Delayed-onset hypothesis of antipsychotic action - A hypothesis tested and rejected
Delayed-onset hypothesis of antipsychotic action - A hypothesis tested and rejected
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DOI：
10.1001/archpsyc.60.12.1228
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发表时间：
2003-12-01
影响因子：
--
通讯作者：
Zipursky, RB
中科院分区：
文献类型：
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作者：
Agid, O;Kapur, S;Zipursky, RB
背景：要了解抗精神病药物的作用机制，了解这些药物生效的时间过程至关重要。当前的抗精神病药作用模型假定作用“延迟起效”。目的：通过荟萃分析研究检验抗精神病药作用的延迟起效假说。数据来源和研究选择：选择报告治疗前 4 周期间抗精神病药反应的主动或安慰剂对照试验结果的双盲研究。这些研究是通过搜索 MEDLINE，1996 年至 2001 年找到的； 1982 年至 2001 年护理和联合健康累积指数； EMBASE，1980 年至 2001 年； ACP 期刊俱乐部； Cochrane 系统评价数据库；以及有效性审查摘要数据库。通过手动搜索对这些来源的线索进行跟踪。数据综合：确定了 42 项已发表的研究，包括 7450 名患者和 119 项独立的反应与时间曲线。简要精神病评定量表和阳性和阴性症状量表的总分在第 1 周下降了 13.8%，在第 2 周下降了 8.1%，在第 3 周下降了 4.2%，在第 4 周下降了 4.7%。即使在消除安慰剂治疗的估计效果并且结果仅限于量表的精神病子量表时，这种“早发”改善模式仍然存在。 结论：本分析拒绝了普遍持有的抗精神病药反应延迟的假设。相反，这些发现表明抗精神病药物反应在治疗的第一周就开始并随着时间的推移而累积。此外，前 2 周治疗的改善效果比随后 2 周治疗的改善更大。所提出的抗精神病药物的作用机制需要考虑到这种早发的抗精神病作用。
Context: To understand the mechanism of action of antipsychotic drugs, it is critical to recognize the time course over which these medications take effect. Current models of antipsychotic action presume a "delayed onset" of action.Objective: To test the delayed-onset hypothesis of antipsychotic action via a meta-analytic study.Data Sources and Study Selection: Double-masked studies that reported results from active or placebo-controlled trials of antipsychotic response during the first 4 weeks of treatment were selected. These studies were identified by searching MEDLINE, 1996 to 2001; the Cumulative Index to Nursing and Allied Health, 1982 to 2001; EMBASE, 1980 to 2001; the ACP Journal Club; the Cochrane Database of Systematic Reviews; and the Database of Abstracts of Reviews of Effectiveness. Leads from these sources were followed up by manual searches.Data Synthesis: Forty-two published studies, including 7450 patients and 119 independent response vs time curves, were identified. Reductions in total scores on the Brief Psychiatric Rating Scale and the Positive and Negative Syndrome Scale were 13.8% during week 1,8.1% during week 2,4.2% during week 3, and 4.7% during week 4. This pattern of "early-onset" improvement was present even after the estimated effect of placebo treatment was removed and when results were restricted to the psychotic subscales of the scales.Conclusions: This analysis rejects the commonly held hypothesis that antipsychotic response is delayed. Rather, these findings suggest that the antipsychotic response starts in the first week of treatment and accumulates over time. Furthermore, greater improvement occurs in the first 2 treatment weeks than in the subsequent 2 treatment weeks. Proposed mechanisms of action of antipsychotic drugs need to account for this early-onset antipsychotic effect.