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Rafizadeh, Reza

University of British Columbia

Antipsychotic medications are the primary treatment for schizophrenia and schizoaffective disorder (SAD), but their impact on non-nicotine substance use disorder (NSUD) comorbidity is not well understood. Preliminary evidence indicates that clozapine might be more effective than other antipsychotics for treating co-occurring NSUDs, though it is underused due to its side effects and delayed initiation. This thesis aimed to assess whether clozapine improves NSUD-related outcomes and to identify factors influencing its metabolism for personalized dosing. A systematic review and meta-analysis of 31 studies showed that clozapine was linked to lower odds of psychiatric hospitalization and higher odds of abstinence, particularly with alcohol use disorder. Clozapine was also associated with the lowest risk of initial NSUD onset in schizophrenia compared to other antipsychotics. In a cohort study of 87 individuals with schizophrenia or SAD and severe methamphetamine or amphetamine-type SUD, clozapine treatment was associated with increased odds of maintaining abstinence from methamphetamine use and a decreased rate of relapses. Factors like co-prescription of psychostimulants and younger age were linked to higher relapse rates. Finally, a multiple linear regression analysis of 343 steady-state clozapine plasma concentrations identified that fluvoxamine co-prescription and elevated CRP levels significantly decreased clozapine metabolism, potentially increasing toxicity risk. Obesity, non-smoking status, and female sex also impacted clozapine metabolism but to a lesser extent. In conclusion, clozapine shows potential for improving outcomes in schizophrenia with co-occurring NSUDs. Identifying patient-specific factors that affect clozapine metabolism is crucial for safer, personalized dosing.

Text

2024-07-24

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/88689

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/