Preliminary evidence suggests that evening chronotype is related to poorer efficacy of selective serotonin reuptake inhibitors. It is unknown whether this is specific to particular medications, self-rated chronotype, or efficacy. In the Australian Genetics of Depression Study ( = 15,108; 75% women; 18–90 years; 68% with ≥1 other lifetime diagnosis), a survey recorded experiences with 10 antidepressants, and the reduced Morningness-Eveningness Questionnaire was used to estimate chronotype. A chronotype polygenic score was calculated. Age- and sex-adjusted regression models (Bonferroni-corrected) estimated associations among antidepressant variables (how well the antidepressant worked [efficacy], duration of symptom improvement, side effects, discontinuation due to side effects) and self-rated and genetic chronotypes. The chronotype polygenic score explained 4% of the variance in self-rated chronotype ( = 0.21). Higher self-rated eveningness was associated with poorer efficacy of escitalopram (odds ratio [OR] = 1.04; 95% CI, 1.02 to 1.06; = .000035), citalopram (OR = 1.03; 95% CI, 1.01 to 1.05; = .004), fluoxetine (OR = 1.03; 95% CI, 1.01 to 1.05; = .001), sertraline (OR = 1.02; 95% CI, 1.01 to 1.04; = .0008), and desvenlafaxine (OR = 1.03; 95% CI, 1.01 to 1.05; = .004), and a profile of increased side effects (80% of those recorded; ORs = 0.93–0.98), with difficulty getting to sleep the most common. Self-rated chronotype was unrelated to duration of improvement or discontinuation. The chronotype polygenic score was only associated with suicidal thoughts and attempted suicide (self-reported). While our measures are imperfect, and not of circadian phase under controlled conditions, the model coefficients suggest that dysregulation of the phenotypic chronotype relative to its genetic proxy drove relationships with antidepressant outcomes. The idea that variation in circadian factors influences response to antidepressants was supported and encourages exploration of circadian mechanisms of depressive disorders and antidepressant treatments.

中文翻译：

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患有抑郁症的晚间睡眠型报告选择性血清素再摄取抑制剂的效果较差：一项基于调查的自我评价研究

初步证据表明，夜间睡眠模式与选择性血清素再摄取抑制剂的较差疗效有关。目前尚不清楚这是否特定于特定药物、自评时间型或疗效。在澳大利亚抑郁症遗传学研究中（= 15,108；75% 女性；18-90 岁；68% 患有 ≥1 种其他终生诊断），一项调查记录了使用 10 种抗抑郁药的经验，并使用简化的早晚问卷来估计睡眠时间型。计算了时间型多基因评分。年龄和性别调整回归模型（Bonferroni 校正）估计了抗抑郁药变量（抗抑郁药的疗效[功效]、症状改善持续时间、副作用、因副作用而停药）与自评和遗传时间型之间的关联。时型多基因评分解释了自评时型中 4% 的方差 (= 0.21)。自评夜间性较高与艾司西酞普兰（优势比 [OR] = 1.04；95% CI，1.02 至 1.06；= .000035）、西酞普兰（OR = 1.03；95% CI，1.01 至 1.05；= .000035）疗效较差相关。 004)、氟西汀 (OR = 1.03; 95% CI, 1.01 至 1.05; = .001)、舍曲林 (OR = 1.02; 95% CI, 1.01 至 1.04; = .0008) 和去甲文拉法辛 (OR = 1.03; 95% CI，1.01 至 1.05；= .004），副作用增加（记录的 80%；OR = 0.93–0.98），其中最常见的是入睡困难。自评时间型与改善或停止的持续时间无关。时型多基因评分仅与自杀想法和自杀未遂（自我报告）相关。虽然我们的测量是不完善的，并且不是受控条件下的昼夜节律阶段，但模型系数表明表型计时型相对于其遗传代理的失调驱动了与抗抑郁药结果的关系。昼夜节律因素的变化影响抗抑郁药反应的观点得到了支持，并鼓励探索抑郁症和抗抑郁治疗的昼夜节律机制。