Behind the heterogeneity in the long-term course of first-episode psychosis: different psychotic symptom trajectories are associated with different patterns of cannabis and stimulant use

Background: The long-term course of psychosis is highly variable. Data-driven classification of long-term psychotic symptom trajectories and identification of trajectory-associated risk factors could assist treatment planning and improve long-term outcomes. However, few studies have used this approach, and knowledge about underlying mechanisms is limited. Here, we identify long-term psychotic symptom trajectories and investigate the potential role of illness-concurrent cannabis and stimulant use.Methods: A total of 192 participants with first-episode psychosis from the Norwegian TOP study were followed up successfully after 10 years. Psychotic symptom trajectories were estimated using growth mixture modeling and tested for their association with baseline characteristics and cannabis and stimulant use during the follow-up (FU) period.Results: Four trajectories were identified: (1) Stable Psychotic Remission (54.2%), (2) Delayed Psychotic Remission (15.6%), (3) Psychotic Relapse (7.8%), (4) Persistent Psychotic Symptoms (22.4%). At baseline, all unfavorable symptom trajectories (2-4) were characterized by a higher number of schizophrenia diagnoses, higher symptom severity, and longer duration of untreated psychosis. Compared to the Stable Psychotic Remission trajectory, unstable trajectories (2,3) showed distinct, temporally converging associations with cannabis/stimulant use during the FU-period, with dose-dependent effects for cannabis but not stimulants in the following manner: Delayed Psychotic Remission: higher rates of frequent cannabis and stimulant use during the first 5 FU-years, Psychotic Relapse: higher rates of sporadic stimulant use throughout the entire FU-period. The Persistent Psychosis trajectory showed higher rates of frequent cannabis use during the first 5 FU-years only, indicating that factors other than substance use contributed to the persisting psychotic symptoms throughout the illness.Conclusions: The risk for an adverse long-term course could be mitigated by treatment of substance use, where particular attention should be devoted to preventing the use of stimulants while the use reduction of cannabis may already yield positive effects.