Centre for Human Drug Research, Leiden, The Netherlands.
Leiden University Medical Center, Leiden, The Netherlands.
Transl Psychiatry. 2019 Sep 3;9(1):216. doi: 10.1038/s41398-019-0553-z.
Excessive arousal has a role in the pathophysiology of major depressive disorder (MDD). Seltorexant (JNJ-42847922/MIN-202) is a selective antagonist of the human orexin-2 receptor (OX2R) that may normalize excessive arousal and thereby attenuate depressive symptoms. In this study, the effects of night-time arousal suppression on depressive symptoms were investigated. 47 MDD patients with a total Inventory of Depressive Symptomatology (IDS) score of ≥30 at screening were included in a randomized, double-blind, diphenhydramine-, and placebo-controlled multicentre study. Symptoms of depression were rated using the 17-item Hamilton Depression Rating Scale (HDRS). Effects on sleep were evaluated by polysomnography and by the Leeds Sleep Evaluation Questionnaire (LSEQ). To investigate the safety and tolerability of seltorexant, vital signs, suicidal ideation and adverse events were monitored. At baseline the severity of depressive symptoms correlated with sleep efficiency (SE), wake after sleep onset (WASO), duration of stage 2 sleep, and ruminations. Ten days of treatment with seltorexant (and not diphenhydramine) resulted in a significant improvement of core depressive symptoms compared to placebo; the antidepressant efficacy of seltorexant was maintained with continued treatment up to 28 days. Compared to placebo, the antidepressant efficacy of seltorexant coincided with an overall increase in (left posterior) EEG power and a relative increase in delta- and decrease in theta-, alpha- and beta power during stage 2 sleep. Treatment with seltorexant was associated with mild, self-limiting adverse drug reactions. Seltorexant affected core symptoms of depression in the absence of overt changes in the hypnogram; in contrast, diphenhydramine was not efficacious.
过度觉醒在重度抑郁症（MDD）的病理生理学中起作用。Seltorexant（JNJ-42847922/MIN-202）是人类食欲素-2 受体（OX2R）的选择性拮抗剂，可能使过度觉醒正常化，从而减轻抑郁症状。在这项研究中，研究了夜间觉醒抑制对抑郁症状的影响。47 名 MDD 患者在筛选时的总抑郁症状量表（IDS）评分≥30 分，被纳入一项随机、双盲、苯海拉明和安慰剂对照的多中心研究。使用 17 项汉密尔顿抑郁评定量表（HDRS）评定抑郁症状。通过多导睡眠图和利兹睡眠评估问卷（LSEQ）评估睡眠效果。为了研究 seltorexant 的安全性和耐受性，监测了生命体征、自杀意念和不良事件。在基线时，抑郁症状的严重程度与睡眠效率（SE）、睡眠后觉醒（WASO）、第二阶段睡眠持续时间和反刍相关。与安慰剂相比，seltorexant 治疗 10 天可显著改善核心抑郁症状；与安慰剂相比，seltorexant 的抗抑郁疗效在继续治疗 28 天内得以维持。与安慰剂相比，seltorexant 的抗抑郁疗效与 EEG 功率（左后）的总体增加以及第二阶段睡眠时 delta 功率的相对增加和 theta、alpha 和 beta 功率的相对减少相一致。seltorexant 治疗与轻度、自限性的药物不良反应相关。Seltorexant 在没有明显改变催眠图的情况下影响核心抑郁症状；相反，苯海拉明无效。
