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Antidepressant Choice and Psychotherapy in Treatment-Resistant Adolescents

Cognitive behavioral therapy adds incremental benefit to any antidepressant therapy.

Clinical practice guidelines recommend psychotherapy (usually cognitive behavioral therapy [CBT]), antidepressants, or both) but offer less guidance on what to do if initial treatment fails. At least 40% of depressed adolescents do not have adequate clinical responses to these treatments.

In a multisite, randomized, U.S. government–funded trial, 334 adolescents (age range, 12–18) who did not respond to at least 8 weeks of selective serotonin reuptake inhibitor (SSRI) therapy at recommended dosages received either a different SSRI or venlafaxine (a serotonin-norepinephrine reuptake inhibitor; Effexor and generics), with or without CBT. A total of 231 adolescents completed the full 12-week trial; adverse effects (more common with venlafaxine) were the reason for discontinuation by 40% of dropouts. Patients in the SSRI group received fluoxetine, paroxetine, or citalopram. Antidepressants were adjusted to maximum tolerated dosages, and CBT was delivered weekly. The primary outcome was clinical improvement in two assessments of depression and global functioning. CBT, compared with no CBT, yielded the most significant difference in an intent-to-treat analysis (55% improvement in response rate vs. 41%). No difference was observed between the two medication groups (47% improvement with SSRIs vs. 48% with venlafaxine).

Comment: These results suggest that clinicians should be more aggressive about providing CBT for adolescents with treatment-resistant depression (an admittedly difficult goal in many healthcare settings), regardless of which antidepressant is chosen. These adolescents had been depressed for a mean of about 2 years before their enrollment, so these response rates are encouraging.

— Thomas L. Schwenk, MD

Published in Journal Watch General Medicine February 26, 2008

Citation(s):

Brent D et al. Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depression: The TORDIA randomized controlled trial. JAMA 2008 Feb 27; 299:901.

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