Rates of 5 common antidepressant side effects among new adult and adolescent cases of depression: a retrospective US claims study

Clin Ther. 2012 Jan;34(1):113-23. doi: 10.1016/j.clinthera.2011.11.024. Epub 2011 Dec 16.


Background: Antidepressants are the first-line treatment for depression, yet medication-related side effects may be associated with antidepressant discontinuation before reaching a period of exposure believed to result in effectiveness. There is a gap in knowledge of the prevalence of side effects across commonly prescribed antidepressants and the effect of the type of antidepressant on the likelihood of side effects in real-world clinical practice.

Objective: The aim of this study was to estimate and compare the prevalence of headaches, nausea or vomiting, agitation, sedation, and sexual dysfunction among patients diagnosed with depression who initiated monotherapy across different classes of antidepressants and to estimate the effect of the type of antidepressant on the likelihood of each of the 5 side effects.

Methods: A retrospective cohort of patients aged ≥13 who were newly diagnosed with depression and began antidepressant monotherapy was created using LifeLink managed care claims from 1998 to 2008. Antidepressant groups included selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), bupropion, phenylpiperazine, and tetracyclic antidepressants. Prevalence of headache, nausea or vomiting, agitation, sedation, and sexual dysfunction were compared across antidepressant groups. Propensity-adjusted Cox proportional hazards regression was used to estimate the likelihood of each of the 5 side effects for each antidepressant group compared with SSRIs, adjusted for demographic, clinical, and treatment characteristics.

Results: The study cohort included 40,017 patients (3617 adolescents, aged 13-18 years, and 36,400 adults, aged ≥19 years; mean age = 45 years; 67% female) with a new episode of depression who were initiated on antidepressant monotherapy within 30 days of diagnosis (SSRI [66%], bupropion [14%], SNRI [12%], other [8%]). The most common side effects were headache (up to 17/1000 person-months of therapy in adults and adolescents) and nausea (up to 7.2/1000 in adults, 9.3/1000 in adolescents). Relative to adults receiving SSRIs, adults receiving SNRIs had a higher risk of nausea (hazard ratio [HR] = 1.26; 95%CI,1.05-1.51). Adults (HR = 0.78; 95% CI, 0.62-0.96) and adolescents (HR = 0.43; 95% CI, 0.21-0.87) taking bupropion were less likely to experience headaches compared with adults and adolescents, respectively, taking an SSRI. Adolescents receiving a tetracyclic were more likely to experience headaches than adolescents receiving an SSRI (HR = 3.16; 95%CI, 1.13-8.84).

Conclusions: Prevalence and risk of the 5 side effects varied across types of antidepressants for both adults and adolescents. Results from this study were consistent with prior clinical trials, suggesting that variation in side effect profiles exists in a more generalized managed care population.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Antidepressive Agents / adverse effects*
  • Databases as Topic
  • Depression / diagnosis
  • Depression / drug therapy*
  • Depression / epidemiology
  • Headache / chemically induced*
  • Headache / epidemiology
  • Humans
  • Managed Care Programs
  • Middle Aged
  • Nausea / chemically induced*
  • Nausea / epidemiology
  • Prevalence
  • Propensity Score
  • Proportional Hazards Models
  • Psychomotor Agitation / epidemiology
  • Psychomotor Agitation / etiology*
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Sexual Dysfunction, Physiological / chemically induced*
  • Sexual Dysfunction, Physiological / epidemiology
  • Sleep / drug effects*
  • United States / epidemiology
  • Vomiting / chemically induced*
  • Vomiting / epidemiology
  • Young Adult


  • Antidepressive Agents