Article pour les cliniciens
Efficacité et acceptabilité comparatives de 21 antidépresseurs pour le traitement aigu des adultes atteints d'un trouble dépressif majeur: une revue systématique et méta-analyse en réseau.
PMID: 29477251
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Médecine familiale (MF)/Médecine générale (MG)Relevance - 7/7
Intérêt médiatique - 6/7 -
Médecine interne générale - Soins primairesRelevance - 7/7
Intérêt médiatique - 6/7 -
PsychiatrieRelevance - 7/7
Intérêt médiatique - 6/7 -
- MF/MG/Santé mentaleRelevance - 6/7
Intérêt médiatique - 5/7
Résumé (en anglais)
BACKGROUND: Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder.
METHODS: We did a systematic review and network meta-analysis. We searched Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, the websites of regulatory agencies, and international registers for published and unpublished, double-blind, randomised controlled trials from their inception to Jan 8, 2016. We included placebo-controlled and head-to-head trials of 21 antidepressants used for the acute treatment of adults (=18 years old and of both sexes) with major depressive disorder diagnosed according to standard operationalised criteria. We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression; or patients with a serious concomitant medical illness. We extracted data following a predefined hierarchy. In network meta-analysis, we used group-level data. We assessed the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Primary outcomes were efficacy (response rate) and acceptability (treatment discontinuations due to any cause). We estimated summary odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with PROSPERO, number CRD42012002291.
FINDINGS: We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89-2·41) for amitriptyline and 1·37 (1·16-1·63) for reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72-0·97) and fluoxetine (0·88, 0·80-0·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1·30, 1·01-1·68). When all trials were considered, differences in ORs between antidepressants ranged from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability, with wide CrIs on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19-1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51-0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43-0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30-2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low.
INTERPRETATION: 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. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants.
FUNDING: National Institute for Health Research Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science.
Commentaires cliniques (en anglais)
Family Medicine (FM)/General Practice (GP)
A huge network meta-analysis. It shows that they're all effective, and some cause more drop-outs (the proxy for 'acceptability'). As the authors say, this should assist in shared decision-making. Some data from unpublished data are not available.
Family Medicine (FM)/General Practice (GP)
Really, the key information in this "big data" research is found in Figure 4 on page 8. I think the take-aways from studying this Figure are that all the antidepressants are more or less equivalently effective and generally well tolerated. The exceptions would seem to be that Clomipramine, Reboxetine and, perhaps, Duloxetine that may be more likely to be NOT tolerated. So, choose your antidepressant and use it. I did find it bothersome that Imipramine and Nortriptyline were not included.
Family Medicine (FM)/General Practice (GP)
A Herculean effort that compares 21 different antidepressants as to efficacy and tolerability. Not all of these antidepressants are available in the USA. Combination therapy was not assessed. Studies assessing depression in those with serious medical illnesses were excluded. I found it very interesting that amitriptyline, a drug infrequently used for treatment of depression in the USA, is the most efficacious of these 21 drugs (though not the best tolerated).
FM/GP/Mental Health
Appreciate seeing head-to-head comparison data for drug classes. While these data are not easily parsed, they affirm efficacy and tolerability of three popular generic and cheap choices, namely amitriptyline, mirtazipine, and escitalopram.
General Internal Medicine-Primary Care(US)
The discussion between a physician and patient regarding which antidepressant to start centers around finding a drug that has a good chance of working and a side effect profile that is acceptable to the patient. There are other factors such as insurance of course, but this review although broad in scope, provides a good starting point for shared decision-making.
General Internal Medicine-Primary Care(US)
It is very useful to know that the antidepressants listed were all better than placebo and that some are more effective than others. I have read that some antidepressants are in fact not better than placebo. The tolerability list was what I would expect.
General Internal Medicine-Primary Care(US)
This well done network meta-analysis is quite complicated and will likely readily exceed the attention span of many overworked primary care providers. However, the information provided is new, relevant, and important to primary care.
Psychiatry
The choice of antidepressant medication for a medication naïve patient involves many factors including medication efficacy and side effects, cost and patient characteristics including specific symptoms and other medical factors. This study is very comprehensive and provides some information that will inform clinical decision making but it will probably not have a dramatic effect on individuals' practice.
Psychiatry
Gold standard article that will hopefully put an end to the preposterous claim that antidepressants are no more effective than placebo. This should be required reading in medical school. My only criticism is that depression is treated as a single uniform entity, and efficacy between agents is based on that assumption. This completely misses the greater efficacy of certain agents for depression featuring insomnia, for other depressions featuring anxiety, for other depressions featuring lethargy, for other depressions featuring obsessions, and for other depression with atypical features. Although that is completely beyond the power of a mega meta-analysis, it would have been nice for this to be acknowledged. This study does not show which agents are superior in major depression; it demonstrates which agents were superior in the majority of published trials. We are left with the impression that amitriptyline is the drug to turn to first, which is absurd, but so be it.
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