Extended Therapy for Depressed Adolescents: A “TAD” Better?

January 26, 2009

An NIMH-sponsored study found that extending the duration of therapy for depressed adolescents increased the rate of response and decreased relapse rates relative to acute, short-term treatment.

An NIMH-sponsored study found that extending the duration of therapy for depressed adolescents increased the rate of response and decreased relapse rates relative to acute, short-term treatment.

The Treatment for Adolescents With Depression Study (TADS) conducted by Paul Rohde, PhD, Oregon Research Institute, and colleagues demonstrates a benefit from extended treatment in this age group-a benefit that had been inferred from studies in adults.1 Although there is a relatively high rate of relapse and recurrence in adolescents with depression, Rohde and colleagues1 found that an 18-week maintenance therapy course following 12 weeks of acute and 6 weeks of continuation treatment resulted in a sustained response in three-quarters of patients who did not fully respond in the acute treatment phase.

TADS also provides the first large-scale, controlled contrast of the effects of psychosocial and pharmacotherapeutic treatments on depression in adolescents.1 Although response rates during the 12-week acute therapy were higher in medication treatment arms than with cognitive-behavioral therapy (CBT) alone, the rates of sustained response were comparable at the end of the maintenance phase. In addition, responders to acute treatment with CBT alone had significantly lower rates of relapse during the following 24 weeks than those initially responsive to medication.

"Given that a larger proportion of patients recover from [medication] therapy than CBT but the sustained response may not be as enduring," the researchers indicate, "one hypothesis for future research is that [medication] monotherapy needs to be augmented once depression recovery has occurred, and CBT would seem to be a reasonable place to start."1

TADS randomized 439 adolescents with major depression to treatment with fluoxetine (Prozac), fluoxetine and CBT, CBT monotherapy, or placebo. Fluoxetine was begun at a dosage of 10 mg/d (titrated to 40 mg/d by week 8 as necessary). CBT was provided in 15 sessions during the acute treatment phase. Partial responders to CBT received 6 additional weekly sessions in the continuation phase, while responders received biweekly sessions. Maintenance treatment with CBT consisted of a "booster" session every 6 weeks. Response to treatment was assessed by a change in Clinical Global Impression ratings from baseline.

A total of 270 patients completed the 12-week acute phase, and 202 remained in the study throughout the 36 weeks. Nonresponders to the initial 12 weeks of placebo were relieved from randomized assignment to choose their treatment.

The highest rates of response to acute treatment occurred with combination treatment (70.9%) and with fluoxetine alone (67.5%); 42.1% of patients initially responded to CBT alone. Although there were only 32 patients in the latter group, a statistically significantly high­er percentage of these patients (96.9%) had a sustained treatment response through the maintenance period than did responders to combination therapy (88.5%) or those initially responsive to fluox­etine alone (74.1%).

The value of extending treatment beyond the acute phase was reflected not only in the number of patients who had a sustained response after initial improvement but also in the eventual improvement of those who did not respond during the 12 weeks of acute treatment. Among those who had an inadequate response to acute treatment, 55% met criteria for response by the completion of maintenance treatment. An additional 19% had possibly reached this threshold.

These findings of sustained response, the investigators note, "can be used by the clinician and the family to guide important decisions regarding the optimal course of treatment after the acute phase."

References:

1. Rohde P, Silva SG, Tonev ST, et al. Achievement and maintenance of sustained response during the Treatment for Adolescents With Depression Study continuation and maintenance therapy. Arch Gen Psychiatry. 2008;65:447-455.