, panic anxiety and psychotic features, have been identified as clinical precursors of BD. The prodromal symptoms like [hypo]mania often appears to be long enough to encourage early identification and timely intervention. CONCLUSIONS The predictive value of any risk factor identified remains largely unknown. Prospective controlled studies are urgently needed for prevention and effective treatment.
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Affiliation(s)
- Gianni L Faedda
- Mood Disorders Center, New York, NY, USA.,International Consortium for Mood and Psychotic Disorders Research, McLean Hospital, Belmont, MA, USA
| | - Ross J Baldessarini
- International Consortium for Mood and Psychotic Disorders Research, McLean Hospital, Belmont, MA, USA.,Department of Psychiatry, Harvard Medical School, Mailman Research Center, McLean Hospital, Boston, MA, USA
| | - Ciro Marangoni
- Department of Psychiatry-District 3, ULSS 9 Scaligera, Verona, Italy
| | - Andreas Bechdolf
- Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany.,Department of Psychiatry, Psychotherapy and Psychosomatics, Vivantes Hospital am Urban and Vivantes Hospital im Friedrichschain, Charite Universitätsmedizin, Berlin, Germany
| | - Michael Berk
- IMPACT Strategic Research Centre, University Hospital Geelong, Barwon Health, Deakin University, Geelong, VIC, Australia.,Orygen, The National Center of Excellence in Youth Mental Health, Parkville, VIC, Australia.,The Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia
| | - Boris Birmaher
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Philippe Conus
- Treatment and Early Intervention in Psychosis Program (TIPP), Département de Psychiatrie CHUV, Université de Lausanne, Lausanne, Switzerland
| | - Melissa P DelBello
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Anne C Duffy
- Department of Psychiatry, Student Wellness Services, Queen's University, Kingston, ON, Canada
| | - Manon H J Hillegers
- Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.,Department of Child and Adolescent Psychiatry, Erasmus medical Center Rotterdam, Rotterdam, The Netherlands
| | - Andrea Pfennig
- Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Technische Universität Dresden, Dresden, Germany
| | - Robert M Post
- Bipolar Collaborative Network, Bethesda, MD, USA.,Department of Psychiatry, George Washington University School of Medicine, Washington, DC, USA
| | - Martin Preisig
- Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland
| | - Aswin Ratheesh
- IMPACT Strategic Research Centre, University Hospital Geelong, Barwon Health, Deakin University, Geelong, VIC, Australia.,Orygen, The National Center of Excellence in Youth Mental Health, Parkville, VIC, Australia.,The Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia
| | - Paola Salvatore
- Department of Psychiatry, Harvard Medical School, Mailman Research Center, McLean Hospital, Boston, MA, USA.,Psychiatry Section, Department of Neuroscience, School of Medicine, University of Parma, Parma, Italy
| | - Mauricio Tohen
- Department of Psychiatry & Behavioral Sciences, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
| | - Gustavo H Vázquez
- International Consortium for Mood and Psychotic Disorders Research, McLean Hospital, Belmont, MA, USA.,Psychiatry, Queen's University, Kingston, ON, Canada
| | - Eduard Vieta
- Bipolar Disorder Unit, Institute of Neuroscience, Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, Barcelona, Spain
| | - Lakshmi N Yatham
- Department of Psychiatry, Mood Disorders Centre, University of British Columbia, Vancouver, BD, Canada
| | - Eric A Youngstrom
- Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Anna Van Meter
- Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA.,The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, NY, USA
| | - Christoph U Correll
- Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA.,The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, NY, USA.,The Feinstein Institute for Medical Research, Center for Psychiatric Neuroscience, Manhasset, NY, USA.,Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany
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47
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Hong M, Ha TH, Lee S, Oh S, Myung W. Clinical Correlates of Alcohol Use Disorder in Depressed Patients with Unipolar and Bipolar Disorder. Psychiatry Investig 2019; 16:926-932. [PMID: 31698557 PMCID: PMC6933138 DOI: 10.30773/pi.2019.0182] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Accepted: 10/27/2019] [Indexed: 12/28/2022] Open
Abstract
OBJECTIVE Alcohol use disorder (AUD) is one of the most frequent comorbid conditions in mood disorders. We aimed to examine the relationships between clinical phenotypes of acutely depressed subjects and co-occurring AUD. METHODS Clinical assessment including diagnosis of mood disorder and co-occurring AUD, the severity of depressive or manic symptoms, and affective temperaments were conducted in 137 subjects suffering from a major depressive episode. According to the presence of AUD, clinical variables were compared between the two groups. Using binary logistic regression models, the effects of mood symptoms and affective temperaments on the risk of AUD were determined. RESULTS Severity of manic symptoms, suicidal ideation, and childhood trauma were higher in the AUD group than in the non-AUD group. Scores for irritable and hyperthymic temperament were higher and the score for anxious temperament was lower in the AUD group. In regression models adjusting confounders, anxious temperament was an independent protector against AUD. On the other hand, the diagnosis of bipolar disorder and the irritable manic symptom dimension increased the risk of AUD. CONCLUSION Anxious temperament decreased the AUD risk, whereas irritable manic symptoms increased the risk during depression. AUD in mood disorders may be an expression of manic psychopathology.
