Pharmacological Treatments for Mood Disorders with Comorbid Substance Use Disorders: Systematic Review and Meta-Analysis

Background: Mood disorders comorbid with substance use disorders (SUDs) present significant clinical challenges. Pharmacological treatments proved to be effective for management of mood symptoms and depression among substance addicted individuals. However, there is lack of comprehensive literature describing the effectiveness of pharmacological drugs for treatment of patients having mood disorder comorbid with SUDs. Thus, this study aimed to evaluate the efficacy of pharmacological treatments for patients with mood disorders and comorbid SUDs by adopting systematic review and meta-analysis research approach. Methods: A systematic search was conducted in PubMed, EMBASE, APA PsychNet and Cochrane Library from January 2010 to April 2025. Randomized controlled trials examining pharmacological interventions in adults with mood disorders and SUDs were included. Primary outcomes were changes in depressive symptoms (Hamilton Depression Rating Scale; HAM-D) and manic symptoms (Young Mania Rating Scale; YMRS). Random-effects meta-analyses were performed. Results: Eleven studies (1,218 participants) were included. For depression, pharmacological treatments showed significant benefit in bipolar disorder with cannabis use (MD = -6.25; 95% CI: -6.36 to -6.14; p<0.00001) but not with cocaine or alcohol use. For mania, treatments improved symptoms in bipolar disorder with cocaine use (MD = 1.33; 95% CI: 1.08 to 1.58; p<0.00001) but worsened symptoms with alcohol use. Overall effects were non-significant for both depression (MD = -2.34; 95% CI: -5.07 to 0.39) and mania (MD = 0.45; 95% CI: -0.89 to 1.79) outcomes. Conclusions: Pharmacological treatments show mixed efficacy for mood symptoms in patients with mood disorders and comorbid SUDs, with effects varying by type of substance use. Further research is needed to develop targeted interventions for this complex patient population.