Clinical Inquiries

Which SSRIs most effectively treat depression in adolescents?

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We don’t know which selective serotonin reuptake inhibitors (SSRIs) are the most effective and safe because no studies have compared these antidepressants with each other.

Three SSRI antidepressant medications—fluoxetine, sertraline, and escitalopram—produce modest improvements (about 5% to 10%) in standardized depression scores without a significant increase in the risk of suicide-related outcomes (suicidal behavior or ideation) in adolescent patients with major depression of moderate severity. As a group, however, the newer-generation antidepressants, including SSRIs, increase suicide-related outcomes by 50%. Citalopram, paroxetine, venlafaxine, and mirtazapine don’t improve depression scores (strength of recommendation [SOR]: A, meta-analyses of randomized controlled trials [RCTs]).

An updated national guideline recommends specific psychological therapy for adolescents with mild depression and combined psychotherapy and fluoxetine for moderate or severe depression, with sertraline or citalopram as second-line agents (SOR: A, RCTs).


A Cochrane systematic review (19 RCTs; 3335 patients, total) of newer-generation antidepressants for treating depression in adolescents found that, overall, they produced both a small decrease in symptom severity scores and an increased risk of suicide-related outcomes.1

Three SSRIs slightly lower one symptom severity score

Investigators performed a meta-analysis of all trials (14 RCTs; 2490 patients, total) that used the same standardized symptom severity score (the Children’s Depression Rating Scale—Revised [CDRS-R], range 17 to 113 points) to evaluate the following medications: fluoxetine, sertraline, escitalopram, citalopram, paroxetine, venlafaxine, and mirtazapine.1

All participants were outpatients who met criteria for a primary diagnosis of major depression, excluding comorbid conditions. The CDRS-R scores were evaluated by clinicians; the mean baseline score was 57 (40 is considered a threshold score for diagnosis, and above 60 indicates severe symptoms). Only 5 trials reported patients’ self-rated depression symptom severity (in patients taking fluoxetine and paroxetine) and none reported improvement. Treatment courses ranged from 8 to 12 weeks.

As a group, the newer antidepressants slightly reduced CDRS-R scores in adolescents (by 4.21 points, 95% confidence interval [CI], 0.41-5.95) but increased suicide-related outcomes (relative risk [RR]=1.47; 95% CI, 0.99-2.19). The individual antidepressants fluoxetine, sertraline, and escitalopram each produced statistically significant but clinically small reductions in CDRS-R scores of 5% to 10% without significantly increasing suicide-related outcomes (TABLE1). The other medications evaluated individually didn’t improve CDRS-R scores, and only venlafaxine increased suicide-related outcomes.

Efficacy and safety of newer antidepressants in adolescents image


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