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In Young People With Depression, Adding Medication to CBT Doesn't Improve First-Line Treatment

August 12, 2019

By Marilynn Larkin

NEW YORK—Adding fluoxetine to cognitive behavioral therapy (CBT) did not reduce depressive symptoms in young people with moderate-to-severe major depressive disorder, researchers say.

"The results weren't particularly surprising. There has been a lot of contention about the value of antidepressant medications for depression in young people," Dr. Christopher Davey of Orygen Youth Health in Parkville, Victoria, Australia told Reuters Health.

"The advice to use combined treatment with CBT and medication in young people with relatively severe depression comes from the 2004 Treatment for Adolescents with Depression Study (TADS)," he said by email. ( "That study showed a benefit for combined treatment with CBT and fluoxetine compared to CBT alone, but one of its flaws was that neither the patients nor their clinicians were masked with respect to treatment allocation. Given that we know the placebo effect is particularly powerful in young people, I had wondered whether the same effect would be shown in a properly blinded study."

Dr. Davey and colleagues randomized 153 patients with moderate-to-severe depression to one 20 mg capsule of fluoxetine or one placebo pill daily for 12 weeks. All participants received CBT, delivered by therapists in weekly 50-minute sessions, and attended interviews and assessments at baseline, weeks 4, 8, and 12.

Patients ranged in age from 15 to 25 (mean, 19.6); about 41% were male.

The primary outcome was change in the interviewer-rated Montgomery-Åsberg Depression Rating Scale (MADRS) score at 12 weeks.

As reported online July 29 in The Lancet Psychiatry, participants had severe depression at baseline: mean MADRS score, 33.6 in the placebo group, and 32.2 in the fluoxetine group.

High proportions of participants in both groups had anxiety disorder comorbidity (61% in the placebo group and 64% in the fluoxetine group), as well as past-month suicidal ideation (71% and 78%, respectively).

Seventy-seven percent of the placebo group and 84% of the fluoxetine group completed follow-up at week 12. Both groups showed statistically similar reductions in MADRS scores: −13.7 with placebo and −15.1 with fluoxetine.

Rates of remission (i.e., MADRS scores of 7 or less) were also statistically similar: 19% in the placebo group and 24% in the fluoxetine group.

For patients ages 18 and older, adding fluoxetine to CBT showed some evidence for a greater reduction in MADRS scores and a significantly greater reduction in Generalized Anxiety Disorder 7-item scale scores compared with CBT/placebo.

There were five suicide attempts in the CBT/placebo group and one suicide in the CBT/fluoxetine group (OR, 0.2), and no significant between-group differences for other suicidal behaviors.

"We did not show evidence that adding fluoxetine to psychotherapy provided any additional benefit in reducing depressive symptoms," Dr. Davey said. "This was particularly the case for patients who were younger than 18. We did show some benefit for older youth."

"The results suggest that first-line treatment for patients who are younger than 18, many of whom are experiencing their first episode of depression, should be with psychotherapy, even if the depression is relatively severe," he concluded. "I think we should wait before we consider antidepressants."

Dr. Benedetto Vitiello of the University of Turin, Italy, author of a related editorial, said the study is "important because it adds to limited data on the issue of combined treatment in adolescent depression."

"I am not surprised that combined treatment did not beat monotherapy plus placebo, because treatment differences versus placebo are small in depression trials, and one should expect even smaller when comparing two active treatments," he told Reuters Health by email.

"This is definitely a study to take into account when preparing guidelines," he said. "At this point, considering also previous studies, there is no convincing evidence that routine use of CBT plus medication is the best approach for all depressed adolescents."

"Starting with one treatment (CBT or medication) and then adding the other modality if the first step is not sufficiently effective seems to be a more (reasonable) approach," he said, "as suggested in an earlier study." (


Lancet Psychiatry 2019.

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