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Hu J, Kulkarni N, Maliha P, Grossberg G. Prevalence and Treatment of Substance Misuse in Older Adults: Beyond Early Adulthood. Subst Abuse Rehabil 2024; 15:87-98. [PMID: 39045315 PMCID: PMC11264375 DOI: 10.2147/sar.s375653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 07/09/2024] [Indexed: 07/25/2024] Open
Abstract
Substance misuse, traditionally seen as a problem of early to mid-adulthood, is becoming increasingly prevalent among the older adult population (ages ≥65). Diagnosing and treating substance misuse in this vulnerable population is challenging because of multiple pre-existing medical comorbidities as well as polypharmacy. As such, it remains underdiagnosed and underrepresented in the literature. This review provides an overview of the three most commonly misused substances in older adults: alcohol, cannabis, and prescription drugs. It examines epidemiology, societal trends, and treatment options, highlighting the need for targeted research to address the unique challenges faced by older adults. This review also briefly comments on the prevalence and treatment of other illicit drugs in this population.
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Affiliation(s)
- Jiahao Hu
- Department of Psychiatry and Behavioral Neuroscience, Saint Louis University School of Medicine, St Louis, MO, USA
| | - Neha Kulkarni
- Department of Psychiatry and Behavioral Neuroscience, Saint Louis University School of Medicine, St Louis, MO, USA
| | - Peter Maliha
- Department of Psychiatry and Behavioral Neuroscience, Saint Louis University School of Medicine, St Louis, MO, USA
| | - George Grossberg
- Department of Psychiatry and Behavioral Neuroscience, Saint Louis University School of Medicine, St Louis, MO, USA
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2
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McPheeters M, O’Connor EA, Riley S, Kennedy SM, Voisin C, Kuznacic K, Coffey CP, Edlund MD, Bobashev G, Jonas DE. Pharmacotherapy for Alcohol Use Disorder: A Systematic Review and Meta-Analysis. JAMA 2023; 330:1653-1665. [PMID: 37934220 PMCID: PMC10630900 DOI: 10.1001/jama.2023.19761] [Citation(s) in RCA: 53] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 09/12/2023] [Indexed: 11/08/2023]
Abstract
Importance Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality. Objective To compare efficacy and comparative efficacy of therapies for alcohol use disorder. Data Sources PubMed, the Cochrane Library, the Cochrane Central Trials Registry, PsycINFO, CINAHL, and EMBASE were searched from November 2012 to September 9, 2022 Literature was subsequently systematically monitored to identify relevant articles up to August 14, 2023, and the PubMed search was updated on August 14, 2023. Study Selection For efficacy outcomes, randomized clinical trials of at least 12 weeks' duration were included. For adverse effects, randomized clinical trials and prospective cohort studies that compared drug therapies and reported health outcomes or harms were included. Data Extraction and Synthesis Two reviewers evaluated each study, assessed risk of bias, and graded strength of evidence. Meta-analyses used random-effects models. Numbers needed to treat were calculated for medications with at least moderate strength of evidence for benefit. Main Outcomes and Measures The primary outcome was alcohol consumption. Secondary outcomes were motor vehicle crashes, injuries, quality of life, function, mortality, and harms. Results Data from 118 clinical trials and 20 976 participants were included. The numbers needed to treat to prevent 1 person from returning to any drinking were 11 (95% CI, 1-32) for acamprosate and 18 (95% CI, 4-32) for oral naltrexone at a dose of 50 mg/d. Compared with placebo, oral naltrexone (50 mg/d) was associated with lower rates of return to heavy drinking, with a number needed to treat of 11 (95% CI, 5-41). Injectable naltrexone was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, -4.99 days; 95% CI, -9.49 to -0.49 days) Adverse effects included higher gastrointestinal distress for acamprosate (diarrhea: risk ratio, 1.58; 95% CI, 1.27-1.97) and naltrexone (nausea: risk ratio, 1.73; 95% CI, 1.51-1.98; vomiting: risk ratio, 1.53; 95% CI, 1.23-1.91) compared with placebo. Conclusions and Relevance In conjunction with psychosocial interventions, these findings support the use of oral naltrexone at 50 mg/d and acamprosate as first-line pharmacotherapies for alcohol use disorder.
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Affiliation(s)
- Melissa McPheeters
- RTI International–University of North Carolina at Chapel Hill Evidence-Based Practice Center, Chapel Hill
- RTI International, Research Triangle Park, North Carolina
| | | | - Sean Riley
- RTI International–University of North Carolina at Chapel Hill Evidence-Based Practice Center, Chapel Hill
- Department of Internal Medicine, The Ohio State University, Columbus
| | - Sara M. Kennedy
- RTI International–University of North Carolina at Chapel Hill Evidence-Based Practice Center, Chapel Hill
- RTI International, Research Triangle Park, North Carolina
| | - Christiane Voisin
- RTI International–University of North Carolina at Chapel Hill Evidence-Based Practice Center, Chapel Hill
- Department of Internal Medicine, The Ohio State University, Columbus
| | | | - Cory P. Coffey
- Department of Internal Medicine, The Ohio State University, Columbus
| | - Mark D. Edlund
- RTI International, Research Triangle Park, North Carolina
| | | | - Daniel E. Jonas
- RTI International–University of North Carolina at Chapel Hill Evidence-Based Practice Center, Chapel Hill
- Department of Internal Medicine, The Ohio State University, Columbus
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Lin J, Arnovitz M, Kotbi N, Francois D. Substance Use Disorders in the Geriatric Population: a Review and Synthesis of the Literature of a Growing Problem in a Growing Population. CURRENT TREATMENT OPTIONS IN PSYCHIATRY 2023:1-20. [PMID: 37360959 PMCID: PMC10241125 DOI: 10.1007/s40501-023-00291-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 05/22/2023] [Indexed: 06/28/2023]
Abstract
Purpose of review Substance use disorders are becoming increasingly prevalent in the geriatric population, necessitating an updated understanding of the existing literature. This review aims to describe the epidemiology, special considerations, and management of substance use disorders in older adults. Recent findings PubMed, Ovid MEDLINE, and PsychINFO databases were searched from their inception through June 2022 using the following keywords: "substance use disorder," "substance abuse," "abuse," "illicit substances," "illicit drugs," "addiction," "geriatric," "elderly," "older adults," "alcohol," "marijuana," "cannabis," "cocaine," "heroin," "opioid," and "benzodiazepine." Our findings suggest an increasing trend in substance use in older adults despite medical and psychiatric consequences when using such substances. The majority of older patients admitted to substance abuse treatment programs were not referred by healthcare providers, suggesting room for improvement in the screening and discussion of substance use disorders. Our review also suggests that there should be careful consideration of COVID-19 and racial disparities when screening, diagnosing, and treating substance use disorders in the older population. Summary This review provides updated information on epidemiology, special considerations, and management of substance use disorders in older adults. As substance use disorders become more prevalent in older adults, primary care physicians must be prepared to recognize and diagnose substance use disorders as well as collaborate with and refer patients to geriatric medicine, geriatric psychiatry, and addiction medicine.
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Affiliation(s)
- Jenny Lin
- Weill Cornell Medicine, New York, NY USA
| | - Mitchell Arnovitz
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY USA
| | - Nabil Kotbi
- Weill Cornell Medicine, New York Presbyterian/Westchester, 21 Bloomingdale Road, White Plains, NY 10605 USA
| | - Dimitry Francois
- Weill Cornell Medicine, New York Presbyterian/Westchester, 21 Bloomingdale Road, White Plains, NY 10605 USA
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Hurlocker MC, Carlon H, Pearson MR, Hijaz D. Trajectories of change in subclinical anxiety and alcohol use during alcohol treatment: A parallel process growth model. Drug Alcohol Depend 2023; 246:109838. [PMID: 36989706 PMCID: PMC10121922 DOI: 10.1016/j.drugalcdep.2023.109838] [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: 09/24/2022] [Revised: 02/20/2023] [Accepted: 02/21/2023] [Indexed: 03/31/2023]
Abstract
BACKGROUND Anxiety is implicated in the course and prognosis of alcohol use disorder (AUD); however, it is unclear how current AUD treatments affect the joint trajectories of anxiety and alcohol use. We used data from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study to examine the longitudinal relationship between subclinical anxiety symptoms and alcohol use during and following AUD treatment in adults with AUD and no comorbid anxiety disorders. METHODS Univariate and parallel process growth models using five waves of COMBINE study data were analyzed from 865 adults randomized to medication (n = 429) or medication plus psychotherapy (n = 436). Weekly drinking quantity and average weekly anxiety symptoms were measured at baseline, mid-treatment, end-of-treatment, and three follow-up periods. RESULTS Significant positive associations of anxiety symptoms and drinking were found at mid-treatment and over time. Temporal associations revealed that higher mid-treatment anxiety predicted decreases in drinking over time. Baseline anxiety and drinking predicted mid-treatment anxiety and drinking. Only baseline anxiety predicted increases in drinking over time. Group differences revealed mid-treatment drinking predicted decreases in anxiety over time in the medication group. CONCLUSIONS Findings demonstrate the influence of subclinical anxiety on alcohol use during and up to one year after AUD treatment. Baseline anxiety symptoms may influence drinking behavior over the course of treatment. Findings suggest that greater attention to negative affect in AUD treatment is warranted even for those individuals who do have a comorbid anxiety disorder.
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Affiliation(s)
- Margo C Hurlocker
- Department of Psychology, University of New Mexico, Albuquerque, NM 87131, United States; Center on Alcohol, Substance use, And Addictions, University of New Mexico, Albuquerque, NM 87106, United States.
| | - Hannah Carlon
- Department of Psychology, University of New Mexico, Albuquerque, NM 87131, United States
| | - Matthew R Pearson
- Department of Psychology, University of New Mexico, Albuquerque, NM 87131, United States; Center on Alcohol, Substance use, And Addictions, University of New Mexico, Albuquerque, NM 87106, United States
| | - Donia Hijaz
- Department of Psychology, University of New Mexico, Albuquerque, NM 87131, United States
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Reynolds CF, Jeste DV, Sachdev PS, Blazer DG. Mental health care for older adults: recent advances and new directions in clinical practice and research. World Psychiatry 2022; 21:336-363. [PMID: 36073714 PMCID: PMC9453913 DOI: 10.1002/wps.20996] [Citation(s) in RCA: 93] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
The world's population is aging, bringing about an ever-greater burden of mental disorders in older adults. Given multimorbidities, the mental health care of these people and their family caregivers is labor-intensive. At the same time, ageism is a big problem for older people, with and without mental disorders. Positive elements of aging, such as resilience, wisdom and prosocial behaviors, need to be highlighted and promoted, both to combat stigma and to help protect and improve mental health in older adults. The positive psychiatry of aging is not an oxymoron, but a scientific construct strongly informed by research evidence. We champion a broader concept of geriatric psychiatry - one that encompasses health as well as illness. In the present paper, we address these issues in the context of four disorders that are the greatest source of years lived with disability: neurocognitive disorders, major depression, schizophrenia, and substance use disorders. We emphasize the need for implementation of multidisciplinary team care, with comprehensive assessment, clinical management, intensive outreach, and coordination of mental, physical and social health services. We also underscore the need for further research into moderators and mediators of treatment response variability. Because optimal care of older adults with mental disorders is both patient-focused and family-centered, we call for further research into enhancing the well-being of family caregivers. To optimize both the safety and efficacy of pharmacotherapy, further attention to metabolic, cardiovascular and neurological tolerability is much needed, together with further development and testing of medications that reduce the risk for suicide. At the same time, we also address positive aging and normal cognitive aging, both as an antidote to ageism and as a catalyst for change in the way we think about aging per se and late-life mental disorders more specifically. It is in this context that we provide directions for future clinical care and research.
