Insomnia and Somnolence Associated With Second-Generation Antidepressants During the Treatment of Major Depression: A Meta-Analysis

J Clin Psychopharmacol. 2015 Jun;35(3):296-303. doi: 10.1097/JCP.0000000000000329.


Background: Sleep reduction or enhancement is frequently observed with second-generation antidepressant treatments, and they can be beneficial or harmful depending on the symptom profile of each subject. Nevertheless, relatively little attention has been given so far to rank those effects across compounds. The aim of this meta-analysis is to provide quantitative data about short-term rates of insomnia and somnolence associated with 14 second-generation antidepressants during the treatment of major depression.

Methods: A literature search and a search of unpublished documents were performed. Eligible studies focusing on MD patients treated with second-generation antidepressants were entered in the analysis. Our primary outcome measures were insomnia and somnolence rates induced by antidepressants as compared with those associated with placebo. Sensitivity analyses were carried out as well.

Results: Ten second-generation antidepressants showed higher rates of insomnia than placebo. The highest incidence was found for bupropion and desvenlafaxine. Agomelatine was the only antidepressant with a lower likelihood of inducing insomnia than placebo. Eleven antidepressants were associated with higher rates of somnolence than placebo. Fluvoxamine and mirtazapine showed the highest frequency of somnolence. Bupropion induced somnolence to a lower extent than placebo. Sensitivity analyses showed a degree of variation of those findings.

Discussion: Antidepressants are associated with different insomnia and somnolence rates, mainly depending on their mechanisms of action. Despite some limitations, we underscore that the treatment-emergent insomnia and/or somnolence are frequent, and they could be used in clinical practice to face the specific needs of each patient.

Publication types

  • Meta-Analysis

MeSH terms

  • Antidepressive Agents, Second-Generation / adverse effects*
  • Antidepressive Agents, Second-Generation / therapeutic use
  • Depressive Disorder, Major / drug therapy*
  • Disorders of Excessive Somnolence / chemically induced*
  • Humans
  • Sleep / drug effects
  • Sleep Initiation and Maintenance Disorders / chemically induced*


  • Antidepressive Agents, Second-Generation