University of Alberta, Edmonton, Alberta, Canada.
Ann Intern Med. 2012 Oct 2;157(7):498-511. doi: 10.7326/0003-4819-157-7-201210020-00525.
Debate continues about the comparative benefits and harms of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) in treating schizophrenia.
To compare the effects of FGAs with those of SGAs in the treatment of adults aged 18 to 64 years with schizophrenia and related psychosis on illness symptoms, diabetes mellitus, mortality,tardive dyskinesia, and a major metabolic syndrome.
English-language studies from 10 electronic databases to March 2012, reference lists of relevant articles, and gray literature.
Randomized trials for efficacy and cohort studies at least 2 years in duration for adverse events.
Two independent reviewers extracted data from 114 studies involving 22 comparisons and graded the strength of evidence for primary outcomes as insufficient, low, moderate, or high using the Grading of Recommendations Assessment, Development and Evaluation approach.
Few differences of clinical importance were found for core illness symptoms; lack of precision in effect estimates precluded firm conclusions for many comparisons. Moderate-strength evidence showed a clinically important benefit of haloperidol over olanzapine for improving positive symptoms, but the benefit was scale-dependent: It was seen when the Scale for the Assessment of Positive Symptoms was used but not when the Positive and Negative Syndrome Scale (PANSS) was used. Moderate-strength evidence showed a clinically important benefit of olanzapine over haloperidol in improving negative symptoms when the PANSS and the Scale for the Assessment of Negative Symptoms were used. Low-strength evidence showed no difference in mortality for chlorpromazine verus clozapine or haloperidol versus aripiprazole,increased incidence of the metabolic syndrome for olanzapine versus haloperidol (risk differences, 2% and 22%), and higher incidence of tardive dyskinesia for chlorpromazine versus clozapine (risk differences, 5% and 9%). Evidence was insufficient to draw conclusions for diabetes mellitus.
All studies had high or unclear risk of bias. Length of study follow-up was often too brief to adequately measure adverse events. Medication comparisons, dosage, and outcome measurement were heterogenous for head-to-head comparisons. Selective patient populations limit generalizability.
Clear benefits of FGAs versus SGAs for treating schizophrenia remain inconclusive because of variation in assessing outcomes and lack of clinically important differences for most comparisons. The strength of evidence on safety for major medical events is low or insufficient.
Agency for Healthcare Research and Quality.
关于第一代抗精神病药（FGAs）和第二代抗精神病药（SGAs）在治疗精神分裂症方面的相对益处和危害，仍存在争议。
比较 FGAs 和 SGAs 在治疗 18 至 64 岁成人精神分裂症和相关精神病患者时对疾病症状、糖尿病、死亡率、迟发性运动障碍和主要代谢综合征的影响。
2012 年 3 月前 10 个电子数据库的英文研究、相关文章的参考文献列表和灰色文献。
针对疗效的随机试验和至少 2 年的不良事件队列研究。
两名独立评审员从 114 项研究中提取数据，这些研究涉及 22 项比较，并使用推荐评估、制定和评估方法（Grading of Recommendations Assessment, Development and Evaluation approach）对主要结局的证据强度进行评估，分为不足、低、中、高。
对于核心疾病症状，几乎没有发现具有临床重要意义的差异；由于效果估计的不准确性，许多比较都无法得出明确的结论。中度强度证据表明氟哌啶醇在改善阳性症状方面优于奥氮平，但这种益处取决于量表：当使用阳性和阴性症状量表（Positive and Negative Syndrome Scale，PANSS）时没有看到益处，而当使用阳性症状量表（Scale for the Assessment of Positive Symptoms）时则可以看到。中度强度证据表明，在使用 PANSS 和阴性症状量表时，奥氮平在改善阴性症状方面优于氟哌啶醇。低强度证据表明氯丙嗪与氯氮平或氟哌啶醇与阿立哌唑的死亡率没有差异，奥氮平与氟哌啶醇相比，代谢综合征的发生率增加（风险差异为 2%和 22%），氯丙嗪与氯氮平相比，迟发性运动障碍的发生率更高（风险差异为 5%和 9%）。对于糖尿病，证据不足，无法得出结论。
所有研究都存在高或不确定的偏倚风险。研究随访时间往往太短，无法充分测量不良事件。头对头比较的药物比较、剂量和结局测量存在异质性。选择性患者人群限制了其普遍性。
由于评估结果的差异以及大多数比较中缺乏具有临床重要意义的差异，FGAs 与 SGAs 治疗精神分裂症的明确益处仍不明确。主要医疗事件安全性的证据质量低或不足。
医疗保健研究与质量署。
