Treating each and every depressed patient.
Major depressive disorder (MDD) is a prevalent condition with substantial heterogeneity in terms of clinical symptom profiles, overlapping syndromes and degree of severity. The challenge for any new antidepressant is to demonstrate efficacy across the spectrum of patient subpopulations with a diagnosis of MDD. The anxious depressed patient historically has a lower rate of response to traditional antidepressants and high pretreatment anxiety symptoms have also been shown to increase the risk of recurrence. In addition, severity based on standard antidepressant rating scale scores influences treatment outcomes. Some antidepressants display greater placebo separation at higher levels of severity while others fail to separate from placebo in more severe populations. Gender differences in antidepressant response have also been reported in several studies. In particular, women appear to experience a greater side-effect burden with current antidepressants. This is also important in treating late-life depression, where elderly patients are more prone to experiencing side effects and drug interactions. Despite the improved tolerability with SSRIs and other novel antidepressants, restoration of healthy sleep patterns has frequently been lacking. Finally, antidepressant efficacy must include demonstrated relapse prevention during placebo-controlled drug discontinuation trials. As a novel antidepressant with melatonin receptor agonist and 5HT(2C) antagonist properties, agomelatine has demonstrated efficacy in randomized placebo-controlled trials. Additional analyses support the benefits of agomelatine in anxious depression, increasing efficacy with greater baseline severity, including severe late-life depression. Agomelatine has also demonstrated favourable tolerability and efficacy in separate analyses of women and men and displays successful relapse prevention at doses 25 and 50 mg. Both subjective and polysomnographic measures of sleep support increased sleep efficiency and decreased awakenings during agomelatine treatment. Combining these efficacy data with favourable effects on sexual function, CNS and GI systems, there are grounds to endorse the view that agomelatine is a well-tolerated and efficacious antidepressant for a diverse range of depressed populations.
Kennedy
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University Health Network, University of Toronto, Toronto, Ontario, Canada. sidney.kennedy@uhn.on.ca