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Fluoxetine may not be effective in treating depression in teens and young adults


One of the most well-known antidepressants, fluoxetine, may not be as effective in adolescents and young adults as previously thought.

One of the most well-known antidepressants, fluoxetine, may not be as effective in adolescents and young adults as previously thought, according to a new study published in Lancet Psychiatry.

The researchers used the Youth Depression Alleviation–Combined Treatment (YoDA-C) trial, which was a randomized, double-blind, placebo-controlled, multicenter clinical trial. Participants, aged 20 to 25 years, had moderate-to-severe major depressive disorder (MDD) and had gone to 1 of 4 clinical centers in metropolitan Melbourne, Australia, for treatment. Each participant was randomly assigned 1:1 to receive cognitive behavioral therapy (CBT) in weekly 50-minute sessions for 12 weeks and given either fluoxetine at 1 20-mg capsule dose or 1 placebo pill per day. They were interviewed at baseline, week 4, week 8, and week 12, and completed assessments each time.

The trial included 153 teenagers and young adults, with an average age of 19.6 years. They were involved in the trial from February 20, 2013, to December 13, 2016. Seventy-seven of the trial group were allocated to the placebo group and 76 were allocated to the fluoxetine group. Each participant had severe depression at baseline, with an average Montgomery-Åsberg Depression Rating Scale (MADRS) score of 33.6 in the CBT-and-placebo group and MADRS score of 32.2 in the CBT-and-fluoxetine group. There was a high number of participants with anxiety disorder comorbidity (47 [61%] in the placebo group and 49 [64%] in fluoxetine group) and past-month suicidal ideation (55 [71%] in the placebo group and 59 [78%] in the fluoxetine group). Fifty-nine of the placebo group and 64 of the fluoxetine group did follow-up through week 12.

After the 12 weeks of treatment, both groups saw reductions in their MADRS scores: -13.7 (95% confidence interval [CI], -16.0 to -11.4) in the placebo group and -15.1 (95% CI, -17.4 to -12.9) in the fluoxetine group. No significant between-group difference was seen in the MADRS scores (-1.4, -4.7 to 1.8; P=0.39). In the placebo group, there were 5 suicide attempts during the study and there was 1 suicide attempt in the fluoxetine group. No significant between-group differences were seen for other suicidal behaviors.


The researchers concluded that adding fluoxetine to CBT saw no reduction in depressive symptoms in teenagers and young adults with moderate-to-severe MDD. Adding medication could be helpful in people who had comorbid anxiety symptoms or for older pediatric patients.

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