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Duan X, Liu H, Hu X, Yu Q, Kuang G, Liu L, Zhang S, Wang X, Li J, Yu D, Huang J, Wang T, Lin Z, Xiong N. Insomnia in Parkinson's Disease: Causes, Consequences, and Therapeutic Approaches. Mol Neurobiol 2025; 62:2292-2313. [PMID: 39103716 PMCID: PMC11772535 DOI: 10.1007/s12035-024-04400-4] [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] [Received: 12/09/2023] [Accepted: 07/24/2024] [Indexed: 08/07/2024]
Abstract
Sleep disorders represent prevalent non-motor symptoms in Parkinson's disease (PD), affecting over 90% of the PD population. Insomnia, characterized by difficulties in initiating and maintaining sleep, emerges as the most frequently reported sleep disorder in PD, with prevalence rates reported from 27 to 80% across studies. Insomnia not only significantly impacts the quality of life of PD patients but is also associated with cognitive impairment, motor disabilities, and emotional deterioration. This comprehensive review aims to delve into the mechanisms underlying insomnia in PD, including neurodegenerative changes, basal ganglia beta oscillations, and circadian rhythms, to gain insights into the neural pathways involved. Additionally, the review explores the risk factors and comorbidities associated with insomnia in PD, providing valuable insights into its management. Special attention is given to the challenges faced by healthcare providers in delivering care to PD patients and the impact of caregiving roles on patients' quality of life. Overall, this review provides a comprehensive understanding of insomnia in PD and highlights the importance of addressing this common sleep disorder in PD patients.
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Affiliation(s)
- Xiaoyu Duan
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Duke Kunshan University, No. 8 Duke Avenue, Kunshan, 215316, Jiangsu, China
| | - Hanshu Liu
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xinyu Hu
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Qinwei Yu
- Department of Neurology, Wuhan Red Cross Hospital, 392 Hongkong Road, Wuhan, Hubei, China
| | - Guiying Kuang
- Department of Neurology, Wuhan Red Cross Hospital, 392 Hongkong Road, Wuhan, Hubei, China
| | - Long Liu
- Department of Neurology, Wuhan Red Cross Hospital, 392 Hongkong Road, Wuhan, Hubei, China
| | - Shurui Zhang
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xinyi Wang
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jingwen Li
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Danfang Yu
- Department of Neurology, Wuhan Red Cross Hospital, 392 Hongkong Road, Wuhan, Hubei, China
| | - Jinsha Huang
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Tao Wang
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zhicheng Lin
- Laboratory of Psychiatric Neurogenomics, McLean Hospital, Harvard Medical School, Belmont, MA, 02478, USA
| | - Nian Xiong
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Rizk H, Monaghan NP, Shah S, Liu Y, Keith BA, Jeong S, Nguyen SA. Efficacy of a Serotonin-Norepinephrine Reuptake Inhibitor as a Treatment for Meniere Disease: A Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg 2024; 150:935-942. [PMID: 39235772 PMCID: PMC11378064 DOI: 10.1001/jamaoto.2024.2241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Accepted: 07/08/2024] [Indexed: 09/06/2024]
Abstract
Importance Meniere disease accounts for up to 15% of new vestibular diagnoses,; however, the optimal treatment has yet to be identified. A conservative treatment that would reduce or stop the vertigo episodes has not been identified. Objective To determine the efficacy of a serotonin-norepinephrine reuptake inhibitor, venlafaxine, compared to placebo in treating patients with Meniere disease. Design, Setting, and Participants This was a randomized, double-blind, placebo-controlled, crossover pilot study spanning 22 weeks of follow-up. The clinical trial took place at a single-center tertiary referral center in Charleston, South Carolina. Participants were eligible if they were 18 years or older, had definite Meniere disease criteria as defined by Barany criteria, had at least 2 episodes in the last month, had not received intratympanic gentamycin, skull base surgery, or radiation therapy to the head or neck, not currently taking diuretics for Meniere disease, not currently taking oral steroids, and not currently taking serotonin-modulating medication. Patients were enrolled between February 2020 and September 2023. Interventions Patients received either 1 venlafaxine tablet, 37.5 mg, taken daily by mouth for 8 weeks or 1 placebo tablet taken daily by mouth for 8 weeks. Group 1 received placebo during phase 1 of the trial and venlafaxine in phase 2 of the trial. Group 2 received venlafaxine during phase 1 of the trial and placebo in phase 2 of the trial. Main Outcomes and Measures The main outcomes included the number of episodes and scores on the following scales: Dizziness Handicap Inventory, Neuropsychological Vertigo Inventory, Meniere Disease Patient-Oriented Symptom Index, 20-Item Short Form Health Survey, Penn State Worry Questionnaire, Cognitive Failure Questionnaire. Results A total of 182 patients were screened, and 40 participants with Meniere disease enrolled in the trial. The mean (SD) age of participants was 56.6 (14.3) years, and 22 (55%) were female. Participants had a mean (SD) of 13.8 (10.1) episodes per phase at baseline, 5.4 (4.4) episodes (Δ8.4) during the venlafaxine phase, and 5.0 (4.6) episodes (Δ8.8) during the placebo phase. No significant difference was identified between venlafaxine and placebo groups in the number of episodes or quality-of-life metrics. Conclusions and Relevance This randomized clinical trial failed to identify a difference between venlafaxine and placebo in number of episodes and other quality-of-life metrics. Future studies may benefit from different dosing regimens, larger cohorts, and longer lengths of therapy. Trial Registration ClinicalTrials.gov Identifier: NCT04218123.
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Affiliation(s)
- Habib Rizk
- Department of Otolaryngology–Head and Neck Surgery, Medical University of South Carolina, Charleston
| | - Neil P. Monaghan
- Department of Otolaryngology–Head and Neck Surgery, Medical University of South Carolina, Charleston
- College of Medicine, Medical University of South Carolina, Charleston
| | - Sunny Shah
- Department of Otolaryngology–Head and Neck Surgery, Medical University of South Carolina, Charleston
| | - Yuan Liu
- Department of Otolaryngology–Head and Neck Surgery, Loma Linda University Health, Loma Linda, California
| | - Brian A. Keith
- Department of Otolaryngology–Head and Neck Surgery, Medical University of South Carolina, Charleston
- School of Osteopathic Medicine, Campbell University, Lillington, North Carolina
| | - Seth Jeong
- Department of Otolaryngology–Head and Neck Surgery, The State University of New York Upstate, Syracuse
| | - Shaun A. Nguyen
- Department of Otolaryngology–Head and Neck Surgery, Medical University of South Carolina, Charleston
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Galbally M, Watson SJ, Spigset O. Depression and antidepressant treatment in the development of hypertensive disorders of pregnancy: Results from a prospective cohort study. Aust N Z J Psychiatry 2023; 57:520-527. [PMID: 35786007 DOI: 10.1177/00048674221106915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Hypertensive disorders of pregnancy are associated with longer term cardiovascular risk. Understanding if depression or antidepressant use in pregnancy is associated with HDP is important in identifying those potentially vulnerable to poorer health in later life. This study examines if depression and antidepressants are associated with HDP. METHODS In all, 815 pregnant women were recruited within an Australian pregnancy cohort study at less than 20 weeks of pregnancy, all undertook the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and were assigned to four groups for this paper: those with unmedicated depression meeting criteria for current depression (n = 97), those taking selective serotonin reuptake inhibitors in early pregnancy (n = 101), those taking serotonin and noradrenaline reuptake inhibitors in early pregnancy (n = 31), and those without depression or taking antidepressant medication (control; n = 586). Women were then assessed again following birth. Hypertensive disorders of pregnancy were diagnosed according to the Society of Obstetric Medicine in Australia and New Zealand Guidelines. RESULTS Use of serotonin and noradrenaline reuptake inhibitors (SNRIs) (adjusted risk ratio = 9.10, 95% confidence interval = [3.82, 21.67]) and unmedicated depression (adjusted risk ratio = 3.11, 95% confidence interval = [1.32, 7.35]) were independently associated with significantly higher risk for developing hypertensive disorders of pregnancy compared to controls. Selective serotonin reuptake inhibitors (SSRIs) use did not confer any increased risk. Higher doses of SNRIs, but not selective serotonin reuptake inhibitors, were associated with significantly higher risk for developing HDP (adjusted risk ratio = 4.83, 95% confidence interval = [1.50, 15.58]). CONCLUSIONS Our findings suggest that those with depression in pregnancy and/or on an serotonin and noradrenaline reuptake inhibitor should have closer surveillance for the development of hypertensive disorders of pregnancy. These findings support treatment of depression in pregnancy, however, also the consideration of class of antidepressant.
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Affiliation(s)
- Megan Galbally
- School of Clinical Sciences, Department of Psychiatry, Monash University, Clayton, VIC, Australia
- Health Futures Institute, Murdoch University, Murdoch, WA, Australia
| | - Stuart J Watson
- Health Futures Institute, Murdoch University, Murdoch, WA, Australia
| | - Olav Spigset
- Department of Clinical Pharmacology, St. Olav's University Hospital, Trondheim, Norway
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
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Kahl KG, Stapel B, Correll CU. Psychological and Psychopharmacological Interventions in Psychocardiology. Front Psychiatry 2022; 13:831359. [PMID: 35370809 PMCID: PMC8966219 DOI: 10.3389/fpsyt.2022.831359] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 02/18/2022] [Indexed: 01/08/2023] Open
Abstract
Patients with mental disorders have an increased risk to develop cardiovascular disease (CVD), and CVD are frequently comorbid with especially adjustment, anxiety and depressive disorders. Therefore, clinicians need to be aware of effective and safe psychological and pharmacological treatment strategies for patients with comorbid CVD and mental disorders. Cognitive behavioral therapy and third-wave of cognitive-behavioral therapy are effective for patients with CVD and mental disorders. Internet-based psychological treatments may also be considered. In more severe cases, psychopharmacological drugs are frequently used. Although generally well tolerated and efficacious, drug- and dose-dependent side effects require consideration. Among antidepressants, selective serotonin reuptake inhibitors, selective serotonin and noradrenalin reuptake inhibitors, and newer antidepressants, such as mirtazapine, bupropion, agomelatine, and vortioxetine, can be considered, while tricyclic antidepressants should be avoided due to their cardiac side effects. Mood stabilizers have been associated with arrhythmias, and some first- and second-generation antipsychotics can increase QTc and metabolic side effects, although substantial differences exist between drugs. Benzodiazepines are generally safe in patients with CVD when administered short-term, and may mitigate symptoms of acute coronary syndrome. Laboratory and ECG monitoring is always recommended in psychopharmacological drug-treated patients with CVD. Presence of a heart disease should not exclude patients from necessary interventions, but may require careful risk-benefit evaluations. Effectively and safely addressing mental disorders in patients with CVD helps to improve both conditions. Since CVD increase the risk for mental disorders and vice versa, care providers need to screen for these common comorbidities to comprehensively address the patients' needs.
