Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
Department of Data Science, Drug Development Division, Sumitomo Pharma Co., Ltd., Tokyo, Japan.
Psychiatry Clin Neurosci. 2023 Jun;77(6):338-344. doi: 10.1111/pcn.13534. Epub 2023 Mar 7.
This study aimed to examine symptom changes during short-term discontinuation of antipsychotics up to 3 weeks including the placebo washout phase in acute schizophrenia.
The data from three double-blind, randomized, controlled trials comparing lurasidone versus placebo in patients with acute exacerbation of schizophrenia were 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, and factors associated with score changes were explored.
Among 2154 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 duration of the discontinuation phase was 5.9 ± 2.5 days. The PANSS total and CGI-S scores significantly changed from 94.0 ± 9.5 to 95.4 ± 10.5 (P < 0.001) and from 4.9 ± 0.6 to 4.9 ± 0.7 (P = 0.041), 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 vs gradual) of antipsychotic discontinuation.
Symptoms may not worsen to a clinically meaningful degree after short-term discontinuation of non-clozapine antipsychotics up to 3 weeks in patients with acute exacerbation of schizophrenia, suggesting that antipsychotic efficacy persists at least several days after discontinuation. This finding supports once-daily dosing regimen of antipsychotics and abrupt antipsychotic discontinuation when switching to another antipsychotic.
本研究旨在探讨精神分裂症急性发作患者短期（最长 3 周）停用抗精神病药物（包括安慰剂洗脱期）期间的症状变化。
分析了三项比较鲁拉西酮与安慰剂治疗精神分裂症急性加重患者的双盲、随机、对照试验的数据。采用阳性和阴性症状量表（PANSS）总分和临床总体印象严重度量表（CGI-S）评分评估症状严重程度。比较抗精神病药物停药阶段前后的评分，并探讨与评分变化相关的因素。
在参与试验的 2154 名患者中，600 名接受抗精神病药物单药治疗并完成抗精神病药物停药阶段的患者纳入分析。没有患者接受氯氮平治疗。停药阶段的平均持续时间为 5.9±2.5 天。PANSS 总分和 CGI-S 评分分别从 94.0±9.5 降至 95.4±10.5（P<0.001）和从 4.9±0.6 降至 4.9±0.7（P=0.041），差异具有统计学意义；然而，绝对差值很小。评分变化与先前抗精神病药物的类型或剂量、停药持续时间或策略（突然停药与逐渐停药）无关。
在精神分裂症急性发作患者中，短期（最长 3 周）停用非氯氮平抗精神病药物后，症状可能不会恶化到具有临床意义的程度，这表明停药后至少数天内抗精神病药物仍具有疗效。这一发现支持抗精神病药物每日一次给药方案和在转换为另一种抗精神病药物时突然停药。
