Division of Psychiatry, University College London, Faculty of Brain Sciences, London, UK.
Institute of Clinical Trials and Methodology, University College London, London, UK.
Psychol Med. 2022 Oct;52(13):2814-2821. doi: 10.1017/S0033291720004985. Epub 2021 Jan 12.
According to the cognitive neuropsychological model, antidepressants reduce symptoms of depression and anxiety by increasing positive relative to negative information processing. Most studies of whether antidepressants alter emotional processing use small samples of healthy individuals, which lead to low statistical power and selection bias and are difficult to generalise to clinical practice. We tested whether the selective serotonin reuptake inhibitor (SSRI) sertraline altered recall of positive and negative information in a large randomised controlled trial (RCT) of patients with depressive symptoms recruited from primary care.
The PANDA trial was a pragmatic multicentre double-blind RCT comparing sertraline with placebo. Memory for personality descriptors was tested at baseline and 2 and 6 weeks after randomisation using a computerised emotional categorisation task followed by a free recall. We measured the number of positive and negative words correctly recalled (hits). Poisson mixed models were used to analyse longitudinal associations between treatment allocation and hits.
A total of 576 participants (88% of those randomised) completed the recall task at 2 and 6 weeks. We found no evidence that positive or negative hits differed according to treatment allocation at 2 or 6 weeks (adjusted positive hits ratio = 0.97, 95% CI 0.90-1.05, = 0.52; adjusted negative hits ratio = 0.99, 95% CI 0.90-1.08, = 0.76).
In the largest individual placebo-controlled trial of an antidepressant not funded by the pharmaceutical industry, we found no evidence that sertraline altered positive or negative recall early in treatment. These findings challenge some assumptions of the cognitive neuropsychological model of antidepressant action.
根据认知神经心理学模型,抗抑郁药通过增加积极信息相对于消极信息的处理来减轻抑郁和焦虑症状。大多数关于抗抑郁药是否改变情绪处理的研究都使用了来自初级保健的健康个体的小样本,这导致了低统计效力和选择偏差,并且难以推广到临床实践。我们测试了选择性 5-羟色胺再摄取抑制剂(SSRI)舍曲林是否在一项针对抑郁症状患者的大型随机对照试验(RCT)中改变了积极和消极信息的回忆,该试验是从初级保健中招募的。
PANDA 试验是一项实用的多中心双盲 RCT,比较了舍曲林与安慰剂。使用计算机化情绪分类任务和自由回忆测试,在基线和随机分组后 2 周和 6 周测试人格描述符的记忆。我们测量了正确回忆的积极和消极单词数量(命中数)。使用泊松混合模型分析治疗分配与命中数之间的纵向关联。
共有 576 名参与者(88%随机分配)在 2 周和 6 周时完成了回忆任务。我们没有发现治疗分配在 2 周或 6 周时对积极或消极命中数有任何影响(调整后的积极命中比=0.97,95%CI 0.90-1.05, =0.52;调整后的消极命中比=0.99,95%CI 0.90-1.08, =0.76)。
在最大的一项由制药行业资助的抗抑郁药个体安慰剂对照试验中,我们没有发现舍曲林在早期治疗中改变积极或消极回忆的证据。这些发现挑战了抗抑郁药作用的认知神经心理学模型的一些假设。