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Affiliation(s)
- Kai G Kahl
- Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hanover, Germany
| | - Britta Stapel
- Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hanover, Germany
| | - Christoph U Correll
- Department of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, United States.,Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United States.,Department of Child and Adolescent Psychiatry, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Maddiboyina B, Jhawat V, Sivaraman G, Sunnapu O, Nakkala RK, Naik MH, Gulia M. Formulation Development and Characterization of Controlled Release Core-in-cup Matrix Tablets of Venlafaxine HCl. CURRENT DRUG THERAPY 2021. [DOI: 10.2174/1574885515666200331104440] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
Venlafaxine HCl is a selective serotonin reuptake inhibitor, which is given in
the treatment of depression. The delivery of the drug at a controlled rate can be of great importance for
a prolonged effect.
Objective:
The objective was to prepare and optimize the controlled release core in a cup matrix tablet
of venlafaxine HCl using the combination of hydrophilic and hydrophobic polymers to prolong the
effect with rate controlled drug release.
Methods:
The controlled release core in cup matrix tablets of venlafaxine HCl was prepared using
HPMC K5, K4, K15, HCO, IPA, aerosol, magnesium stearate, hydrogenated castor oil and micro crystalline
cellulose PVOK-900 using wet granulation technique. Total ten formulations with varying concentrations
of polymers were prepared and evaluated for different physicochemical parameters such
FTIR analysis for drug identification. In-vitro drug dissolution study was performed to evaluate the
amount of drug release in 24 hrs, drug release kinetics study was performed to fit the data in zero order,
first order, Hixson-crowell and Higuchi equation to determine the mechanism of drug release and stability
studies for 3 months as observed.
Results:
The results of hardness, thickness, weight variation, friability and drug content study were in
an acceptable range for all formulations. Based on the in vitro dissolution profile, formulation F-9was
considered to be the optimized, extending the release of 98.32% of drug up to 24 hrs. The data fitting
study showed that the optimized formulation followed the zero order release rate kinetics and when
compared with the innovator product (flavix XR), showed better drug release profile.
Conclusion:
The core-in-cup technology has the potential to control the release rate of freely water
soluble drugs for single administration per day by optimization with the combined use of hydrophilic
and hydrophobic polymers.
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Affiliation(s)
- Balaji Maddiboyina
- Department of Pharmaceutical Sciences, Vishwa Bharathi College of Pharmaceutical Sciences, Guntur, A.P, India
| | - Vikas Jhawat
- Department of Pharmacy, School of Medical & Allied Sciences, GD Goenka University, Gurugram, Haryana, India
| | - Gandhi Sivaraman
- Department of Chemistry, Gandhigram Rural Institute Deemed University, Dindigul, Tamilnadu, India
| | - Omprakash Sunnapu
- Department of Pharmaceutical Sciences, Anna University, Dindigul, Tamilnadu, India
| | - Ramya Krishna Nakkala
- Department of Pharmaceutical Sciences, Vishwa Bharathi College of Pharmaceutical Sciences, Guntur, A.P, India
| | - Mudavath Hanuma Naik
- Department of Pharmaceutical Sciences, Vishwa Bharathi College of Pharmaceutical Sciences, Guntur, A.P, India
| | - Monika Gulia
- Department of Pharmacy, School of Medical & Allied Sciences, GD Goenka University, Gurugram, Haryana, India
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The Effect of Venlafaxine on Electrocardiogram Intervals During Treatment for Depression in Older Adults. J Clin Psychopharmacol 2020; 40:553-559. [PMID: 33044352 PMCID: PMC7606781 DOI: 10.1097/jcp.0000000000001287] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE/BACKGROUND Venlafaxine is a commonly used antidepressant with both serotonergic and noradrenergic activity. There are concerns that it may prolong the corrected QT interval (QTc), and older adults may be at higher risk for this adverse effect, especially at higher dosages of the medication. METHODS/PROCEDURES In this secondary analysis of a prospective clinical trial, we measured changes in QTc and other electrocardiogram (ECG) parameters in 169 adults 60 years or older with a major depressive disorder treated acutely with venlafaxine extended release up to 300 mg daily. We examined the relationship of venlafaxine dosage and ECG parameters, as well as the relationship between serum levels of venlafaxine and ECG parameters. FINDINGS/RESULTS Venlafaxine exposure was not associated with an increase in QTc. Heart rate increased with venlafaxine treatment, whereas the PR interval shortened, and QRS width did not change significantly. The QTc change from baseline was not associated with venlafaxine dosages or serum concentrations. Age, sex, cardiovascular comorbidities, and depression remission status did not predict changes in QTc with venlafaxine. IMPLICATIONS/CONCLUSIONS Venlafaxine treatment did not prolong QTc or other ECG parameters, even in high dosages in older depressed adults. These findings indicate that venlafaxine does not significantly affect cardiac conduction in most older patients.
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Kaur H, Sidana A, Singh T. Comparison of efficacy and tolerability of escitalopram and venlafaxine in treatment-naïve patients with unipolar nonpsychotic depression: Is there a need to revisit the prescription patterns? JOURNAL OF MENTAL HEALTH AND HUMAN BEHAVIOUR 2019. [DOI: 10.4103/jmhhb.jmhhb_21_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Schifano F, Chiappini S. Is There a Potential of Misuse for Venlafaxine and Bupropion? Front Pharmacol 2018; 9:239. [PMID: 29618978 PMCID: PMC5871746 DOI: 10.3389/fphar.2018.00239] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Accepted: 03/05/2018] [Indexed: 12/11/2022] Open
Abstract
Objective: Traditionally, studies on the non-medical use of pharmaceutical products have focused on controlled substances; e.g., opiates/opioids; and benzodiazepines. Although both bupropion and venlafaxine have been reported as being misused, only anecdotal reports have been made available so far. Hence, the European Monitoring Agency (EMA) Adverse Drug Reactions (ADRs), misuse/abuse/dependence and withdrawal, venlafaxine- and bupropion-related, database was here analyzed. Methods: All EMA spontaneous reports relating to venlafaxine (2005–2016) and bupropion (2003–2016) notifications were here analyzed, to provide a descriptive analysis by source, gender, age, and type of report. The UK-based, 2000–2016, Yellow Card Scheme pharmacovigilance database, bupropion and venlafaxine withdrawal reports were compared as well with those pertaining to fluoxetine and paroxetine. Results: Out of 20,720 (bupropion) and 47,516 (venlafaxine) total number of ADRs, some 2,232 (10.8%), and 4,071 (8.5%) misuse/abuse/dependence ADRs were respectively associated with bupropion and venlafaxine. Conversely, bupropion withdrawal-related ADRs were here reported in 299/20,720 (1.44%) cases and in 914/47,516 (1.92%) cases for venlafaxine. Overall, all bupropion and venlafaxine misuse-/abuse-/dependence- and withdrawal-ADRs were related to a respective number of 264 and 447 patients. According to the Proportional Reporting Ratio (PRR) computation, in comparison with venlafaxine bupropion resulted to be more frequently misused/abused (PRR: 1.50), but less frequently associated with both dependence (PRR: 0.92) and withdrawal (PRR: 0.77) issues. Yellow Card Scheme data suggested that paroxetine and venlafaxine, in comparison with fluoxetine and bupropion, were associated with higher number of withdrawal-related reports. Conclusions: The dopaminergic, stimulant-like, bupropion activities may be associated with its possible recreational value. Present data may confirm that the occurrence of a withdrawal syndrome may be a significant issue for venlafaxine-treated patients.
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Affiliation(s)
- Fabrizio Schifano
- Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom
| | - Stefania Chiappini
- Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom
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Abstract
Venlafaxine is a selective serotonin and norepinephrine reuptake inhibitor commonly used for the treatment of depression. Although listed as an adverse reaction, seizure activity associated with a therapeutic dose of venlafaxine has rarely been documented. A review of the literature reveals only 2 cases of venlafaxine-induced seizures, both of which were generalized tonic-clonic seizures in patients on doses at the higher end of the therapeutic range. We report the case of a 44-year-old woman undergoing antituberculosis therapy who suffered complex partial seizures after ingestion of a low therapeutic dose of venlafaxine extended release (ER). Her first seizure was observed soon after venlafaxine ER was titrated from 37.5 to 75 mg daily, with a total of 9 witnessed complex partial seizures. After titrating the dose of the venlafaxine ER back down to 37.5 mg daily and beginning lamotrigine anticonvulsant therapy, the patient exhibited no further seizures. The development of seizure activity under therapeutic dosing of venlafaxine should be brought to the attention of the health care prescriber. The potential for drug-drug interactions involving venlafazine, particularly in combination with multiple drugs, such as isoniazid and levofloxacin, needs to be recognized.
