Compared with SSRIs and benzodiazepines, trazodone adds deep sleep and spares REM
STUDY: Meng L et al, Front Psychiatry 2026
STUDY TYPE: Systematic review and meta-analysis
FUNDING: Weifang Youth Medical Talent Support Project (China)
Background
Most people with depression sleep poorly. SSRIs suppress REM sleep, and benzodiazepines trade deep sleep for lighter stage 2 sleep. Trazodone is an underutilized antidepressant that may improve sleep quality.
The Study
- 8 studies of 980 adults with depression and sleep problems: 5 randomized controlled trials and 3 single-arm studies.
- Trazodone doses ranged from 50 to 400 mg daily, for 1 night to 6 weeks.
- Sleep-lab data came from 5 small studies of 6 to 23 patients each. Depression and safety data came from larger placebo-controlled trials.
Results
Compared with baseline, trazodone:
- Added about 50 minutes of total sleep
- Shortened time to fall asleep by about 15 minutes
- Raised deep (slow-wave) sleep by 8 percentage points and lowered stage 2 sleep by 9 points
- Left REM sleep unchanged
In two small placebo-controlled trials, trazodone added 27 minutes of sleep and reduced nighttime waking by 20 minutes. The deep-sleep shift there fell short of significance.
Trazodone improved Depression scale (HAM-D) scores and raised response rates by 44% relative to placebo. Somnolence was about four times as common, dizziness three times, and dropouts for side effects nearly five times.
Most sleep data came from uncontrolled studies, several from the 1990s.
Practice Implications
- Don’t overlook trazodone for depression. Consider all-at-night dosing to prevent daytime fatigue, although there is a small risk with this strategy.
- When using for depression, outcomes are improved by raising the dose slowly, titrating over four weeks, to prevent spikes in the dysphoria-producing mcpp metabolite. Learn how to use it in our Carlat review.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