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Affiliation(s)
| | - Dilip V. Jeste
- Department of PsychiatryUniversity of California San DiegoLa JollaCAUSA
| | | | - Dan G. Blazer
- Department of Psychiatry and Behavioral SciencesDuke UniversityDurhamNCUSA
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Neurocognitive and substance use disorders in older adults: challenges and evidence. ADVANCES IN DUAL DIAGNOSIS 2022. [DOI: 10.1108/add-01-2022-0004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Purpose
This study aims to review the presentation of substance use disorders in older adults, how addiction intertwines with neurocognitive disorders and how to approach this vulnerable population.
Design/methodology/approach
Electronic data searches of PubMed, Medline and the Cochrane Library (years 2000–2021) were performed using the keywords “neurocognitive,” “dementia,” “substance use,” “addiction,” “older adults” and “elderly.” The authors, in consensus, selected pivotal studies and conducted a narrative synthesis of the findings.
Findings
Research about substance use disorders in older adults is limited, especially in those with superimposed neurocognitive disorders. Having dual diagnoses can make the identification and treatment of either condition challenging. Management should use a holistic multidisciplinary approach that involves medical professionals and caregivers.
Originality/value
This review highlights some of the intertwining aspects between substance use disorders and neurocognitive disorders in older adults. It provides a comprehensive summary of the available evidence on treatment in this population.
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Graham DP, Harding MJ, Nielsen DA. Pharmacogenetics of Addiction Therapy. Methods Mol Biol 2022; 2547:437-490. [PMID: 36068473 DOI: 10.1007/978-1-0716-2573-6_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Drug addiction is a serious relapsing disease that has high costs to society and to the individual addicts. Treatment of these addictions is still in its nascency, with only a few examples of successful therapies. Therapeutic response depends upon genetic, biological, social, and environmental components. A role for genetic makeup in the response to treatment has been shown for several addiction pharmacotherapies with response to treatment based on individual genetic makeup. In this chapter, we will discuss the role of genetics in pharmacotherapies, specifically for cocaine, alcohol, and opioid dependences. The continued elucidation of the role of genetics should aid in the development of new treatments and increase the efficacy of existing treatments.
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Affiliation(s)
- David P Graham
- Michael E. DeBakey Veterans Affairs Medical Center, and the Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA
| | - Mark J Harding
- Michael E. DeBakey Veterans Affairs Medical Center, and the Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA
| | - David A Nielsen
- Michael E. DeBakey Veterans Affairs Medical Center, and the Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
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Dufort A, Samaan Z. Problematic Opioid Use Among Older Adults: Epidemiology, Adverse Outcomes and Treatment Considerations. Drugs Aging 2021; 38:1043-1053. [PMID: 34490542 PMCID: PMC8421190 DOI: 10.1007/s40266-021-00893-z] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/15/2021] [Indexed: 11/23/2022]
Abstract
With the aging population, an increasing number of older adults (> 65 years) will be affected by problematic opioid use and opioid use disorder (OUD), with both illicit and prescription opioids. Problematic opioid use is defined as the use of opioids resulting in social, medical or psychological consequences, whereas OUD is a form of problematic use that meets diagnostic criteria as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. Problematic use of opioids by older adults is associated with a number of pertinent adverse effects, including sedation, cognitive impairment, falls, fractures and constipation. Risk factors for problematic opioid use in this population include pain, comorbid medical illnesses, concurrent alcohol use disorder and depression. Treatment of OUD consists of acute detoxification and maintenance therapy. At this time, there have been no randomized controlled trials examining the effectiveness of pharmacological interventions for OUD in this population, with recommendations based on data from younger adults. Despite this, opioid agonist therapy (OAT) is recommended for both stages of treatment in older adults with OUD. Buprenorphine is recommended as a first line agent over methadone in the older adult population, due to a more favourable safety profile and relative accessibility. Use of methadone in this population is complicated by risk of QT interval prolongation and respiratory depression. Available observational data suggests that older adults respond well to OAT and age should not be a barrier to treatment. Further research is required to inform treatment decisions in this population.
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Affiliation(s)
- Alexander Dufort
- Department of Psychiatry and Behavioural Neurosciences, St. Joseph's Healthcare Hamilton, McMaster University, West 5th Campus, Administration-B3, 100 West 5th, Hamilton, ON, L8N 3K7, Canada.
| | - Zainab Samaan
- Department of Psychiatry and Behavioural Neurosciences, St. Joseph's Healthcare Hamilton, McMaster University, West 5th Campus, Administration-B3, 100 West 5th, Hamilton, ON, L8N 3K7, Canada
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, ON, Canada
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Fenollal-Maldonado G, Brown D, Hoffman H, Kahlon C, Grossberg G. Alcohol Use Disorder in Older Adults. Clin Geriatr Med 2021; 38:1-22. [PMID: 34794695 DOI: 10.1016/j.cger.2021.07.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
As the number of older adults worldwide continues to grow, we observe a proportional growth of substance use. Despite the myriad of complications alcohol use disorder (AUD) has on the body with regards to organ systems and mental health, the topic has been underresearched in the older adult population. Thus, it is important to create awareness about the growing problem of AUD among older adults. In this way, we can mitigate the long-term complications and side effects observed with alcohol abuse in this vulnerable population.
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Affiliation(s)
- Gabriela Fenollal-Maldonado
- Department of Psychiatry and Behavioral Neuroscience, Division of Geriatric Psychiatry, St. Louis University School of Medicine, 1438 South Grand Boulevard, St Louis, MO 63104, US.
| | - Derek Brown
- Department of Psychiatry and Behavioral Neuroscience, Division of Geriatric Psychiatry, St. Louis University School of Medicine, 1438 South Grand Boulevard, St Louis, MO 63104, US
| | - Heidi Hoffman
- Saint Louis University School of Medicine, St. Louis University, 1438 South Grand Boulevard, St Louis, MO 63104, US
| | - Chanchal Kahlon
- Saint Louis University School of Medicine, St. Louis University, 1438 South Grand Boulevard, St Louis, MO 63104, US
| | - George Grossberg
- Department of Psychiatry and Behavioral Neuroscience, Division of Geriatric Psychiatry, St. Louis University School of Medicine, 1438 South Grand Boulevard, St Louis, MO 63104, USA
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Wallhed Finn S, Lundin A, Sjöqvist H, Danielsson AK. Pharmacotherapy for alcohol use disorders - Unequal provision across sociodemographic factors and co-morbid conditions. A cohort study of the total population in Sweden. Drug Alcohol Depend 2021; 227:108964. [PMID: 34518028 DOI: 10.1016/j.drugalcdep.2021.108964] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 07/20/2021] [Accepted: 07/25/2021] [Indexed: 11/16/2022]
Abstract
BACKGROUND Pharmacotherapy for alcohol use disorders (AUD) is effective. However, knowledge about utilization of, and patient characteristics associated with prescriptions is scarce. The aim is to investigate prescriptions of pharmacotherapy for AUD in Sweden across time, sociodemographics, domicile and comorbid conditions. METHOD This is a national cohort study, comprising 132 733 adult patients with AUD diagnosis between 2007 and 2015. The exposure variables were age, sex, income, education, family constellation, domicile, origin, concurrent psychiatric and somatic co-morbid diagnoses. Logistic regression analyses were used to obtain odds ratios (OR) for any filled prescription of AUD pharmacotherapy; Acamprosate, Disulfiram, Naltrexone or Nalmefene during 12 months after AUD diagnosis. RESULTS During the study period, the proportion of individuals who received pharmacotherapy ranged between 22.80 and 23.94 % (χ2(64) = 72.00, p = .23). Female sex, age 31-45, higher education and income, living in a big city, co-habiting and born in Sweden, bar Norway, Denmark and Iceland, were associated with higher odds of pharmacotherapy. Concurrent somatic diagnosis was associated with lower odds of pharmacotherapy but psychiatric diagnosis higher (aOR = 0.61 95 % CI 0.59-0.63 and aOR = 1.61 95 % CI 1.57-1.66 respectively). CONCLUSIONS Pharmacotherapy for AUD is underutilized. The proportion of individuals with a prescription did not change between 2007 and 2015. Provision of treatment is unequal across different groups in society, where especially older age, lower income and education, and co-morbid somatic diagnosis were associated with lower odds of prescription. There is a need to develop treatment provision, particularly for individuals with co-morbid somatic conditions.
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Affiliation(s)
- Sara Wallhed Finn
- Department of Global Public Health, Karolinska Institutet, 171 77, Stockholm, Sweden; Mottagningen För alkohol och hälsa, Stockholm Center for Dependency Disorders, Health Care Services, Riddargatan 1, 114 35, Stockholm, Sweden.
| | - Andreas Lundin
- Department of Global Public Health, Karolinska Institutet, 171 77, Stockholm, Sweden; Centre for Epidemiology and Community Medicine, Stockholm Region, Sweden
| | - Hugo Sjöqvist
- Department of Global Public Health, Karolinska Institutet, 171 77, Stockholm, Sweden
| | - Anna-Karin Danielsson
- Department of Global Public Health, Karolinska Institutet, 171 77, Stockholm, Sweden
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Chick J, Andersohn F, Guillo S, Borchert K, Toussi M, Braun S, Haas JS, Kuppan K, Lemming OM, Reines EH, Tubach F. Safety and Persistence of Nalmefene Treatment for Alcohol Dependence. Results from Two Post-authorisation Safety Studies. Alcohol Alcohol 2021; 56:556-564. [PMID: 34196359 PMCID: PMC8406067 DOI: 10.1093/alcalc/agab045] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/28/2021] [Accepted: 06/03/2021] [Indexed: 12/04/2022] Open
Abstract
Aims Two post-authorisation studies assessed the safety and persistence of patients’ use of nalmefene. Methods The START study (EUPAS5678) was a non-interventional, multi-country, prospective, 18-month (8 follow-up visits) cohort study including outpatients initiating nalmefene for the first time. The multi-database retrospective cohort study (MDRC, EUPAS14083) included baseline and follow-up data from German, Swedish and UK healthcare databases. Both studies permitted ‘all comers’ without explicit exclusion criteria; predefined subgroups of interest included the elderly (≥65 years) as well as patients with significant psychiatric and/or somatic comorbidities. Results START study: Overall, the mean duration of nalmefene treatment was 10.3 ± 7.3 months (N = 1348), with 49.0% of patients treated for ≥1 year; frequent reasons for treatment discontinuation were ‘goal reached’ and ‘drug cost’. The most frequently reported adverse drug reactions (ADRs) were nausea (4.7%), dizziness (3.2%) and insomnia (2.0%). ADR rates appeared higher in the elderly subpopulation (18.6% reported ≥1 ADR vs. 12.0% in the total population) but were not higher in the other predefined subgroups. MDRC study: The database follow-up analysis followed 2892 patients over 18 months for whom the duration of nalmefene treatment was between 2 and 3 months and <5% of patients used nalmefene for ≥1 year. Conclusions Despite the inclusion of a wider patient population (e.g. elderly patients and those with relevant co-morbidities), the safety and tolerability profile of nalmefene given in routine practice was consistent with previous clinical studies. The differing rates of persistence beyond 1 year likely reflect the different methodologies and highlight the relevance of psychosocial support at follow-up visits.
