Psychosis Relapse Common During Assured Antipsychotic Treatment

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Researchers conducted a systematic review and meta-analysis to assess the incidence and predictors of psychosis relapse in individuals receiving treatment with antipsychotic agents.

Assured antipsychotic treatment may not prevent subsequent exacerbations for a proportion of individuals whose illness is stabilized on continuous antipsychotic treatment, according to results of a study published in Lancet Psychiatry.

Although individuals with schizophrenia-spectrum disorders often experience relapses, increasing the risk of morbidity or mortality, the cause of these relapses has not yet been determined.

To establish if relapses were due to poor medication adherence, researchers conducted a systematic review and individual participant data meta-analysis of 19 clinical trial cohorts. Individuals (N=5130) diagnosed with a schizophrenia-spectrum disorder and who had taken part in a clinical trial with at least one treatment group assigned to a long-acting injectable antipsychotic were included. Participants were divided into 2 groups: 2938 (57.27%) with prospective symptom remission (PSR) as determined by rating psychotic symptoms as mild or less on assessments, and 2192 (42.73%) without PSR.

Among the entire population, the incidence rate of relapse was 22.97 events per 100 participant-years; the incidence rate was 14.76 events per 100 participant-years among individuals with PSR and 36.51 events per 100-participant years among those without PSR. Individuals who experienced relapse reported significant functional decline compared with those who did not experience relapse (standardized mean difference [SMD], -0.76; 95% CI, -1.14 to -0.37; P =.0001). Risk for relapse was significantly associated with moderate or worse tardive dyskinesia at baseline (hazard ratio [HR], 2.39; 95% CI, 1.05-5.42; P =.038), substance use disorder (HR, 1.55; 95% CI 1.15-2.10; P =.0037), residence in the United States (HR, 1.55; 95% CI, 1.27-1.90; P <.0001), male sex (HR, 1.19; 95% CI, 1.03-1.39; P =.0227), and age at diagnosis (HR, 0.97; 95% CI, 0.96-0.99, P <.0001).

The study results indicate that relapse in individuals who have been diagnosed with a schizophrenia-spectrum disorder despite assured antipsychotic treatment is relatively common. More than 20% of individuals will experience relapse within 1 year, including those who had demonstrated symptom remission. Relapse was also found to be associated with significant worsening in functioning.

Differences in study design among the datasets resulted in large variation in incidence rates of relapse between cohorts. As observation periods were limited to a maximum of 2 years, there are no data on relapse frequency after this period. The reliance on data from industry-sponsored trials may bias data toward less complex and less severely ill patients. Future studies including large sample sizes of individuals of varying disorder severity and homogeneous study methodology are warranted.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Rubio JM, Schoretsanitis G, John M, Tiihonen J, et al. Psychosis relapse during treatment with long-acting injectable antipsychotics in individuals with schizophrenia-spectrum disorders: an individual participant data meta-analysis. Lancet Psychiatry. 2020;7(9):749-761.