Do sleep changes mediate the anti‐depressive and anti‐suicidal response of intravenous ketamine in treatment‐resistant depression?
Nelson B Rodrigues, Roger S McIntyre, Orly Lipsitz, Danielle S. Cha, Bing Cao, Yena Lee, Hartej Gill, Leanna M.W. Lui, Wiesław Jerzy Cubała, Roger Ho, Margarita Shekotikhina, Kayla M Teopiz, Mehala Subramaniapillai, Kevin Kratiuk, Rodrigo B. Mansur, Joshua D. Rosenblat
Journal of Sleep Research June 16, 2021 DOI: 10.1111/jsr.13400 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 323 |
| Population | Adults with treatment-resistant depression |
| Intervention | Intravenous ketamine |
| Duration | Four infusions |
| Topics | Anxiety Depression Ketamine Esketamine |
| Keywords | Insomnia Depression economics Suicidal ideation Morning Antidepressant Sleep system call Major depressive episode Confidence interval Sleep onset Anesthesia Poison control Injury prevention Mood |
| Citations | 28 |
| Key findings | Improvements in sleep symptoms partially mediated the antidepressant and anti-suicidal effects of IV ketamine in patients with TRD. |
Abstract
Summary 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‐SR 16 ) 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‐SR 16 . 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.
Comparable studies
Other observational and cohort studies on ketamine for anxiety, most cited first.
Citations in the library
Cited by 14
- Effect of Ketamine on Sleep in Treatment-Resistant Depression: A Systematic Review Pharmaceuticals April 1, 2023
- Functional changes in sleep-related arousal after ketamine administration in individuals with treatment-resistant depression. Translational Psychiatry June 4, 2024
- Hypersomnia as a predictor of response to intravenous ketamine/intranasal esketamine in treatment resistant depression. Journal of Affective Disorders 2024
- Patient-reported outcomes on sleep quality and circadian rhythm during treatment with intravenous ketamine for treatment-resistant depression. Therapeutic Advances in Psychopharmacology 2024
- Effects of stress on endophenotypes of suicide across species: A role for ketamine in risk mitigation Neurobiology of Stress April 20, 2022
and 9 more in the library
Cites 6
- Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study Biological Psychiatry November 4, 2015
- The use of ketamine as an antidepressant: a systematic review and meta‐analysis Human Psychopharmacology: Clinical and Experimental April 7, 2015
- Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder The International Journal of Neuropsychopharmacology June 7, 2012
- The effect of intravenous, intranasal, and oral ketamine in mood disorders: A meta-analysis. Journal of Affective Disorders November 1, 2020
- Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder International Journal of Environmental Research and Public Health April 17, 2018
and 1 more in the library