From the Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
Division of Psychiatry, Imperial College, London, United Kingdom.
J Clin Psychopharmacol. 2023;43(6):498-506. doi: 10.1097/JCP.0000000000001768.
PURPOSE/BACKGROUND: Quetiapine is a first-line augmenting agent for treatment-resistant depression (TRD) and is used off-label in insomnia. Quetiapine and its active metabolite norquetiapine act mostly on 5-HT2A, 5-HT2C, H1, and D2 as antagonists and on 5-HT1A as partial agonists. Patients with TRD often have comorbid personality disorder (PD), and evidence suggests an association between sleep disturbance and recovery among patients with PD. Here, we aimed to evaluate the effects of quetiapine on sleep in TRD patients with and without PD (PD+/PD-).
METHODS/PROCEDURES: We reviewed health records of 38 patients with TRD (20 TRD/PD+) who had been treated with a pharmacotherapy regimen including quetiapine. Clinical outcomes were determined by comparing changes in sleep items of the Hamilton Depression Rating Scale at the beginning (T0) and after 3 months of an unchanged treatment (T3).
FINDINGS/RESULTS: Patients with TRD/PD+ and TRD/PD- taking quetiapine showed significant improvement in sleep items from T0 to T3 (P < 0.001, ηp2 ≥ 0.19). There was a significant personality × time interaction for sleep-maintenance insomnia (P = 0.006, ηp2 = 0.23), with TRD/PD+ showing a greater improvement at T3 compared with TRD/PD- (P = 0.01). While exploring other sleep items, no personality × time interaction was found. In the TRD/PD- group, improvement in sleep items was associated with an overall improvement in depressive symptoms (r = 0.55, P = 0.02).
IMPLICATIONS/CONCLUSIONS: Quetiapine induced greater improvements in sleep-maintenance insomnia among TRD/PD+ patients than TRD/PD-. These findings suggest quetiapine could have a therapeutic role for insomnia in PD underscoring a distinct underlying neurobiological mechanism of sleep disturbance in people living with PD.
目的/背景:喹硫平是治疗抵抗性抑郁症(TRD)的一线增效药物,也被用于治疗失眠的适应证外。喹硫平和其活性代谢物去甲喹硫平主要作为拮抗剂作用于 5-HT2A、5-HT2C、H1 和 D2,作为部分激动剂作用于 5-HT1A。TRD 患者常伴有共病人格障碍(PD),有证据表明睡眠障碍与 PD 患者的康复之间存在关联。在这里,我们旨在评估喹硫平对伴或不伴 PD(PD+/PD-)的 TRD 患者睡眠的影响。
方法/程序:我们回顾了 38 名接受包括喹硫平在内的药物治疗方案治疗的 TRD 患者(20 名 TRD/PD+)的健康记录。通过比较汉密尔顿抑郁评定量表(HAMD)中睡眠项目在治疗开始(T0)和 3 个月未改变治疗(T3)时的变化,来确定临床结果。
结果/发现:服用喹硫平的 TRD/PD+和 TRD/PD-患者的睡眠项目从 T0 到 T3 均有显著改善(P<0.001,ηp2≥0.19)。对于维持性失眠,人格与时间存在显著的交互作用(P=0.006,ηp2=0.23),与 TRD/PD-相比,TRD/PD+在 T3 时的改善更为显著(P=0.01)。在探索其他睡眠项目时,未发现人格与时间的交互作用。在 TRD/PD-组中,睡眠项目的改善与抑郁症状的总体改善相关(r=0.55,P=0.02)。
意义/结论:喹硫平在 TRD/PD+患者中引起的维持性失眠改善大于 TRD/PD-患者。这些发现表明,喹硫平可能对 PD 患者的失眠有治疗作用,突出了 PD 患者睡眠障碍的一个独特潜在神经生物学机制。