Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Canada.
Department of Psychiatry, University of Toronto, Canada.
J Clin Psychiatry. 2017 Feb;78(2):223-228. doi: 10.4088/JCP.15m10286.
To examine effects of different antipsychotic discontinuation strategies on clinical outcomes in patients with schizophrenia undergoing a switch to clozapine.
This pilot, 8-week, double-blind, randomized controlled trial was conducted from May 1999 to July 2004. Outpatients with a diagnosis of schizophrenia or schizoaffective disorder based on the Structured Clinical Interview for DSM-IV and eligible for a switch to clozapine were included. Participants were randomly assigned to the immediate discontinuation (prior antipsychotics were discontinued at baseline) or gradual discontinuation (prior antipsychotics were reduced by 25% each week) group. For each group, clozapine was gradually increased to 300 mg/d at day 12, with this dose maintained for 3 weeks and thereafter adjusted as needed. Clinical outcome measures included the Brief Psychiatric Rating Scale (BPRS), UKU Side Effect Rating Scale, and extrapyramidal symptoms scales.
Thirty-three patients were enrolled; 15 and 18 patients were assigned to the immediate and gradual discontinuation groups, respectively. While significant improvements were observed in BPRS total scores after the switch to clozapine in both groups (P values < .001), no significant differences were found on any clinical outcome measures between the groups; however, additional analyses revealed a significant interaction between group and time for the UKU Psychic Side Effects subscale scores (P = .038).
This preliminary study demonstrated no statistically significant differences in efficacy or tolerability between immediate and gradual antipsychotic discontinuation strategies when switching to clozapine in patients with schizophrenia; however, due to the small sample size, larger-scale trials are needed to confirm these results.
ClinicalTrials.gov identifier: NCT02640300.
研究不同抗精神病药物停药策略对接受氯氮平换药的精神分裂症患者临床结局的影响。
这是一项为期 8 周的试点、双盲、随机对照试验，于 1999 年 5 月至 2004 年 7 月进行。纳入符合 DSM-IV 结构临床访谈诊断为精神分裂症或分裂情感障碍且有资格换用氯氮平的门诊患者。参与者被随机分配到立即停药（基线时停用先前的抗精神病药物）或逐渐停药（每周减少 25%）组。对于每组，氯氮平在第 12 天逐渐增加到 300mg/d，维持该剂量 3 周，然后根据需要进行调整。临床结局测量包括简明精神病评定量表（BPRS）、UKU 副作用评定量表和锥体外系症状量表。
共纳入 33 例患者，其中 15 例和 18 例患者分别被分配到立即停药组和逐渐停药组。两组患者换用氯氮平后 BPRS 总分均显著改善（P 值均<.001），但两组间任何临床结局指标均无显著差异；然而，进一步分析显示 UKU 精神副作用亚量表评分的组间和时间存在显著交互作用（P=.038）。
这项初步研究表明，在精神分裂症患者换用氯氮平时，立即停药与逐渐停药策略在疗效或耐受性方面没有统计学上的显著差异；然而，由于样本量较小，需要更大规模的试验来证实这些结果。
ClinicalTrials.gov 标识符：NCT02640300。
