Effectiveness of antidepressants: an evidence myth constructed from a thousand randomized trials?

Antidepressants, in particular newer agents, are among the most widely prescribed medications worldwide with annual sales of billions of dollars. The introduction of these agents in the market has passed through seemingly strict regulatory control. Over a thousand randomized trials have been conducted with antidepressants. Statistically significant benefits have been repeatedly demonstrated and the medical literature is flooded with several hundreds of "positive" trials (both pre-approval and post-approval). However, two recent meta-analyses question this picture. The first meta-analysis used data that were submitted to FDA for the approval of 12 antidepressant drugs. While only half of these trials had formally significant effectiveness, published reports almost ubiquitously claimed significant results. "Negative" trials were either left unpublished or were distorted to present "positive" results. The average benefit of these drugs based on the FDA data was of small magnitude, while the published literature suggested larger benefits. A second meta-analysis using also FDA-submitted data examined the relationship between treatment effect and baseline severity of depression. Drug-placebo differences increased with increasing baseline severity and the difference became large enough to be clinically important only in the very small minority of patient populations with severe major depression. In severe major depression, antidepressants did not become more effective, simply placebo lost effectiveness. These data suggest that antidepressants may be less effective than their wide marketing suggests. Short-term benefits are small and long-term balance of benefits and harms is understudied. I discuss how the use of many small randomized trials with clinically non-relevant outcomes, improper interpretation of statistical significance, manipulated study design, biased selection of study populations, short follow-up, and selective and distorted reporting of results has built and nourished a seemingly evidence-based myth on antidepressant effectiveness and how higher evidence standards, with very large long-term trials and careful prospective meta-analyses of individual-level data may reach closer to the truth and clinically useful evidence.     

The 9th annual INDUS-EM 2013 Emergency Medicine Summit, “Principles,Practices, and Patients,” a level one international meeting,Kerala University of Health Sciences and Jubilee Mission Medical College and Research Institute,Thrissur, Kerala,India, October 23–27, 2013

INDUS-EM is India’s only level one conference imparting and exchanging quality knowledge in acute care. Specifically, in general and specialized emergency care and training in trauma, burns, cardiac, stroke, environmental and disaster medicine. It provides a series of exchanges regarding academic development and implementation of training tools related to developing future academic faculty and residents in Emergency Medicine in India. The INDUS-EM leadership and board of directors invited scholars from multiple institutions to participate in this advanced educational symposium that was held in Thrissur, Kerala in October 2013.     

A Two-Dimensional Theory of Health

The starting point for the contemporary debate about theories of health should be the holistic theory of Lennart Nordenfelt, claims George Khushf, not the refuted theory of Christopher Boorse. The present paper is an attempt to challenge Nordenfelt and to present an alternative theory to his and other theories, including Boorse’s. The main problems with Nordenfelt’s theory are that it is relativistic, that it leads to counter-intuitive results as to what goals can count as healthy, that it focuses on the wrong kind of abilities, that it makes measuring health extra difficult, and that it does not give us a sufficient account of health, at most a necessary one. The alternative theory proposed is two-dimensional. First, health is to have developed the abilities and dispositions that members of one’s culture typically develop, and be able to use them, in acceptable circumstances; and second, health is to experience positive moods and sensations, the kinds that have internal causes. The theory solves the problems attached to Nordenfelt’s theory by not being individual relativistic, by eliminating the goals in the definition, by giving an alternative interpretation of “ability,” by making health easier to measure, and by adding the dimension of well-being that, together with health as ability, not only gives us a necessary, but also a sufficient, account of health.