Agomelatine for Bipolar Depression: A Chronotherapeutic Agent?

Background: Bipolar Disorder is a severe psychiatric condition, characterized by depressive and manic mood states. Depressive mood remains a problem for most patients, as this is the predominant mood state, and because the options we have for treating depression remain scarce. Therefore, the quest for new treatment options is ongoing. Objective: We focus here on one approach in particular, regarding the known influence of factors that disrupt the circadian rhythm in the precipitation of new episodes, as well as the methods available to restore this rhythm, and a new treatment which could theoretically be particularly good for this purpose: Agomelatine. How does it work? What relation does it have to circadian timing? What do we know of its efficacy in treating bipolar depression? And finally, is it an acceptable treatment? Method: We performed a literature review about the relation of melatonin to circadian cycles, the disruption of circadian rhythms in Bipolar Disorder, chronotherapeutics and finally on agomeltine’s pharmacodynamic profile and use to treat bipolar depression. Conclusion: Agomelatine shows two very interesting mechanisms of action, a potent overactivation of dopaminergic and noradrenergic neurons in the prefrontal cortex and the amelioration of sleep and more importantly, the amelioration of sleep structure and regulation of circadian rhythms. These may represent an effective option for the depressive phase in bipolar disorder, both as an acute treatment and as a prevention for future relapse.