Mood Disorders, Circadian Rhythms, Melatonin and Melatonin Agonists

Recent advances in the understanding of circadian rhythms have led to an interest in the treatment of major depressive disorder with chronobiotic agents. Many tissues have autonomous circadian rhythms, which are orchestrated by the master clock, situated in the suprachiasmatic nucleus (SNC). Melatonin (N-acetyl-5-hydroxytryptamine) is secreted from the pineal gland during darkness. Melatonin acts mainly on MT1 and MT2 receptors, which are present in the SNC, regulating physiological and neuroendocrine functions, including circadian entrainment, referred to as the chronobiotic effet. Circadian rhythms has been shown to be either misaligned or phase shifted or decreased in amplitude in both acute episodes and relapse of major depressive disorder (MDD) and bipolar disorder. Manipulation of circadian rhythms either using physical treatments (such as high intensity light) or behavioral therapy has shown promise in improving symptoms. Pharmacotherapy using melatonin and pure melatonin receptor agonists, while improving sleep, has not been shown to improve symptoms of depression. A novel antidepressant, agomelatine, combines 5HT2c antagonist and melatonin agonist action, and has shown promise in both acute treatment of MDD and in preventing relapse

Agomelatine in unipolar depression in clinical practice: a retrospective chart review

Agomelatine (Valdoxan), a synthetic melatonergic receptor agonist at the MT1 and MT2 receptors, was first used in the management of sleep disorder. Its 5HT2C receptor antagonistic properties support its antidepressant potential. It is currently licensed in the UK, Europe and USA for the treatment of major depressive disorder. Although the randomized controlled evidence base for its use is growing, there are no retrospective, naturalistic studies available. We aimed to determine the tolerability and clinical effectiveness of agomelatine in unipolar depression. We also examined whether being refractory to treatment altered clinical outcome. Forty-eight patient records were examined. Twenty-five percent were treatment refractory: Clinical Global Impression (CGI) Severity score at the start of treatment was 3.81 compared with 3.38 at the end of treatment. Fifty-four percent improved at least minimally; only 12.5% were much or very much improved. Treatment-refractory patients had a poorer outcome with higher discontinuation rates and lower CGI Improvement (p = 0.0205). Treatment-refractory patients also had a higher CGI Severity score at the end of treatment than at treatment commencement (3.92 versus 3.75), although this was not statistically significant