Clozapine and long-acting injectable antipsychotics worked best for preventing relapse in first-episode psychosis patients who also had cannabis use disorder | Research

The takeaway

In a Swedish nationwide cohort of 1,820 patients with first-episode psychosis and cannabis use disorder, clozapine and long-acting injectable antipsychotics were associated with the largest reductions in psychiatric hospitalization.

Psychiatrists treating patients with co-occurring psychosis and cannabis use disorder; clinical researchers studying antipsychotic effectiveness.

Clozapine: 57% psychotic relapse reduction, 86% SUD hospitalization reduction

What the researchers found

Any antipsychotic use reduced psychotic relapse risk by 33%. Clozapine showed the lowest relapse risk (aHR 0.43) and an 86% reduction in substance use disorder hospitalizations (aHR 0.14). LAI formulations of risperidone (aHR 0.40), aripiprazole (aHR 0.42), and paliperidone (aHR 0.46) also performed well. Among oral non-clozapine options, aripiprazole was best (aHR 0.61).

Why it matters

Patients with both psychosis and cannabis use disorder are common but understudied. This is one of the first large studies to compare antipsychotic effectiveness specifically in this population, using a design that controls for the many confounders typical of substance-using patients.

The numbers in context

1,820 patients (84.73% male, mean age 26.80). Clozapine: 57% psychotic relapse reduction, 86% SUD hospitalization reduction. LAI risperidone: 60% relapse reduction. LAI aripiprazole: 58% reduction. LAI paliperidone: 54% reduction. Oral aripiprazole: 39% reduction.

How the study worked

Nationwide Swedish cohort study using register data from 2006-2021. 1,820 patients with first-episode psychosis and co-occurring cannabis use disorder. Within-individual Cox regression models, which control for all time-stable confounders by comparing each patient to themselves across different treatment periods.

What this study cannot tell us

Observational design despite within-individual analysis. Cannabis use disorder was identified by diagnosis codes, which may not capture all users. Selection bias for clozapine (typically reserved for treatment-resistant cases). Swedish population may not generalize globally.

How to read the evidence

Large nationwide cohort with within-individual design controlling for stable confounders. Strong methodology for an observational study.

When this study was published

2024 study

The bigger picture

The finding that clozapine dramatically reduced both psychotic relapse and substance use hospitalizations suggests it may address both conditions simultaneously, potentially through its unique pharmacological profile. LAI formulations may benefit this population partly by ensuring medication adherence.

Questions still open

Why did clozapine so dramatically reduce substance use hospitalizations? Would earlier clozapine use (before treatment resistance develops) be even more effective in this population?

Common questions

What are long-acting injectable antipsychotics?

Antipsychotic medications given as injections every few weeks to months instead of daily pills. They help ensure consistent medication levels and are particularly useful when adherence to daily pills is challenging.

Why is clozapine not used more widely?

Clozapine requires regular blood monitoring because of a rare but serious risk of lowering white blood cell counts. It is typically reserved for patients who have not responded to other antipsychotics.

Read the original research

Antipsychotic Use and Psychiatric Hospitalization in First-Episode Non-affective Psychosis and Cannabis Use Disorder: A Swedish Nationwide Cohort Study.

Schizophrenia bulletin, 50(6), 1287-1294

View on PubMed ↗Publisher’s paper ↗

Citation

Denissoff, Alexander; Taipale, Heidi; Tiihonen, Jari; Di Forti, Marta; Mittendorfer-Rutz, Ellenor; Tanskanen, Antti; Mustonen, Antti; Niemelä, Solja. (2024). Antipsychotic Use and Psychiatric Hospitalization in First-Episode Non-affective Psychosis and Cannabis Use Disorder: A Swedish Nationwide Cohort Study.. Schizophrenia bulletin, 50(6), 1287-1294. https://doi.org/10.1093/schbul/sbae034