ImportanceCognitive deficits are a substantial part of the symptoms of schizophrenia spectrum disorders (SSDs) and contribute heavily to the burden of disease. Antipsychotic drugs are not cognitive enhancers, but due to their different receptor-binding profiles, they could differ in their effects on cognition. No previous network meta-analysis compared antipsychotics to placebo, which is important to determine whether use of these drugs is associated with cognitive performance in SSDs at all.ObjectiveTo determine the association of treatment with various antipsychotics and cognition in patients with SSDs.Data SourcesCochrane Schizophrenia Trials Register through June 25, 2023.Study SelectionRandomized clinical trials examining the effects on cognition of antipsychotic drugs or placebo in participants with SSD.Data Extraction and SynthesisA systematic review and random-effects frequentist network meta-analysis was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses–Network Meta-analysis reporting guideline.Main Outcomes and MeasuresThe primary outcome was change in overall cognition score calculated for each study. Secondary outcomes included cognitive domains, quality of life, and functioning.ResultsThis study included 68 studies involving 9525 participants (mean [SD] age, 35.1 [8.9] years; 5878 male [70%] and 2890 [30%] female; some studies did not provide this information). There were few clear differences between antipsychotics, but first-generation dopamine antagonists haloperidol (standardized mean difference [SMD], 0.04; 95% CI, −0.25 to 0.33) and fluphenazine (SMD, 0.15; 95% CI, −0.39 to 0.69) as well as clozapine (SMD, 0.12; 95% CI, −0.23 to 0.48) ranked low. No individual antipsychotic was associated with a clearly better outcome than placebo, but antipsychotics as a group were, with small effect sizes (mean SMDs: adrenergic/low dopamine, 0.21; serotonergic/dopaminergic, 0.26; muscarinic, 0.28; dopaminergic, 0.40).Conclusion and RelevanceAlthough data are relatively sparse, those reviewed in this study suggest that first-generation dopamine antagonists and clozapine should be avoided when cognitive deficits are a concern. Antipsychotics are not procognitive drugs. The overall small superior outcomes compared to placebo may be explained by less disordered thought patterns associated with fewer positive symptoms rather than cognitive deficits in the proper sense. The findings also suggest that harmonizing measurement of cognitive function in randomized clinical trials would be beneficial.

中文翻译：

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抗精神病药物和认知功能


重要性认知缺陷是精神分裂症谱系障碍 （SSD） 症状的重要组成部分，并严重增加了疾病负担。抗精神病药物不是认知增强剂，但由于它们的受体结合特征不同，它们对认知的影响可能不同。以前的网络荟萃分析没有将抗精神病药物与安慰剂进行比较，这对于确定使用这些药物是否与 SSD 的认知能力相关很重要。目的确定 SSD 患者与各种抗精神病药物和认知的相关性.数据源Cochrane 精神分裂症试验注册库至 2023 年 6 月 25 日.研究选择随机临床试验检查抗精神病药物或安慰剂对 SSD 参与者认知的影响。资料提取和综合按照系统评价和荟萃分析的首选报告项目-网络荟萃分析报告指南进行系统评价和随机效应频率主义网络荟萃分析。主要结局和测量主要结局是为每项研究计算的总体认知评分的变化。次要结局包括认知领域、生活质量和功能。结果本研究包括 68 项研究，涉及 9525 名参与者 （平均 [SD] 年龄，35.1 [8.9] 岁;5878 名男性 [70%] 和 2890 名 [30%] 女性;一些研究没有提供此信息）。抗精神病药之间几乎没有明显差异，但第一代多巴胺拮抗剂氟哌啶醇 （标准化均数差 [SMD]，0.04;95% CI，-0.25 至 0.33）和氟奋奋静 （SMD，0.15;95% CI，-0.39 至 0.69）以及氯氮平 （SMD，0.12;95% CI，-0.23 至 0.48） 排名较低。 没有单独的抗精神病药与明显优于安慰剂的结局相关，但抗精神病药作为一个组是相关的，效应量较小（平均 SMD：肾上腺素能/低多巴胺，0.21;血清素能/多巴胺能，0.26;毒蕈碱，0.28;多巴胺能，0.40）。结论和相关性尽管数据相对稀少，但本研究中回顾的数据表明，当担心认知缺陷时，应避免使用第一代多巴胺拮抗剂和氯氮平。抗精神病药不是促认知药物。与安慰剂相比，总体上较小的优越结局可能是由于与较少的阳性症状相关的较少的无序思维模式，而不是正确意义上的认知缺陷。研究结果还表明，在随机临床试验中协调认知功能的测量将是有益的。