Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, De Crespigny Park, London, SE5 8AF, UK.
Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, London, W12 0NN, UK.
Mol Psychiatry. 2021 Apr;26(4):1310-1320. doi: 10.1038/s41380-019-0502-5. Epub 2019 Aug 30.
The response to antipsychotic treatment in schizophrenia appears to vary, and as such it has been proposed that different subtypes of schizophrenia exist, defined by treatment-response. This has not been formally examined using meta-analysis. Randomised controlled trials comparing placebo and antipsychotics in acute treatment of schizophrenia listed in PubMed, EMBASE and PsycINFO from inception until 30 November 2018 were examined. Relative variability of symptomatic improvement in antipsychotic-treated individuals compared to placebo-treated individuals was quantified using coefficient of variation ratio (CVR). Mean difference in symptom change was quantified using Hedges' g. In addition, individual patient data from two clinical trials was examined in terms of both the distribution of total symptom change, and the variability of individual symptoms and symptom factors. In total, 11,006 articles were identified. Sixty six met inclusion criteria, reporting on 17,202 patients. Compared with placebo, antipsychotic-treated patients demonstrated greater total symptom improvement (g = 0.47, p < 0.001) and reduced variability in symptomatic improvement for total (CVR = 0.86, p < 0.001), positive (CVR = 0.89, p < 0.001), and negative symptoms (CVR = 0.86, p = 0.001). Lower variability in antipsychotic-response relative to placebo was associated with studies published earlier (z = 3.98, p < 0.001), younger patients (z = 3.07, p = 0.002), higher dose treatments (z = -2.62, p = 0.009), and greater mean-difference in symptom-change (z = -5.70, p < 0.001). In the individual patient dataset (N = 522 patients), antipsychotic treated patients did not show significantly increased variability for any individual symptom, and there was no evidence of a bimodal distribution of response. Compared to placebo, antipsychotic treatment shows greater improvement and lower variability of change in total, positive and negative symptoms. This is contrary to the hypothesis that there is a subtype of antipsychotic non-responsive schizophrenia. Instead our findings, provide evidence for a relatively homogeneous effect of antipsychotic treatment in improving symptoms of schizophrenia.
抗精神病药物治疗精神分裂症的反应似乎存在差异，因此有人提出，存在不同的精神分裂症亚型，其定义是基于治疗反应。这尚未通过荟萃分析进行正式检验。本研究在 PubMed、EMBASE 和 PsycINFO 中检索了自成立至 2018 年 11 月 30 日发表的比较精神分裂症急性治疗中安慰剂和抗精神病药物的随机对照试验。使用变异系数比（CVR）来量化抗精神病药物治疗个体相对于安慰剂治疗个体的症状改善的相对变异性。使用 Hedges' g 量化症状变化的均值差异。此外，还根据总症状变化的分布以及个体症状和症状因素的变异性，检查了两项临床试验的个体患者数据。总共确定了 11006 篇文章。66 篇符合纳入标准，共纳入 17202 例患者。与安慰剂相比，抗精神病药物治疗的患者表现出更大的总症状改善（g=0.47，p<0.001），并且在总症状改善方面的变异性降低（CVR=0.86，p<0.001），阳性（CVR=0.89，p<0.001）和阴性症状（CVR=0.86，p=0.001）。与安慰剂相比，抗精神病药物反应的变异性较低与研究发表较早（z=3.98，p<0.001）、患者较年轻（z=3.07，p=0.002）、较高剂量治疗（z=-2.62，p=0.009）和症状变化的平均差异较大（z=-5.70，p<0.001）有关。在个体患者数据集（N=522 例患者）中，抗精神病药物治疗患者的任何单个症状的变异性均未显著增加，并且没有证据表明存在反应的双峰分布。与安慰剂相比，抗精神病药物治疗可显著改善阳性和阴性症状，且改善的变异性较低。这与抗精神病药物治疗的非反应性精神分裂症亚类的假设相反。相反，我们的发现为抗精神病药物治疗改善精神分裂症症状的相对均匀效应提供了证据。
