The Effects of Newer Antidepressants on Occupational Impairment in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

CNS Drugs. 2016 May;30(5):405-17. doi: 10.1007/s40263-016-0334-7.


Background and objectives: A substantial proportion of the disease burden of major depressive disorder (MDD) results from impairments in occupational functioning, including disability and reduced productivity. Accumulating evidence suggests that antidepressants can improve functional as well as symptomatic outcomes in patients with MDD. We examined the treatment effects of newer antidepressants on occupational impairment in MDD, based on a systematic review and meta-analysis of randomized controlled trials (RCTs).

Methods: We searched MEDLINE, EMBASE, and for the period 1 January 1992 to 15 June 2015 to identify RCTs of newer antidepressants (excluding tricyclic antidepressants and monoamine oxidase inhibitors), with or without a placebo condition, that included a validated measure of occupational functioning in patients with MDD. Abstracts were scanned for eligibility by two independent reviewers and investigators of unpublished studies were contacted to obtain data. Study data were extracted and double-entered for accuracy. We selected the Sheehan Disability Scale Work/School subscale (SDS-Work) for the meta-analysis because it was the most consistently used assessment of occupational impairment. Analysis employed a random-effects model.

Results: The systematic review initially identified 42 RCTs but only 28 (67 %) had data on occupational outcomes that were published or obtained from investigators. The SDS-Work subscale was used in 25 of 28 trials; five other assessments of occupational functioning were used in seven trials. Data were synthesized from 17 placebo-controlled studies (n = 7031) that used the SDS-Work subscale. Antidepressants (n = 4722) were significantly superior to placebo (n = 2309) in improving SDS-Work scores at 8 weeks, with a mean difference of 0.73 [95 % confidence interval (CI) 0.60-0.86] and a standardized mean difference of 0.28 (95 % CI 0.23-0.33), representing small effects.

Limitations: Few included trials reported on the employment status of their samples, and most trials were of short-term treatment duration (8-12 weeks). Several RCTs that collected data on occupational outcomes were also excluded from the review and meta-analysis because their data were unpublished and unobtainable.

Conclusions: Our meta-analysis suggests that newer antidepressants have a small, positive impact on occupational impairment in the short-term, but the clinical significance of this impact is questionable. To improve assessment of this important outcome, future research studies should use more comprehensive measures of occupational functioning, productivity and impairment, and longer treatment durations.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antidepressive Agents / therapeutic use*
  • Depressive Disorder, Major / drug therapy*
  • Humans
  • Outcome Assessment, Health Care*
  • Randomized Controlled Trials as Topic*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Treatment Outcome


  • Antidepressive Agents
  • Serotonin Uptake Inhibitors