Amitriptyline for inpatients and SSRIs for outpatients with depression? Systematic review and meta-regression analysis

Pharmacopsychiatry. 2004 May;37(3):93-7. doi: 10.1055/s-2004-818985.


Background: Although the selective serotonin reuptake inhibitors (SSRIs) are widely used as first-line agents in depression, amitriptyline, a reference tricyclic (TCA) agent, has the edge in terms of efficacy over control antidepressants (ADs), but it is not clear whether this advantage can be attributed to a more favourable profile in inpatients, but not in outpatients, with depression. The aim of this study was to investigate the contribution of study setting on outcome in clinical trials comparing amitriptyline with any other AD.

Methods: A systematic review and meta-regression analysis of amitryptiline randomised clinical trials was carried out. The electronic search yielded 181 randomised clinical trials, 47% enrolling inpatients and 53% outpatients with depression.

Results: Both on a dichotomous and continuous out-come, amitriptyline was more effective than control agents in in-patients [Peto odds ratio (OR): 1.22, 95%, Confidence Interval (CI): 1.04, 1.42; Standardised Mean Difference (SMD): 0.28, 95 %,Cl: 0.08, 0.46], but not in outpatients (Peto OR: 1.01, 95%, CI: 0.88,1.17; SMD: 0.10,95% CI: -0.02,0.23). Among inpatients amitriptyline was significantly more effective than TCA and nonsignificantly more effective than the SSRIs. Among outpatients no statistically significant differences emerged between amitriptyline and TCA and between amitriptyline and the SSRIs. Amitriptylinewas less well tolerated than control agents in outpatients (Peto OR: 0.90, 95%, CI: 0.81, 0.99), but not in inpatients (Peto OR:1.09, 95% CI: 0.95, 1.25).

Conclusions: These data suggest that a reasonable approach could be the first-line prescription of newer agents in the routine outpatient care of depressive subjects, and the use of amitriptyline in inpatients with severe depression.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adrenergic Uptake Inhibitors / therapeutic use*
  • Amitriptyline / therapeutic use*
  • Depression / drug therapy*
  • Drug Evaluation
  • Humans
  • Inpatients*
  • Outpatients*
  • Psychiatric Status Rating Scales
  • Regression Analysis
  • Serotonin Uptake Inhibitors / therapeutic use*


  • Adrenergic Uptake Inhibitors
  • Serotonin Uptake Inhibitors
  • Amitriptyline