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Affiliation(s)
- Minseok Hong
- Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Tae Hyon Ha
- Mood Disorders Clinic & Clinical Affective Neuroscience Laboratory, Department of Psychiatry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Suyeon Lee
- Mood Disorders Clinic & Clinical Affective Neuroscience Laboratory, Department of Psychiatry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Sunghee Oh
- Mood Disorders Clinic & Clinical Affective Neuroscience Laboratory, Department of Psychiatry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Woojae Myung
- Mood Disorders Clinic & Clinical Affective Neuroscience Laboratory, Department of Psychiatry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
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48
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Estrada-Prat X, Van Meter AR, Camprodon-Rosanas E, Batlle-Vila S, Goldstein BI, Birmaher B. Childhood factors associated with increased risk for mood episode recurrences in bipolar disorder-A systematic review. Bipolar Disord 2019; 21:483-502. [PMID: 31025494 PMCID: PMC6768757 DOI: 10.1111/bdi.12785] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND Bipolar Disorder (BD) is a recurrent illness associated with high morbidity and mortality. The frequency of mood episode recurrence in BD is highly heterogeneous and significantly impacts the person's psychosocial functioning and well-being. Understanding the factors associated with mood recurrences could inform the prognosis and treatment. The objective of this review is to summarize the literature on factors, present during childhood, that influence recurrence. METHODOLOGY A systematic review of PubMed (1946-2017) and PsycINFO (1884-2017) databases was conducted to identify candidate studies. Search terms included bipolar disorder, episodes, predictors, recurrences, and course. Study characteristics, risk for bias, and factors associated with recurrence were coded by two raters according to predetermined criteria. RESULTS Twenty child studies and 28 adult studies that retrospectively evaluated childhood variables associated with mood recurrences were included. Early age of onset, low socioeconomic status, comorbid disorders, inter-episode subsyndromal mood symptoms, BD-I/II subtypes, presence of stressors, and family history of BD were associated with higher number of recurrences. LIMITATIONS Risk factors and mood recurrences were assessed and defined in different ways, limiting generalizability. CONCLUSION Multiple factors are associated with increased risk of mood episode recurrence in BD. Interventions targeting modifiable factors could reduce the impact of BD. For example, treatment of comorbid disorders and subsyndromal mood symptoms, coupled with appropriate cognitive behavioral and family-focused therapies could ameliorate risk related to many clinical factors. When coupled with social services to address environmental factors, the number of episodes could be reduced and the course of BD significantly improved.
