Antidepressants Have Significant Effect in Adults with Major Depression

March 7, 2018

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Antidepressants are statistically significantly more effective than placebo in adults with major depression, according to a massive systematic review and network meta-analysis.

"All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials," Dr. Andrea Cipriani of the University of Oxford, in the U.K., and colleagues write in The Lancet, online February 21.

"These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants," they advise.

Dr. Cipriani and colleagues searched bibliographic databases from their inception to January of 2016 to compare and rank 21 antidepressants for the acute treatment of adults with unipolar major depressive disorder. They also searched the websites of drug regulators and contacted drugmakers for supplemental information.

They excluded quasi-randomized trials; trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression; and patients with a serious concurrent medical illness.

Of the 28,552 citations they identified, they included 522 trials with a total of more than 116,000 participants in their analyses. All the antidepressants studied had significantly higher response rates than placebo, with odd ratios (ORs) ranging from 1.37 for reboxetine to 2.13 for amitriptyline.

However, the effect sizes were “mostly modest,” the researchers write. They do not address the clinical significance of the effects.

Only agomelatine (OR, 0.84) and fluoxetine (OR, 0.88) had significantly fewer dropouts than placebo, while clomipramine had more dropouts than placebo (OR, 1.30).

Considering all the trials, the differences in antidepressant ORs ranged from 1.15 to 1.55 for efficacy and from 0.64 to 0.83 for acceptability. In the head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine and vortioxetine were more effective than other antidepressants (ORs ranged from 1.19 to 1.96). By contrast, fluoxetine, fluvoxamine, reboxetine, and trazodone were the least effective (ORs ranged from 0.51 to 0.84).

Agomelatine, citalopram, escitalopram, fluoxetine, sertraline and vortioxetine were tolerated better than the other antidepressants (ORs ranged from 0.43 to 0.77), while amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone and venlafaxine had the highest dropout rates (ORs ranged from 1.30 to 2.32).

Overall, 46 (9%) of the 522 trials were rated as having high risk of bias, 380 (73%) trials as having moderate risk of bias, and 96 (18%) as having low risk. The certainty of evidence ranged from moderate to very low.

"The findings from this network meta-analysis represent the most comprehensive currently available evidence base to guide the initial choice about pharmacological treatment for acute major depressive disorder in adults," the authors write.

But they caution, "All statements comparing the merits of one antidepressant with another must be tempered by the potential limitations of the methodology, the complexity of specific patient populations, and the uncertainties that might result from choice of dose or treatment setting. We hope that these results will assist in shared decision making between patients, carers, and their clinicians.

Dr. Sagar V. Parikh, a professor of psychiatry at the University of Michigan, in Ann Arbor, told Reuters Health by email that the findings that some antidepressants work a bit better than others confirms clinical experience.

"It is interesting to see an old antidepressant, amitriptyline, make the list, and surprising to see sertraline and duloxetine not make the list. The continued difference versus placebo was reassuring given the huge number of studies and the fact that unpublished data were included," he said.

"Antidepressants are among the most commonly prescribed medications, so we always need to keep close watch on efficacy, safety, and tolerability," advised Dr. Parikh, who co-authored an editorial about the study. "More clinicians should ask patients if they want to start with a slightly stronger drug, or need to choose a drug that may be more tolerable. These findings help doctors and patients engage more easily in shared decision making."

"These findings were entirely based on results after 8 weeks of treatment. If something is better at 8 weeks, is it still better at 6 months or a year? No studies answer that very important question," he noted.

Dr. Cipriani was not available for comments by publication time.

The National Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science funded the study. Several authors reported financial relationships with pharmaceutical companies that manufacture antidepressants.


Lancet 2018.

(c) Copyright Thomson Reuters 2018. Click For Restrictions -

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