Management of insomnia symptoms in depressed patients treated with agomelatine, mirtazapine and trazodone: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Insomnia is a common symptom in depressive disorder, affecting up to 80% of those patients. Evidences suggest that sleep symptom improvements could alleviating depressive symptoms and reducing relapse. This article evaluated the efficacy of three antidepressants-agomelatine, mirtazapine, and trazodone-in treating insomnia symptoms in depressed patients, with a focus on polysomnographic (PSG) data, subjective sleep experience, improvement in depressive symptoms, and adverse drug reactions.

METHODS

A systematic search of PubMed, Cochrane Library, MEDLINE, Embase, and Web of Science was conducted for studies published from 1974 to August 2025; 30 studies (16 randomized controlled trials and 14 non-randomized controlled trials) were included. The primary outcomes were PSG measures; secondary outcomes included PSQI and HAMD scores, as well as adverse medication reactions.

RESULTS

The PSG results showed that agomelatine may not significantly change percentage N1 of sleep period time (N1%) and Latency of REM sleep (L-REM). Mirtazapine significantly increased total sleep time (TST), slow-wave sleep of sleep period time (SWS%), and sleep efficiency (SE%), while reducing percentage wake after sleep onset of sleep period time (WASO%). Trazodone notably improved TST, and SE%. For adverse effects, agomelatine was well-tolerated; mirtazapine commonly caused weight gain and sedation; and trazodone frequently led to dizziness, sedation, headache, nausea, and somnolence.

CONCLUSION

All three medications significantly enhance subjective sleep perception and alleviate depressive symptoms. However, agomelatine may lack a definitive effect on improving objective sleep parameters in depressed patients. Future studies should involve larger, high-quality trials with unified methodologies to strengthen the reliability of conclusions.