What happens with adverse events during 6 months of treatment with selective serotonin reuptake inhibitors?

J Clin Psychiatry. 2005 Jul;66(7):859-63. doi: 10.4088/jcp.v66n0708.


Objective: Although adverse events are a key factor in compliance, their evolution during treatment with antidepressants is poorly documented. Therefore, the time course of adverse events during 6 months of antidepressant treatment was investigated.

Method: 85 psychiatric outpatients with a DSM-IV diagnosis of major depressive disorder (with the exclusion of other DSM-IV Axis I disorders) were enrolled between September 2002 and March 2003 in a multicenter, randomized, double-blind trial with selective serotonin reup-take inhibitors (fluoxetine [N = 42] and paroxetine [N = 43]). At each visit, the presence and severity of treatment-emergent adverse events were assessed systematically using the UKU Side Effect Rating Scale (UKU). General linear mixed modeling was used to investigate the predictors of the time course of adverse events.

Results: Overall, the number of at least moderately severe adverse events decreased with time. More severely depressed patients reported overall more (at least moderately severe) adverse events than less severely depressed patients (p = .0002), but the decrease in reported adverse events was comparable over time. Men (N = 30) and women (N = 55) reported initially the same number of at least moderately severe adverse events, but the habituation was more rapid in men (p < .0001). Completers (N = 58) and dropouts (N = 27) did not differ initially, but completers' habituation was more rapid (p = .014). The habituation of adverse events was also more rapid in recurrent than in first-episode patients but only in men (p = .0025).

Conclusion: The time course of adverse events varies with the severity of depression, sex, completer or dropout status, and recurrent versus first-episode depression.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Adverse Drug Reaction Reporting Systems / statistics & numerical data*
  • Data Interpretation, Statistical
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / psychology
  • Double-Blind Method
  • Female
  • Fluoxetine / adverse effects
  • Fluoxetine / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Paroxetine / adverse effects
  • Paroxetine / therapeutic use
  • Patient Dropouts
  • Recurrence
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Severity of Illness Index
  • Sex Factors
  • Time Factors
  • Treatment Outcome


  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Paroxetine