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Affiliation(s)
| | - Frank Andersohn
- Frank Andersohn Consulting and Research Services, Mandelstr. 16, 10409 Berlin, Germany
| | - Sylvie Guillo
- INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié Salpêtrière, Sorbonne Université, 27 rue Chaligny, 75012 Paris, France.,Département de Santé Publique, Centre de Pharmacoépidémiologie (Cephepi), CIC-1901, F75013, Paris, France
| | | | - Massoud Toussi
- IQVIA, Tour D2, 17 bis Place des Reflets, 92400 Courbevoie, France
| | | | | | | | | | | | - Florence Tubach
- INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié Salpêtrière, Sorbonne Université, 27 rue Chaligny, 75012 Paris, France.,Département de Santé Publique, Centre de Pharmacoépidémiologie (Cephepi), CIC-1901, F75013, Paris, France
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12
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Nega S, Marquez P, Hamid A, Ahmad SM, Lutfy K. The role of pituitary adenylyl cyclase activating polypeptide in affective signs of nicotine withdrawal. J Neurosci Res 2020; 98:1549-1560. [PMID: 32476165 DOI: 10.1002/jnr.24649] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 04/17/2020] [Accepted: 05/04/2020] [Indexed: 12/12/2022]
Abstract
Recent evidence implicates endogenous pituitary adenylyl cyclase activating polypeptide (PACAP) in the aversive effect of nicotine. In the present study, we assessed if nicotine-induced conditioned place preference (CPP) or affective signs of nicotine withdrawal would be altered in the absence of PACAP and if there were any sex-related differences in these responses. Male and female mice lacking PACAP and their wild-type controls were tested for baseline place preference on day 1, received conditioning with saline or nicotine (1 mg/kg) on alternate days for 6 days and were then tested for CPP the next day. Mice were then exposed to four additional conditioning and were tested again for nicotine-induced CPP 24 hr later. Controls were conditioned with saline in both chambers and tested similarly. All mice were then, 96 hr later, challenged with mecamylamine (3 mg/kg), and tested for anxiety-like behaviors 30 min later. Mice were then, 2 hr later, forced to swim for 15 min and then tested for depression-like behaviors 24 hr later. Our results showed that male but not female mice lacking PACAP expressed a significant CPP that was comparable to their wild-type controls. In contrast, male but not female mice lacking PACAP exhibited reduced anxiety- and depression-like behaviors compared to their wild-type controls following the mecamylamine challenge. These results suggest that endogenous PACAP is involved in affective signs of nicotine withdrawal, but there is a sex-related difference in this response.
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Affiliation(s)
- Shiromani Nega
- Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA
| | - Paul Marquez
- Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA
| | - Abdul Hamid
- Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA
| | - Syed Muzzammil Ahmad
- Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA
| | - Kabirullah Lutfy
- Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA
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Panin F, Peana AT. Sleep and the Pharmacotherapy of Alcohol Use Disorder: Unfortunate Bedfellows. A Systematic Review With Meta-Analysis. Front Pharmacol 2019; 10:1164. [PMID: 31680952 PMCID: PMC6811753 DOI: 10.3389/fphar.2019.01164] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 09/10/2019] [Indexed: 12/13/2022] Open
Abstract
Background: Sleep disorders are commonly associated with acute and chronic use of alcohol and with abstinence. To date, there are four approved drugs to treat alcohol use disorder (AUD): disulfiram, acamprosate, naltrexone, and nalmefene. These AUD therapies reduce the craving and risk of relapse into heavy drinking, but little is known about their effect on sleep. As recent evidences indicate a crucial role of sleep disorders in AUD, claiming that sleep problems may trigger alcohol abuse and relapses, it is fundamental to clarify the impact of those drugs on the sleep quality of AUD patients. This systematic review aims to answer the question: how does the pharmacotherapy for AUD affect sleep? Methods: We searched PubMed, Embase, CINAHL Plus, Cochrane, and Scopus using sleep- and AUD pharmacotherapy-related keywords. The articles included were appraised using the CASP checklists, and the risk of bias was assessed following the Cochrane risk-of-bias assessment tool. Finally, we pooled sleep outcomes in a meta-analysis to measure the overall effect. Results and Conclusion: We included 26 studies: only three studies focused on sleep as a main outcome, two with polysomnography (objective measurement), and one with subjective self-reported sleep, while all the other studies reported sleep problems among the adverse effects (subjective report). The only study available on disulfiram showed reduced REM sleep. Acamprosate showed no/little effect on self-reported sleep but improved sleep continuity and architecture measured by polysomnography. The two opioidergic drugs naltrexone and nalmefene had mainly detrimental effect on sleep, giving increased insomnia and/or somnolence compared with placebo, although not always significant. The meta-analysis confirmed significantly increased somnolence and insomnia in the naltrexone group, compared with the placebo. Overall, the currently available evidences show more sleep problems with the opioidergic drugs (especially naltrexone), while acamprosate seems to be well tolerated or even beneficial. Acamprosate might be a more suitable choice when patients with AUD report sleep problems. Due to the paucity of information available, and with the majority of results being subjective, more research on this topic is needed to further inform the clinical practice, ideally with more objective measurements such as polysomnography.
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Affiliation(s)
- Francesca Panin
- Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, Cambridge, United Kingdom
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Tampi RR, Chhatlani A, Ahmad H, Balaram K, Dey J, Escobar R, Lingamchetty T. Substance use disorders among older adults: A review of randomized controlled pharmacotherapy trials. World J Psychiatry 2019; 9:78-82. [PMID: 31559148 PMCID: PMC6757194 DOI: 10.5498/wjp.v9.i5.78] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 08/01/2019] [Accepted: 08/07/2019] [Indexed: 02/05/2023] Open
Abstract
Substance use disorders (SUDs) are a growing problem among older adults. Acamprosate, disulfiram, and naltrexone are United States Food and Drug Administration (referred to as FDA) approved for the treatment of alcohol use disorder, and buprenorphine is approved for the treatment of opiate use disorder among adults. However, the data on the use of these medications for the treatment of SUDs among older adults are unclear from randomized controlled trials (referred to as RCTs). A review of the literature indicates that there are only two RCTs that evaluated the use of pharmacologic agents for SUDs among older adults (≥ 50 years). One trial evaluated the use of naltrexone when compared to placebo for the treatment of alcohol use disorder among individuals, 50-70 years in age. The other trial evaluated the use of naltrexone or placebo as adjuncts with sertraline in the treatment of alcohol use disorder among individuals older than 55 years in age. Both trials indicated that the use of naltrexone reduced the rates of relapse among older adults with alcohol use disorder. However, we did not identify any RCTs that studied the use of buprenorphine, acamprosate, or disulfiram for SUDs among older adults. Based on available evidence, it would be safe to conclude that limited data indicate some efficacy for naltrexone in the treatment of alcohol use disorder among older adults. However, data from controlled trials on the use of other medications that are FDA approved for the treatment of SUDs among younger adults are nonexistent among older adults with SUDs.
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Affiliation(s)
- Rajesh R Tampi
- Department of Psychiatry and Behavioral Sciences, Cleveland Clinic Akron General, Ohio, NH 44106, United States
- Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44109, United States
| | | | - Hajra Ahmad
- Department of Psychiatry, MetroHealth, Cleveland, OH 44109, United States
- Case Western Reserve University School of Medicine, Cleveland, OH 44109, United States
| | - Kripa Balaram
- Department of Psychiatry, MetroHealth, Cleveland, OH 44109, United States
- Case Western Reserve University School of Medicine, Cleveland, OH 44109, United States
| | - Joel Dey
- Department of Psychiatry, MetroHealth, Cleveland, OH 44109, United States
- Case Western Reserve University School of Medicine, Cleveland, OH 44109, United States
| | - Ricardo Escobar
- Department of Psychiatry, MetroHealth, Cleveland, OH 44109, United States
- Case Western Reserve University School of Medicine, Cleveland, OH 44109, United States
| | - Thejasvi Lingamchetty
- Department of Psychiatry, MetroHealth, Cleveland, OH 44109, United States
- Case Western Reserve University School of Medicine, Cleveland, OH 44109, United States
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15
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Taylor E, Timko C, Harris AHS, Yu M, Finlay AK. Receipt of pharmacotherapy for alcohol use disorder by justice-involved women in the Veterans Health Administration. Addict Sci Clin Pract 2019; 14:1. [PMID: 30602392 PMCID: PMC6317204 DOI: 10.1186/s13722-018-0129-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Accepted: 12/18/2018] [Indexed: 01/30/2023] Open
Abstract
Background Alcohol use disorder (AUD) and unhealthy drinking are prevalent among women involved in the criminal justice system and women military veterans. Pharmacotherapy—including naltrexone, topiramate, acamprosate, and disulfiram—for AUD is one form of effective treatment that is associated with better health and criminal justice outcomes. The current study examined the association of justice involvement with receipt of pharmacotherapy for AUD, as well as other patient factors that may explain variation in receipt of pharmacotherapy for AUD among women veterans who receive care at Veterans Health Administration (VHA) facilities.
Methods Using national VHA clinical records, we examined all women VHA patients who received an AUD diagnosis during an outpatient or inpatient visit in fiscal years (FY) 2014–2017. We compared patient characteristics by justice status, defined as contact with one of the VHA’s justice outreach programs, and used a mixed-effects logistic regression model to test whether justice involvement was independently associated with odds of receiving pharmacotherapy for AUD. Results Of 10,511 women veterans diagnosed with AUD in FY2017, 852 (8%) met our definition of justice-involved. Since FY2014, the percentage of women veterans who received pharmacotherapy for AUD increased (14–21%). Women justice-involved veterans and those who were homeless had higher odds of receiving pharmacotherapy for AUD (OR 1.29, CI 1.15–1.45; OR 1.35, CI 1.25–1.47). Women veterans age 55 or older or who were African-American had lower odds of receiving pharmacotherapy (OR 0.74, CI 0.67–0.82; OR 0.73, CI 0.68–0.79). Conclusions While women involved in the criminal justice system face many barriers to accessing health and social services, women justice-involved veterans had higher odds of receiving pharmacotherapy for AUD at VHA facilities compared to women veterans with no justice involvement. Legal mandates and supportive programming directed towards veterans in the criminal justice system may explain the higher rate of receipt of pharmacotherapy observed among justice-involved women veterans. Women veterans who are homeless may also have more opportunities to access and use pharmacotherapy for AUD compared to their housed counterparts.
