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Adolescents with SSRI-resistant depression: CBT plus antidepressant switch more effective than medication switch alone

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What is the best strategy for adolescents with depression who don’t respond to initial SSRIs?


334 adolescents (12–18 years old) with a primary diagnosis of major depressive disorder who had not responded to a 2-month trial with an SSRI. Main exclusions: non-response to ⩾2 trials of an SSRI or to venlafaxine (⩾4 weeks at dose ⩾150 mg) or CBT (⩾7 sessions); already receiving CBT; taking psychoactive medications (except those on stable doses of stimulants or hypnotics for ⩾12 weeks); bipolar spectrum disorder; psychosis; pervasive developmental disorder or autism; eating disorders; or substance abuse or dependence.


US academic and community clinics; 2000–2006.


One of four 12-week regimens: switch to a second, different SSRI (paroxetine, fluoxetine or citalopram at 20–40 mg daily); switch to venlafaxine (150–225 mg daily); switch to second SSRI plus CBT; switch to venlafaxine plus CBT. CBT was delivered by experienced therapists with at least master’s level qualifications.


Adequate clinical response (score ⩽2 on the …

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  • Source of funding: National Institute of Mental Health, and Advanced Center for Early-Onset Mood and Anxiety Disorders.

  • Additional notes are published online only at


  • Competing interests: BD has attended educational meetings sponsored by Lilly.