Antipsychotics may prevent relapse in first-episode psychosis with cannabis use disorder

Key takeaways:

• Clozapine and second-generation long-acting formulations of certain antipsychotics decreased risk for hospitalization due to psychotic relapse.
• Antipsychotic polytherapy reduced risk for all outcomes studied.

Some antipsychotics other than olanzapine lowered the risk for hospitalization due to psychotic relapse among individuals with first-episode psychosis and co-occurring cannabis use disorder, according to a study in Schizophrenia Bulletin.

Cannabis use is common among patients with first-episode psychosis (FEP), with continued use being “associated with elevated severity of psychotic symptoms and increased frequency and duration of relapses,” Alexander Denissoff, MD, of the department of psychiatry at University of Turku in Finland, and colleagues wrote.

For this reason, “improving outcomes of FEP patients with dual disorders is of paramount importance, as relapse after the index psychotic episode is associated with adverse clinical outcomes,” the researchers added.

Using register-linkage data from a Swedish nationwide cohort from 2006 to 2021, Denissoff and colleagues examined the real-world treatment outcomes of 1,820 patients (84.73% male; mean age, 26.8 years; standard deviation, 8.25 years) with FEP and co-occurring cannabis use disorder (CUD).

The main outcome of the study was hospitalization due to psychotic relapse; secondary outcomes included hospitalization due to any psychiatric disorder or substance use disorder (SUD).

The researchers applied within-individual Cox regression models with HRs and 95% CIs to study the association of the use of different antipsychotics with the outcomes of interest.

During a mean follow-up of 6.13 years, 1,111 of the patients were hospitalized for psychotic relapse.

Overall, antipsychotic polytherapy was associated with a 40% reduced risk for psychotic relapse (adjusted HR = 0.6; 95% CI, 0.51-0.7), a 31% reduced risk for subsequent hospitalization due to any psychiatric disorder (aHR = 0.69; 95% CI, 0.61-0.78) and a 33% reduced risk for subsequent hospitalization due to any SUD (aHR = 0.67; 95% CI, 0.57-0.78).

“This is of significance, as previous findings on the efficacy of antipsychotic polytherapy have been mixed and this form of treatment has been discouraged in clinical guidelines,” the researchers wrote.

Further, compared with nonuse, the use of any antipsychotic was associated with a 33% decreased risk for psychotic relapse (aHR = 0.67; 95% CI, 0.6-0.75).

A total of 1,038 patients were prescribed oral olanzapine. Despite being the most frequently prescribed antipsychotic, it was associated with only a modest risk reduction with respect to the outcomes studied.

“This was surprising, as meta-analytic evidence points to olanzapine and amisulpride to be more efficacious than other nonclozapine agents in FEP,” Denissoff and colleagues wrote.

In addition to oral clozapine (aHR = 0.43; 95% CI, 0.29-0.64), long-acting injectable (LAI) formulations of risperidone (aHR = 0.4; 95% CI, 0.22-0.71), aripiprazole (aHR = 0.42; 95% CI, 0.27-0.65), and paliperidone (aHR = 0.46; 95% CI, 0.3-0.69) were associated with the lowest risk of psychotic relapse, according to the researchers.

Aripiprazole was associated with the lowest risk for relapse among oral nonclozapine antipsychotics (aHR = 0.61; 95% CI, 0.45-0.83).

Researchers found the lowest risk for hospitalization due to any psychiatric diagnosis with use of LAI formulations of aripiprazole (aHR = 0.45; 95% CI, 0.3-0.67) and paliperidone (aHR = 0.43; 95% CI, 0.29-0.64) and oral clozapine (aHR = 0.44; 95% CI, 0.31-0.6).

Also, clozapine was associated with an 86% decreased risk for subsequent hospitalization due to SUD (aHR = 0.14; 95% CI, 0.05-0.44).

“While clozapine was found to be associated with a substantial risk reduction of subsequent hospitalization due to SUDs, this finding might not be void of selection bias,” the researchers wrote. “Thus, these 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.”