BARCELONA – Among the handful of top publications on mood disorders during the first three-quarters of 2018 was a landmark comparison of the efficacy and acceptability of 21 antidepressants for acute treatment of major depressive disorder, Íria Grande, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.
Dr. Iria Grande
Dr. Grande, a psychiatrist at the bipolar disorders clinic of the University of Barcelona, shared her personal top picks.
‘Antidepressants work’
This epic systematic review and network meta-analysis (Lancet. 2018 Apr 7;391[10128]:1357-66) encompassed 522 randomized double-blind trials with 116,477 participants with major depressive disorder assigned to 21 antidepressants or placebo, in some instances with an additional active comparator antidepressant arm. The report is a major extension of previous work by the same multinational group of investigators (Lancet. 2009 Feb 28;373[9665]:746-58), who initially scrutinized 12 older antidepressants in a total population only one-quarter the size of the updated analysis.
Based upon this vast randomized trial evidence, some of which came from unpublished studies tracked down by the investigators, the 21 antidepressants were rank-ordered in terms of effectiveness and acceptability. But in Dr. Grande’s view, the most important study finding wasn’t which antidepressant donned the crown of most effective or patient acceptable, it was the fact that all 21 drugs proved significantly more effective than placebo, with odds ratios ranging from 2.13 at the top end to 1.37 for reboxetine.
“The results showed antidepressants work. All of the antipsychiatry system is trying to show us that antidepressants do not work in major depression. Well, in this study, it has been proven that all antidepressants are more effective than placebo in major depressive disorder. I think social media should be made aware of that. (Lead investigator) Dr. Andrea Cipriani talked on the BBC about this article, and it had a high impact,” according to Dr. Grande.
All but three of the 21 antidepressants were deemed to be as acceptable as placebo, based upon study dropout rates. The exceptions were agomelatine and fluoxetine, which were 12%-14% more acceptable than placebo. “That’s strange, I think, but that’s what the clinical trial results showed,” she noted. The findings on clomipramine, which was 30% less acceptable than placebo, make sense, Dr. Grande said, “due to its muscarinic effects.”
She took issue with some of the specific study findings. For example, the two top-rated antidepressants in terms of efficacy were amitriptyline and mirtazapine, with odds ratios of 2.13 and 1.89, respectively.
“As a clinician, I don’t consider mirtazapine to be one of the best antidepressants, especially in major depression,” she said. “But these are the results, and as always, we have to adapt the evidence-based medicine and consider it from our clinical point of view.”
The investigators conducted a subanalysis restricted to placebo-controlled head-to-head studies with a comparator antidepressant which Dr. Grande found more interesting and informative than the overall analysis. In the head-to-head analysis, vortioxetine emerged as the top-rated antidepressant, both in efficacy, with an odds ratio of 2.0, as well as in acceptability.