Antipsychotics and relapse risk in persons with first-episode psychosis and co-occurring cannabis use disorder

Background

Cannabis use is associated with an increased relapse rate in persons with psychosis and in general, antipsychotic medications are effective in reducing relapses in psychosis. There is a lack of research on the effectiveness of antipsychotics regarding patients with concomitant cannabis use and psychosis, and regarding comparative effectiveness of specific antipsychotics. We aimed to study real-world effectiveness of antipsychotics for preventing psychosis relapses among persons with first-episode psychosis and co-occurring cannabis use disorder.  

Methods

Swedish nationwide registers were utilized to identify persons with first-episode psychosis and co-occurring cannabis use disorder (first-time diagnosis of psychosis as ICD-10 F20-F29, with concomitant recording of F12) during the years 2006-2021. Association between use of specific antipsychotics (oral vs. long-acting injectable, LAI, forms) and risk of hospitalization due to psychosis relapse was investigated in within-individual design where each person acts as his/her own control to minimize selection bias, analyzed with stratified Cox models. 

Results

The cohort of persons with first-episode psychosis and co-occurring cannabis use diorder included 1820 patients (85% men, mean age 26.8, SD 8.3). Of them, 81.9% used antipsychotics during the follow-up and 63.6% were re-recorded with a cannabis use-related diagnosis, indicating persistent use. During the follow-up, 61% (N=1111) of the cohort experienced psychosis relapse. Compared with non-use, use of any antipsychotic was associated with a 33% decreased risk of relapse (aHR 0.67, 95%CI 0.60-0.72). The lowest risk of relapse was found for risperidone-LAI (0.40, 0.22-0.71), aripiprazole-LAI (0.42, 0.27-0.65), clozapine (0.43, 0.29-0.64), paliperidone-LAI (0.46, 0.30-0.69) and antipsychotic polytherapy (0.60, 0.51-0.70). Of oral non-clozapine antipsychotics, aripiprazole was associated with the lowest risk of relapse (0.61, 0.45-0.83). 

Conclusions 

Antipsychotics are effective in relapse prevention in patients with first-episode psychosis and co-occurring cannabis use disorder. These findings support the use of long-acting injectable formulations of second-generation antipsychotics in relapse prevention in these patients.