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Affiliation(s)
- Emmeline Taylor
- Department of Veterans Affairs Health Care System, Center for Innovation to Implementation, Palo Alto, CA, 94304, USA. .,, 795 Willow Road (MPD-152), Menlo Park, CA, 94025, USA.
| | - Christine Timko
- Department of Veterans Affairs Health Care System, Center for Innovation to Implementation, Palo Alto, CA, 94304, USA.,Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Alex H S Harris
- Department of Veterans Affairs Health Care System, Center for Innovation to Implementation, Palo Alto, CA, 94304, USA.,Department of Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Mengfei Yu
- Department of Veterans Affairs Health Care System, Center for Innovation to Implementation, Palo Alto, CA, 94304, USA
| | - Andrea K Finlay
- Department of Veterans Affairs Health Care System, Center for Innovation to Implementation, Palo Alto, CA, 94304, USA.,Department of Veterans Affairs, National Center on Homelessness Among Veterans, Menlo Park, CA, 94025, USA
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Ahmed R, Kotapati VP, Khan AM, Hussain N, Hussain M, Dar S, Kumar J, Begum GA, Esang M, Brainch N, Ahmed S. Adding Psychotherapy to the Naltrexone Treatment of Alcohol Use Disorder: Meta-analytic Review. Cureus 2018; 10:e3107. [PMID: 30338182 PMCID: PMC6175267 DOI: 10.7759/cureus.3107] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Background It remains unclear if naltrexone combined with psychotherapy is superior to naltrexone alone in treating alcohol use disorders (AUD). The current meta-analysis examined the hypothesis that psychotherapy is a significant moderator that influences AUD-related outcomes and that naltrexone combined with psychotherapy is associated with significantly better AUD-related outcomes than naltrexone alone. Methods A total of 30 studies (Nnaltrexone = 2317; Nplacebo = 2056) were included. Random effects model meta-analyses were carried out for each of the studied outcomes. Subsequently, the random effects model pooled estimates from studies with and without psychotherapy were compared using a Wald test. A mixed-effect model, incorporating psychotherapy as a moderator, was used to examine the impact of psychotherapy on treatment outcomes. Results Naltrexone had a significant treatment effect on abstinence relapse and Gamma-Glutamyl Transferase levels, but not cravings. The pooled estimates for studies with and without psychotherapy were not significantly different for any of the studied outcomes. Psychotherapy was not a significant moderator in the mixed effects models for any of the studied outcomes. Conclusions Naltrexone treatment is efficacious in reducing alcohol consumption, but not reducing cravings. Adding psychotherapy on top naltrexone did not result in any significant additional benefit for AUD patients.
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Affiliation(s)
- Rizwan Ahmed
- Psychiatry, Liaquat College of Medicine & Dentistry, Karachi, PAK
| | | | - Ali M Khan
- Psychiatry Resident, University of Texas Rio Grande Valley, Harlingen, Texas, USA
| | - Nuzhat Hussain
- Psychiatry, Penn State University College of Medicine, Pennsylvania, USA
| | | | - Sara Dar
- Psychiatry, Brigham and Women's Hospital, Boston, USA
| | | | | | - Michael Esang
- Behavioral Health Sciences, Nassau University Medical Center, East Meadow, USA
| | | | - Saeed Ahmed
- Behavioral Health Sciences, Nassau University Medical Center, East Meadow, USA
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17
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Zaveri NT, Marquez PV, Meyer ME, Polgar WE, Hamid A, Lutfy K. A Novel and Selective Nociceptin Receptor (NOP) Agonist (1-(1-((cis)-4-isopropylcyclohexyl)piperidin-4-yl)-1H-indol-2-yl)methanol (AT-312) Decreases Acquisition of Ethanol-Induced Conditioned Place Preference in Mice. Alcohol Clin Exp Res 2018; 42:461-471. [PMID: 29215139 DOI: 10.1111/acer.13575] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2017] [Accepted: 11/30/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Nociceptin/orphanin FQ, the endogenous peptide agonist for the opioid receptor-like receptor (also known as NOP or the nociceptin receptor), has been shown to block the acquisition and expression of ethanol (EtOH)-induced conditioned place preference (CPP). Here, we report the characterization of a novel small-molecule NOP ligand AT-312 (1-(1-((cis)-4-isopropylcyclohexyl)piperidin-4-yl)-1H-indol-2-yl)methanol) in receptor binding and GTPγS functional assays in vitro. We then investigated the effect of AT-312 on the rewarding action of EtOH in mice using the CPP paradigm. Further, using mice lacking the NOP receptor and their wild-type controls, we also examined the involvement of NOP in the effect of AT-312. Motivational effects of AT-312 alone were also assessed in the CPP paradigm. METHODS Female mice lacking NOP and/or their wild-type controls received conditioning in the presence or absence of the NOP agonist [AT-312 (1, 3, and 10 mg/kg) or the control NOP agonist SCH221510 (10 mg/kg)] followed by saline/EtOH for 3 consecutive days (twice daily) and tested for CPP in a drug-free state on the next day. RESULTS Our in vitro data showed that AT-312 is a high-affinity, selective NOP full agonist with 17-fold selectivity over the mu opioid receptor and >200-fold selectivity over the kappa opioid receptor. The results of our in vivo studies showed that AT-312 reduced EtOH CPP at the lowest dose (1 mg/kg) tested but completely abolished EtOH CPP at higher doses (3 or 10 mg/kg) compared to their vehicle-treated control group. AT-312 (3 mg/kg) did not alter EtOH-induced CPP in mice lacking NOP, confirming that AT-312 reduced EtOH CPP through its action at the NOP receptor. AT-312 (3 mg/kg) did not induce reward or aversion when administered alone, showing that the novel small-molecule NOP agonist shows efficacy in blocking EtOH-induced CPP via the NOP receptor. CONCLUSIONS Together, these data suggest that small-molecule NOP agonists have the potential to reduce alcohol reward and may be promising as medications to treat alcohol addiction.
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Affiliation(s)
| | - Paul V Marquez
- College of Pharmacy, Western University of Health Sciences, Pomona, California
| | | | | | - Abdul Hamid
- College of Pharmacy, Western University of Health Sciences, Pomona, California
| | - Kabirullah Lutfy
- College of Pharmacy, Western University of Health Sciences, Pomona, California
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18
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Van't Veer A, Smith KL, Cohen BM, Carlezon WA, Bechtholt AJ. Kappa-opioid receptors differentially regulate low and high levels of ethanol intake in female mice. Brain Behav 2016; 6:e00523. [PMID: 27688945 PMCID: PMC5036438 DOI: 10.1002/brb3.523] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2015] [Revised: 04/21/2016] [Accepted: 05/28/2016] [Indexed: 12/31/2022] Open
Abstract
INTRODUCTION Studies in laboratory animals and humans indicate that endogenous opioids play an important role in regulating the rewarding value of various drugs, including ethanol (EtOH). Indeed, opioid antagonists are currently a front-line treatment for alcoholism in humans. Although roles for mu- and delta-opioid receptors have been characterized, the contribution of kappa-opioid receptors (KORs) is less clear. There is evidence that changes in KOR system function can decrease or increase EtOH drinking, depending on test conditions. For example, female mice lacking preprodynorphin - the precursor to the endogenous KOR ligand dynorphin - have reduced EtOH intake. Considering that KORs can regulate dopamine (DA) transmission, we hypothesized that KORs expressed on DA neurons would play a prominent role in EtOH intake in females. METHODS We used a Cre/loxP recombination strategy to ablate KORs throughout the body or specifically on dopamine uptake transporter (DAT)-expressing neurons to investigate the role of KORs on preference for and intake of EtOH (2-bottle choice), the transition from moderate to excessive EtOH drinking (intermittent EtOH access), and binge EtOH drinking (drinking in the dark [DID]). RESULTS KOR deletion decreased preference for EtOH, although this effect was less pronounced when EtOH intake increased beyond relatively low levels. DISCUSSION Our findings indicate that KOR activation increases EtOH drinking via effects mediated, at least in part, by KORs on DA neurons. While the mechanisms of this regulation remain unknown, previous work suggests that alterations in negative reinforcement processes or sensitivity to the sensory properties of EtOH can affect preference and intake.
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Affiliation(s)
- Ashlee Van't Veer
- Department of Psychiatry Harvard Medical School McLean Hospital Belmont MA USA; National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda MD USA
| | - Karen L Smith
- Department of Psychiatry Harvard Medical School McLean Hospital Belmont MA USA
| | - Bruce M Cohen
- Department of Psychiatry Harvard Medical School McLean Hospital Belmont MA USA
| | - William A Carlezon
- Department of Psychiatry Harvard Medical School McLean Hospital Belmont MA USA
| | - Anita J Bechtholt
- Department of Psychiatry Harvard Medical School McLean Hospital Belmont MA USA; National Institute on Alcohol Abuse and Alcoholism National Institutes of Health Bethesda MD USA
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19
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Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of Evidence. Drug Saf 2016; 39:627-45. [DOI: 10.1007/s40264-016-0416-y] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Lutfy K, Zaveri NT. The Nociceptin Receptor as an Emerging Molecular Target for Cocaine Addiction. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2015; 137:149-81. [PMID: 26810001 DOI: 10.1016/bs.pmbts.2015.10.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Cocaine addiction is a global public health and socioeconomic issue that requires pharmacological and cognitive therapies. Currently there are no FDA-approved medications to treat cocaine addiction. However, in preclinical studies, interventions ranging from herbal medicine to deep-brain stimulation have shown promise for the therapy of cocaine addiction. Recent developments in molecular biology, pharmacology, and medicinal chemistry have enabled scientists to identify novel molecular targets along the pathways involved in drug addiction. In 1994, a receptor that showed a great deal of homology to the traditional opioid receptors was characterized. However, endogenous and exogenous opioids failed to bind to this receptor, which led scientists to name it opioid receptor-like receptor, now referred to as the nociceptin receptor. The endogenous ligand of NOPr was identified a year later and named orphanin FQ/nociceptin. Nociceptin and NOPr are widely distributed throughout the CNS and are involved in many physiological responses, such as food intake, nociceptive processing, neurotransmitter release, etc. Furthermore, exogenous nociceptin has been shown to regulate the activity of mesolimbic dopaminergic neurons, glutamate, and opioid systems, and the stress circuit. Importantly, exogenous nociceptin has been shown to reduce the rewarding and addictive actions of a number of drugs of abuse, such as psychostimulants, alcohol, and opioids. This paper reviews the existing literature on the role of endogenous nociceptin in the rewarding and addictive actions of cocaine. The effect of exogenous nociceptin on these processes is also reviewed. Furthermore, the effects of novel small-molecule NOPr ligands on these actions of cocaine are discussed. Overall, a review of the literature suggests that NOPr could be an emerging target for cocaine addiction pharmacotherapy.
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Affiliation(s)
- Kabirullah Lutfy
- Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, California, USA.
