Cannabis use was the strongest predictor of relapse in first-episode schizophrenia over three years | Research

The takeaway

Among 119 patients in remission after a first episode of schizophrenia, 49.6% relapsed within three years, and cannabis use was the factor most strongly associated with relapse (93.2% of relapsers used cannabis vs. 56.7% who stayed in remission).

Psychiatrists, early intervention clinicians, patients with psychosis, and family members.

93% of relapsers used cannabis vs. 57% of non-relapsers

What the researchers found

Cannabis consumption was dramatically higher among those who relapsed (93.2%) compared to those who maintained remission (56.7%, p<0.001). Other relapse-associated factors included higher antipsychotic doses, polypharmacy, benzodiazepine use, and side effects. Notably, 22% of those who remained in remission were not taking any antipsychotic.

Why it matters

The strength of the association between cannabis use and relapse in first-episode schizophrenia underscores cannabis cessation as a potentially modifiable target for preventing second episodes.

The numbers in context

119 patients followed; 49.6% relapsed within 3 years. Cannabis use: 93.2% in relapsers vs. 56.7% in remitters (p<0.001). Antipsychotic doses: 381.93 vs. 242.29 mg chlorpromazine equivalents/day (p=0.028). 22% of non-relapsers were off antipsychotics.

How the study worked

Naturalistic longitudinal study following 119 patients in remission after first-episode schizophrenia across 15 tertiary centers in Spain over three years. Sociodemographic, clinical, treatment, and substance use data analyzed.

What this study cannot tell us

Observational design cannot prove cannabis caused relapse. Higher antipsychotic doses and polytherapy in relapsers may reflect more severe illness. Cannabis use was self-reported. No data on cannabis potency or frequency.

How to read the evidence

Multi-center longitudinal cohort with 3-year follow-up, but observational design limits causal inference.

When this study was published

Published in 2022.

The bigger picture

The finding that cannabis use outperformed all other measured variables in distinguishing relapsers from non-relapsers adds to the growing body of evidence that cannabis is a critical factor in early psychosis outcomes.

Questions still open

Would targeted cannabis cessation programs reduce relapse rates? Does the type or potency of cannabis matter? Why were some patients stable without antipsychotics while others relapsed despite treatment?

Common questions

How common is relapse after a first episode of schizophrenia?

In this study, nearly half (49.6%) of patients who initially achieved remission relapsed within three years, highlighting the vulnerability of this early period.

Was cannabis the only factor linked to relapse?

No, but it was the most strongly associated factor. Relapsers also had higher antipsychotic doses, more polypharmacy, more benzodiazepine use, and more reported side effects, though these may reflect more severe illness rather than causes of relapse.

Read the original research

Clinical and treatment predictors of relapse during a three-year follow-up of a cohort of first episodes of schizophrenia.

Schizophrenia research, 243, 32-42

View on PubMed ↗Publisher’s paper ↗

Citation

Bioque, Miquel; Mezquida, Gisela; Amoretti, Sílvia; García-Rizo, Clemente; López-Ilundain, Jose M; Diaz-Caneja, Covadonga M; Zorrilla, Iñaki; Mané, Anna; Rodriguez-Jimenez, Roberto; Corripio, Iluminada; Pomarol-Clotet, Edith; Ibáñez, Ángela; Usall, Judith; Contreras, Fernando; Mas, Sergi; Vázquez-Bourgon, Javier; Cuesta, Manuel J; Parellada, Mara; González-Pinto, Ana; Hidalgo-Figueroa, María; Bernardo, Miquel. (2022). Clinical and treatment predictors of relapse during a three-year follow-up of a cohort of first episodes of schizophrenia.. Schizophrenia research, 243, 32-42. https://doi.org/10.1016/j.schres.2022.02.026