Sleep disturbances are commonly reported in patients with
treatment-resistant depression (TRD). Available data have shown that intravenous (IV)
ketamine is an effective treatment for patients with TRD and growing data suggest
ketamine may improve overall sleep architecture. In the present study, we evaluated whether changes in sleep symptoms mediated the anti-depressive and/or anti-suicidal effects of IV
ketamine and whether improvement in sleep correlated with a higher likelihood of achieving response or remission. Adults with TRD received four infusions of IV
ketamine at a community-based clinic. Total depressive symptom severity was measured with the Quick Inventory Depressive Symptoms Self-Report 16-Item (QIDS-SR16 ) at baseline and was repeated across four infusions. Suicidal ideation (SI) and four sleep symptoms were measured using the SI item and the five sleep items on the QIDS-SR16 . A total of 323 patients with TRD received IV
ketamine. Self-reported improvements in
insomnia, night-time
restlessness,
hypersomnia, early morning waking, and total sleep were significant partial mediators to the improvements observed in depression severity. Similarly,
insomnia, night-time
restlessness, early morning waking and total sleep improvements mediated the reduction of IV
ketamine on SI. All sleep items, except for
hypersomnia, were associated with an increased likelihood of achieving response or remission. Notably, each point improvement in total sleep score was significantly associated with achieving responder/remitter status (odds ratio 3.29, 95% confidence interval 2.00-5.41).
Insomnia, sleep
restlessness, early morning waking and total sleep improvements were significant mediators of
antidepressant and anti-suicidal improvements in patients with TRD receiving IV
ketamine.