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Donoghue K, Elzerbi C, Saunders R, Whittington C, Pilling S, Drummond C. The efficacy of acamprosate and naltrexone in the treatment of alcohol dependence, Europe versus the rest of the world: a meta-analysis. Addiction 2015; 110:920-30. [PMID: 25664494 DOI: 10.1111/add.12875] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Revised: 11/28/2014] [Accepted: 02/04/2015] [Indexed: 12/20/2022]
Abstract
AIMS To determine the efficacy of acamprosate and naltrexone in the treatment of those who are alcohol-dependent in reducing lapse/relapse to alcohol consumption and treatment discontinuation, and to examine whether a proportion of the variance in study outcome can be explained by the country in which the trials have taken place. METHOD A systematic review and meta-analysis of randomized controlled trials published before September 2013 was conducted. The primary outcome measures were the efficacy of acamprosate or naltrexone in reducing lapse/relapse compared to placebo in the treatment of alcohol dependence and treatment discontinuation. Twenty-two randomized controlled trials (RCTs) of the efficacy of acamprosate met inclusion criteria for the meta-analysis, with a total of 2649 participants in the acamprosate group and 2587 in the placebo group. Twenty-seven RCTs of the efficacy of naltrexone met inclusion criteria for the meta-analysis, with a total of 2253 participants in the naltrexone group and 1946 in the placebo group. A random-effects model using a Mantel-Haenszel method was applied to conduct the meta-analysis. Variance in study outcomes was explored using subgroup analysis of Europe versus the rest of the world (ROW). RESULTS The risk of returning to any drinking at 6 months was significantly lower for acamprosate [risk ratio (RR) = 0.83, 95% confidence interval (CI) = 0.78-0.89]. There was little difference in the risk of participants discontinuing treatment for any reason (RR = 0.91, 95% CI = 0.83-1.00) or due to adverse events (RR = 1.30, 95% CI = 0.96-1.75) for the acamprosate compared to placebo groups. The risk of individuals returning to any drinking at approximately 3 months was reduced significantly for the naltrexone group (RR = 0.92, 95% CI = 0.86-1.00), as was the risk of individuals relapsing to heavy drinking at 3 months (RR = 0.85, 95% CI = 0.78-0.93). There was no significant difference between naltrexone and placebo for the risk of individuals discontinuing treatment for any reason (RR = 0.94, 95% CI = 0.84-1.05). There was a significantly greater risk of participants in the naltrexone group discontinuing treatment due to adverse events compared to placebo (RR = 1.72, 95% CI = 1.10-2.70). Subgroup analysis by country (Europe versus ROW) revealed no difference in risk between acamprosate and placebo for the outcomes returning to any drinking at 6 months and discontinuing treatment due to adverse events. For the outcome discontinuation of treatment for any reason, there was a significant difference in RR between Europe and the ROW (χ(2) = 11.65, P <0.001) for acamprosate. Acamprosate was associated with a reduction in risk of discontinuing treatment for Europe (RR = 0.86, 95% CI = 0.79-0.95), but an increase in risk of discontinuing treatment for ROW (RR = 1.23, 95% CI = 1.03-1.48). CONCLUSIONS Both acamprosate and naltrexone appear to reduce the risk of individuals returning to drinking alcohol in those who are alcohol-dependent. The country in which a randomized control trial (RCT) for the efficacy of acamprosate and naltrexone is completed does not appear to explain the variance in trial outcomes for returning to drinking alcohol or discontinuing drinking due to adverse effects. However, the country in which the RCT of acamprosate are completed may be important for explaining the variance between studies for the outcome 'discontinuing treatment for any reason'.
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Affiliation(s)
- Kim Donoghue
- National Addiction Centre, Addictions Department, King's College London, UK
| | - Catherine Elzerbi
- National Addiction Centre, Addictions Department, King's College London, UK
| | - Rob Saunders
- Centre for Outcomes Research and Effectiveness, Research Department of Clinical, Educational and Health Psychology, University College London, London, UK
| | - Craig Whittington
- Centre for Outcomes Research and Effectiveness, Research Department of Clinical, Educational and Health Psychology, University College London, London, UK
| | - Stephen Pilling
- Centre for Outcomes Research and Effectiveness, Research Department of Clinical, Educational and Health Psychology, University College London, London, UK
| | - Colin Drummond
- National Addiction Centre, Addictions Department, King's College London, UK
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Affiliation(s)
- Rob M Kok
- Department of Old Age,Parnassia Psychiatric Institute,Mangostraat 1,2552 KS The Hague,The Netherlands
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Abstract
Although the myth that older adults do not use mood-altering substances persists, evidence suggests that substance use among older adults has been underidentified for decades. The baby boom generation is unique in its exposure to, attitudes toward, and prevalence of substance use-causing projected rates of substance use to increase over the next twenty years. Given their unique biological vulnerabilities and life stage, older adults who misuse substances require special attention. Prevalence rates of substance use and misuse among older adults, methods of screening and assessment unique to older adults, and treatment options for older adults are reviewed.
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Affiliation(s)
- Alexis Kuerbis
- Department of Mental Health Services and Policy Research, Research Foundation for Mental Hygiene, Inc, Columbia University Medical Center, 3 Columbus Circle, Suite 1404, New York, NY 10019, USA.
| | - Paul Sacco
- University of Maryland School of Social Work, 525 West Redwood Street, Baltimore, MD 21201, USA
| | - Dan G Blazer
- Department of Psychiatry and Behavioral Sciences, Academic Development, Duke University, DUMC 3003, Durham, NC 27710, USA
| | - Alison A Moore
- Department of Medicine, Division of Geriatrics, David Geffen School of Medicine at UCLA, 10945 Le Conte Avenue, Suite 2339, Los Angeles, CA 90095, USA
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Nielsen DA, Nielsen EM, Dasari T, Spellicy CJ. Pharmacogenetics of addiction therapy. Methods Mol Biol 2014; 1175:589-624. [PMID: 25150877 DOI: 10.1007/978-1-4939-0956-8_15] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Drug addiction is a serious relapsing disease that has high costs to society and to the individual addicts. Treatment of these addictions is still in its nascency, with only a few examples of successful therapies. Therapeutic response depends upon genetic, biological, social, and environmental components. A role for genetic makeup in the response to treatment has been shown for several addiction pharmacotherapies. For several addiction pharmacotherapies, response to treatment varies based on individual genetic makeup. In this chapter, we discuss the role of genetics in pharmacotherapies, specifically for cocaine, alcohol, and opioid dependences. The elucidation of the role of genetics should aid in the development of new treatments and increase the efficacy of existing treatments.
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Affiliation(s)
- David A Nielsen
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA,
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Litten RZ, Castle IJP, Falk D, Ryan M, Fertig J, Chen CM, Yi HY. The placebo effect in clinical trials for alcohol dependence: an exploratory analysis of 51 naltrexone and acamprosate studies. Alcohol Clin Exp Res 2013; 37:2128-37. [PMID: 23889231 DOI: 10.1111/acer.12197] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2012] [Accepted: 04/17/2013] [Indexed: 01/07/2023]
Abstract
BACKGROUND The placebo effect often undermines efforts to determine treatment effectiveness in clinical trials. A significant placebo response occurs in alcohol trials, but it is not well understood. The purpose of this study was to characterize the placebo response across multiple naltrexone and acamprosate studies. METHODS Fifty-one trials, 3 with a naltrexone and an acamprosate arm, 31 with at least 1 naltrexone arm, and 17 with at least 1 acamprosate arm, were identified from Cochrane reviews and PubMed search. To be included in this study, patients had to be at least 18 years old, abstinent from alcohol before randomization, and meet a diagnosis of alcohol dependence. Pearson correlation coefficients (rp ) and simple linear regression were used to describe the strength of linear relationships between placebo response and treatment effect size. Spearman's rank correlation coefficients (rs ) were used to examine the strength of associations between study characteristics and placebo response. RESULTS For the end point measures of percent days abstinent and total abstinence, a negative relationship was evident between placebo response and treatment effect size in the naltrexone trials (rp = -0.55, p < 0.01 and rp = -0.20, p = 0.35, respectively) as well as in the acamprosate trials (rp = -0.45, p = 0.09 and rp = -0.56, p = 0.01, respectively). The placebo response for percent days abstinent was negatively correlated with mean age of participants (rs = -0.42, p = 0.05) across naltrexone trials and positively correlated with publication year (rs = 0.57, p = 0.03) across acamprosate trials. However, these 2 study characteristics were not significantly correlated with treatment effect size. CONCLUSIONS The placebo response varied considerably across trials and was negatively correlated with the treatment effect size. Additional studies are required to fully understand the complex nature of the placebo response and to evaluate approaches to minimize its effects.
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Affiliation(s)
- Raye Z Litten
- Division of Treatment and Recovery Research , National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland
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Kuerbis A, Sacco P. A review of existing treatments for substance abuse among the elderly and recommendations for future directions. SUBSTANCE ABUSE-RESEARCH AND TREATMENT 2013; 7:13-37. [PMID: 23471422 PMCID: PMC3583444 DOI: 10.4137/sart.s7865] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Background With population aging, there is widespread recognition that the healthcare system must be prepared to serve the unique needs of substance using older adults (OA) in the decades ahead. As such, there is an increasingly urgent need to identify efficient and effective substance abuse treatments (SAT) for OA. Despite this need, there remains a surprising dearth of research on treatment for OA. Aims of review This review describes and evaluates studies on SAT applied to and specifically designed for OA over the last 30 years with an emphasis on methodologies used and the knowledge gained. Methods Using three research databases, 25 studies published in the last 30 years which investigated the impact of SAT on OA and met specific selection criteria were reviewed. Results A majority of the studies were methodologically limited in that they were pre-to-post or post-test only studies. Of the randomized controlled trials, many were limited by sample sizes of 15 individuals or less per group, making main effects difficult to detect. Thus, with caution, the literature suggests that among treatment seeking OA, treatment, whether age-specific or mixed-age, generally works yielding rates of abstinence comparable to general populations and younger cohorts. It also appears that with greater treatment exposure (higher dosage), regardless of level of care, OA do better. Finally, based on only two studies, age-specific treatment appears to potentiate treatment effects for OA. Like younger adults, OA appear to have a heterogeneous response to treatments, and preliminary evidence suggests a possibility of treatment matching for OA. Conclusions Expansion of research on SAT for OA is urgently needed for maximum effectiveness and efficiency of the healthcare system serving these individuals. Future research needs to include laboratory and community based randomized controlled trials with high internal validity of previously vetted evidenced-based practices, including Motivational Interviewing, cognitive behavioral therapy, and medications such as naltrexone, to determine the best fit for OA.
