The placebo-nocebo response in patients with depression: do we need to reconsider our treatment approach and clinical trial designs?

Conflicting data and misunderstanding of placebo and nocebo phenomena are essential components of the great scandal related to the treatment of depressive disorders. This scandal has two opposite aspects: glorification and vilification, contradictory estimates about under-prescription and over-prescription of antidepressant drugs. More than twenty years ago, Cassano (1992) cautioned that “depression is one of the great scandals of medicine” because “it is an underdiagnosed and undertreated disorder. Only a small percentage of depression is recognized, appropriately defined and studied. In addition, a limited number of patients receive treatment, and many of those who are treated receive inadequate dosages of antidepressant drugs. Furthermore, despite evidence showing that depression recurs and recommendation advocating the benefits of long-term maintenance treatment to prevent recurrence, only a few patients receive long-term treatment for depression”. Recently, Stahl (2013) also cautioned that “the true scandal lies in the treatment of the depressive disorders. A third of patients in a real life never fill their first antidepressant prescription, and for those who do, perhaps less than half get a second month of treatment and maybe less than a quarter get an adequate trial of 3 months or longer”. Despite the overall increase in number of depressed people seeking help, only half of them receive any form of treatment, and only about half of these receive adequate treatment (Kessler et al. 2003, Wancata & Friedrich 2011, Yapko 2013). From the opposite and vilifying view antidepressants reflect one of the major medicalization of living problems in modern society (Ioannidis 2008). Antidepressants are among the most widely prescribed medications all over the world although they are “little more than a deceptive product of greedy, lying pharmaceutical companies that sell hope to the hopeless” (see Yapko 2013). Selective and distorted reporting of RCTs results has been claimed to be a major problem. According to the critics antidepressants are not effective and their sideeffects and costs do not justify their use in clinical practice. Antidepressants are depicted as placebos with side-effects. Unfortunately, patients are affected by these attitudes through public media in different harmful ways. Depression, antidepressants and placebo-nocebo response