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Mease PJ, Zimetbaum PJ, Duh MS, Vekeman F, Guérin A, Boerstoel-Streefland M, Jiang W, Lefebvre P. Epidemiologic Evaluation of Cardiovascular Risk in Patients Receiving Milnacipran, Venlafaxine, or Amitriptyline: Evidence from French Health Data. Ann Pharmacother 2017; 45:179-88. [DOI: 10.1345/aph.1p391] [Citation(s) in RCA: 7] [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: Milnacipran, a selective serotonin and norepinephrine reuptake inhibitor, is approved by the Food and Drug Administration for the management of fibromyalgia. It has been available for many years in several countries outside the US for the treatment of depression. OBJECTIVE: To conduct population-based analyses comparing the risk of serious cardiovascular (CV) events (eg, acute myocardial infarction, stroke, congestive heart failure) associated with treatment with milnacipran compared with venlafaxine and amitriptyline, 2 other commonly prescribed drugs that also inhibit reuptake of norepinephrine and serotonin. METHODS: Information from the French Thales electronic health record database from 2001 to 2007 was used. Patients with 1 or more prescriptions for milnacipran, venlafaxine, or amitriptyline; 180 or more days of continuous eligibility prior to the first prescription; and no prior CV event diagnoses during the 180-day baseline period were included. A retrospective, matched-cohort design was employed. The incidence rates of CV events between cohorts receiving milnacipran, venlafaxine, and amitriptyline were compared using unadjusted incidence rate ratio (IRR) and adjusted conditional IRR based on Poisson regression. RESULTS: We identified 4452 milnacipran-venlafaxine and 3761 milnacipran-amitriptyline matched pairs. The matched cohorts had similar baseline characteristics. The unadjusted IRRs of any CV events, comparing milnacipran with venlafaxine or amitriptyline, were 1.02 (95% CI 0.73 to 1.44) and 1.30 (95% CI 0.90 to 1.89), respectively. Adjusted IRRs confirmed the statistical similarity in the CV event risk between milnacipran and venlafaxine (adjusted IRR = 1.29, 95% CI 0.76 to 2.17) or amitriptyline (adjusted IRR = 1.06, 95% CI 0.59 to 1.89). CONCLUSIONS: This French population-based study found that the risk of CV events was not significantly different for patients receiving milnacipran versus those receiving venlafaxine or amitriptyline.
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Telles-Correia D, Barbosa A, Cortez-Pinto H, Campos C, Rocha NBF, Machado S. Psychotropic drugs and liver disease: A critical review of pharmacokinetics and liver toxicity. World J Gastrointest Pharmacol Ther 2017; 8:26-38. [PMID: 28217372 PMCID: PMC5292604 DOI: 10.4292/wjgpt.v8.i1.26] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Revised: 11/02/2016] [Accepted: 11/16/2016] [Indexed: 02/06/2023] Open
Abstract
The liver is the organ by which the majority of substances are metabolized, including psychotropic drugs. There are several pharmacokinetic changes in end-stage liver disease that can interfere with the metabolization of psychotropic drugs. This fact is particularly true in drugs with extensive first-pass metabolism, highly protein bound drugs and drugs depending on phase I hepatic metabolic reactions. Psychopharmacological agents are also associated with a risk of hepatotoxicity. The evidence is insufficient for definite conclusions regarding the prevalence and severity of psychiatric drug-induced liver injury. High-risk psychotropics are not advised when there is pre-existing liver disease, and after starting a psychotropic agent in a patient with hepatic impairment, frequent liver function/lesion monitoring is advised. The authors carefully review the pharmacokinetic disturbances induced by end-stage liver disease and the potential of psychopharmacological agents for liver toxicity.
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Abstract
Objective:To review principles of drug-induced liver injury (DILI), summarize characteristics of antidepressant-mediated liver Injury, and provide recommendations for monitoring and management.Data Sources:A search relating to antidepressant-induced liver injury was performed using MEDLINE (1966–March 2007). Search terms included antidepressant, cholestasis, hepatotoxicity, jaundice, liver injury, toxic hepatitis, and transaminases. Reference citations not Identified in the initial database search were also utilized.Study Selection and Data Extraction:All English-language case reports, letters, and review articles identified from the data sources were used. Case reports and letters relating to hepatotoxicity from antidepressant overdose were excluded.Data Synthesis:Antidepressant-induced liver injury described in published cases were of the idiopathic type and, by definition, cannot be predicted based on dose or specific risk factors. Paroxetine had the largest number of cases within the selective serotonin-reuptake inhibitor class. Nefazodone, a serotonin–norepinephrine reuptake inhibitor, appeared to have the most serious cases and is the only antidepressant agent that carries a Food and Drug Administration Black Box Warning regarding hepatotoxiciiy. The tricyclic antidepressants and monoamine oxidase Inhibitors are capable of producing hepatotoxicity, but fewer cases with these agents have been reported in the past 15 years, possibly due to a decline in their use. Causality has not been well established in all reports due to the concurrent use of other drugs and/or underlying liver disease.Conclusions:Most antidepressant agents have the potential to produce idiopathic liver injury. There is no way to prevent idiopathic DILI, but the severity of the reaction may be minimized with prompt recognition and early withdrawal of the agent. The clinician must be careful to provide ongoing therapy of the underlying depressive disorder and be aware of possible drug discontinuation syndromes should potential hepatotoxicity be suspected.
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Wang Z, Wu H, Stone WS, Zhuang J, Qiu L, Xu X, Wang Y, Zhao Z, Han F, Zhao Z. Body weight and basal metabolic rate in childhood narcolepsy: a longitudinal study. Sleep Med 2016; 25:139-144. [PMID: 27823707 DOI: 10.1016/j.sleep.2016.06.019] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Revised: 05/30/2016] [Accepted: 06/02/2016] [Indexed: 02/01/2023]
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Perlemuter G, Cacoub P, Valla D, Guyader D, Saba B, Batailler C, Moore K. Characterisation of Agomelatine-Induced Increase in Liver Enzymes: Frequency and Risk Factors Determined from a Pooled Analysis of 7605 Treated Patients. CNS Drugs 2016; 30:877-88. [PMID: 27342740 DOI: 10.1007/s40263-016-0351-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Antidepressant-induced liver injury is a major concern and a liver monitoring scheme has been recommended by the European Medicines Agency for agomelatine. OBJECTIVE The objective of this study was to assess the liver safety and identify the characteristics of patients who developed a significant increase in transaminases whilst taking agomelatine. METHOD A retrospective pooled analysis of changes in transaminase levels in 9234 patients treated with agomelatine (25 or 50 mg/day; n = 7605) or placebo (n = 1629) from 49 phase II and III studies was undertaken. A significant increase in transaminase levels was defined as an increase to >3 times the upper limit of normal (ULN) (>3 × ULN). Final causality was determined in a case-by-case review by five academic experts. RESULTS Serum transaminases increased to >3 × ULN in 1.3 and 2.5 % of patients treated with 25 and 50 mg of agomelatine, respectively, compared with 0.5 % for placebo. The onset of increased transaminases occurred before 12 weeks in 64 % of patients. The median time to recovery (to ≤2 × ULN) was 14 days following treatment withdrawal. Liver function tests recovered in 36.1 % of patients despite continuation of agomelatine, suggesting the presence of a liver adaptive mechanism. No cases of acute liver failure or fatal outcome occurred. Patients with elevated transaminases at baseline, secondary to obesity/fatty liver disease, had an equally increased risk of developing further elevations of transaminases with agomelatine and placebo. CONCLUSION Incidence of abnormal transaminases was low and dose dependent. No specific population was identified regarding potential risk factors. Withdrawal of agomelatine led to rapid recovery, and some patients exhibited an adaptive phenomenon. Overall, in clinical trials, the liver profile of agomelatine seems safe when serum transaminases are monitored.
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Affiliation(s)
- Gabriel Perlemuter
- Univ. Paris-Sud, Univ. Paris-Saclay, CHU Bicêtre, 94270, Kremlin-Bicêtre, France.
- AP-HP, Hôpital Antoine-Béclère, Service d'Hépato-Gastroentérologie et Nutrition, DHU Hepatinov, 157 rue de la Porte de Trivaux, 92140, Clamart, France.
- INSERM U996, IPSIT, Labex Lermit, Clamart, France.
| | - Patrice Cacoub
- Sorbonne Universités, UPMC Université Paris 06, UMR 7211, Paris, France
- Inflammation-Immunopathology-Biotherapy Department (DHU i2B), 75005, Paris, France
- INSERM, UMR_S 959, 75013, Paris, France
- CNRS, FRE3632, 75005, Paris, France
- Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, 75013, Paris, France
| | - Dominique Valla
- DHU UNITY, Service d'Hépatologie, AP-HP, Hôpital Beaujon, Clichy, France
- CRI, UMR1149, Université Paris Diderot, Paris, France
- INSERM U1149, Paris, France
| | - Dominique Guyader
- Liver Disease Unit and INSERM U991, CHU Pontchaillou, Rennes, France
- University of Rennes 1, CHU de Rennes, Rennes, France
| | - Barbara Saba
- Institut de Recherches Internationales Servier, 92415, Suresnes, France
| | - Cécile Batailler
- Institut de Recherches Internationales Servier, 92415, Suresnes, France
| | - Kevin Moore
- UCL Institute of Liver and Digestive Health, University College London, Royal Free Campus, London, UK
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Abstract
Objective: To report the findings from the case of a patient developing first-time seizure activity following an overdose of venlafaxine. Case Summary: A 27-year-old man with major depression ingested 60 venlafaxine 75-mg capsules in an apparent suicide attempt. The patient experienced generalized seizure activity 9 and 11 hours after ingestion. The electroencephalogram showed a pathologic pattern, with several generalized epileptiform discharges. Venlafaxine was discontinued, and no further sequelae were observed. Discussion: The Naranjo probability scale indicated a probable relationship between the seizures and venlafaxine overdose. The mechanism of seizures associated with venlafaxine overdose is unclear. Neurotransmitters play an important role in seizure genesis, and hepatic damage may occur. Conclusions: Clinicians should be aware of proconvulsant effect and the risk of hepatocellular injury from venlafaxine overdose when prescribing this drug.
