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Selective Serotonin Reuptake Inhibitors Are Effective in Improving the Clinical Symptoms of Major Depression in Adolescents


  • In adolescents with major depression, are SSRIs more effective than placebo in improving symptoms?

Clinical Bottom Lines

  1. The SSRI paroxetine (Paxil) demonstrated greater improvement compared to placebo in several assessments of adolescent depression, notably the Hamilton Rating Scale for Depression.1
  2. Need to treat 6 adolescents with major depression with paroxetine to have one from achieve a Hamilton Rating Scale for Depression score < 8.

Summary of Key Evidence

  1. Randomized, placebo-controlled, multicenter, parallel-design, double-blind study.1
  2. 275 male and female adolescents ages 12-18 with major depression, diagnosed by clinical interview, DSM-IV criteria, symptom duration of >8 weeks, Hamilton Rating Scale for Depression score >12/17, Children's Global Assessment Scale score < 60, and Peabody Picture Vocabulary Test > 80.
  3. Excluded were those with co-existing DSM-IV diagnoses such as bipolar, schizoaffective, and substance abuse disorders, as well as those with current suicidal ideation with intent or plan, recent trial of antidepressant medication, or pregnancy.
  4. 8 week study, only 69% follow-up (losses accounted for by adverse reactions and protocol violation especially). Withdrawal rates for adverse events were 9.7% in paroxetine group and 6.9% in placebo group.
  5. 3 arms of study: 1) paroxetine 20-40mg/day 2) imipramine 50-300mg/day 3) placebo.
  6. Adverse effects of paroxetine included headache, nausea, dizziness, dry mouth, somnolence.
  7. Paroxetine separated statistically from placebo at endpoints among four parameters: response, Hamilton Rating Scale for Depression depressed mood item, Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version depressed mood item, and Clinical Global Impression Score of very much improved or much improved.1

Additional Comments

  • Lifetime prevalence of major depression in adolescents and young adults is estimated from 9%2 to 25%.3
  • Very few placebo-controlled studies have investigated the efficacy of SSRI therapy for adolescents with major depression; tricyclic antidepressants have been investigated in many more.1
  • Hamilton Rating Scale for Depression: 17-point scale first developed in 1960's consisting of questions about mood, guilt, suicide, insomnia, work, activities, psychomotor retardation, agitation, anxiety, somatic symptoms.4


  1. Keller M, et al. Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial. Journal of the American Academy of Child & Adolescent Psychiatry 2001; 40 (7): 762-772.
  2. Rushton J, Forcier M, Schectman R. Epidemiology of depressive symptoms in the National Longitudinal Study of Adolescent Health. Journal of the American Academy of Child & Adolescent Psychiatry 2002; 41 (2): 199-205.
  3. Kessler R, Avenevoli S, Merikangas K. Mood disorders in children and adolescents: an epidemiologic perspective. Biological Psychiatry 2001; 49 (12): 1002-1014.
  4. Hamilton Rating Scale for Depression (Ham-D) Scoresheet.

CAT Author: Megan Clipp, MD

CAT Appraisers: <Reviewers>, MD

Date appraised: March 25, 2002

Last updated October 15, 2002
Department of Pediatrics and Communicable Diseases
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