A systematic review of newer pharmacotherapies for depression in adults: evidence report summary

Ann Intern Med. 2000 May 2;132(9):743-56. doi: 10.7326/0003-4819-132-9-200005020-00011.


Background: Depressive disorders are persistent, recurring illnesses that cause great suffering for patients and their families.

Purpose: To evaluate the benefits and adverse effects of newer pharmacotherapies and herbal treatments for depressive disorders in adults and adolescents.

Data sources: English-language and non-English-language literature from 1980 to January 1998 was identified from a specialized registry of controlled trials, meta-analyses, and experts.

Study selection: Randomized trials evaluating newer antidepressants (such as serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and St. John's wort) that reported clinical outcomes were selected.

Data extraction: Two persons independently abstracted data that were then synthesized descriptively; some data were pooled by using a random-effects model.

Data synthesis: Of 315 eligible trials, most evaluated antidepressants in adults with major depression, were conducted among outpatients, and examined acute-phase treatment. Newer antidepressants were more effective than placebo for major depression (relative benefit, 1.6 [95% CI, 1.5 to 1.7]) and dysthymia (relative benefit, 1.7 [CI, 1.3 to 2.3]). They were effective among older adults and primary care patients. Efficacy did not differ among newer agents or between newer and older agents. Hypericum (St. John's wort) was more effective than placebo for mild to moderate depression (risk ratio, 1.9 [CI, 1.2 to 2.8]), but publication bias may have inflated the estimate of benefit. Newer and older antidepressants did not differ for overall discontinuation rates, but side effect profiles varied significantly. Data were insufficient for determining the efficacy of newer antidepressants for subsyndromal depression, depression with coexisting medical or psychiatric illness, or depression in adolescents.

Conclusions: Newer antidepressants are clearly effective in treating depressive disorders in diverse settings. Because of similar efficacy, both newer and older antidepressants should be considered when making treatment decisions. Better information is urgently needed on the efficacy of newer antidepressants in patients with nonmajor depression and in special populations, including adolescents.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Age Factors
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use*
  • Antidepressive Agents, Tricyclic / adverse effects
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Depressive Disorder / drug therapy*
  • Humans
  • Hypericum / therapeutic use
  • Lymphatic Diseases / drug therapy
  • Monoamine Oxidase Inhibitors / adverse effects
  • Monoamine Oxidase Inhibitors / therapeutic use
  • Patient Dropouts
  • Phytotherapy
  • Plants, Medicinal
  • Practice Guidelines as Topic
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Thymus Gland


  • Antidepressive Agents
  • Antidepressive Agents, Tricyclic
  • Monoamine Oxidase Inhibitors
  • Serotonin Uptake Inhibitors