Department of Psychiatry, Sheba Medical Center, Tel Hashomer, Israel.
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Schizophr Bull. 2021 Jul 8;47(4):1077-1087. doi: 10.1093/schbul/sbaa198.
Two previous randomized controlled trials (RCTs) suggested that adjunctive aspirin is efficacious in treating schizophrenia. We conducted two 16-week double-blind randomized placebo-controlled RCTs of adjunctive 1000 mg aspirin vs placebo in schizophrenia. Study 1 included 200 patients, with Positive and Negative Syndrome Scale (PANSS) total score as the primary outcome. Study 2 included 160 patients with C-reactive protein (CRP) >1 mg/L at baseline; the primary outcome was PANSS-positive score. Dropout rates for aspirin/placebo were 12% in study 1 and 20% in study 2. Differences in outcome between aspirin and placebo were calculated with linear regression, adjusting for the baseline value of the outcome. No statistically significant between-group differences were found in primary or secondary outcomes in either study. Study 1: mean difference in PANSS at 16 weeks was -3.9 (95% CI: -8.4 to 0.5, P = .10, effect size (ES) = -0.25) and at 8 weeks was -3.5 (95% CI: -7.5 to 0.5, P = .11, ES = -0.22). Study 2: mean difference in PANSS at 16 weeks was 0.3 (95% CI: -4.1 to 4.7, P = .90, ES = 0.02) and in positive PANSS was 0.5 (95% CI: -1.0 to 2.1, P = .50, ES = 0.11). A meta-analysis of these data with the existing studies, excluding one with large baseline differences in total PANSS, found that the overall estimate of the effect of adjunctive aspirin on the PANSS total score comparing group means at the end of the study was -2.9 (95% CI: -6.6 to 0.7; P = .21), favoring aspirin. Our studies and meta-analysis failed to find a statistically significant improvement in the symptoms of schizophrenia from adjunctive aspirin therapy in comparison to placebo in schizophrenia. Trial registration: study 1: Clinicaltrials.gov: NCT01320982; study 2 (high CRP): EudraCT Number: 2014-000757-36.
两项先前的随机对照试验（RCT）表明，阿司匹林辅助治疗精神分裂症是有效的。我们进行了两项为期 16 周的双盲随机安慰剂对照 RCT，以评估阿司匹林 1000mg 辅助治疗与安慰剂在精神分裂症中的疗效。研究 1 纳入了 200 例患者，以阳性和阴性综合征量表（PANSS）总分作为主要结局。研究 2 纳入了基线时 C 反应蛋白（CRP）>1mg/L 的 160 例患者，主要结局为 PANSS 阳性评分。阿司匹林/安慰剂组的脱落率分别为研究 1 的 12%和研究 2 的 20%。使用线性回归计算阿司匹林与安慰剂之间在主要和次要结局方面的差异，同时调整结局的基线值。在这两项研究中，均未发现主要或次要结局存在组间统计学显著差异。研究 1：16 周时，PANSS 的平均差值为-3.9（95%CI：-8.4 至 0.5，P=0.10，ES=-0.25），8 周时为-3.5（95%CI：-7.5 至 0.5，P=0.11，ES=-0.22）。研究 2：16 周时，PANSS 的平均差值为 0.3（95%CI：-4.1 至 4.7，P=0.90，ES=0.02），阳性 PANSS 的平均差值为 0.5（95%CI：-1.0 至 2.1，P=0.50，ES=0.11）。对这些数据进行的荟萃分析与已有的研究进行了合并，排除了一项 PANSS 总分基线差异较大的研究，结果发现，与安慰剂相比，辅助阿司匹林治疗对研究结束时 PANSS 总分的总体效应估计值为-2.9（95%CI：-6.6 至 0.7；P=0.21），有利于阿司匹林。我们的研究和荟萃分析均未能发现与安慰剂相比，辅助阿司匹林治疗在改善精神分裂症症状方面具有统计学意义的改善。试验注册：研究 1：Clinicaltrials.gov：NCT01320982；研究 2（高 CRP）：EudraCT 编号：2014-000757-36。
