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Meta-Analysis
. 2020 Nov;65(11):749-769.
doi: 10.1177/0706743720915420. Epub 2020 Apr 17.

Pharmacological Treatment of Mood Disorders and Comorbid Addictions: A Systematic Review and Meta-Analysis: Traitement Pharmacologique des Troubles de L'humeur et des Dépendances Comorbides: Une Revue Systématique et une Méta-Analyse

Paul R A Stokes  1   2   3 , Tahir Jokinen  1 , Sami Amawi  1 , Mutahira Qureshi  2 , Muhammad Ishrat Husain  4   5 , Lakshmi N Yatham  6 , John Strang  3   7 , Allan H Young  1   2   3
Affiliations
Meta-Analysis

Pharmacological Treatment of Mood Disorders and Comorbid Addictions: A Systematic Review and Meta-Analysis: Traitement Pharmacologique des Troubles de L'humeur et des Dépendances Comorbides: Une Revue Systématique et une Méta-Analyse

Paul R A Stokes et al. Can J Psychiatry. 2020 Nov.

Abstract
in English, French

Objective: Addiction comorbidity is an important clinical challenge in mood disorders, but the best way of pharmacologically treating people with mood disorders and addictions remains unclear. The aim of this study was to assess the efficacy of pharmacological treatments for mood and addiction symptoms in people with mood disorders and addiction comorbidity.

Methods: A systematic search of placebo-controlled randomized controlled trials investigating the effects of pharmacological treatments in people with bipolar disorder (BD) or major depressive disorder (MDD), and comorbid addictions was performed. Treatment-related effects on mood and addiction measures were assessed in a meta-analysis, which also estimated risks of participant dropout and adverse effects.

Results: A total of 32 studies met systematic review inclusion criteria. Pharmacological therapy was more effective than placebo for improving manic symptoms (standardized mean difference [SMD] = -0.15; 95% confidence interval [95% CI], -0.29 to -0.02; P = 0.03) but not BD depressive symptoms (SMD = -0.09; 95% CI, -0.22 to 0.03; P = 0.15). Quetiapine significantly improved manic symptoms (SMD = -0.23; 95% CI, -0.39 to -0.06; P = 0.008) but not BD depressive symptoms (SMD = -0.07; 95% CI, -0.23 to 0.10; P = 0.42). Pharmacological therapy was more effective than placebo for improving depressive symptoms in MDD (SMD = -0.16; 95% CI, -0.30 to -0.03; P = 0.02). Imipramine improved MDD depressive symptoms (SMD = -0.58; 95% CI, -1.03 to -0.13; P = 0.01) but Selective serotonin reuptake Inhibitors (SSRI)-based treatments had no effect (SMD = -0.06; 95% CI, -0.30 to 0.17; P = 0.60). Pharmacological treatment improved the odds of alcohol abstinence in MDD but had no effects on opiate abstinence.

Conclusions: Pharmacological treatments were significantly better than placebo in improving manic symptoms, MDD depressive symptoms, and alcohol abstinence but were not better for bipolar depression symptoms. Importantly, quetiapine was not more effective than placebo in improving bipolar depression symptoms nor were SSRI's for the treatment of MDD depression. Our findings highlight the need for further high-quality clinical trials of treatments for mood disorders and comorbid addictions.

Objectif :: La comorbidité de la dépendance est un important problème clinique dans les troubles de l’humeur, mais la meilleure façon de traiter les personnes souffrant de troubles de l’humeur et de dépendances en pharmacologie demeure indéfinie. Cette étude visait à évaluer l’efficacité des traitements pharmacologiques pour les symptômes de l’humeur et de dépendance au sein des troubles de l’humeur avec comorbidité de la dépendance.

Méthodes :: Une recherche systématique des essais randomisés contrôlés par placebo et recherchant les effets des traitements pharmacologiques chez les personnes souffrant de trouble bipolaire (TB) ou de trouble dépressif majeur (TDM) et de dépendances comorbides a été menée. Les effets liés au traitement sur les mesures de l’humeur et de la dépendance ont été évalués dans une méta-analyse qui estimait également les risques d’abandon des participants et les effets indésirables.

Résultats :: Trente-deux études satisfaisaient aux critères d’inclusion de la revue systématique. La thérapie pharmacologique était plus efficace que le placebo pour améliorer les symptômes de manie (différence moyenne normalisée DMN = −0.15; IC à 95% −0.29 à −0.02; P = 0.03) mais pas les symptômes dépressifs du TB (DMN = −0.09; IC à 95% −0.22 à 0,03; P = 0.15). La quétiapine améliorait significativement les symptômes de manie (DMN = −0.23; IC à 95% −0.39 à −0.06; P = 0.008) mais pas les symptômes dépressifs du TB (DMN = −0.07; IC à 95% −0.23 à 0.10; P = 0.42). La thérapie pharmacologique était plus efficace que le placebo pour améliorer les symptômes dépressifs du TDM (DMN = −0.16; IC à 95% −0.30 à −0.03; P = 0.02). L’imipramine améliorait les symptômes dépressifs du TDM (DMN = −0.58; IC à 95% −1.03 à −0.13; P = 0.01) mais les traitements à base d’ISRS n’avaient aucun effet (DMN = −0.06; IC à 95% −0.30 à 0.17; P = 0.60). Le traitement pharmacologique améliorait les probabilités d’abstinence d’alcool dans le TDM mais n’avait aucun effet sur l’abstinence d’opiacés.