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Affiliation(s)
- Asli Sarandöl
- ASLI SARANDÖL MD, Psychiatrist, Department of Psychiatry, Uludag University Medical School, Bursa, Turkey
| | - Bilgen Taneli
- BILGEN TANELI MD, Emeritus Professor of Psychiatry, Department of Psychiatry, Uludag University Medical School
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Tian Y, Du J, Spagna A, Mackie MA, Gu X, Dong Y, Fan J, Wang K. Venlafaxine treatment reduces the deficit of executive control of attention in patients with major depressive disorder. Sci Rep 2016; 6:28028. [PMID: 27306061 PMCID: PMC4910055 DOI: 10.1038/srep28028] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Accepted: 05/23/2016] [Indexed: 01/03/2023] Open
Abstract
Attention plays an essential role in supporting other cognitive functions and behavior, and disturbance of attention is one of the most common symptoms in major depressive disorder (MDD). Although treatment with venlafaxine for MDD symptoms has been shown to reduce deficits in cognition and emotion regulation, it remains unclear whether venlafaxine improves specific attentional functions. We used the Attention Network Test to measure the attentional functions of alerting, orienting, and executive control before and after treatment with venlafaxine in patients with MDD compared to untreated healthy controls. Before treatment, the MDD group showed a selective impairment in alerting and executive control of attention, while there were no significant group differences in the orienting function. The interaction between group and session was significant for executive control, and after treatment with venlafaxine, the performance of the MDD group on executive control of attention was not significantly different from that of controls. Reported symptoms of MDD were also significantly reduced after treatment with venlafaxine. These results demonstrate that treatment with venlafaxine selectively normalizes the executive control function of attention in addition to improving clinical symptoms in MDD.
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Affiliation(s)
- Yanghua Tian
- Department of Neurology, the First Hospital of Anhui Medical University, Hefei, Anhui Province, China
| | - Jing Du
- Department of Neurology, the Second Hospital of Anhui Medical University, Hefei, Anhui Province, China
| | - Alfredo Spagna
- Department of Psychology, Queens College, the City University of New York, Flushing, NY, USA
| | - Melissa-Ann Mackie
- Department of Psychology, Queens College, the City University of New York, Flushing, NY, USA
| | - Xiaosi Gu
- Center for BrainHealth, School of Behavioral and Brain Sciences, the University of Texas at Dallas, Dallas, TX, 75235, USA
| | - Yi Dong
- Anhui Mental Health Center, Hefei, Anhui Province, China
| | - Jin Fan
- Department of Psychology, Queens College, the City University of New York, Flushing, NY, USA
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Kai Wang
- Department of Neurology, the First Hospital of Anhui Medical University, Hefei, Anhui Province, China
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Stoetzer C, Papenberg B, Doll T, Völker M, Heineke J, Stoetzer M, Wegner F, Leffler A. Differential inhibition of cardiac and neuronal Na(+) channels by the selective serotonin-norepinephrine reuptake inhibitors duloxetine and venlafaxine. Eur J Pharmacol 2016; 783:1-10. [PMID: 27130441 DOI: 10.1016/j.ejphar.2016.04.051] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2016] [Revised: 04/17/2016] [Accepted: 04/26/2016] [Indexed: 11/18/2022]
Abstract
Duloxetine and venlafaxine are selective serotonin-norepinephrine-reuptake-inhibitors used as antidepressants and co-analgesics. While venlafaxine rather than duloxetine induce cardiovascular side-effects, neither of the substances are regarded cardiotoxic. Inhibition of cardiac Na(+)-channels can be associated with cardiotoxicity, and duloxetine was demonstrated to block neuronal Na(+)-channels. The aim of this study was to investigate if the non-life threatening cardiotoxicities of duloxetine and venlafaxine correlate with a weak inhibition of cardiac Na(+)-channels. Effects of duloxetine, venlafaxine and amitriptyline were examined on endogenous Na(+)-channels in neuroblastoma ND7/23 cells and on the α-subunits Nav1.5, Nav1.7 and Nav1.8 with whole-cell patch clamp recordings. Tonic block of the cardiac Na(+)-channel Nav1.5 and rat-cardiomyocytes (CM) revealed a higher potency for duloxetine (Nav 1.5 IC50 14±1µM, CM IC50 27±3µM) as compared to venlafaxine (Nav 1.5 IC50 671±26µM, CM IC50 452±34µM). Duloxetine was as potent as the cardiotoxic antidepressant amitriptyline (IC50 13±1µM). While venlafaxine almost failed to induce use-dependent block on Nav1.5 and cardiomyocytes, low concentrations of duloxetine (1, 10µM) induced prominent use-dependent block similar to amitriptyline. Duloxetine, but not venlafaxine stabilized fast and slow inactivation and delayed recovery from inactivation. Duloxetine induced an unselective inhibition of neuronal Na(+)-channels (IC50 ND7/23 23±1µM, Nav1.7 19±2µM, Nav1.8 29±2). Duloxetine, but not venlafaxine inhibits cardiac Na(+)-channels with a potency similar to amitriptyline. These data indicate that an inhibition of Na(+)-channels does not predict a clinically relevant cardiotoxicity.
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Affiliation(s)
- Carsten Stoetzer
- Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany.
| | - Bastian Papenberg
- Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany
| | - Thorben Doll
- Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany; Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany; Department of Craniomaxillofacial Surgery, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany; Department of Neurology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany
| | - Marc Völker
- Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany
| | - Joerg Heineke
- Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany
| | - Marcus Stoetzer
- Department of Craniomaxillofacial Surgery, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany
| | - Florian Wegner
- Department of Neurology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany
| | - Andreas Leffler
- Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany
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Patel R, Reiss P, Shetty H, Broadbent M, Stewart R, McGuire P, Taylor M. Do antidepressants increase the risk of mania and bipolar disorder in people with depression? A retrospective electronic case register cohort study. BMJ Open 2015; 5:e008341. [PMID: 26667012 PMCID: PMC4679886 DOI: 10.1136/bmjopen-2015-008341] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2015] [Revised: 07/20/2015] [Accepted: 07/30/2015] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES To investigate the association between antidepressant therapy and the later onset of mania/bipolar disorder. DESIGN Retrospective cohort study using an anonymised electronic health record case register. SETTING South London and Maudsley National Health Service (NHS) Trust (SLaM), a large provider of inpatient and community mental healthcare in the UK. PARTICIPANTS 21,012 adults presenting to SLaM between 1 April 2006 and 31 March 2013 with unipolar depression. EXPOSURE Prior antidepressant therapy recorded in electronic health records. MAIN OUTCOME MEASURE Time to subsequent diagnosis of mania or bipolar disorder from date of diagnosis of unipolar depression, censored at 31 March 2014. METHODS Multivariable Cox regression analysis with age and gender as covariates. RESULTS The overall incidence rate of mania/bipolar disorder was 10.9 per 1000 person-years. The peak incidence of mania/bipolar disorder incidence was seen in patients aged between 26 and 35 years (12.3 per 1000 person-years). Prior antidepressant treatment was associated with an increased incidence of mania/bipolar disorder ranging from 13.1 to 19.1 per 1000 person-years. Multivariable analysis indicated a significant association with selective serotonin reuptake inhibitors (HR 1.34, 95% CI 1.18 to 1.52) and venlafaxine (1.35, 1.07 to 1.70). CONCLUSIONS In people with unipolar depression, antidepressant treatment is associated with an increased risk of subsequent mania/bipolar disorder. These findings highlight the importance of considering risk factors for mania when treating people with depression.
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Affiliation(s)
- Rashmi Patel
- Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology & Neuroscience, London, UK
| | - Peter Reiss
- Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology & Neuroscience, London, UK
| | - Hitesh Shetty
- Biomedical Research Centre Nucleus, South London and Maudsley NHS Foundation Trust, London, UK
| | - Matthew Broadbent
- Biomedical Research Centre Nucleus, South London and Maudsley NHS Foundation Trust, London, UK
| | - Robert Stewart
- Department of Psychological Medicine, King's College London, Institute of Psychiatry, Psychology & Neuroscience, London, UK
| | - Philip McGuire
- Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology & Neuroscience, London, UK
| | - Matthew Taylor
- Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology & Neuroscience, London, UK
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20
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Francesconi G, Orsolini L, Papanti D, Corkery JM, Schifano F. Venlafaxine as the 'baby ecstasy'? Literature overview and analysis of web-based misusers' experiences. Hum Psychopharmacol 2015. [PMID: 26216559 DOI: 10.1002/hup.2476] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
INTRODUCTION Venlafaxine is one of the most frequently prescribed antidepressants worldwide, despite its toxicity risk in overdose. Furthermore, the molecule has been recently identified at the EU-wide level as one of the novel psychoactive substances. This paper aims at investigating the potential of misuse, taking into account both the existing literature and the analysis of the misusers' experiences as described in venlafaxine misuse web reports. METHODS A literature search was performed using PubMed, Embase, and Medline. Posts/threads relating to venlafaxine misuse issues were identified through Google® and Yahoo® English-language searches. Resulting websites' data were then qualitatively assessed, and information was collected on a range of issues, including dosage, drug intake modalities, untoward drug effects, and association with other recreational drugs. RESULTS A few literature case reports focusing on venlafaxine as a misusing drug were here identified. The molecule was here typically ingested or snorted at dosages up to 10-15 times higher than those clinically advised, obtaining MDMA/amphetamine-like stimulant and psychedelic effects. Polydrug misuse was commonly reported. Venlafaxine appeared to be widely available online for sale. CONCLUSIONS Physicians should carefully evaluate patients for history of drug dependence and observe them for signs of venlafaxine misuse.
