Cannabis Use and Symptomatic Relapse in First Episode Schizophrenia: Trigger or Consequence? Data from the OPTIMISE Study

Background and Hypothesis: This analysis examined the relationship between cannabis use, compliance with antipsychotics and risk for relapse in patients in remission following a first episode of schizophrenia, schizophreniform, or schizoaffective disorder. Study Design: Analyses were performed on data from a large European study on first episode of schizophrenia, schizophreniform, or schizoaffective disorder (OPTiMiSE). After 10 weeks of antipsychotic treatment, 282/446 patients (63%) met criteria for symptomatic remission; of whom 134/282 (47.5%) then completed a 1-year follow-up. Cross-lagged models and mediation models investigated the temporal relationships between cannabis use, compliance with antipsychotics, social functioning, and symptomatic worsening/relapse. Study Results: Compared to nonusers, cannabis use increased risk for relapse, adjusted hazard ratio (HR)=3.03 (SE=0.32), P<.001, even in patients who were compliant with antipsychotic medication, adjusted HR=2.89, (SE=0.32), P<.001. Cannabis use preceded symptomatic worsening and was followed by worsening of Positive and Negative Syndrome Scale total score at the 1-year end-point (standardized β=0.62, SE=0.19, P=.001) and by worsening of social functioning (coef=-0.66, P ≤. 001). Conclusions: In patients in remission from their first episode of schizophrenia, schizophreniform, or schizoaffective disorder, cannabis use increases the rate of relapse in both compliant and noncompliant individuals. Importantly, the temporal relationship between cannabis and relapse was that cannabis use preceded later relapse, noncompliance, and decrease in social functioning, and not that patients began to relapse, then used cannabis. Further research with a precision psychiatry approach might identify those patients in particular danger of relapse when using cannabis.