Agomelatine: A Novel Antidepressant Therapy

States was estimated to be 9%. Major depression can lead to deleterious effects on the medical, social, and vocational lives of sufferers in addition to costing the economy more than $50 billion per year as a result of treatment costs and lost productivity. Despite a steady increase in the size of the antidepressant armamentarium, no randomized clinical trial has demonstrated at least a 50% response for major depression (much less for the more significant endpoint of remission). Furthermore, all available antidepressants trace their mechanisms of action back to the biogenic amine hypothesis, raising the question of whether other avenues might produce more effective treatments. To that end, we examine the data for the efficacy, safety, and comparative effectiveness of agomelatine, a novel antidepressant. Disruptions of the sleep-wake cycle are key features of mood disorders, and residual symptoms, including sleep disturbances, are well-known risk factors for relapse. Furthermore, various manipulations of circadian rhythm (eg, rapid eye movement [REM] sleep deprivation, phase advancement) may produce antidepressant activity. Thus, influencing circadian rhythm patterns could be a potential antidepressant strategy. The core biological clock is located in the suprachiasmatic nucleus (SCN) in the anterior hypothalamus. The rhythms generated by the SCN are continuously synchronized by photic and nonphotic signals (Figure 1). The primary nonphotic inputs to the SCN originate in the median raphe nucleus, a major site of serotonergic neurons. The SCN projects to the pineal gland, stimulating the synthesis of melatonin, which provides negative feedback onto the pineal gland. Although it is neither a pacemaker nor does it function independently as an antidepressant, its main function is to set the endogenous clock’s sensitivity to light. Melatonin also acts to set the onset and duration of darkness by producing phase shifts in the signal patterns of the SCN. Data from rodent and primate studies indicate that the serotonergic projections onto the SCN serve to modulate After participating in this CME activity, the psychiatrist should be better able to: • Evaluate the pharmacologic profile of agomelatine and its potential mechanism of action. • Interpret the trial data supporting the efficacy of agomelatine in the treatment of major depression. • Compare the adverse-effect profile of agomelatine with that of other commonly used antidepressants.