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Affiliation(s)
- Alexis Kuerbis
- Research Foundation for Mental Hygiene, Inc, and Columbia University Medical Center
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Maisel NC, Blodgett JC, Wilbourne PL, Humphreys K, Finney JW. Meta-analysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful? Addiction 2013; 108:275-93. [PMID: 23075288 PMCID: PMC3970823 DOI: 10.1111/j.1360-0443.2012.04054.x] [Citation(s) in RCA: 276] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2011] [Revised: 02/14/2012] [Accepted: 08/09/2012] [Indexed: 12/11/2022]
Abstract
AIMS Although debates over the efficacy of oral naltrexone and acamprosate in treating alcohol use disorders tend to focus on their global efficacy relative to placebo or their efficacy relative to each other, the underlying reality may be more nuanced. This meta-analysis examined when naltrexone and acamprosate are most helpful by testing: (i) the relative efficacy of each medication given its presumed mechanism of action (reducing heavy drinking versus fostering abstinence) and (ii) whether different ways of implementing each medication (required abstinence before treatment, detoxification before treatment, goal of treatment, length of treatment, dosage) moderate its effects. METHODS A systematic literature search identified 64 randomized, placebo-controlled, English-language clinical trials completed between 1970 and 2009 focused on acamprosate or naltrexone. RESULTS Acamprosate had a significantly larger effect size than naltrexone on the maintenance of abstinence, and naltrexone had a larger effect size than acamprosate on the reduction of heavy drinking and craving. For naltrexone, requiring abstinence before the trial was associated with larger effect sizes for abstinence maintenance and reduced heavy drinking compared with placebo. For acamprosate, detoxification before medication administration was associated with better abstinence outcomes compared with placebo. CONCLUSIONS In treatment for alcohol use disorders, acamprosate has been found to be slightly more efficacious in promoting abstinence and naltrexone slightly more efficacious in reducing heavy drinking and craving. Detoxification before treatment or a longer period of required abstinence before treatment is associated with larger medication effects for acamprosate and naltrexone respectively.
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Affiliation(s)
- Natalya C. Maisel
- Center for Health Care Evaluation, VA Palo Alto Health Care System (152MPD), 795 Willow Rd., Menlo Park, CA 94025
| | - Janet C. Blodgett
- Center for Health Care Evaluation, VA Palo Alto Health Care System (152MPD), 795 Willow Rd., Menlo Park, CA 94025
| | - Paula L. Wilbourne
- Center for Health Care Evaluation, VA Palo Alto Health Care System (152MPD), 795 Willow Rd., Menlo Park, CA 94025
| | - Keith Humphreys
- Center for Health Care Evaluation, VA Palo Alto Health Care System (152MPD), 795 Willow Rd., Menlo Park, CA 94025,Stanford University Stanford School of Medicine, Department of Psychiatry & Behavioral Sciences, 401 N. Quarry Road, Stanford, CA 94305-5717
| | - John W. Finney
- Center for Health Care Evaluation, VA Palo Alto Health Care System (152MPD), 795 Willow Rd., Menlo Park, CA 94025,Stanford University Stanford School of Medicine, Department of Psychiatry & Behavioral Sciences, 401 N. Quarry Road, Stanford, CA 94305-5717
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Agosti V, Nunes EV, O'Shea D. Do manualized psychosocial interventions help reduce relapse among alcohol-dependent adults treated with naltrexone or placebo? A meta-analysis. Am J Addict 2012; 21:501-7. [PMID: 23082827 DOI: 10.1111/j.1521-0391.2012.00270.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND During the past decade, several novel medication treatments and psychosocial interventions have been tested. Overall, their impact on reducing alcohol use and preventing relapse has been modest. These outcomes have spurred researchers to investigate whether the addition of manualized psychosocial therapies with demonstrated efficacy to pharmacotherpy would have a synergistic effect. OBJECTIVES We conducted a meta-analysis to test the hypothesis that the addition of manualized psychosocial therapies would reduce the frequency of relapse. RESULTS This review analyzed data from six studies. Among studies that used random assignment to manually guided psychosocial interventions, the rates of relapse between the naltrexone plus a psychosocial intervention and naltrexone without a psychosocial intervention were very similar. Among patients allocated to placebo, similar rates of relapse were also found between Cognitive Behavioral Therapy (CBT) and non-CBT. In studies which used manualized psychotherapies as a platform, relapse rates were similar between naltrexone and placebo. In contrast, studies using Treatment As Usual psychotherapy as a platform demonstrated lower rates of relapse in the naltrexone group, compared to placebo group. CONCLUSIONS We conclude that CBT does not appear to offer benefits beyond those derived from study medications. SCIENTIFIC SIGNIFICANCE The benefit of the addition of CBT to medication in preventing relapse may be limited.
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Affiliation(s)
- Vito Agosti
- Depression Evaluation Service, New York State Psychiatric Institute, New York, New York 10032, USA.
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Lingford-Hughes AR, Welch S, Peters L, Nutt DJ. BAP updated guidelines: evidence-based guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity: recommendations from BAP. J Psychopharmacol 2012; 26:899-952. [PMID: 22628390 DOI: 10.1177/0269881112444324] [Citation(s) in RCA: 163] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
The British Association for Psychopharmacology guidelines for the treatment of substance abuse, harmful use, addiction and comorbidity with psychiatric disorders primarily focus on their pharmacological management. They are based explicitly on the available evidence and presented as recommendations to aid clinical decision making for practitioners alongside a detailed review of the evidence. A consensus meeting, involving experts in the treatment of these disorders, reviewed key areas and considered the strength of the evidence and clinical implications. The guidelines were drawn up after feedback from participants. The guidelines primarily cover the pharmacological management of withdrawal, short- and long-term substitution, maintenance of abstinence and prevention of complications, where appropriate, for substance abuse or harmful use or addiction as well management in pregnancy, comorbidity with psychiatric disorders and in younger and older people.
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Alcohol use disorders in the elderly: a brief overview from epidemiology to treatment options. Exp Gerontol 2012; 47:411-6. [PMID: 22575256 DOI: 10.1016/j.exger.2012.03.019] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2011] [Revised: 02/09/2012] [Accepted: 03/27/2012] [Indexed: 11/24/2022]
Abstract
Alcohol-use-disorders (AUDs) afflict 1-3% of elderly subjects. The CAGE, SMAST-G, and AUDIT are the most common and validated questionnaires used to identify AUDs in the elderly, and some laboratory markers of alcohol abuse (AST, GGT, MCV, and CDT) may also be helpful. In particular, the sensitivity of MCV or GGT in detecting alcohol misuse is higher in older than in younger populations. The incidence of medical and neurological complications during alcohol withdrawal syndrome in elderly alcoholics is higher than in younger alcoholics. Chronic alcohol abuse is associated with tissue damage to several organs. Namely, an increased level of blood pressure is more frequent in the elderly than in younger adults, and a greater vulnerability to the onset of alcoholic liver disease, and an increasing risk of breast cancer in menopausal women have been described. In addition, the prevalence of dementia in elderly alcoholics is almost 5 times higher than in non-alcoholic elderly individuals, approximately 25% of elderly patients with dementia also present AUDs, and almost 20% of individuals aged 65 and over with a diagnosis of depression have a co-occurring AUD. Moreover, prevention of drinking relapse in older alcoholics is, in some cases, better than in younger patients; indeed, more than 20% of treated elderly alcohol-dependent patients remain abstinent after 4 years. Considering that the incidence of AUDs in the elderly is fairly high, and AUDs in the elderly are still underestimated, more studies in the fields of epidemiology, prevention and pharmacological and psychotherapeutic treatment of AUDs in the elderly are warranted.
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Abstract
The ageing of the population brings particular challenges to psychiatric practice. Although the clinical presentation of common psychiatric disorders such as mood and psychotic disorders is largely similar to those in younger adults, late life presentations tend to be more complex as co-morbidity with dementia and physical illness is common. Suicide tends to increase with age in most countries. In this chapter we argue that the aetiology of disorders may be best understood within a stress vulnerability model in which neurobiological and psychosocial factors interplay. We further present that management strategies need to be comprehensive, incorporating physical, social, pharmacological, and psychological treatments appropriate to each case. We close with a call for the use of specialised multi-disciplinary services to improve the overall quality of care.
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Affiliation(s)
- C Wijeratne
- School of Psychiatry, University of New South Wales, Sydney, Australia
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33
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Reece AS. Hypothalamic opioid-melanocortin appetitive balance and addictive craving. Med Hypotheses 2011; 76:132-7. [PMID: 20926200 DOI: 10.1016/j.mehy.2010.09.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2010] [Revised: 08/17/2010] [Accepted: 09/06/2010] [Indexed: 10/19/2022]
Abstract
Whilst the parallels between drug and food craving are receiving increasing attention, the recently elucidated complex physiology of the hypothalamic appetite regulatory centres has been largely overlooked in the efforts to understand drug craving which is one of the most refractory and problematic aspects of drug and behavioural addictions. Important conceptual gains could be made by researchers from both appetite and addiction neuroscience if they were to have an improved understanding of each others' disciplines. It is well known in addiction medicine that the use of many substances is elevated in opiate dependency. There is voluminous evidence of very high rates of drug use in opiate agonist maintained patients, and the real possibility exists that opiate agonist therapy therefore increases drug craving. Conversely, opiate antagonist therapy with naloxone or naltrexone has been shown to reduce most chemical and behavioural addictions, and naltrexone is now being developed together with bupropion as the anti-obesity drug "Contrave". Hypothalamic melanocortins, particularly α-MSH, are known to constitute the main brake to consumptive behaviour of food. There is a well described antagonism between melanocortins and opioids at many loci including the hypothalamus. Administration of exogenous opiates is known to both suppress α-MSH and to stimulate hedonic food consumption. Opiate maintenance programs are associated with weight gain. As monoamines, opioids and cannabinoids are known to be involved in appetite regulation, and as endorphin opioids are known to be perturbed in other addictions, further exploration of the hypothalamic appetite regulatory centre would appear to be an obvious, albeit presently largely overlooked, locus in which to study drug and other craving mechanisms.
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Affiliation(s)
- Albert Stuart Reece
- University of Western Australia, Clinical Neurosciences, 39 Gladstone Rd., Highgate Hill, Brisbane, Queensland 4101, Australia.
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Kalapatapu RK, Vadhan NP, Rubin E, Bedi G, Cheng WY, Sullivan MA, Foltin RW. A pilot study of neurocognitive function in older and younger cocaine abusers and controls. Am J Addict 2011; 20:228-39. [PMID: 21477051 DOI: 10.1111/j.1521-0391.2011.00128.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
This pilot study compared basic neurocognitive functioning among older and younger cocaine abusers and control participants, as a preliminary assessment of whether specific cognitive deficits exist in an aged cocaine-abusing population. We hypothesized an interaction between aging and cocaine abuse, such that older cocaine abusers would exhibit decreased neuropsychological test performance relative to both younger cocaine abusers and older control participants. Four groups (n = 20 each) were examined: older cocaine abusers (ages 51-70), younger cocaine abusers (ages 21-39), and two non-illicit substance-using control groups. Basic neuropsychological and psychiatric measures were administered to all participants. Older participants performed more poorly than younger participants on the Mini-Mental State Examination (MMSE, p < .01), Digit Span Backward (p < .01), and Trail Making Test (TMT) Parts A and B (p < .01). Cocaine abusers performed more poorly than controls on TMT A (p < .01). Older and younger cocaine abusers used similar amounts of cocaine (p > .05). Older cocaine abusers performed more poorly than older control participants and younger cocaine abusers on the Digit Span Forward (p < .0125). Older cocaine abusers also performed more poorly than younger cocaine abusers on TMT A (p < .0125). This study provides preliminary evidence that older cocaine abusers use a significant amount of cocaine and that there is an interaction between aging and cocaine abuse on psychomotor speed, attention, and short-term memory. Future examination of neurocognitive function in older cocaine abusers is clearly warranted.
