Another antidepressant for teens bites the dust

A new study shows fluoxetine is not effective for adolescents with severe depression

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The last remaining antidepressant thought to be helpful for adolescents with major depression has been knocked down by an RCT showing it’s no better than placebo.

The Melbourne-based trial involved 153 people, aged 15 to 25 years, with major depressive disorder.

Participants were randomly assigned to receive CBT and placebo or CBT and 20 to 40mg of fluoxetine per day.

After three months, the people taking fluoxetine had the same improvement in depression symptoms as those taking the placebo.

While SSRIs are more effective than placebos in adults with major depression, “the findings on antidepressants in young people, in general, have suggested poor efficacy,” Professor Philip Mitchell, a psychiatrist at UNSW who was not involved in the study, said.

“In fact, the only one that had been demonstrated to be effective in adolescents had been fluoxetine,” he said.

The SSRI fluoxetine was the only antidepressant that appeared to have any benefit in children and adolescents with major depressive disorder in a 2016 meta-analysis published in The Lancet.

“That struck many of us as an odd finding before. Why would one SSRI be more effective than any of the others?” Professor Mitchell said.

“This new study suggests that fluoxetine really is probably no different in efficacy to the other antidepressants in this age group.”

An exploratory analysis of the Melbourne data showed that there was a slight additional benefit from fluoxetine in patients with comorbid anxiety disorders. (Around 60% of patients in the study also had anxiety disorders.)

This post-hoc analysis also showed a significant benefit from fluoxetine in patients that were aged over 18 years.

“While that is really interesting, you’ve just got to be cautious about how much you can interpret from a post-hoc analysis,” Professor Mitchell said.

This result does mirror a 2018 meta-analysis in The Lancet, which found that 21 antidepressants were more effective than a placebo for adults with major depressive disorder.

“In adults with moderate-to-severe depression there certainly is strong evidence for antidepressants,” Professor Mitchell siad.

Why adults responded better to SSRIs than young people was “a bit of a conundrum” within the field of psychiatry, he said.

Professor Mitchell speculated that depression in younger people was more likely to be due to psychosocial factors that were better treated with CBT.

“That would not be surprising,” he said. “Adolescence is a period of large change in people’s lives.”

There was some concern that SSRIs might increase the risk of suicide in younger people, but this latest study provided some reassurance on that front,  Professor Mitchell said.

There was one suicide attempt in the CBT and fluoxetine group and five suicide attempts in the CBT and placebo group in the study, which was a non-significant difference, according to the author.

“These are very small numbers,” Professor Mitchell said.

“But it would give a clinician more confidence that if they need to prescribe antidepressants to young people there is not an indication that it’s going to make them more suicidal.”

The Lancet Psychiatry 2019, July 29