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Affiliation(s)
- Giulia Francesconi
- Academic Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy.,School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Herts, UK
| | - Laura Orsolini
- Academic Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy.,School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Herts, UK
| | - Duccio Papanti
- Medical School of Trieste, Italy.,School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Herts, UK
| | - John M Corkery
- School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Herts, UK
| | - Fabrizio Schifano
- School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Herts, UK
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21
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Sultana J, Spina E, Trifirò G. Antidepressant use in the elderly: the role of pharmacodynamics and pharmacokinetics in drug safety. Expert Opin Drug Metab Toxicol 2015; 11:883-92. [DOI: 10.1517/17425255.2015.1021684] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Accelerated hypertension after venlafaxine usage. Case Rep Psychiatry 2014; 2014:659715. [PMID: 25328745 PMCID: PMC4190979 DOI: 10.1155/2014/659715] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2014] [Revised: 07/12/2014] [Accepted: 07/16/2014] [Indexed: 11/18/2022] Open
Abstract
Venlafaxine is the first antidepressant that acts via inhibiting serotonin and noradrenaline reuptake. Hypertension is observed in doses exceeding 300 mg/day and is the most feared complication. We report a patient with accelerated hypertension after venlafaxine use observed at a dose of 150 mg/day. A 23-year-old patient with symptoms of insomnia, depression, anhedonia, fatigue admitted our clinic. Venlafaxine at a dose of 75 mg/day was initiated after he was diagnosed with major depressive disorder. After 5 months, venlafaxine dose was uptitrated to 150 mg/day due to inadequate response to drug. After using venlafaxine for ten months at the dose of 150 mg/day, he admitted our clinic with headache and epistaxis. He was hospitalized after his blood pressure was measured as 210/170 mmHg. No secondary causes for hypertension were found, and venlafaxine treatment was considered possible etiologic factor. After stopping venlafaxine treatment, his blood pressure was reverted back to normal limits. While mild elevation of blood pressure could be observed after venlafaxine treatment, this case shows that accelerated hypertension with a diastolic blood pressure rise above 120 mmHg could be observed at relatively low doses of venlafaxine. Close monitoring of blood pressure is necessary after initiation of treatment, as accelerated hypertension could cause endorgan damage with potentially catastrophic results.
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23
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Teng R, Kujacic M, Hsia J. Evaluation of the Pharmacokinetic Interaction Between Ticagrelor and Venlafaxine, a Cytochrome P-450 2D6 Substrate, in Healthy Subjects. Clin Ther 2014; 36:1217-25. [DOI: 10.1016/j.clinthera.2014.06.024] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Revised: 05/30/2014] [Accepted: 06/23/2014] [Indexed: 02/01/2023]
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Trugman JM, Palmer RH, Ma Y. Milnacipran effects on 24-hour ambulatory blood pressure and heart rate in fibromyalgia patients: a randomized, placebo-controlled, dose-escalation study. Curr Med Res Opin 2014; 30:589-97. [PMID: 24188161 DOI: 10.1185/03007995.2013.861812] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVE To characterize milnacipran effects on systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) in fibromyalgia patients using 24-hour ambulatory blood pressure monitoring (ABPM). METHODS This dose-escalation study included a 7-week double-blind treatment period and 2-week single-blind discontinuation period. Patients were randomized 2:1 to milnacipran (n = 210) or placebo (n = 111), with 50% of patients classified as 'hypertensive' at baseline (SBP ≥130 mmHg, DBP ≥85 mmHg, or current antihypertensive medication). Analyses were conducted at Weeks 4 and 7, after milnacipran dosages were escalated to 100 and 200 mg/day, respectively. Outcome measures included changes from baseline in mean ambulatory SBP, DBP, and heart rate for the 12-hour periods following the morning dose (post-AM dose) or evening dose (post-PM dose), and the entire 24-hour monitoring period. Primary outcome parameter was change from baseline in mean SBP for the 12-hour period post-AM dose. Safety analyses included adverse events and sitting vital sign readings taken at study visits. RESULTS Milnacipran increased ABPM vital signs at Week 4 (100 mg/day) and Week 7 (200 mg/day). Increases in the 12-hour period post-AM dose were similar at Weeks 4 and 7 (both visits: SBP and DBP, 4 to 5 mmHg; HR, 13 to 14 bpm). Mean increases in ambulatory vital signs were generally comparable between hypertensive and normotensive patients over 24-hour periods. Normal patterns of diurnal variation in blood pressure and heart rate were maintained in patients receiving milnacipran. Sitting vital signs were consistent with ABPM findings. Nausea was the most common adverse event observed with milnacipran. CONCLUSIONS Fibromyalgia patients receiving milnacipran in this ABPM study had mean increases in blood pressure and heart rate that were consistent with those observed in clinical efficacy trials. Diurnal variation was preserved and changes were not greater in hypertensive patients than in non-hypertensive patients. These findings cannot necessarily be generalized to other patient populations. CLINICAL TRIAL REGISTRATION This study was registered on clinicaltrials.gov (ID: NCT00618956).
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Diaper A, Rich AS, Wilson SJ, Craig K, Dourish CT, Dawson GR, Nutt DJ, Bailey JE. Changes in cardiovascular function after venlafaxine but not pregabalin in healthy volunteers: a double-blind, placebo-controlled study of orthostatic challenge, blood pressure and heart rate. Hum Psychopharmacol 2013; 28:562-75. [PMID: 23955418 DOI: 10.1002/hup.2346] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2012] [Accepted: 06/26/2013] [Indexed: 11/06/2022]
Abstract
It is generally thought that venlafaxine raises blood pressure at higher doses; however, some studies have found no effect or a decrease in blood pressure. The aim of this study was to evaluate the cardiovascular (CV) effects of 3 weeks of dosing with venlafaxine, pregabalin and placebo on young healthy adults. Fifty-four participants, of mean age 23.1 years (sd 4.68), 29 male, were randomised into three parallel groups. Each group received one of the three drugs, dosed incrementally over a 3-week period to reach daily doses of 150 mg/day venlafaxine and 200 mg/day pregabalin. Blood pressure sphygmomanometer measurements, heart rate measurements, and orthostatic challenges recorded continuously beat-to-beat were performed weekly over this period and 5 days after treatment cessation. Results showed resting systolic blood pressure (SBP) and resting and standing diastolic blood pressure (DBP) and heart rate (HR) were significantly raised by venlafaxine compared with the pregabalin and placebo groups. SBP drop on standing was larger, the resulting overshoot was smaller, and recovery was slower on venlafaxine. HR recovery was significantly impaired by venlafaxine. CV changes were observed after only 1 week of dosing at 112.5 mg/day. These effects of venlafaxine are likely to be due to its action of noradrenergic reuptake inhibition.
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Affiliation(s)
- Alison Diaper
- Psychopharmacology Unit; University of Bristol; Bristol UK
| | - Ann S. Rich
- Psychopharmacology Unit; University of Bristol; Bristol UK
| | - Sue J. Wilson
- Psychopharmacology Unit; University of Bristol; Bristol UK
- Neuropsychopharmacology Unit, Division of Experimental Medicine; Imperial College London; UK
| | | | | | | | - David J. Nutt
- Neuropsychopharmacology Unit, Division of Experimental Medicine; Imperial College London; UK
| | - Jayne E. Bailey
- Severnside Alliance for Translational Research; School of Medical Sciences, University of Bristol; Bristol UK
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Malhi GS, Hitching R, Berk M, Boyce P, Porter R, Fritz K. Pharmacological management of unipolar depression. Acta Psychiatr Scand Suppl 2013:6-23. [PMID: 23586873 DOI: 10.1111/acps.12122] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To be used in conjunction with 'Psychological management of unipolar depression' [Lampe et al. Acta Psychiatr Scand 2013;127(Suppl. 443):24-37] and 'Lifestyle management of unipolar depression' [Berk et al. Acta Psychiatr Scand 2013;127(Suppl. 443):38-54]. To provide clinically relevant recommendations for the use of pharmacological treatments in depression derived from a literature review. METHOD Using our previous Clinical Practice Guidelines [Malhi et al. Clinical practice recommendations for bipolar disorder. Acta Psychiatr Scand 2009;119(Suppl. 439):27-46] as a foundation, these clinician guidelines target key practical considerations when prescribing pharmacotherapy. A comprehensive review of the literature was conducted using electronic database searches (PubMed, MEDLINE), and the findings have been synthesized and integrated alongside clinical experience. RESULTS The pharmacotherapy of depression is an iterative process that often results in partial and non-response. Beyond the initiation of antidepressants, the options within widely used strategies, such as combining agents and switching between agents, are difficult to prescribe because of the paucity of pertinent research. However, there is some evidence for second-line strategies, and a non-prescriptive algorithm can be derived that is based broadly on principles rather than specific steps. CONCLUSION Depression is by its very nature a heterogeneous illness that is consequently difficult to treat. Invariably, situation-specific factors often play a significant role and must be considered, especially in the case of partial and non-response. Consulting with colleagues and trialling alternate treatment paradigms are essential strategies in the management of depression.
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Affiliation(s)
| | | | | | - P. Boyce
- Discipline of Psychiatry; Sydney Medical School; University of Sydney; Sydney; NSW; Australia
| | - R. Porter
- Department of Psychological Medicine; University of Otago; Christchurch; New Zealand
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Abstract
There are a variety of noradrenergic antidepressants available, most of which act by inhibiting neuronal noradrenaline re-uptake, although few drugs are specific for this action. Where drugs have numerous actions the adverse effects of noradrenaline reuptake may be difficult to isolate, although in this respect the adverse effects of reboxetine, a specific noradrenaline re-uptake inhibitor, are illuminating. Noradrenergic antidepressants typically cause minor changes in blood and heart rate, sweating and insomnia. Other pharmacological actions shown by non-specific antidepressants may act to worsen or mitigate these adverse effects. Noradrenergic drugs are less likely than selective serotonin reuptake inhibitors (SSRIs) to cause sexual dysfunction but more likely to cause urinary hesitancy. Doubts remain over the relative propensity for antidepressants with different modes of action to cause diabetes and hyponatraemia. Noradrenergic actions do not seem to confer a risk of death in overdose.
