This month’s post is again from Ken Pope’s listserv, where he kindly provides daily summaries of current articles in the field. His post is as follows:
Lancet includes an article: “Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.”
The authors are Andrea Cipriani, Prof Toshi A Furukawa, MD†, Georgia Salanti, PhD†, Anna Chaimani, PhD, Lauren Z Atkinson, MSc, Yusuke Ogawa, MD, Prof Stefan Leucht, MD, Henricus G Ruhe, PhD, Erick H Turner, MD, Prof Julian P T Higgins, PhD, Prof Matthias Egger, PhD, Nozomi Takeshima, MD, Yu Hayasaka, MD, Hissei Imai, MD, Kiyomi Shinohara, MD, Aran Tajika, MD, Prof John P A Ioannidis, MD, Prof John R Geddes, MD.
AS USUAL, FOR THOSE WHO WOULD LIKE ACCESS TO THIS ARTICLE, I’LL INCLUDE *BOTH*THE AUTHOR’S EMAIL ADDRESS (FOR REQUESTING ELECTRONIC REPRINTS) *AND* A LINK TO THE COMPLETE ARTICLE AT THE END BELOW.
Here’s how it opens:
Psychiatric disorders account for 22·8% of the global burden of diseases.1 The leading cause of this disability is depression, which has substantially increased since 1990, largely driven by population growth and ageing.2 With an estimated 350 million people affected globally, the economic burden of depressive disorders in the USA alone has been estimated to be more than US$210 billion, with approximately 45% attributable to direct costs, 5% to suicide-related costs, and 50% to workplace costs.3 This trend poses a substantial challenge for health systems in both developed and developing countries, with the need to treat patients, optimise resources, and improve overall health care in mental health.
Grouped into various classes of drugs with slightly different mechanisms of action, antidepressants are widely used treatments for major depressive disorder, which are available worldwide. However, there is a long-lasting debate and concern about their efficacy and effectiveness, because short-term benefits are, on average, modest; and because long-term balance of benefits and harms is often understudied.4 Therefore, innovation in psychopharmacology is of crucial importance, but the identification of new molecular targets is difficult, primarily because of the paucity of knowledge about how antidepressants work.5 In routine practice, clinicians have a wide choice of individual drugs and they need good evidence to make the best choice for each individual patient. Network meta-analyses of existing datasets make it possible to estimate comparative efficacy, summarise and interpret the wider picture of the evidence base, and to understand the relative merits of the multiple interventions.6 Therefore, in this study, we aimed to do a systematic review and network meta-analysis to inform clinical practice by comparing different antidepressants for the acute treatment of adults with unipolar major depressive disorder.
Here’s an excerpt from the Discussion section:
We found that all antidepressants included in the meta-analysis were more efficacious than placebo in adults with major depressive disorder and the summary effect sizes were mostly modest.
Some antidepressants, such as escitalopram, mirtazapine, paroxetine, agomelatine, and sertraline had a relatively higher response and lower dropout rate than the other antidepressants.
By contrast, reboxetine, trazodone, and fluvoxamine were associated with generally inferior efficacy and acceptability profiles compared with the other antidepressants, making them less favourable options. To make our results as relevant and robust as possible to inform clinical practice, we decided to focus on head-to-head studies and at the same time emphasise the certainty of the retrieved evidence. Our assessment overall found few differences between antidepressants when all data were considered, while there was more diversity in the range of efficacy and dropout patterns seen across the head-to-head comparisons than the meta-analysis of antidepressants versus placebo.
The present findings in adults contrast with the efficacy of antidepressants in children and adolescents, for which fluoxetine is probably the only antidepressant that might reduce depressive symptoms.21
This differential efficacy across age groups might reflect heterogeneous mechanisms and causes of depression,22 smaller number of studies in young people, or different methodological issues affecting adult and paediatric trials.23
The effect sizes were also smaller in more recent and larger placebo-controlled trials than in older and smaller ones, which might be an indicator of bias.
Here’s how the article ends: “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. All statements comparing the merits of one antidepressant with another must be tempered by the potential limitations of the methodology,32the 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.”
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—Niels Bohr, Nobel Prize in Physics (1885-1962)