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Background: Preliminary evidence suggest clozapine is associated with more favorable impact on concurrent substance use disorder related outcomes in patients with concurrent schizophrenia spectrum disorders (SSD). At the same time, there is a dearth of evidence with regards to clozapine outcomes in the context of concurrent methamphetamine or amphetamine use disorder (MAUD)., Aims: To examine whether clozapine use decreases rate of methamphetamine or amphetamine (MA) relapses and increases the likelihood of maintaining abstinence from any MA use., Methods: A descriptive-analytic retrospective cohort study was conducted on individuals with SSD-MAUD in an inpatient provincial treatment and rehabilitation center for concurrent disorders. Antipsychotic exposure was categorized as "on clozapine" or "on other antipsychotic(s)." Data were collected using electronic health records. Logistic regression was used to examine association of clozapine treatment with likelihood of complete abstinence from MA use for the duration of antipsychotic exposure. Negative binomial regression was used to examine association of clozapine treatment with rate of MA relapses for the duration of antipsychotic exposure., Results: The majority of the 87 included patients were male. Ethnicity was diverse, with the largest groups self-identifying as Indigenous and European. Clozapine use was both associated with increased likelihood of maintaining abstinence from MA use (adjusted odds ratio (aOR) = 3.05, 95% confidence intervals (CI) = 1.15-8.1, p  = 0.025), and decreased rate of MA relapses (aRR = 0.45, 95% CI = 0.25-0.82, p  = 0.009) for the duration of antipsychotic exposure. Co-prescription of psychostimulants was associated with increased rate of MA relapses (aRR = 2.43, 95% CI = 1.16-5.10, p  = 0.019)., Conclusion(s): In this study, clozapine use compared with other antipsychotics in SSD was associated with improved outcomes related to severe concurrent MAUD. Co-prescription of psychostimulant medications was associated with a poor outcome., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RR, LF, HM, NM, and SP have none to declare; MD reports receiving personal fees from Eisai Ltd, Otsuka, Winterlight Labs, and the Ontario Brain Institute; CAB is founder and CEO of Sequence2Script Inc.; WGH is a consultant to AbbVie, and Translational Life Sciences; and CGS is a consultant to Clearmind Medicine.