Navigating the challenges of substance use and psychopathology in depression, bipolar disorder, and schizophrenia

Introduction: Dealing with Substance use disorders (SUDs) in conjunction with psychopathological conditions such as Major Depressive Disorder (MDD), bipolar disorder (BD), and schizophrenia - often referred to as dual diagnosis or co-occurring disorders - poses significant challenges for both patients and clinicians, requiring integrated treatment approaches that simultaneously tackle both substance use and psychopathology. Aim and methods: The objective of this systematic review is to analyse and summarize the existing research on the various pharmacological treatments for dual diagnosis, providing a comprehensive understanding of their effectiveness and identifying areas requiring further exploration. The systematic review was structured in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on the International Prospective Register of Systematic Reviews (PROSPERO) with the id number CRD 42024500114. Results: The analysis of the available literature identified 66 articles, 29 related to SUDs & schizophrenia, 20 focused on SUDs & MDD, and 17 on SUDs & BD. Overall, most manuscripts recording SUDs concerned the following drugs: alcohol (N = 26), cannabis (N = 19), opioids (N = 10), cocaine (N = 10), and amphetamine (N = 3), while several studies described SUDs in general (N = 12). Findings were presented thematically based on the type of intervention for each of the main conditions recorded. In the case of psychotic symptoms and SUDs, aripiprazole appeared to be the most used medication in the maintenance therapy not only for its effectiveness but also for its safety profile. Alternatively, despite the side effects, clozapine showed a good efficacy in the management of symptoms and in terms of relapse prevention. Moreover, long-acting medications might be an effective option in the control of impulsivity and psychotic symptoms, but also in first-episode psychosis, reducing relapse and rehospitalization. With regard to the treatment of MDD/BD and SUDs, there are mixed findings regarding the best medication for symptom control; notably, different degrees of efficacy were recorded if added to psychological/behavioural interventions, or combined with specific SUD treatments, such as opioid receptor agonist/antagonist therapies or the anti-glutamatergic drugs acamprosate/memantine, etc. CONCLUSION: The current body of evidence includes mixed findings in terms of which medication is superior in controlling symptoms, according to the specific psychopathology, the specific SUD involved, the treatment setting, and the primary objective of care. Overall, pharmacological treatments for dual diagnosis are complex and require personalized approaches considering the heterogeneity of the population. Future research should focus on developing individualized treatment plans and understanding the biological underpinnings of dual diagnosis to create more targeted, effective pharmacological interventions.