Review of how ketamine affects sleep and body-clock rhythms in depression and bipolar disorder

The question

Does ketamine change sleep and circadian (body clock) patterns in people with major depression or bipolar disorder, and do those changes help predict who responds to treatment?

What they did

Researchers searched four large research databases (PubMed, Embase, PsychInfo and Web of Science) for studies measuring sleep or circadian rhythms in people treated with ketamine or its related forms, esketamine and arketamine. The search returned 830 records. After screening, 26 studies including a total of 1,694 patients with major depressive disorder or bipolar disorder met the inclusion criteria and were summarized.

What they found

Across the included studies, ketamine treatment was associated with better self-reported sleep quality. There was preliminary evidence that sleep problems before treatment, and early improvements in sleep after treatment, may predict who responds to ketamine’s antidepressant effects. Some studies also reported beneficial effects on objectively measured sleep and circadian rhythms, but the authors urge caution because only a small number of such studies have been published.

The fine print

This is a narrative synthesis of 26 studies rather than a pooled statistical analysis, and the abstract reports no effect sizes, doses or follow-up lengths. The included studies varied in design and quality, and much of the sleep data was self-reported rather than measured objectively. Evidence on objective circadian measures came from very few studies. This summary is based on the abstract only.

What it means

Sleep may be an important piece of how ketamine affects mood, and early sleep changes could turn out to be a useful signal of who will respond, but the evidence so far is preliminary and mostly based on self-reported sleep.

Evidence grade: Low. A systematic review that pools studies of mixed design without a meta-analysis, and the authors describe much of the evidence as preliminary and limited in number.

This summary is based on the study’s published abstract.