Real-world effectiveness of antipsychotic medication in relapse prevention after cannabis-induced psychosis

Background: 

The association of cannabis use and primary psychoses is well established. In contrast, the prognosis of substance-induced psychoses (SIP) is poorly understood. Among SIPs, cannabis-induced psychotic disorder (CIP) associates with the worst prognosis with up to 46% of individuals converting into schizophrenia. 

Psychosis relapse is associated with poor prognosis and antipsychotic medication is effective in preventing relapses in primary psychoses. However, to date there are only few studies where the effectiveness of antipsychotic medication in relapse prevention is studied in patients with psychotic disorder and cannabis use.    

We aimed to examine whether antipsychotic medication after first onset of CIP is effective in preventing future hospitalizations due to any primary or substance-induced psychosis.

Methods: 

Data are based on Swedish nationwide registers where a population-based cohort of patients with incident CIP (n=1772; ICD-10 F12.5) were sampled from the National Patient Register and Social Insurance register during the years 2006-2021. Patients were followed-up from CIP - diagnosis until emigration, death or end of the data linkage (December 2021). Drug use data were gathered from the Prescribed Drug Register from July 2005 to December 2021 and modelled into drug use periods with the PRE2DUP method. 

We used within-individual Cox-regression model with hazard rations (aHRs) and 95%CIs to study real-world effectiveness of different antipsychotic medications in preventing future psychosis hospitalization due to primary psychotic disorder (ICD-10 F20-F29) or any SIP (ICD-10 F1x.5). Temporal order of treatments, time since cohort entry, and time-varying use of other psychotropic drugs were adjusted for.

Results:

The cohort included 1772 patients with CIP of which 1490 (84.1%) were men and the mean (SD) age was 26.6 (8.3) years at first diagnosis. Of the cohort, 1298 (73.3%) had used antipsychotics and 889 (50.2%) experienced psychosis hospitalization during the follow-up.

Any antipsychotic use (vs. no-use) was effective in preventing psychosis hospitalization (aHR 0.70; 95%CI 0.62-0.80). Of the specific antipsychotics (vs. no use), oral aripiprazole (aHR 0.50; 95%CI 0.33–0.76), long-acting injectable antipsychotics (aHR 0.58; 95%CI 0.45–0.74), antipsychotic polytherapy (aHR 0.68; 95%CI 0.57–0.82), other oral antipsychotic monotherapy (aHR 0.71; 95%CI 0.55–0.92) and oral olanzapine (aHR 0.75; 95%CI 0.63-0.90) were effective in preventing psychosis hospitalizations whereas risperidone (aHR 0.88; 95%CI 0.63–1.24) and quetiapine (aHR 0.90; 95%CI 0.65–1.24) did not reach statistical significance.

Conclusions:

Antipsychotic medications especially oral aripiprazole and long-acting injectable antipsychotics were effective in relapse prevention in patients with CIP. This carries an important message that oral and long-acting injectable antipsychotic medications should be also considered in relapse prevention after CIP.