1 The fair interpretation of these claims is that the placebo response is lower in severely depressed patients than in mild-to-moderate cases.2,3 Unfortunately, severe cases are frequently not recruited in efficacy trials, favoring the placebo response that produces negative results. In some publications, negative study results are taken as evidence that antidepressants are nothing but risky placebos.4 Such reports are hailed in some quarters and the lay press notoriously emphasizes the risk of such medications while neglecting their benefits. The subsequent loss of confidence is sobering, as depressed people, who should be treated with

antidepressants, Inhibitors,research,lifescience,medical might not be because they expect that these drugs may not help. In fact, depression poses an enormous load on any economy and is a potentially Danusertib lethal disease, as suicide

related to depression is a major cause of death in industrialized countries. The discovery and development of antidepressants Inhibitors,research,lifescience,medical in the 1950s markedly reduced this burden, but it is beyond question that better antidepressant drugs are needed. Currently available antidepressants have three major drawbacks: (i) They work in too few people, ie, response rates within 6 to 8 weeks are around 70% while remission rates are sometimes considerably lower; (ii) It takes too long until they work, ie, patients have to Inhibitors,research,lifescience,medical wait, sometimes more than

2 months, until they get markedly better; and Inhibitors,research,lifescience,medical (iii) despite substantial improvement among new antidepressants, they still have too many side effects that include tiredness, restlessness, sexual dysfunction, weight gain, and in some cases even aggressiveness.5 Great strides have been made in improving diagnosis of depressive disorder and its acceptance. As a result of such destigmatization, more cases are diagnosed and treated, but as shown in a recent analysis in Organisation for Economic Cooperation and Development (OECD) countries, there are Inhibitors,research,lifescience,medical still more than 50% of cases not receiving any treatment at all.6 In the light of this pressing need to improve the situation by treating many more patients with better antidepressants, it is perplexing that despite the enormous market potential almost all pharmaceutical industries in Europe and in the United States have put antidepressant research and development on hold. The papers in this Adenosine issue document that the skepticism at the management level of pharmaceutical companies is unjustified, and I will add a few other examples to underscore this. I will also make a few suggestions on how the situation of antidepressant drug discovery and development can be improved. The diagnostic controversy Diagnostic classification of psychiatric disorders has been a major problem in drug development in the past, and will be so in the future.