Conclusions :: Les traitements pharmacologiques étaient significativement meilleurs que les placebos pour améliorer les symptômes de manie, les symptômes dépressifs du TDM et l’abstinence d’alcool, mais n’étaient pas plus efficaces pour les symptômes de la dépression bipolaire. Notablement, la quétiapine n’était pas plus efficace que le placebo pour améliorer les symptômes de la dépression bipolaire, pas plus que ne l’étaient les ISRS pour le traitement de la dépression du TDM. Nos résultats mettent en lumière le besoin d’autres essais cliniques de grande qualité sur les traitements des troubles de l’humeur et des dépendances comorbides.

Keywords: addictions; antidepressants; bipolar disorders; comorbidity; major depressive disorder; meta-analysis; pharmacotherapy; randomized controlled trial; systematic reviews.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Stokes reports grants and nonfinancial support from Corcept Therapeutics, nonfinancial support from Janssen Research and Development LLC, personal fees from Frontiers in Psychiatry, personal fees from Allergan, outside the submitted work. Mr. Jokinen, Dr. Amawi, and Dr. Qureshi have nothing to disclose. Dr. Husain has received grants from the Stanley Medical Research Institute and the Physicians’ Services Incorporated (PSI) Foundation. Prof. Yatham reports grants from Sumitomo Dainippon Pharma Co. Ltd. and Canadian Institutes of Health Research, personal fees from Alkermes, Allergan, Sumitomo Dainippon, Lundbeck, Otsuka, and Sunovion, and other support from CANMAT, Lundbeck, and Valeant. Prof. Sir Strang reports grants from Martindale Pharma, other from Martindale Pharma, grants from Mundipharma, other from Mundipharma, grants from Braeburn Pharma, other from Braeburn Pharma, grants from Indivior, from Molteni, outside the submitted work. In addition, Prof. Sir Strang has a patent Euro-Celtique issued and a patent King’s College London pending. Prof. Young reports personal fees from Lundbeck, grants and personal fees from Janssen, grants from Compass, personal fees from Livanova, personal fees from Bionomics, personal fees from Allegan, and personal fees from Sunovion, outside the submitted work. Prof Young has given paid lectures and advisory boards for the following companies with drugs used in affective and related disorders: Lundbeck, Sunovion, Servier, Livanova, Janssen, Allegan, and Bionomics. He has been a consultant to Johnson & Johnson and Livanova. Prof. Young has no shareholdings in pharmaceutical companies. Prof. Young is the principal investigator in the Restore-Life VNS registry study funded by LivaNova and was a lead investigator for Embolden Study (AZ), BCI Neuroplasticity study, and Aripiprazole Mania Study. Investigator initiated studies from AZ, Eli Lilly, Lundbeck, Wyeth, and Janssen. Prof Young has received grant funding (past and present) from NIMH (USA), CIHR (Canada), NARSAD (USA), Stanley Medical Research Institute (USA), MRC (UK), Wellcome Trust (UK), Royal College of Physicians (Edin), BMA (UK), UBC-VGH Foundation (Canada), WEDC (Canada), CCS Depression Research Fund (Canada), MSFHR (Canada), NIHR (UK), and Janssen (UK).

Figures

Figure 1.
Figure 1.
Preferred reporting items for systematic reviews and meta-analyses flow diagram of search results.
Figure 2.
Figure 2.
Treatment effects on mania scores in bipolar disorder with addiction comorbidity.
Figure 3.
Figure 3.
Effect of treatment on depression scores in bipolar disorder with addiction comobidity.
Figure 4.
Figure 4.
Treatment effects on depression scores in participants with major depressive disorder and comorbid addictions.
Figure 5.
Figure 5.
Effects of treatment on alcohol consumption in participants with mood disorders and comorbid addictions.
Figure 6.
Figure 6.
Effects of treatment on alcohol abstinence in participants with major depressive disorder and comorbid alcohol use disorder.
Figure 7.
Figure 7.
Effects of treatment on end-of-trial negative urine drug screens in participants with mood disorders and comorbid addictions.
Figure 8.
Figure 8.
(A) Risk of treatment-associated dropout in participants with bipolar disorder. (B) Risk of treatment-associated dropout in participants with major depressive disorder.
None
See this image and copyright information in PMC

References

    1. Stokes PRA, Kalk NJ, Young AH. Bipolar disorder and addictions: the elephant in the room. Br J Psychiatry. 2017;211(3):132–134. - PubMed
    1. Blanco C, Compton WM, Saha TD, et al. Epidemiology of DSM-5 bipolar I disorder: results from the national epidemiologic survey on alcohol and related conditions—III. J Psychiatr Res. 2017;84:310–317. - PMC - PubMed
    1. Hasin DS, Sarvet AL, Meyers JL, et al. Epidemiology of adult DSM-5 major depressive disorder and its specifiers in the United States. JAMA Psychiatry. 2018;75(4):336–346. - PMC - PubMed
    1. Jones L, Metcalf A, Gordon-Smith K, et al. Gambling problems in bipolar disorder in the UK: prevalence and distribution. Br J Psychiatry. 2015;207(4):328–333. - PMC - PubMed
    1. Goldberg JF, Garno JL, Leon AC, Kocsis JH, Portera L. A history of substance abuse complicates remission from acute mania in bipolar disorder. J Clin Psychiatry. 1999;60(11):733–740. - PubMed

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