Does short-term antipsychotic discontinuation worsen symptoms in acute schizophrenia? A pooled analysis of placebo washout data

Abstract This study aimed to examine symptom changes during short-term discontinuation of antipsychotics and address whether antipsychotic withdrawal can induce a rapid symptom exacerbation (i.e., rebound psychosis). The data from three double-blind, randomized, controlled trials comparing lurasidone versus placebo in patients with acute exacerbation of schizophrenia were pooled and analyzed. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS) total and the Clinical Global Impression–Severity scale (CGI-S) scores. The scores before and after the antipsychotic discontinuation phase were compared. Factors associated with score changes were also explored. Among 2,154 patients participating in the trials, 600 who received antipsychotic monotherapy and completed the antipsychotic discontinuation phase were included in the analysis. No patients received clozapine. The mean ± standard deviation of the duration of the discontinuation phase was 5.9 ± 2.5 days. The PANSS total and CGI-S scores statistically significantly changed from 94.0 ± 9.5 to 95.4 ± 10.5 and from 4.9 ± 0.6 to 4.9 ± 0.7, respectively, during this phase; however, the absolute difference was minimal. The score changes were not associated with the type or dose of prior antipsychotics, or the duration or strategy (abrupt versus gradual) of antipsychotic discontinuation. Symptoms did not worsen to a clinically meaningful degree after a short-term discontinuation of non-clozapine antipsychotics in patients with acute exacerbation of schizophrenia, suggesting that the efficacy of antipsychotics persists at least several days after discontinuation. This finding casts doubt on the existence of rebound psychosis.