Early-onset hypothesis of antipsychotic drug action: A hypothesis tested, confirmed and extended
Early-onset hypothesis of antipsychotic drug action: A hypothesis tested, confirmed and extended
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DOI：
10.1016/j.biopsych.2005.02.023
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发表时间：
2005-06-15
影响因子：
10.6
通讯作者：
Kane, JM
中科院分区：
文献类型：
--
作者：
Leucht, S;Busch, R;Kane, JM
背景：最近的一项荟萃分析驳斥了教科书中几十年来一直描述的“抗精神病药物作用延迟发作假说”。由于荟萃分析容易出现许多方法学问题，我们试图通过a)使用个体患者数据的大型数据库而不是荟萃分析，b)包括另一种抗精神病药物，以及c)将分析从四周延长到一年。数据包括1708例有阳性症状的精神分裂症患者，我们检验了随着时间的推移简明精神病评定量表(BPRS)的递增百分比。结果：证实了“抗精神病作用的早期发作假说”，即到第二周的总体和阳性症状的减少大于到第四周的额外减少(p<；.0001)。此外，在一个有长期数据的子集中(n=748)，在观察的病例中，大约68%的一年平均BPR变化在四周时就已经实现了。结论：相当数量的抗精神病药物效应似乎发生在治疗的第一周。随后的分析需要确定抗精神病药物在被认为无效和实施替代策略之前应该试验多长时间。
Background: A recent meta-analysis rejected the "delayed onset of antipsychotic action hypothesis" that had been described in textbooks for decades. Since meta-analyses are prone to a number of methodological problems, we attempted a replication by a) using a large database of individual patient data rather than meta-analysis, b) including another antipsychotic and c) extending the analysis from four weeks to one year.Methods: We pooled the data of seven randomized trials involving amisulpride. The data included 1708 patients with schizophrenia and positive symptoms and we examined the incremental percentage Brief Psychiatric Rating Scale (BPRS) reduction over time.Results: The "early onset of antipsychotic action hypothesis" was confirmed, as the reduction of overall and positive symptoms until week two was larger than the additional reduction until week four (p < .0001). Furthermore, in a subset with long-term data (n = 748) approximately 68% of the mean BPRS change at one year was already achieved at four weeks in the observed cases.Conclusions: A substantial amount of the antipsychotic drug effect seems to occur during the first weeks of treatment. Subsequent analyses are needed to establish how long an antipsychotic should be tried before it is considered ineffective and alternative strategies implemented.