Effects of clozapine treatment on the improvement of substance use disorders other than nicotine in individuals with schizophrenia spectrum disorders: A systematic review and meta-analysis

Abstract

Background: Antipsychotic medications are the mainstay of treatment for schizophrenia and are associated with a reduction in psychiatric hospitalization and overall mortality. Some evidence suggest that antipsychotic medications might have a varying effect on the improvement of comorbid substance use disorders (SUDs), with clozapine showing more favorable outcomes. Aim: We systematically reviewed all available evidence on effects of clozapine on the improvement of SUDs other than nicotine. Methods: Electronic searches of MEDLINE, Embase, PsycINFO, and CINHAL were conducted up to March 1, 2022. Studies of any methodological design involving two concepts: (1) clozapine and (2) SUD terms (excluding nicotine) were included. For SUD outcomes with three or more comparative studies with available raw data meta-analysis was performed. SUD outcomes not meeting criteria for meta-analysis were described qualitatively. Risk of bias was examined using “Downs and Black,” and “Q-Coh” instruments. Results: The majority of individuals in the included 31 studies were male and of European ancestry. Abstinence was the most common outcome. Most of the studies were of low-to-moderate quality, and none of the studies met all the quality criteria. Pooled findings from four observational studies in samples of patients with predominantly comorbid alcohol use disorder showed that clozapine treatment is associated with significantly higher odds of remaining abstinent. In addition clozapine was associated with decreased odds of psychiatric hospitalization in all but one observational study. Conclusions: Our systematic review and meta-analysis builds upon previous reviews, and it suggests the association of clozapine treatment with significantly higher odds of remaining abstinent from substance use and decreased likelihood of psychiatric hospitalization, compared with continuing treatment with other antipsychotic medications. Still, the validity of this association needs greater exploration and providing recommendations for the utility of clozapine in individuals without treatment-resistant psychosis and comorbid SUDs would be premature.

The patient journey project in Italian mental health services: results from a co-designed survey on clinical interventions and current barriers to improve the care of people living with schizophrenia

“…On the one hand, a feasible option is to provide LAI antipsychotics regimen as several evidence demonstrated it efficacy in treatment comorbid substance abuse in PLWS ( 78 – 80 ). On the other hand, meta-analytic evidence suggested that clozapine was superior to other AP in reducing substance misuse ( 81 ), while other findings observed that clozapine is strongly associated with reduced risk of developing substance use disorders among PLWS ( 82 ) maintaining them abstinent from misuse ( 83 ).…”

Investigating the Effectiveness of Brexpiprazole in Subjects with Schizophrenia Spectrum Illness and Co-Occurring Substance Use Disorder: A Prospective, Multicentric, Real-World Study

“…Initial studies have indicated that atypical antipsychotics like clozapine, risperidone, and olanzapine have demonstrated effectiveness in managing psychotic symptoms and reducing substance use in individuals with DDs [ 22 , 23 , 24 , 25 , 26 ]. Specifically, according to recent studies, clozapine treatment is linked to markedly higher chances of maintaining abstinence from substance use and a reduced probability of psychiatric hospitalization in comparison to continued treatment with other antipsychotic medications [ 27 , 28 ]. This reduction in the intensity of craving could be mediated by the intrinsic characteristics of clozapine.…”

Association of clozapine treatment and rate of methamphetamine or amphetamine relapses and abstinence among individuals with concurrent schizophrenia spectrum and amphetamine use disorder: A retrospective cohort study

“…Antipsychotic medications are the mainstay of treatment in SSD; yet, there is sparse research examining their impact on highly prevalent concurrent SUD outcomes. Some preliminary evidence, mainly from observational studies, have shown that clozapine is associated with more favorable effects on improving concurrent SUD outcomes compared with other antipsychotic medications ( Rafizadeh et al, 2022 ). There is, however, a dearth of evidence about its effects on outcomes related to concurrent MAUD in particular.…”