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Affiliation(s)
- Raj K Kalapatapu
- Substance Use Research Center, New York State Psychiatric Institute, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
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35
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Abstract
Alcohol use disorders cause significant morbidity and mortality in the geriatric population. This review article begins with a hypothetical case for illustration, asking what the primary care physician could do for a geriatric patient with alcohol abuse over a course of four office visits. Various aspects of alcohol use disorders in the geriatric population are reviewed, such as range of alcohol use, epidemiology, medical/psychiatric impact, detection, comprehensive treatment planning, modalities of psychotherapy, medication management, and resources for clinicians/patients.
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Affiliation(s)
- Raj K Kalapatapu
- Department of Psychiatry, Columbia University/New York State Psychiatric Institute, New York, NY 10032, USA.
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36
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Rösner S, Hackl-Herrwerth A, Leucht S, Vecchi S, Srisurapanont M, Soyka M. Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev 2010:CD001867. [PMID: 21154349 DOI: 10.1002/14651858.cd001867.pub3] [Citation(s) in RCA: 86] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Alcohol dependence belongs to the globally leading health risk factors. Therapeutic success of psychosocial programs for relapse prevention is moderate and could be increased by an adjuvant treatment with the opioid antagonists naltrexone and nalmefene. OBJECTIVES To determine the effectiveness and tolerability of opioid antagonists in the treatment of alcohol dependence. SEARCH STRATEGY We searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE and CINAHL in January 2010 and inquired manufacturers and researchers for unpublished trials. SELECTION CRITERIA All double-blind randomised controlled trials (RCTs) which compare the effects of naltrexone or nalmefene with placebo or active control on drinking-related outcomes. DATA COLLECTION AND ANALYSIS Two authors independently extracted outcome data. Trial quality was assessed by one author and cross-checked by a second author. MAIN RESULTS Based on a total of 50 RCTs with 7793 patients, naltrexone reduced the risk of heavy drinking to 83% of the risk in the placebo group RR 0.83 (95% CI 0.76 to 0.90) and decreased drinking days by about 4%, MD -3.89 (95% CI -5.75 to -2.04). Significant effects were also demonstrated for the secondary outcomes of the review including heavy drinking days, MD - 3.25 (95% CI -5.51 to -0.99), consumed amount of alcohol, MD - 10.83 (95% CI -19.69 to -1.97) and gamma-glutamyltransferase, MD - 10.37 (95% CI -18.99 to -1.75), while effects on return to any drinking, RR 0.96 (95 CI 0.92 to 1.00) missed statistical significance. Side effects of naltrexone were mainly gastrointestinal problems (e.g. nausea: RD 0.10; 95% CI 0.07 to 0.13) and sedative effects (e.g. daytime sleepiness: RD 0.09; 95% CI 0.05 to 0.14). Based on a limited study sample, effects of injectable naltrexone and nalmefene missed statistical significance. Effects of industry-sponsored studies, RR 0.90 (95% CI 0.78 to 1.05) did not significantly differ from those of non-profit funded trials, RR 0.84 (95% CI 0.77 to 0.91) and the linear regression test did not indicate publication bias (P = 0.765). AUTHORS' CONCLUSIONS Naltrexone appears to be an effective and safe strategy in alcoholism treatment. Even though the sizes of treatment effects might appear moderate in their magnitudes, these should be valued against the background of the relapsing nature of alcoholism and the limited therapeutic options currently available for its treatment.
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Affiliation(s)
- Susanne Rösner
- Psychiatric Hospital, University of Munich, Nußbaumstr. 7, Munich, Germany, 80336
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37
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Abstract
The number of older adults needing substance abuse treatment is projected to rise significantly in the next few decades. This paper will focus on the epidemic of prescription use disorders in older adults. Particular vulnerabilities of older adults to addiction will be considered. Specifically, the prevalence and patterns of use of opioids, stimulants, and benzodiazepines will be explored, including the effects of these substances on morbidity and mortality. Treatment intervention strategies will be briefly discussed, and areas for future research are suggested.
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Affiliation(s)
- Raj K Kalapatapu
- Department of Psychiatry, Division on Substance Abuse, New York State Psychiatric Institute, Columbia University, New York, New York 10032, USA.
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38
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Reece AS. Clinical safety of 1500 mg oral naltrexone overdose. BMJ Case Rep 2010; 2010:2010/sep06_1/bcr0420102871. [PMID: 22778191 DOI: 10.1136/bcr.04.2010.2871] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
This case represents a clinical overdose of the largest known dose of oral naltrexone, equivalent to the taking of a whole bottle of the oral naltrexone preparation. The patient's intention was to control craving for alcohol and opiates. The patient quickly settled with expectant management. As such it demonstrates that earlier concerns that have been voiced in this area, particularly relating to naltrexone-related hepatotoxicity and depression, may have been overstated, at least in the experience of this patient. This patient's course was marked only by gastric irritation, of which she had some history. As such the present profile provides case report evidence consistent with more robust views of the patient safety of naltrexone itself, and opposing more cautious views. Her polydrug craving was suppressed for a period of 2 weeks, which raises the important question of the mechanism of action of naltrexone's generalised suppression of refractory hedonic consumptive addictive behaviours.
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Abstract
Although it is often not considered and frequently undiagnosed, addiction disorders are a significant problem in the elderly. Elders are at a higher risk for the consequences of abuse or addiction owing to changes related to aging, multiple medications and chronic illness. The consequences of addiction disorders in this population include delirium, memory loss, suicide, falls and fractures, as well as drug–drug or drug–disease interactions. Abuse or addiction to alcohol or prescription or illicit drugs often presents differently in the elderly, may be inadvertent or prescriber-related and requires a different approach to assessment. Coexisting psychiatric or physical disorders together with addiction need to be considered in the overall functional status of the elderly. Treatment should be individualized based on the patient’s needs, readiness for change and available resources, and should vary from brief outpatient intervention to inpatient care. Treatment outcomes for elders are as good as or better than the outcome of younger adults. With an increasing proportion of the population becoming elders and the aging of ‘baby boomers,’ an increase in addiction in this population, including to illicit drugs, is expected in the near future. Education of the public, as well as healthcare professionals, along with reassessment of the prevalence of these disorders in this population using age-appropriate criteria, are needed, since more resources will be required in order to treat these individuals in the near future.
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Affiliation(s)
- Steven W Clay
- Department of Family Medicine, Ohio University College of Osteopathic Medicine, OH, USA
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41
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Brown ES, Carmody TJ, Schmitz JM, Caetano R, Adinoff B, Swann AC, John Rush A. A randomized, double-blind, placebo-controlled pilot study of naltrexone in outpatients with bipolar disorder and alcohol dependence. Alcohol Clin Exp Res 2009; 33:1863-9. [PMID: 19673746 DOI: 10.1111/j.1530-0277.2009.01024.x] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Alcohol dependence is extremely common in patients with bipolar disorder and is associated with unfavorable outcomes including treatment nonadherence, violence, increased hospitalization, and decreased quality of life. While naltrexone is a standard treatment for alcohol dependence, no controlled trials have examined its use in patients with co-morbid bipolar disorder and alcohol dependence. In this pilot study, the efficacy of naltrexone in reducing alcohol use and on mood symptoms was assessed in bipolar disorder and alcohol dependence. METHODS Fifty adult outpatients with bipolar I or II disorders and current alcohol dependence with active alcohol use were randomized to 12 weeks of naltrexone (50 mg/d) add-on therapy or placebo. Both groups received manual-driven cognitive behavioral therapy designed for patients with bipolar disorder and substance-use disorders. Drinking days and heavy drinking days, alcohol craving, liver enzymes, and manic and depressed mood symptoms were assessed. RESULTS The 2 groups were similar in baseline and demographic characteristics. Naltrexone showed trends (p < 0.10) toward a greater decrease in drinking days (binary outcome), alcohol craving, and some liver enzyme levels than placebo. Side effects were similar in the 2 groups. Response to naltrexone was significantly related to medication adherence. CONCLUSIONS Results suggest the potential value and acceptable tolerability of naltrexone for alcohol dependence in bipolar disorder patients. A larger trial is needed to establish efficacy.
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Affiliation(s)
- E Sherwood Brown
- Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
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Snyder JL, Bowers TG. The Efficacy of Acamprosate and Naltrexone in the Treatment of Alcohol Dependence: A Relative Benefits Analysis of Randomized Controlled Trials. THE AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE 2009; 34:449-61. [DOI: 10.1080/00952990802082198] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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LEE ARTHUR, TAN SHAWN, LIM DOMINIC, WINSLOW RM, WONG KE, ALLEN JOHN, HALL WAYNE, PARKER GORDON. Naltrexone in the treatment of male alcoholics-an effectiveness study in Singapore. Drug Alcohol Rev 2009. [DOI: 10.1080/09595230124192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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A micro opioid receptor gene polymorphism (A118G) and naltrexone treatment response in adherent Korean alcohol-dependent patients. Psychopharmacology (Berl) 2009; 201:611-8. [PMID: 18795264 DOI: 10.1007/s00213-008-1330-5] [Citation(s) in RCA: 70] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2008] [Accepted: 09/01/2008] [Indexed: 12/20/2022]
Abstract
RATIONALE Previous studies have demonstrated an association between genetic polymorphisms of the mu opioid receptor gene (OPRM1) and response to naltrexone treatment. The Asp40 variant genotype previously shown to be associated with naltrexone treatment response is known to be relatively common among Koreans. OBJECTIVES This study was conducted to prospectively investigate the relationship between genotype and response to open-label naltrexone treatment in Korean alcohol-dependent subjects. MATERIALS AND METHODS Sixty-three alcohol-dependent subjects were prescribed naltrexone for 12 weeks in combination with cognitive behavioral therapy. Thirty-two subjects were adherent, taking the medication at least 80% of the treatment days [16 Asn40 (A/A) patients and 16 Asp40 variant (A/G or G/G) patients]. RESULTS Subjects adherent to naltrexone treatment with one or two copies of the Asp40 allele took a significantly longer time than the Asn40 group to relapse (p=0.014). Although not significant, the Asn40 group treated with naltrexone had a 10.6 times greater relapse rate than the Asp40 variant group. There was no significant difference between the Asn40 group and the Asp40 variant group treated with naltrexone in rates of abstinence. CONCLUSIONS These results demonstrating a higher therapeutic effect of naltrexone in Korean alcohol-dependent individuals with the Asp40 variant genotype than the Asn40 genotype are consistent with previous study results in individuals of European descent. This is the first study to examine the pharmacogenetics treatment response to naltrexone in non-European subjects.
