Relapse prevention and residual symptoms: a closer analysis of placebo-controlled continuation studies with escitalopram in major depressive disorder, generalized anxiety disorder, social anxiety disorder, and obsessive-compulsive disorder

J Clin Psychiatry. 2010 Feb;71(2):121-9. doi: 10.4088/JCP.08m04749blu. Epub 2009 Dec 1.


Objective: Analyses of data from 4 relapse-prevention studies with escitalopram were conducted in order to compare patients with and without residual symptoms with regard to relapse rates and global illness during double-blind, 24-week continuation periods.

Method: Clinical Global Impressions-Severity of Illness scores and relapse status in 4 studies published from 2005 to 2007, 1 each in major depressive disorder (MDD), generalized anxiety disorder, social anxiety disorder, and obsessive-compulsive disorder (OCD), were analyzed using mixed-effects model repeated measures as a function of Montgomery-Asberg Depression Rating Scale (MADRS) scores on items 1, 3, and 7 at randomization.

Results: All studies showed a statistically significant (P < .0001) standardized effect size of about 0.7 for escitalopram versus placebo, with a number needed to treat approximately 4. Patients with residual symptoms (MADRS score > 0) and without residual symptoms (MADRS score = 0) at the start of continuation treatment were defined by how patients scored on 3 core items of the MADRS: depressed mood (observed), inner or psychic tension, and lassitude. At randomization, patients with a residual symptom were globally more ill than patients without such a symptom. Patients who did not continue active treatment worsened, even if they were initially free of a residual symptom. In contrast, patients who continued receiving escitalopram remained stable or further improved, regardless of residual symptoms or diagnosis. No clear picture emerged regarding whether patients with residual symptoms had a higher relapse rate.

Conclusions: The presence of residual symptoms is associated with significantly worse overall illness severity in all 4 diagnostic groups and with a higher (although not significantly) risk of relapse for patients with MDD or OCD. The greatest difference in all of the studies was between patients treated with escitalopram (relapse rates ~ 20%) and placebo (relapse rates of about 50%).

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Activities of Daily Living
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Anxiety Disorders / diagnosis
  • Anxiety Disorders / drug therapy
  • Anxiety Disorders / prevention & control*
  • Citalopram / therapeutic use*
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / prevention & control*
  • Humans
  • Longitudinal Studies
  • Placebos
  • Psychiatric Status Rating Scales
  • Randomized Controlled Trials as Topic
  • Secondary Prevention
  • Severity of Illness Index
  • Treatment Outcome


  • Antidepressive Agents, Second-Generation
  • Placebos
  • Citalopram