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Child Psychiatrist /Adult Psychiatrist

Efficacy of Antipsychotics for First-Episode Psychosis and Cannabis Use Disorder

Keypoint: Second-generation long-acting injectable antipsychotics reduce the risk for hospitalization among patients with first-episode psychosis and co-occurring cannabis use disorder.


Clozapine, oral aripiprazole, and long-acting injectable (LAI) formulations of risperidone, aripiprazole, and paliperidone decrease the risk for hospitalization due to psychotic relapse among patients with first-episode psychosis (FEP) and comorbid cannabis use disorder (CUD). These findings from a nationwide cohort study were published in Schizophrenia Bulletin.

Although cannabis use following a FEP event is associated with elevated psychotic symptom severity and more relapses, up to 50% of individuals with FEP have comorbid CUD. Yet, no nationwide studies have evaluated real-world outcomes of antipsychotic treatments among individuals with FEP and CUD.

To address this knowledge gap, investigators used data from Swedish national registers to evaluate the efficacy of antipsychotics in reducing the risk for hospitalization among patients with FEP and co-occurring CUD. The primary exposure was dispensations of antipsychotic medications for FEP between 2005 and 2021 to individuals (N=1820) aged 16 to 64 years with co-occurring CUD diagnosed between 2006 and 2021. The primary study outcomes were hospitalization due to psychotic disorder, any psychiatric disorder, and/or any substance use disorder – confirmed via International Classification of Diseases, Tenth Revision (ICD-10), codes.

Of the 1820 individuals included for analysis, 84.73% were boys and men, 43.57% achieved a medium level of education, and 55.55% earned income from work. On average, individuals were 26.8 (SD, 8.3) years of age. At the time of FEP, 33.9% of individuals had a diagnosis of harmful cannabis use, 32.4% had cannabis-induced psychosis, 20.6% had cannabis dependence, and 13.1% had other cannabis-related diagnoses.

Most individuals were hospitalized for psychotic relapse (61%), any psychiatric diagnosis (76%), and any SUD (63%) during a mean follow-up of 6.13 years.

The investigators found that the risk for hospitalization due to psychotic relapse was significantly lower among individuals who used LAI risperidone (hazard ratio [HR], 0.40), LAI aripiprazole (HR, 0.42), clozapine (HR, 0.43), LAI paliperidone (HR, 0.46), polytherapy (HR, 0.60), aripiprazole (HR, 0.61), and olanzapine (HR, 0.80). The risk for hospitalization was not decreased with LAI olanzapine, quetiapine, or risperidone. Overall, the use of any antipsychotic was associated with a 33% reduction of psychotic relapse risk (HR, 0.67), relative to non-use.

When evaluating the risk for hospitalization for any psychiatric disorder, HRs were significantly lower among individuals who used LAI paliperidone (HR, 0.43), clozapine (HR, 0.44), LAI aripiprazole (HR, 0.45), LAI risperidone (HR, 0.53), polytherapy (HR, 0.69), aripiprazole (HR, 0.73), and olanzapine (HR, 0.83). Similarly, LAI olanzapine, quetiapine, and risperidone were not associated with significantly lower risk.

For hospitalization due to any SUD, clozapine (HR, 0.14), LAI risperidone (HR, 0.33), LAI paliperidone (HR, 0.37), LAI aripiprazole (HR, 0.58), polytherapy (HR, 0.67), and olanzapine (HR, 0.82) were associated with decreased risk.

The investigators concluded, “[T]hese findings encourage the early use of [second-generation antipsychotic] LAIs as an important secondary prevention strategy to reduce rates of hospitalization in FEP patients with comorbid CUD.”

This study was limited by not having access to data about cannabis use trajectories, however, 63.6% of the study population were re-diagnosed with CUD during follow-up.

Note: This article originally appeared on Psychiatry Advisor

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