Efficacy and safety of selective serotonin reuptake inhibitors in the treatment of depression in children and adolescents: practitioner review

Clin Drug Investig. 2006;26(5):247-55. doi: 10.2165/00044011-200626050-00002.


Background: Given the widespread reports involving the use of selective serotonin reuptake inhibitors (SSRIs) in children, the present paper reviews and discusses published double-blind, placebo-controlled studies assessing the safety and efficacy of SSRIs in children and adolescents with major depressive disorder.

Methods: Published and unpublished double-blind, placebo-controlled studies of SSRIs in children and adolescents with depression during the years 1990-2004 were reviewed. A MEDLINE search was performed using the words 'depression', 'randomised controlled trial', 'SSRIs', 'children' and 'adolescents'. The GlaxoSmithKline website was also searched for relevant studies on paroxetine. Outcome measures were the Clinical Global Impressions scale, the Children's Depression Rating Scale-Revised, the Hamilton Rating Scale for Depression, the depression subscales of the Kiddie Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version, and the Montgomery and Asberg Depression Rating Scale. Adverse effects and withdrawal rates are reported.

Results: There were seven randomised, placebo-controlled trials involving 1619 children and adolescents aged 6-18 years in total. The SSRIs fluoxetine, paroxetine, sertraline and citalopram were reported to exhibit safety and efficacy for treatment of depression in children and adolescents. Reanalysis of published and unpublished studies by the US FDA and the UK's Medicines and Healthcare products Regulatory Agency (MHRA) raised alerts regarding higher suicidal ideation rates from SSRIs in this population. Present guidelines are discussed.

Conclusions: SSRIs remain a first-line pharmacological treatment for depression in children and adolescents for whom psychotherapy has failed or is unavailable. Suicidal ideation and behaviours merit close monitoring. More studies are needed.

Publication types

  • Meta-Analysis

MeSH terms

  • Adolescent
  • Child
  • Depression / drug therapy*
  • Depression / psychology
  • Disease Progression
  • Humans
  • Psychiatric Status Rating Scales
  • Randomized Controlled Trials as Topic
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Severity of Illness Index
  • Sex Factors
  • Suicide, Attempted / statistics & numerical data
  • Time Factors
  • Treatment Outcome


  • Serotonin Uptake Inhibitors