Initial Severity of Schizophrenia and Efficacy of Antipsychotics Participant-Level Meta-analysis of 6 Placebo-Controlled Studies
Initial Severity of Schizophrenia and Efficacy of Antipsychotics Participant-Level Meta-analysis of 6 Placebo-Controlled Studies
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DOI：
10.1001/jamapsychiatry.2014.2127
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发表时间：
2015-01-01
期刊：
影响因子：
25.8
通讯作者：
Leucht, Stefan
中科院分区：
文献类型：
--
作者：
Furukawa, Toshi A.;Levine, Stephen Z.;Leucht, Stefan
重要的抗精神病药物是精神分裂症治疗的中流砥柱，其疗效在数百个随机临床试验中得到了很好的证实。目的考察精神分裂症基线严重程度对抗精神病药物疗效的影响。设计、设置和参与者对3个关键的急性精神分裂症随机试验(n=611)和3个以精神分裂症的阴性症状为主的关键试验(n=475)的参与者水平数据进行荟萃分析。得分范围为30-210)和阴性症状评定量表(SANS；得分范围为0-125)，直至基线后6周。用8个相互竞争的混合效应模型对药物组和安慰剂组的基线和变化分数之间的关系进行重复测量。结果最佳拟合模型显示，对于两种类型的患者，基线症状严重程度和治疗之间的交互作用具有统计学意义(P<；.01)。基线严重程度越大，积极治疗和安慰剂之间的差异越大。在急性治疗中，轻度患者PANSS改变评分的平均差值为9.5分(基线PANSS评分为58分)，中度患者为13.7分(基线PANSS评分为75分)，重度患者为18.8分(基线PANSS评分为95分)，重症患者为24.0分(基线PANSS评分为116分)。在治疗以阴性症状为主的患者中，中度患者的SANS变化评分的平均差异为1.7(基线SANS评分为55)，重度患者的SANS变化评分的平均差异为5.7(基线SANS评分为70)，重症患者的SANS变化评分的平均差异为9.7(基线SANS评分为85)。结论和相关性我们可以期待抗精神病药物对所有可能接受急性精神分裂症治疗的患者以及具有主要阴性症状的高度症状患者的益处。在光谱的最温和的一端，临床医生需要意识到，患者在症状改善方面受益较少，但可能会经历抗精神病药物的全部不良影响。临床医生还需要意识到，除了治疗活动症状，这是本研究的重点，抗精神病药物还有另一个重要作用，即防止缓解期患者的复发。
IMPORTANCE Antipsychotic drugs constitute the mainstay in the treatment of schizophrenia, and their efficacy is well established in hundreds of randomized clinical trials. However, it is not known whether they are effective or how effective they are across the wide range of baseline symptom severity.OBJECTIVE To examine the influence of baseline severity of schizophrenia on the efficacy of antipsychotic drugs.DESIGN, SETTING, AND PARTICIPANTS Meta-analysis of participant-level data from 3 pivotal randomized trials of acute schizophrenia (n = 611) and 3 pivotal trials in patients with predominantly negative symptoms of schizophrenia (n = 475).INTERVENTIONS Olanzapine or risperidone vs placebo, and amisulpride vs placebo.MAIN OUTCOMES AND MEASURES Change scores on the Positive and Negative Syndrome Scale (PANSS; score range, 30-210) and the Scale for the Assessment of Negative Symptoms (SANS; score range, 0-125) up to 6 weeks after baseline. The relationship between baseline and change scores for the drug and placebo groups was examined with 8 competing mixed-effects models for repeated measures.RESULTS The best-fitting models showed that, for both types of patients, the interactions between baseline symptom severity and treatment were statistically significant (P < .01). The greater the baseline severity was, the greater the magnitude of the differences was between active treatment and placebo. In acute treatment, the mean differences in PANSS change scores were 9.5 points for patients who were mildly ill at baseline (baseline PANSS score of 58), 13.7 for moderately ill patients (baseline PANSS score of 75), 18.8 for markedly ill patients (baseline PANSS score of 95), and 24.0 for severely ill patients (baseline PANSS score of 116). In treatment of predominantly negative symptoms, the mean differences in SANS change scores were 1.7 for those who were moderately ill (baseline SANS score of 55), 5.7 for markedly ill patients (baseline SANS score of 70), and 9.7 for severely ill patients (baseline SANS score of 85).CONCLUSIONS AND RELEVANCE We can expect benefits of antipsychotic drugs for the full spectrum of patients likely to be treated for acute schizophrenia and for highly symptomatic patients with predominantly negative symptoms. Toward the mildest end of the spectrum, clinicians need to be aware that patients benefit less in terms of symptom improvement but may experience full adverse effects of antipsychotics. Clinicians also need to be aware that in addition to the treatment of active symptoms, which was the focus of this study, antipsychotics have another important action, namely to prevent relapses among patients in remission.