Onset of action of antidepressants: results of different analyses

Hum Psychopharmacol. 2002 Jun;17 Suppl 1:S27-32. doi: 10.1002/hup.386.


Because the value of antidepressants is hampered by their delay in onset of action, considerable attention has been focused on developing a drug that acts more rapidly. However, although specific studies are now ongoing, there have been no peer-reviewed prospective onset of action trials published in the literature to date. Some data are currently available from post-hoc pooled analyses and numerous methods have been developed for evaluating the onset of action; these include the time to response, the time to onset of therapeutic effect, pattern analysis and survival analyses. Such an analysis of four large-scale, double-blind studies has provided evidence for an earlier onset of action with mirtazapine than with the SSRIs (fluoxetine, paroxetine and citalopram). Significant differences were seen between mirtazapine and the SSRIs after 1 week of treatment. This effect was consistent across the four different methodologies and appears to be due to a specific antidepressant effect rather than an early effect on, for example, sleep. These findings await confirmation from specifically designed prospective onset of action studies.

Publication types

  • Review

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology
  • Adrenergic alpha-Antagonists / therapeutic use
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use*
  • Clinical Trials as Topic
  • Depressive Disorder / drug therapy*
  • Humans
  • Mianserin / analogs & derivatives*
  • Mianserin / pharmacology
  • Mianserin / therapeutic use
  • Mirtazapine
  • Psychiatric Status Rating Scales
  • Serotonin Uptake Inhibitors / pharmacology
  • Serotonin Uptake Inhibitors / therapeutic use
  • Time Factors
  • Treatment Outcome


  • Adrenergic alpha-Antagonists
  • Antidepressive Agents
  • Serotonin Uptake Inhibitors
  • Mianserin
  • Mirtazapine