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45
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Oslin DW, Lynch KG, Pettinati HM, Kampman KM, Gariti P, Gelfand L, Ten Have T, Wortman S, Dundon W, Dackis C, Volpicelli JR, O'Brien CP. A placebo-controlled randomized clinical trial of naltrexone in the context of different levels of psychosocial intervention. Alcohol Clin Exp Res 2008; 32:1299-308. [PMID: 18540910 DOI: 10.1111/j.1530-0277.2008.00698.x] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND Naltrexone is approved for the treatment of alcohol dependence when used in conjunction with a psychosocial intervention. This study was undertaken to examine the impact of 3 types of psychosocial treatment combined with either naltrexone or placebo treatment on alcohol dependency over 24 weeks of treatment: (1) Cognitive-Behavioral Therapy (CBT) + medication clinic, (2) BRENDA (an intervention promoting pharmacotherapy) + medication clinic, and (3) a medication clinic model with limited therapeutic content. METHODS Two hundred and forty alcohol-dependent subjects were enrolled in a 24-week double-blind placebo-controlled study of naltrexone (100 mg/d). Subjects were also randomly assigned to 1 of 3 psychosocial interventions. All patients were assessed for alcohol use, medication adherence, and adverse events at regularly scheduled research visits. RESULTS There was a modest main treatment effect for the psychosocial condition favoring those subjects randomized to CBT. Intent-to-treat analyses suggested that there was no overall efficacy of naltrexone and no medication by psychosocial intervention interaction. There was a relatively low level of medication adherence (50% adhered) across conditions, and this was associated with poor outcome. CONCLUSIONS Results from this 24-week treatment study demonstrate the importance of the psychosocial component in the treatment of alcohol dependence. Moreover, results demonstrate a substantial association between medication adherence and treatment outcomes. The findings suggest that further research is needed to determine the appropriate use of pharmacotherapy in maximizing treatment response.
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Affiliation(s)
- David W Oslin
- Center for the Study of Addictions, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
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Soyka M, Kranzler HR, Berglund M, Gorelick D, Hesselbrock V, Johnson BA, Möller HJ, Soyka M, Kranzler HR, Berglund M, Gorelick D, Hesselbrock V, Johnson BA, Möller HJ, THE WFSBP TASK FORCE ON TREATMENT G. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Substance Use and Related Disorders, Part 1: Alcoholism. World J Biol Psychiatry 2008; 9:6-23. [PMID: 18273737 DOI: 10.1080/15622970801896390] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
These practice guidelines for the biological treatment of substance use disorders were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal during the development of these guidelines was to review systematically all available evidence pertaining to the treatment of substance use disorders, and to reach a consensus on a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by physicians evaluating and treating people with substance use disorders and are primarily concerned with the biological treatment of adults suffering from substance use disorders. The data used to develop these guidelines were extracted primarily from various national treatment guidelines for substance use disorders, as well as from meta-analyses, reviews and randomized clinical trials on the efficacy of pharmacological and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorized into four levels of evidence (A-D). This first part of the guidelines covers the treatment of alcohol dependence; Part 2 will be devoted to the treatment of drug dependence.
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Affiliation(s)
- Michael Soyka
- Psychiatric Hospital Meiringen, Meiringen, Switzerland
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47
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Zanjani F, Mavandadi S, TenHave T, Katz I, Durai NB, Krahn D, Llorente M, Kirchner J, Olsen E, Van Stone W, Cooley S, Oslin DW. Longitudinal course of substance treatment benefits in older male veteran at-risk drinkers. J Gerontol A Biol Sci Med Sci 2008; 63:98-106. [PMID: 18245767 DOI: 10.1093/gerona/63.1.98] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND This investigation aims to determine the 12-month drinking trajectory of older at-risk drinkers in treatment. Furthermore, the drinking trajectory between at-risk drinkers who had met the threshold suggestive of alcohol dependence (problem at-risk drinkers) and those who did not meet this threshold (nonproblematic at-risk drinkers) were compared. METHODS This investigation is a component of the PRISM-E (Primary Care Research in Substance Abuse and Mental Health for the Elderly) Study, a multisite randomized trial comparing service use, outcomes, and cost between Integrated (IC) versus Enhanced Specialty Referral (ESR) care models for older (65+ years) adults with depression, anxiety, and/or at-risk alcohol consumption. This investigation focuses only on at-risk drinkers, generally defined as exceeding recommended drinking limits, which in the case of older adults has been classified as consuming more than one drink per day. Two hundred fifty-eight randomized older at-risk drinkers were examined, of whom 56% were problem drinkers identified through the Short Michigan Alcohol Screening Test-Geriatric version. RESULTS Over time, all at-risk drinkers showed a significant reduction in drinking. Problem drinkers showed reductions in average weekly consumption and number of occurrences of binge drinking at 3, 6, and 12 months, whereas nonproblematic drinkers showed significant reductions in average weekly consumption at 3, 6, and 12 months and number of occurrences of binge drinking at only 6 months. IC treatment assignment led to higher engagement in treatment, which led to better binge drinking outcomes for problem drinkers. Despite significant reductions in drinking, approximately 29% of participants displayed at-risk drinking at the end of the study. CONCLUSIONS Results suggest that older at-risk drinkers, both problem and nonproblematic, show a considerable decrease in drinking, with slightly greater improvement evidenced in problem drinkers and higher engagement in treatment seen in those assigned to IC.
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Affiliation(s)
- Faika Zanjani
- Graduate Center for Gerontology, University of Kentucky, Lexington, KY 41094, USA.
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48
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Rösner S, Leucht S, Lehert P, Soyka M. Acamprosate supports abstinence, naltrexone prevents excessive drinking: evidence from a meta-analysis with unreported outcomes. J Psychopharmacol 2008; 22:11-23. [PMID: 18187529 DOI: 10.1177/0269881107078308] [Citation(s) in RCA: 87] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Two pharmacological agents have repeatedly been shown to be efficacious for relapse prevention in alcohol dependence: The putative glutamate-antagonist acamprosate and the opioid-antagonist naltrexone. Clinical evidence for both drugs is based on various outcome criteria. Whereas for acamprosate primarily abstinence maintenance has been demonstrated, studies with naltrexone have mostly emphasised the prevention of heavy drinking. The remaining effects of both drugs are not always reported; accordingly the corresponding database is fragmentary. Thus, the primary objective of the present meta-analysis was to complete the efficacy profiles for acamprosate and naltrexone and to compare them with each other. Unreported results, requested from the study investigators and the drug manufacturers, were integrated in the computation of effect sizes. For the meta-analysis, emphasis was placed on the conceptual distinction between having a first drink and returning to heavy drinking. Naltrexone was found to have a significant effect on the maintenance of abstinence as well as the prevention of heavy drinking. Acamprosate was shown only to support abstinence; it did not influence alcohol consumption after the first drink. When the efficacy profiles of the two drugs were compared, acamprosate was found to be more effective in preventing a lapse, whereas naltrexone was better in preventing a lapse from becoming a relapse. The superiority of either one drug or over the other one cannot be determined as a general rule, it rather depends on the therapeutic target. Benefits in the treatment of alcohol dependence might be optimized by matching the efficacy profiles of specific antidipsotropics with the motivational status of alcohol-dependent patients.
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49
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Davidson D, Wirtz PW, Gulliver SB, Longabaugh R. Naltrexone's suppressant effects on drinking are limited to the first 3 months of treatment. Psychopharmacology (Berl) 2007; 194:1-10. [PMID: 17514344 DOI: 10.1007/s00213-007-0807-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2006] [Accepted: 04/13/2007] [Indexed: 10/23/2022]
Abstract
RATIONALE Twelve weeks of naltrexone significantly improves drinking outcomes in alcoholics; however, the clinical benefits of naltrexone decline shortly after treatment is discontinued. OBJECTIVE The present study investigated whether extended treatment with naltrexone significantly improved drinking outcomes. METHODS One hundred forty-six alcohol-dependent patients received broad spectrum treatment or motivational enhancement therapy and either 12 or 24 weeks of naltrexone. The primary dependent variables were percent days abstinent and percent heavy drinking days. RESULTS Using an intention-to-treat analysis, there were no significant differences in percent days abstinence or percent heavy drinking days at the end of phase 2 between patients who received 24 weeks of treatment with naltrexone (chi = 63.23) or patients who received 12 weeks of treatment with naltrexone followed by 12 weeks of treatment with placebo (chi = 65.82). Similarly, the average percent heavy drinking days was not significantly different at the end of phase 2 between the group that received 24 weeks of naltrexone (chi = 21.9) and the group that received 12 weeks of naltrexone followed by 12 weeks of placebo (chi = 22.14). Medication compliance was low in the second phase of the study. Drinking outcomes declined with declining compliance whether patients were taking naltrexone or placebo. CONCLUSIONS The results of this study suggest that administering naltrexone beyond an initial 12 weeks of treatment may not be beneficial to all patients and should be administered along with close medical monitoring to insure compliance.
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Affiliation(s)
- Dena Davidson
- Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
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50
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Steensland P, Simms JA, Holgate J, Richards JK, Bartlett SE. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking. Proc Natl Acad Sci U S A 2007; 104:12518-23. [PMID: 17626178 PMCID: PMC1914040 DOI: 10.1073/pnas.0705368104] [Citation(s) in RCA: 302] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Alcohol dependence is a disease that impacts millions of individuals worldwide. There has been some progress with pharmacotherapy for alcohol-dependent individuals; however, there remains a critical need for the development of novel and additional therapeutic approaches. Alcohol and nicotine are commonly abused together, and there is evidence that neuronal nicotinic acetylcholine receptors (nAChRs) play a role in both alcohol and nicotine dependence. Varenicline, a partial agonist at the alpha4beta2 nAChRs, reduces nicotine intake and was recently approved as a smoking cessation aid. We have investigated the role of varenicline in the modulation of ethanol consumption and seeking using three different animal models of drinking. We show that acute administration of varenicline, in doses reported to reduce nicotine reward, selectively reduced ethanol but not sucrose seeking using an operant self-administration drinking paradigm and also decreased voluntary ethanol but not water consumption in animals chronically exposed to ethanol for 2 months before varenicline treatment. Furthermore, chronic varenicline administration decreased ethanol consumption, which did not result in a rebound increase in ethanol intake when the varenicline was no longer administered. The data suggest that the alpha4beta2 nAChRs may play a role in ethanol-seeking behaviors in animals chronically exposed to ethanol. The selectivity of varenicline in decreasing ethanol consumption combined with its reported safety profile and mild side effects in humans suggest that varenicline may prove to be a treatment for alcohol dependence.
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Affiliation(s)
- Pia Steensland
- Ernest Gallo Clinic and Research Center, University of California, San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608
| | - Jeffrey A. Simms
- Ernest Gallo Clinic and Research Center, University of California, San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608
| | - Joan Holgate
- Ernest Gallo Clinic and Research Center, University of California, San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608
| | - Jemma K. Richards
- Ernest Gallo Clinic and Research Center, University of California, San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608
| | - Selena E. Bartlett
- Ernest Gallo Clinic and Research Center, University of California, San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608
- *To whom correspondence should be addressed. E-mail:
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