Dr Shock MD PhD

Continuation treatment with fluoxetine was superior to placebo in preventing relapse and in increasing time to relapse in children and adolescents with major depression.

This is the conclusion of a randomized placebo controlled trial after a 12-week open-label acute treatment period with 10–40 mg of fluoxetine. Those who responded at the end of 12 weeks of acute treatment were randomly assigned to receive fluoxetine or placebo for an additional 6 months. 102 patients were randomized.Those in the fluoxetine group received the same dose they were receiving in acute treatment. In the placebo group, fluoxetine was not tapered given its long half-life.



Relapse occurred more frequently in participants in the placebo group than in the fluoxetine group (N=36 [69.2%] and N=21 [42.0%], respectively. Even using a stricter definition, relapse was more frequent in the placebo group than in the fluoxetine group (N=25 [48.1%] and N=11 [22.0%], respectively). These differences were statistically significant.

Some practical consequences of these findings:

This suggests that the adult guidelines recommending 6–9 months of overall treatment for major depression would apply equally to children and adolescents. It also reinforces the fact that early-onset depression is associated with high rates of relapse, even though the majority of participants in this sample were in their first episode of major depression.

In another study with adolescents with depression the focus was on the question to what degree do patients not responding to acute anti depressive treatment consisting of fluoxetine, Cognitive Behavioral Therapy or the combination of both subsequently achieve response during continuation and maintenance therapy?

And among those that achieve response during acute anti depressive therapy, how many maintain their response during continuation and maintenance therapy?

Among 95 patients (39.3%) who had not achieved sustained response by week 12 (29.1% combination of fluoxetine and cognitive behavioral therapy, 32.5% fluoxetine alone, and 57.9% Cognitive Behavioral Therapy), sustained response rates during stages 2 and 3 were 80.0% COMB, 61.5% FLX, and 77.3% CBT (difference not significant). Among the remaining 147 patients (60.7%) who achieved sustained response by week 12, CBT patients were more likely than FLX patients to maintain sustained response through week 36 (96.9% vs 74.1%; P = .007; 88.5% of COMB patients maintained sustained response through week 36). Total rates of sustained response by week 36 were 88.4% COMB, 82.5% FLX, and 75.0% CBT.

Thus the majority of adolescents who had not achieved response by week 12 achieved response by week 36: 80% with the combination of fluoxetine and CBT, 61.5% on fluoxetine and 77.3% with CBT alone. These outcomes were not significantly different from each other. Overall adolescents with depression who have not fully responded after 12 weeks of acute treatment three-quarters of them will experience sustained response with further treatment.

Those who had responded by week 12 the majority (82.3% of 147 patients) maintained their sustained response throughout week 36. 15% failed to maintain their acute response with rates differing as a function of treatment modality: 11.5% combination treatment, 25.9% fluoxetine alone and 3.1% CBT alone.


Conclusions
I am jealous, this is excellent research especially the placebo controlled one. These are findings that are easily applicable to practice. We in adult psychiatry have to do with a lot less evidence as far as placebo controlled trials for continuation and maintenance therapy are concerned.
CBT monotherapy in the acute phase has a lower response rate, nevertheless during follow-up only 3.1% failed to sustain that response. A larger proportion of patients respond on fluoxetine but the sustained response is not as enduring as with CBT. Further research could focus on augmenting response on fluoxetine with CBT for enduring this response.

Related articles on this blog about adolescents and depression


Emslie, G.J. (2008). Fluoxetine versus placebo in preventing relapse of major depression in children and adolescents. American Journal of Psychiatry, 165(4), 459-467.

Rohde, P. (2008). Achievement and maintenance of sustained response during the treatment for adolescents with depression study continuation and maintenance therapy. Archives of General Psychiatry, 65(4), 447-455.

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