First-Episode Schizophrenia and Relapses After Antipsychotic Discontinuation

Investigators suggest that treatment with antipsychotics for longer than the current algorithm might be beneficial after the first-episode of schizophrenia.

Relapse rates are high after discontinuing antipsychotic medications in patients following a first episode of schizophrenia, according to a recent article in Schizophrenia Research.

Investigators recruited 193 patients from an ongoing, first-episode schizophrenia follow-up project at Istanbul University, Turkey. Of these, 105 continued in the study. The mean duration of follow-up was 99.1±63.9 months. Fifty-six participants (53.3%) discontinued their antipsychotic medication at least once. Of these, 17 (16.2%) stopped taking their medication at the direction of their psychiatrist after at least 1 year of treatment and 39 (37.1%) made the decision to stop on their own. The remaining patients (n=49) continued taking their medication for the duration of the study.

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In total, 78 patients (74.2%) had a relapse of their symptoms at least once during the follow-up period. The relapse rate was 58.8% in patients who discontinued their medication by a directive from a psychiatrist, 77.5% in patients who continued treatment, and 76.9% in patients who discontinued medication on their own. Of the 78 patients who relapsed, 40 relapsed after discontinuing their antipsychotic medication after a mean duration of treatment of 17.4±12.7 months.

Study limitations included sample bias, lack of randomization, and susceptibility to type 2 error. Patients with a first episode of schizophrenia were admitted to a university hospital, which does not represent practice in the general population. The study also included patients with a potentially better outcome, which limits generalizability of findings. Additionally, because the study design was naturalistic, participants who discontinued their medication were not randomized. Finally, limiting the definition of lack of relapse to only 6 months is considered a relatively short time period compared with other studies.

The authors concluded “that in the early period following treatment discontinuation after [first-episode schizophrenia] FES within naturalistic conditions, probability of relapse is high. These results may be suggesting that one- or two-year duration of antipsychotic treatment after FES recommended by treatment algorithms is not enough.” The investigators suggested that “when considering discontinuation, psychiatrists minimize the risk [for] relapse following discontinuation by taking into account many variables such as premorbid adjustment, functional level before and after FES, treatment response in the early period and patients’ current life problems.”


Ucok A, Kara IA. Relapse rates following antipsychotic discontinuation in the maintenance phase after first-episode of schizophrenia: Results of a long-term follow-up study. [published online October 22, 2019]. Schizophr Res. doi: 10.1016/j.schres.2019.10.015