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Affiliation(s)
- Eromona Whiskey
- Pharmacy Department, South London and Maudsley NHS Foundation Trust, London, UK
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28
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Taylor D, Lenox-Smith A, Bradley A. A review of the suitability of duloxetine and venlafaxine for use in patients with depression in primary care with a focus on cardiovascular safety, suicide and mortality due to antidepressant overdose. Ther Adv Psychopharmacol 2013; 3:151-61. [PMID: 24167687 PMCID: PMC3805457 DOI: 10.1177/2045125312472890] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Depression and anxiety disorders are among the most common disorders treated by general practitioners (GPs) in the UK. Since both disorders are associated with a significantly increased risk of suicide, including with antidepressant overdose, the safety of antidepressants in overdose is of paramount importance. Numerous updates relating to antidepressant safety have been issued by regulators in the UK which may have eroded GP confidence in antidepressants. Venlafaxine, a serotonin nor adrenaline reuptake inhibitor (SNRI) had primary care prescribing restrictions placed on it in 2004 due to concerns about cardiotoxicity and mortality in overdose. Although a review of the evidence led to a reversal of the majority of restrictions in 2006, evidence suggests GPs may still be cautious in their prescribing of venlafaxine and possibly other SNRI antidepressants for patients with depression and anxiety disorders. This paper reviews the evidence pertaining to the safety of SNRI antidepressants from a perspective of cardiovascular safety and overdose. The currently available evidence suggests a marginally higher toxicity of venlafaxine in overdose compared with another SNRI duloxetine and the selective serotonin reuptake inhibitors (SSRIs), although this may be related to differential patterns of prescribing in high-risk patients. Based on this review SNRIs have a positive risk benefit profile in the treatment of depression and generalized anxiety disorder in primary care, especially as second-line agents to SSRIs.
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Affiliation(s)
- David Taylor
- Pharmacy Department, Maudsley Hospital, Denmark Hill, London SE5 8AZ, UK
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Jain RT, Panda J, Srivastava A. Two Formulations of Venlafaxine are Bioequivalent when Administered as Open Capsule Mixed with Applesauce to Healthy Subjects. Indian J Pharm Sci 2012; 73:510-6. [PMID: 22923863 PMCID: PMC3425062 DOI: 10.4103/0250-474x.98989] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2010] [Revised: 09/27/2011] [Accepted: 09/29/2011] [Indexed: 11/16/2022] Open
Abstract
Venlafaxine is a unique antidepressant approved for treatment of various depressive disorders. A single dose, cross-over bioequivalence study was performed with two different formulations of venlafaxine 150 mg extended-release capsules in which the contents of capsule were mixed with applesauce and administered to healthy subjects under fed condition. A total of 24 healthy adult male subjects participated in this randomized, single-dose, non-blinded, two-way crossover study conducted at a single centre and 23 subjects completed the study as per the study protocol. After an overnight fast of 10 h, a high-fat and high-calorie breakfast was served 30 min before dosing. The subjects then received a single dose of either formulation administered with apple sauce followed by 240 ml of water as per randomized schedule in each period separated by a washout period of 7 days. A series of blood samples were collected upto 72 h for estimation of venlafaxine and its active metabolite, O-desmethylvenlafaxine. The quantification of venlafaxine and O-desmethylvenlafaxine was done by LC-MS/MS method and pharmacokinetic and statistical analysis by WinNonlin® 5.2 and SAS® 9.1.3. The results of the study demonstrated bioequivalence of two formulations as the 90% confidence interval for the intra-individual mean ratio of log-transformed Cmax, AUC0-t and AUC0-inf of the test to the reference formulation were found within the defined bioequivalence range of 80.00%-125.00%. Both the formulations were well tolerated. This alternative mode of administration may provide benefits to patients who have difficulty in swallowing the capsule as a whole.
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Affiliation(s)
- Renu T Jain
- Bio-Evaluation Centre, Torrent Pharmaceuticals Ltd, Village Bhat, Gandhi Nagar-382 428, India
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Abstract
A number of different psychotropic agents have been associated with an increased risk of cardiovascular disease, and these relationships have been difficult to interpret due to the presence of confounding factors. Recently, there has been renewed interest in the potential for certain antidepressants to cause QT prolongation, which is a predisposing factor for arrhythmia. However, the optimum means of determining QT remains contentious due to discrepancies between methods that may be readily applied in a clinical setting versus more detailed techniques during regulatory assessment. A number of different pharmacological mechanisms might explain the occurrence of adverse cardiac effects, and these differ according to the type of antidepressant agent. Emerging data indicate that citalopram exhibits a dose-effect relationship for QT prolongation. Whereas cardiotoxicity is readily apparent in the context of intentional antidepressant overdose, the occurrence of cardiac effects as a result of therapeutic administration is less certain. Pre-existing cardiac disease and other factors that independently predispose to arrhythmia are important considerations. Therefore, clinical judgment is needed to evaluate the overall risk or benefit of a particular antidepressant in any patient. Close monitoring should be considered for those at greatest risk of QT prolongation and arrhythmia.
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Affiliation(s)
- W Stephen Waring
- Acute Medical Unit, York Teaching Hospital NHS Foundation Trust, York, UK
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Cognitive Deterioration After Venlafaxine Overdose. J Emerg Med 2011; 40:e103-6. [DOI: 10.1016/j.jemermed.2009.04.059] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2008] [Revised: 01/13/2009] [Accepted: 04/11/2009] [Indexed: 11/23/2022]
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Nichols AI, Tourian KA, Tse SY, Paul J. Desvenlafaxine for major depressive disorder: incremental clinical benefits from a second-generation serotonin–norepinephrine reuptake inhibitor. Expert Opin Drug Metab Toxicol 2010; 6:1565-74. [DOI: 10.1517/17425255.2010.535810] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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Chan AN, Gunja N, Ryan CJ. A comparison of venlafaxine and SSRIs in deliberate self-poisoning. J Med Toxicol 2010; 6:116-21. [PMID: 20237971 DOI: 10.1007/s13181-010-0013-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
To compare the clinical features of deliberate self-poisoning with venlafaxine and selective serotonin reuptake inhibitors (SSRIs) presenting to the emergency department of an Australian tertiary referral hospital. A retrospective cohort study comparing all 36 patients who presented with venlafaxine self-poisoning with 44 randomly selected patients with SSRI self-poisoning between 1997 and 2006. Patients who had overdosed on venlafaxine were older (mean age 37.4 versus 28.8 years, p ≤ 0.001) and generally exhibited a higher degree of suicidal intent (p ≤ 0.017). Median venlafaxine dose taken was 35 defined daily doses (DDDs) compared with SSRIs 19.4 DDDs. Those who ingested venlafaxine were more likely to become confused (25% versus 0%; p = 0) and have mydriasis (19.4% versus 2%; p ≤ 0.02), than those who took SSRIs. One patient from the venlafaxine group died. Compared with SSRI self-poisoners, patients who deliberately ingested venlafaxine were more likely to exhibit serious suicide intent. They were also more likely to be older, take a higher DDD of the drug, and have confusion and mydriasis. This has implications for management of severely depressed and suicidal patients.
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Affiliation(s)
- Agnes N Chan
- Consultation- Liaison Psychiatry, Royal Prince Alfred Hospital, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia.
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Hewett K, Gee MD, Krishen A, Wunderlich HP, Le Clus A, Evoniuk G, Modell JG. Double-blind, placebo-controlled comparison of the antidepressant efficacy and tolerability of bupropion XR and venlafaxine XR. J Psychopharmacol 2010; 24:1209-16. [PMID: 19939870 DOI: 10.1177/0269881109106953] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Bupropion, a noradrenaline/dopamine reuptake inhibitor, and venlafaxine, a serotonin/noradrenaline reuptake inhibitor, are both established antidepressants with proven efficacy in randomized controlled clinical trials. The objective of this double-blind, randomized, placebo- and active-controlled, eight-week, flexible-dose study was to evaluate the efficacy and tolerability of the once-daily extended-release formulations of these two antidepressants compared with placebo. Patients with major depressive disorder were randomized to once-daily treatment with bupropion XR 150 mg (n = 204), the extended-release formulation of venlafaxine (venlafaxine XR) 75 mg (n = 198) or placebo (n = 189) during weeks 1 to 4, with the option to double the dose at week 5 if response was inadequate. In this study, bupropion XR did not demonstrate statistically significant evidence of greater improvement from baseline compared with placebo on week 8 Montgomery Asberg Depression Rating scale scores (primary endpoint) or on secondary endpoints including CGI, HAM-A and responder and remitter analyses. Descriptive statistics for venlafaxine XR indicated separation versus placebo on MADRS total scores at week 8 and other intermediate time points, and on other endpoints including CGI, HAM-A and responder and remitter analyses. Both active treatments elicited improvement on the Sheehan Disability Scale and its subscales and were generally well tolerated at the doses studied. Rates of nausea, dry mouth, dizziness, hyperhidrosis, insomnia, constipation, tremor, anorexia and male sexual dysfunction were elevated in the venlafaxine XR group, consistent with its mixed serotonergic/noradrenergic mechanism. Rates of dry mouth, insomnia and hyperhidrosis were elevated in the bupropion XR group, consistent with its catecholaminergic mechanism.
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Affiliation(s)
- Karen Hewett
- GlaxoSmithKline, Pharmaceuticals, New Frontiers Science Park, Harlow, UK.
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Abstract
A case is presented of the occurrence of an episode of mania apparently induced by desvenlafaxine, in a patient with a history of major depressive disorder and no apparent history of previous mania or hypo-mania. To our knowledge, this is the first such documented case with this new antidepressant. The discussion focuses on the concept of the bipolar spectrum, and how to view patients who have only become manic while taking antidepressants.
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Correction of venlafaxine- and duloxetine-induced transaminase elevations with desvenlafaxine in a patient with Gilbert's syndrome. CNS Spectr 2010; 15:53-5. [PMID: 20394185 DOI: 10.1017/s1092852900000304] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Recent reviews have questioned whether the serotonin-norepinephrine reuptake inhibitor (SNRI) desvenlafaxine succinate offers any practical clinical advantages over existing SNRIs. The following case is one instance where it appears that this SNRI offers unique safety and benefit. Presented is a case report of a patient with Gilbert's syndrome, longstanding social phobia, and more recent depressive disorder not otherwise specified, who was found to have elevated liver transaminases when prescribed both duloxetine and venlafaxine. The patient subsequently responded to desvenlafaxine but without liver abnormalities. In this patient with Gilbert's Syndrome, desvenlafaxine's lack of metabolism through the cytochrome P450 (CYP) 2D6 pathway may explain the avoidance of these abnormalities and thus suggests a possible therapeutic role for this SNRI in similarly susceptible patients.