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Affiliation(s)
- Xavier Estrada-Prat
- Child and Adolescent Psychiatry and Psychology Department of Hospital Sant Joan de Déu of Barcelona, Spain
| | - Anna R. Van Meter
- The Feinstein Institute for Medical Research, The Zucker Hillside Hospital, Department of Psychiatry Research, Glen Oaks, NY
| | - Ester Camprodon-Rosanas
- Child and Adolescent Psychiatry and Psychology Department of Hospital Sant Joan de Déu of Barcelona, Spain
- Children and Adolescent Mental Health Research Group. Institut de Recerca Sant Joan de Déu, Barcelona, Spain
| | - Santiago Batlle-Vila
- Institut de Neuropsiquiatria i Addiccions, Centre de Salut Mental Infantil i Juvenil Sant Martí-La Mina i Ciutat Vella, Parc de Salut Mar, Barcelona, Spain
| | - Benjamin I. Goldstein
- Centre for Youth Bipolar Disorder, Sunnybrook Health Sciences Centre, Toronto, Canada
- Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, Canada
| | - Boris Birmaher
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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49
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Comorbid disorders as moderators of response to family interventions among adolescents with bipolar disorder. J Affect Disord 2019; 246:754-762. [PMID: 30623821 PMCID: PMC6363856 DOI: 10.1016/j.jad.2018.12.125] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Revised: 11/15/2018] [Accepted: 12/24/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND While family interventions have shown efficacy in improving mood symptoms and family functioning in pediatric bipolar disorder, few studies have examined the effects of comorbid psychiatric conditions on patients' symptomatic or functional responses to treatment. METHODS 145 adolescents with bipolar I or II disorder were randomly assigned to family-focused therapy (FFT-A) or a brief psychoeducational therapy (enhanced care; EC) and followed over 2 years. Participants received pharmacotherapy for the study's duration. We examined whether comorbid anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), and disruptive behavior disorders (DBDs; i.e., oppositional defiant and conduct disorder) predicted the proportion of weeks that participants experienced mood symptoms during follow-up, and whether comorbid disorders moderated the effects of treatment assignment on mood symptoms and family conflict. RESULTS Comorbid anxiety was associated with a greater proportion of weeks with depressive symptoms, more severe (hypo)manic symptoms during follow-up, and greater family conflict over the 2-year study. Comorbid ADHD was associated with a greater proportion of weeks with (hypo)manic symptoms, more severe (hypo)manic symptoms, and greater family conflict. Additionally, youth with comorbid ADHD who received FFT-A had more favorable trajectories of (hypo)manic symptoms and family functioning than youth with comorbid ADHD who received EC. Comorbid DBDs were consistently associated with more severe depressive symptoms and greater family conflict throughout the study. LIMITATIONS Randomization to treatments was not stratified on comorbid disorders. The longitudinal trajectories of anxiety, attentional, and disruptive behavior symptoms were not examined. CONCLUSIONS The course of bipolar disorder in adolescents is strongly affected by comorbid disorders. Future research should examine whether adolescents with more complex presentations of bipolar disorder should be treated with different or more intensive psychosocial protocols than adolescents without these presentations.
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50
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Blier P, Margolese HC, Wilson EA, Boucher M. Switching medication products during the treatment of psychiatric illness. Int J Psychiatry Clin Pract 2019; 23:2-13. [PMID: 30732488 DOI: 10.1080/13651501.2018.1508724] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The common practice of switching between branded (reference) medications and their corresponding generic products, between generic products, or even from a generic product to a branded medication during the treatment of central nervous system (CNS) disorders may compromise efficacy and/or tolerability. METHODS We assessed the published literature from March 1, 2010 through June 30, 2017 via PubMed using the MeSH term 'generics, drugs' alone and in combination with class-specific terms (e.g., 'anticonvulsants', 'mood stabilisers'), for studies detailing outcomes following product switches. RESULTS Although some studies comparing the initiation of reference versus generic drugs suggest equivalence between products, several studies detailing a switch between reference and generic products describe reductions in efficacy, reduced medication adherence and persistence, and increased overall health care resource utilization and costs associated with generic substitution. CONCLUSION When product switches are considered, they should only proceed with the full knowledge of both patient and provider.
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Affiliation(s)
- Pierre Blier
- a University of Ottawa Institute of Mental Health Research , Ottawa , ON , Canada
| | | | | | - Matthieu Boucher
- d Department of Pharmacology & Therapeutics , McGill University, McIntyre Medical Science Building , Montréal , QC , Canada.,e Medical Affairs, Pfizer Canada Inc , Kirkland , QC , Canada
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