Adolescents with Treatment Resistant Depression

About 40% of depressed adolescents do not respond to a Selective Serotonin Reuptake Inhibitor (SSRI). The combination of switching to a different antidepressant agent and receiving CBT resulted in a higher rate of clinical response than switching only to a different medication. There was no difference in response to the medication switches, and patients who were switched to a different SSRI experienced fewer adverse effects than patients taking venlafaxine.

This trial doesn’t permit any conclusion to the shorter and more rational strategy of adding cognitive behavioral therapy to the first antidepressant with lack of response. The strategy researched in this trial has a disadvantage of first switching to another antidepressant (SSRI of venlafaxine) together with CBT. This will at least take a couple of weeks.

In this trial adolescents with depression who had not responded to an initial 2-month treatment with an SSRI and had not received cognitive behavioral therapy (CBT) were randomly assigned to switch for 12 weeks to 1 of the following treatment strategies: (1) a second, different SSRI, (2) a different SSRI and CBT, (3) venlafaxine (a selective serotonin and noradrenergic reuptake inhibitor), or (4) venlafaxine and CBT.

In the past combination therapy in adolescents with moderate to severe depression is superior to medication or CBT alone.


They did not control for the greater contact and attention that participants in the combined treatment received (eg, by offering supportive therapy in the non-CBT groups. However, prior to entry, these participants had not responded to a fairly intense regimen of treatment, consisting of a median of 17 weeks of pharmacotherapy and 8 sessions of psychotherapy over the previous 12 weeks. Also, 2 characteristics of this sample, namely high rates of chronicity and clinically significant suicidality, have previously been shown to predict a poor response to supportive therapy in adolescents with depression.Second, the blinding with regard to CBT was compromised in about one-fifth of the sample, but since the effects of CBT persisted even after statistically controlling for the effect of unblinding, the compromise in the blinding alone does not explain our findings. Third, due to our design, we cannot determine whether the addition of CBT would have been beneficial even without making a change in medication.
Brent, D. (2008). Switching to Another SSRI or to Venlafaxine With or Without Cognitive Behavioral Therapy for Adolescents With SSRI-Resistant Depression. The Journal of the American Medical Association, 299(8), 901-913.