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Abstract
In medically complex patients with multiple comorbid illnesses who require concomitant medications, selecting the optimal antidepressant (ie, low risk of adverse effects and/or pharmacokinetic interactions) for an individual patient is critical for positive long-term patient outcomes. The serotonin-norepinephrine reuptake inhibitors (SNRls) are increasingly being used as first-line treatment for major depressive disorder (MDD) and may prove beneficial for treatment of medically complex patients.Thus, it is key for clinicians to evaluate the differences in the pharmacokinetic and tolerability profiles of the SNRI class of antidepressants, evaluating differences both within the class and compared with other antidepressants used to treat MDD.
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Peritogiannis V, Antoniou K, Mouka V, Mavreas V, Hyphantis TN. Duloxetine-induced hypomania: case report and brief review of the literature on SNRIs-induced mood switching. J Psychopharmacol 2009; 23:592-6. [PMID: 18562441 DOI: 10.1177/0269881108089841] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Manic switching during antidepressant treatment has been reported with every class of antidepressant drugs. Serotonin-noradrenaline reuptake inhibitors (SNRIs) have been increasingly used for the treatment of unipolar and bipolar depression and are well tolerated and sufficiently effective because of their dual mechanism of action. A case of duloxetine-induced hypomania in a non-bipolar patient is presented, and a brief review of all cases of SNRIs' induced mania and hypomania has been carried out. The available data suggest that SNRIs, especially venlafaxine, can induce mood switching in patients with bipolar depression and in certain patients with unipolar depression, but the potential of duloxetine and milnacipran to induce manic or hypomanic symptoms cannot be disregarded. Switching appears to be dose-related and treatment initiation with lower doses and upward titration when needed may be preferable in selected cases and may help minimizing the risk of mood switching.
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Affiliation(s)
- V Peritogiannis
- Mobile Psychiatric Unit of the Prefectures of Ioannina and Thesprotia, Society for the Promotion of Mental Health in Epirus, 38 G. Papandreou str., Ioannina 45444, Greece.
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Hewett K, Chrzanowski W, Schmitz M, Savela A, Milanova V, Gee M, Krishen A, Millen L, Leary MO, Modell J. Eight-week, placebo-controlled, double-blind comparison of the antidepressant efficacy and tolerability of bupropion XR and venlafaxine XR. J Psychopharmacol 2009; 23:531-8. [PMID: 18635695 DOI: 10.1177/0269881108089602] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The efficacy, safety and tolerability of bupropion XR and venlafaxine XR was assessed and compared with placebo in adult outpatients with major depressive disorder (MDD). Adults meeting DSM-IV criteria for MDD with a minimum Hamilton Depression Rating Scale (HAMD) 17-Item total score of > or =18 were randomized to eight weeks of double-blind treatment with either bupropion XR (150 mg/day), venlafaxine XR (75 mg/day) or placebo. At the end of the fourth week of treatment, a dosage increase to bupropion XR 300 mg/day or venlafaxine XR 150 mg/day was allowed if, in the opinion of the investigator, response was inadequate. The primary efficacy endpoint was mean change from baseline at week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score last observation carried forward (LOCF). Mean changes from baseline at week 8 (LOCF) in MADRS total score were statistically significant for bupropion XR and venlafaxine XR patients compared to the placebo group: -16.0 for bupropion XR (P = 0.006 vs placebo), -17.1 for venlafaxine XR (P < 0.001 vs placebo) and -13.5 for placebo. Secondary outcomes (including CGI-S, HAM-A, MEI, Q-LES-Q-SF, responder and remitter analyses) also improved significantly for both active treatment groups compared with placebo. The most frequently reported adverse events were dry mouth and insomnia for bupropion XR, and nausea, hyperhidrosis, fatigue, and insomnia for venlafaxine XR. In this double-blind, placebo-controlled trial, bupropion XR at doses up to 300 mg/day and venlafaxine XR at doses up to 150 mg/day demonstrated comparable antidepressant efficacy.
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Affiliation(s)
- K Hewett
- GlaxoSmithKline, New Frontier Science Park, Harlow, UK.
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Malhi GS, Adams D, Porter R, Wignall A, Lampe L, O'Connor N, Paton M, Newton LA, Walter G, Taylor A, Berk M, Mulder RT. Clinical practice recommendations for depression. Acta Psychiatr Scand 2009:8-26. [PMID: 19356154 DOI: 10.1111/j.1600-0447.2009.01382.x] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To provide clinically relevant evidence-based recommendations for the management of depression in adults that are informative, easy to assimilate and facilitate clinical decision making. METHOD A comprehensive literature review of over 500 articles was undertaken using electronic database search engines (e.g. MEDLINE, PsychINFO and Cochrane reviews). In addition articles, book chapters and other literature known to the authors were reviewed. The findings were then formulated into a set of recommendations that were developed by a multidisciplinary team of clinicians who routinely deal with mood disorders. The recommendations then underwent consultative review by a broader advisory panel that included experts in the field, clinical staff and patient representatives. RESULTS The clinical practice recommendations for depression (Depression CPR) summarize evidence-based treatments and provide a synopsis of recommendations relating to each phase of the illness. They are designed for clinical use and have therefore been presented succinctly in an innovative and engaging manner that is clear and informative. CONCLUSION These up-to-date recommendations provide an evidence-based framework that incorporates clinical wisdom and consideration of individual factors in the management of depression. Further, the novel style and practical approach should promote uptake and implementation.
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Affiliation(s)
- G S Malhi
- CADE Clinic, Department of Psychiatry, Royal North Shore Hospital, University of Sydney, NSW, Australia.
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Abstract
Objectives: To compare the efficacy and pharmacologic, pharmacokinetic, drug interaction and adverse effect profiles of duloxetine and venlafaxine. Methods: A systematic review of the literature pertaining to duloxetine and venlafaxine was conducted using a computer-aided search of MEDLINE and EMBASE for the period January 1988 to May 2008 with the following search terms: venlafaxine and duloxetine and depression, clinical studies, pharmacology, drug interactions, pharmacokinetics, adverse effects, safety, case reports and review articles. Results: Duloxetine and venlafaxine have comparable efficacy and share similar pharmacologic profiles but differ somewhat in their pharmacokinetic profiles, drug interactions and adverse effects. Both agents block the reuptake of serotonin and norepinephrine and both are substrates for the cytochrome P450 2D6 isoenzyme; however, duloxetine inhibits these enzymes to a moderate extent, whereas venlafaxine is only a weak inhibitor. Furthermore, duloxetine is more extensively bound to protein than venlafaxine. Venlafaxine is more likely to elevate blood pressure in a dose-related manner. Both duloxetine and venlafaxine have the potential to cause hepatic injury. Conclusions: Although venlafaxine and duloxetine have similar efficacy in the treatment of depression, differences in their adverse effects and pharmacokinetic profiles suggest that one agent may be preferred over the other in certain patient groups.
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Affiliation(s)
- Sylvia Zerjav
- British Columbia Mental Health and Addictions Services, Coquitlam (Zerjav); the Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver (Zerjav); the Fraser Health Authority, Vancouver (Tse); and the Department of Psychiatry, Prince George Regional Hospital, Prince George (Scott), British Columbia. Contact
| | - Gordon Tse
- British Columbia Mental Health and Addictions Services, Coquitlam (Zerjav); the Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver (Zerjav); the Fraser Health Authority, Vancouver (Tse); and the Department of Psychiatry, Prince George Regional Hospital, Prince George (Scott), British Columbia. Contact
| | - Michael J.W. Scott
- British Columbia Mental Health and Addictions Services, Coquitlam (Zerjav); the Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver (Zerjav); the Fraser Health Authority, Vancouver (Tse); and the Department of Psychiatry, Prince George Regional Hospital, Prince George (Scott), British Columbia. Contact
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Taylor D. Antidepressant drugs and cardiovascular pathology: a clinical overview of effectiveness and safety. Acta Psychiatr Scand 2008; 118:434-42. [PMID: 18785947 DOI: 10.1111/j.1600-0447.2008.01260.x] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVE To review data examining the relationships between depression, antidepressants and cardiovascular disease. METHOD Structured searches of PubMed, Medline and Embase conducted in March 2008. RESULTS Depression and cardiovascular disease are closely associated clinical entities. Depression appears both to cause and worsen cardiovascular disease. Cardiovascular disease is in turn associated with a high incidence of depression. Depression is associated with increased mortality in cardiovascular disease, and after myocardial infarction (MI) and stroke. Many antidepressants have cardiotoxic properties. Tricyclic drugs are highly cardiotoxic in overdose and may induce cardiovascular disease and worsen outcome in established cardiovascular disease. Reboxetine, duloxetine and venlafaxine are known to increase blood pressure. Other antidepressants have neutral or beneficial effects in various cardiovascular disorders. CONCLUSION Sertraline, fluoxetine, citalopram, bupropion and mirtazapine appear to be safe to use after MI; the use of sertraline, and response to citalopram and mirtazapine may improve mortality. Paroxetine and citalopram appear to be safe to use in patients with established coronary artery disease. Limited data suggest that a variety of antidepressants are effective and safe to use after stroke.
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Affiliation(s)
- D Taylor
- Pharmacy Department, Maudsley Hospital and Division of Pharmaceutical Sciences, King's College, London, UK.
