Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 2A1, Canada.
Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
CNS Drugs. 2021 Mar;35(3):291-304. doi: 10.1007/s40263-021-00793-1. Epub 2021 Mar 8.
Cognitive deficits are detectable in major depressive disorder (MDD). The cognitive impact of antidepressants remains unclear, as does the cognitive effects of aripiprazole in MDD, a commonly used adjunct with putative pro-cognitive properties.
In this multi-centre, open-label study, cognitive changes associated with escitalopram monotherapy and adjunctive aripiprazole were examined.
Acutely depressed participants with MDD (n = 209) received 8 weeks of escitalopram. Non-responders received an additional 8 weeks of adjunctive aripiprazole (ESC-ARI, n = 88), while responders (ESC-CONT, n = 82) continued escitalopram monotherapy (n = 39 lost to attrition). ESC-ARI, ESC-CONT and matched healthy participants (n = 112) completed the Central Nervous System Vital Signs cognitive battery at baseline, 8 and 16 weeks. Linear mixed models compared participants with MDD cognitive trajectories with healthy participants.
Participants with MDD displayed poorer baseline global cognition (assessed via the Neurocognitive Index), composite memory and psychomotor speed vs healthy participants. There were no statistically significant changes in participants with MDD receiving escitalopram monotherapy from baseline to week 8 in the neurocognitive index, reaction time, complex attention, cognitive flexibility, memory or psychomotor speed. Overall symptom severity changes were not associated with cognitive changes. The ESC-CONT group displayed no significant cognitive changes from weeks 8 to 16; reaction time worsened in the ESC-ARI group (p = 0.008) from weeks 8 to 16, independent of symptom change.
Escitalopram monotherapy in acute MDD did not result in significant cognitive improvements. We provide novel evidence that escitalopram continuation in responders does not adversely affect cognition, but adjunctive aripiprazole in escitalopram non-responders worsens reaction time. Treatments targeting cognitive dysfunction are needed in MDD. CLINICALTRIALS.
NCT01655706; 2 August, 2012.
认知缺陷在重度抑郁症（MDD）中是可检测到的。抗抑郁药的认知影响仍不清楚，阿立哌唑在 MDD 中的认知效应也是如此，阿立哌唑是一种常用的辅助药物，具有潜在的认知益处。
在这项多中心、开放性研究中，我们研究了艾司西酞普兰单药治疗和阿立哌唑辅助治疗相关的认知变化。
患有 MDD 的急性抑郁患者（n=209）接受了 8 周的艾司西酞普兰治疗。无应答者接受了额外的 8 周阿立哌唑辅助治疗（ESC-ARI，n=88），而应答者（ESC-CONT，n=82）继续接受艾司西酞普兰单药治疗（n=39 人因失访而丢失）。ESC-ARI、ESC-CONT 和匹配的健康参与者（n=112）在基线、8 周和 16 周时完成了中枢神经系统生命体征认知测试。线性混合模型将 MDD 患者的认知轨迹与健康参与者进行了比较。
与健康参与者相比，MDD 患者的基线整体认知（通过神经认知指数评估）、复合记忆和精神运动速度较差。在接受艾司西酞普兰单药治疗的 MDD 患者中，从基线到第 8 周，神经认知指数、反应时间、复杂注意力、认知灵活性、记忆或精神运动速度均无统计学意义上的变化。总体症状严重程度的变化与认知变化无关。ESC-CONT 组在第 8 周至 16 周期间无明显认知变化；ESC-ARI 组的反应时间在第 8 周至 16 周期间恶化（p=0.008），这与症状变化无关。
急性 MDD 中单用艾司西酞普兰治疗并未显著改善认知。我们提供了新的证据表明，在应答者中继续使用艾司西酞普兰不会对认知产生不利影响，但在艾司西酞普兰无应答者中添加阿立哌唑会恶化反应时间。MDD 中需要针对认知功能障碍的治疗方法。
临床试验.gov 标识符：NCT01655706；2012 年 8 月 2 日。
