Efficacy of newer medications for treating depression in primary care patients

Am J Med. 2000 Jan;108(1):54-64. doi: 10.1016/s0002-9343(99)00316-2.


Purpose: Several medications have recently been introduced for the treatment of depression. We reviewed the literature to summarize their efficacy in the treatment of depression in adult patients in primary care settings.

Methods: We searched the literature published from 1980 to January 1998 using the Cochrane Collaboration Depression Anxiety and Neurosis Group's specialized registry of 8,451 clinical trials, references from trials and 46 pertinent meta-analyses, and consultation with experts. We included randomized controlled trials of at least 6 weeks' duration that measured clinical outcomes and compared one of 32 newer medications with another newer antidepressant, an older antidepressant, a placebo, or a psychosocial intervention for the treatment of depressed patients in primary care settings. The primary outcome was response rate, defined as the proportion of patients experiencing a 50% or greater improvement in depressive symptoms.

Results: There were 28 randomized controlled trials involving 5,940 adult primary care patients with major depression, depression requiring treatment, dysthymia, or mixed anxiety depression. Newer agents, including selective serotonin re-uptake inhibitors, serotonin norepinephrine inhibitors, reversible inhibitors of monoamine oxidase, and dopamine antagonists, were usually compared with tricyclic agents. Average response rates were 63% for newer agents, 35% for placebo, and 60% for tricyclic agents. Newer agents were significantly more effective than placebo [risk ratio = 1.6; 95% confidence interval (CI), 1.2 to 2.1), but similar to tricyclic agents (risk ratio = 1.0; 95% CI, 0.9 to 1.1). Response rates were similar in the different types of depressive disorders, except that two small trials in frail older patients showed no significant effects of newer agents compared with placebo. Dropout rates as a result of adverse effects were 8% with newer agents and 13% with tricyclic agents (P <0.05).

Conclusions: In primary care settings, newer antidepressants are more effective than placebo and have similar efficacy compared with tricyclic agents in the acute treatment of depression. Dropout rates as a result of adverse effects are lower with newer compared with tricyclic agents. Future studies should compare the effectiveness of different therapies among primary care patients with less severe depression and greater medical and psychiatric comorbidity.

Publication types

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

MeSH terms

  • Antidepressive Agents, Second-Generation / classification
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Depression / drug therapy*
  • Depressive Disorder / drug therapy*
  • Dopamine Antagonists / therapeutic use
  • Dopamine Uptake Inhibitors / therapeutic use
  • Evidence-Based Medicine
  • GABA Agents / therapeutic use
  • Humans
  • Hypericum / therapeutic use
  • Monoamine Oxidase Inhibitors / therapeutic use
  • Phytotherapy
  • Plants, Medicinal
  • Primary Health Care*
  • Publication Bias
  • Randomized Controlled Trials as Topic
  • Research Design
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Serotonin Receptor Agonists / therapeutic use
  • United States


  • Antidepressive Agents, Second-Generation
  • Dopamine Antagonists
  • Dopamine Uptake Inhibitors
  • GABA Agents
  • Monoamine Oxidase Inhibitors
  • Serotonin Receptor Agonists
  • Serotonin Uptake Inhibitors