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Lohoff FW, Rickels K. Desvenlafaxine succinate for the treatment of major depressive disorder. Expert Opin Pharmacother 2008; 9:2129-36. [DOI: 10.1517/14656566.9.12.2129] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Kadiroglu AK, Sit D, Kayabasi H, Tuzcu AK, Tasdemir N, Yilmaz ME. The effect of venlafaxine HCl on painful peripheral diabetic neuropathy in patients with type 2 diabetes mellitus. J Diabetes Complications 2008; 22:241-5. [PMID: 18413214 DOI: 10.1016/j.jdiacomp.2007.03.010] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2006] [Revised: 03/07/2007] [Accepted: 03/26/2007] [Indexed: 11/27/2022]
Abstract
OBJECTIVE The objective of this study was to evaluate the efficacy of venlafaxine HCl in the symptomatic treatment of painful peripheral diabetic neuropathy (PPDN) among patients with type 2 diabetes mellitus (DM). DESIGN This study was designed as a prospective, randomized, and controlled trial. SETTING This study was conducted at the Dicle University Medical Faculty (Diyarbakir, Turkey). PATIENTS Sixty type 2 DM outpatients (47 females and 13 males) with PPDN who had a minimum visual analog scale (VAS) score of 40 mm were enrolled in this study. INTERVENTIONS Patients randomized to the treatment group (n=30) received venlafaxine HCl, whereas those randomized to the control group (n=30) received a combination of vitamins B(1)and B(6) tablets. MEASURES Severity of pain was measured by VAS, Short-Form McGill Pain Questionnaire, and numerical analog scale scores at admission and at the second, fourth, and eighth weeks of the study. Polyneuropathy was supported by electromyelography. OUTCOME In the treatment group, severity of pain was measured as 70.0+/-13.0 in the VAS, as 24.9+/-6.2 in the Short-Form McGill Pain Questionnaire, and as 7.2+/-1.1 in the numerical analog scale. In the control group, it was measured as 73.0+/-8.0 in the VAS, as 26.8+/-6.2 in the Short-Form McGill Pain Questionnaire, and as 7.4+/-0.8 in the numerical analog scale (P>.05). RESULTS The most common form of PPDN was distal symmetrical sensorimotor polyneuropathy in both groups (46.8% vs. 50.0%). At the end of the study, there was a significant difference in severity of pain between the groups. In the treatment group, scores were 8.5+/-5.2 and 3.1+/-1.6 in the Short-Form McGill Pain Questionnaire and numerical analog scale, respectively; in the control group, these were 20.5+/-7.0 and 5.5+/-1.6, respectively (P<.001). CONCLUSIONS Venlafaxine HCl is a safe and well-tolerable analgesic drug in the symptomatic treatment of PPDN; however, it has minimal adverse effects. It showed its efficacy markedly in the second week of therapy.
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Affiliation(s)
- Ali Kemal Kadiroglu
- Department of Nephrology, Dicle University Medical Faculty, Diyarbakir, Turkey
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Abstract
Most antidepressants in clinical use are believed to function by enhancing neurotransmission of serotonin [5-hydroxytryptamine (5-HT)] and/or norepinephrine (NE) via inhibition of neurotransmitter reuptake. Agents that affect reuptake of both 5-HT and NE (serotonin-norepinephrine reuptake inhibitors) have been postulated to offer greater efficacy for the treatment of major depressive disorder (MDD). These dual-acting agents also display a broader spectrum of action, including efficacy for MDD and associated painful physical symptoms, diabetic peripheral neuropathic pain, generalized anxiety disorder, and fibromyalgia syndrome. Substantial preclinical evidence shows that duloxetine, an approved drug for the treatment of MDD, generalized anxiety disorder, and the management of diabetic peripheral neuropathic pain, inhibits reuptake of both 5-HT and NE. This paper reviews clinical and neurochemical evidence of duloxetine's effects on 5-HT and NE reuptake inhibition. The clinical evidence supporting duloxetine's effects on NE reuptake inhibition includes indirect measures such as altered excretion of NE metabolites, cardiovascular effects, and treatment-emergent adverse event profiles similar to those for other drugs believed to act through the inhibition of NE reuptake. In summary, the data presented in this report provide clinical evidence of a mechanism for duloxetine involving both 5-HT and NE reuptake inhibition in humans and are consistent with preclinical evidence for 5-HT/NE reuptake inhibition.
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46
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Miller T, McGoodwin L, Hagemann T. Anticholinergic-type effects following a pediatric venlafaxine overdose. Clin Toxicol (Phila) 2008; 46:338-9. [PMID: 18363135 DOI: 10.1080/15563650601182917] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Efficacy and tolerability of desvenlafaxine succinate treatment for menopausal vasomotor symptoms: a randomized controlled trial. Obstet Gynecol 2008; 111:77-87. [PMID: 18165395 DOI: 10.1097/01.aog.0000297371.89129.b3] [Citation(s) in RCA: 291] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To compare efficacy and safety of desvenlafaxine succinate (desvenlafaxine) with placebo for the treatment of vasomotor symptoms. METHODS This randomized, double-blind, placebo-controlled trial enrolled 707 healthy, postmenopausal women experiencing 50 or more moderate-to-severe hot flushes per week. Participants randomly received desvenlafaxine 50, 100, 150, or 200 mg or placebo daily. Trial duration was 52 weeks. Primary outcomes were change from baseline in average daily number of moderate-to-severe hot flushes and in daily hot flush severity score at weeks 4 and 12. RESULTS Six hundred twenty women with an average of 11 moderate-to-severe hot flushes per day at baseline completed at least one on-therapy evaluation for primary efficacy end points; 519 participants completed 12 weeks of treatment, and 368 completed the study. Desvenlafaxine 100 mg/d achieved a significantly greater reduction compared with placebo in average daily number of hot flushes at weeks 4 (P=.013) and 12 (P=.005), reaching a 64% decrease from baseline at week 12, and the 75% responder rate was significantly higher for desvenlafaxine 100 mg (50%) compared with placebo (29%; P=.003; number needed to treat=4.7) at week 12. Average daily severity of hot flushes was significantly lower in the desvenlafaxine 100-mg group compared with placebo at week 12 (P=.020). Desvenlafaxine-treated women reported significantly more treatment-emergent adverse events than placebo-treated women during the first week of therapy only. CONCLUSION Desvenlafaxine is an effective nonhormonal treatment for vasomotor symptoms in postmenopausal women. Its tolerability profile is consistent with that of other serotonin-norepinephrine reuptake inhibitors. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, www.clinicaltrials.gov, NCT00421031 LEVEL OF EVIDENCE I.
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A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in the treatment of major depressive disorder. Int Clin Psychopharmacol 2007; 22:338-47. [PMID: 17917552 DOI: 10.1097/yic.0b013e3281e2c84b] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
The antidepressant efficacy and safety of desvenlafaxine succinate (desvenlafaxine) were evaluated in a phase III, double-blind, placebo-controlled study. Outpatients with a primary diagnosis of major depressive disorder were treated with fixed once-daily doses of desvenlafaxine 200 or 400 mg for 8 weeks. The primary efficacy measure was change from baseline on the 17-item Hamilton Rating Scale for Depression. At the final on-therapy evaluation, adjusted mean change from baseline in 17-item Hamilton Rating Scale for Depression total score was greater for desvenlafaxine 200 and 400 mg/day vs. placebo. Both desvenlafaxine doses showed greater efficacy than placebo on the secondary efficacy measures, including the Clinical Global Impressions-Improvement scale scores, Montgomery-Asberg Depression Rating Scale scores, CGI-Severity, and 17-item Hamilton Rating Scale for Depression response rate. Desvenlafaxine 200 mg/day was also significantly better than placebo on remission, Visual Analog Scale-Pain Intensity overall scores, and some Visual Analog Scale-Pain Intensity subscale scores. Desvenlafaxine 400 mg/day was significantly better than placebo on selected Visual Analog Scale-Pain Intensity subscale scores. Most adverse events were mild or moderate in severity, and safety assessments revealed few clinically significant changes in vital signs, laboratory tests, and electrocardiogram results. These data provide support for the efficacy and safety of desvenlafaxine in the treatment of major depressive disorder.
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Corya SA, Williamson D, Sanger TM, Briggs SD, Case M, Tollefson G. A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, fluoxetine, and venlafaxine in treatment-resistant depression. Depress Anxiety 2007; 23:364-72. [PMID: 16710853 DOI: 10.1002/da.20130] [Citation(s) in RCA: 108] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Based on preliminary evidence of its usefulness in treatment-resistant depression (TRD), an olanzapine/fluoxetine combination (OFC) was examined in comparison with olanzapine, fluoxetine, and venlafaxine in a TRD population. In this 12-week double-blind study, 483 subjects with unipolar, nonpsychotic TRD, with historic failure on a selective serotonin reuptake inhibitor (SSRI) and prospective failure on open-label venlafaxine, were randomized to an OFC or to an olanzapine, fluoxetine, or venlafaxine monotherapy group. Venlafaxine was continued randomly in the double-blind acute phase to explore the benefits of continuation versus switching therapy. The Montgomery-Asberg Depression Rating Scale (MADRS) total change score at end point was the primary outcome measure. The OFC group had significantly greater improvement in depressive symptoms by week 1 of treatment (MADRS mean change =-7.2, baseline =29.6), in comparison to olanzapine (-4.8, P=.03), fluoxetine (-4.7, P=.03), or venlafaxine (-3.7, P=.002) groups and maintained its statistical separation from all three monotherapy groups through week 6. At end point, the OFC group was significantly different only from the olanzapine group (-14.1 vs. -7.7, P<.001). Analysis of a subgroup of subjects who had an SSRI failure in their current depressive episode (n=334) revealed statistical separation from both olanzapine and fluoxetine (but not venlafaxine) at end point: OFC (-14.6) versus olanzapine (-9.4, P<.001) versus fluoxetine (-10.7, P=.006) versus venlafaxine (-14.7, P=.98). The OFC had a safety profile comparable to its component monotherapies (i.e., olanzapine and fluoxetine), showed a rapid onset of antidepressant effect, and was effective in this TRD sample. At the study end point, OFC, fluoxetine, venlafaxine, and low-dose OFC all appeared to be similarly effective.
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Affiliation(s)
- Sara A Corya
- Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
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