Agomelatine (Valdoxan)

Medical Reviewer

According to its developers Agomelatine (Valdoxan) works faster than conventional serotonin reuptake inhibitors (SSRIs) has fewer side effects of conventional drugs, including weight gain, and won't put a dent in the users sex life. Agomelatine first released in 2009, is approved for the treatment of major depression in 41 countries including the UK, Australia and Canada, but it is not currently available in the U.S.A. So, what's the problem?

Agomelatine works on the hormone melatonin, which helps to regulate the body clock. Melatonin is produced at night but if sleep is disrupted, a common problem with depression, it disrupts the normal process. There is increasing evidence that disruption of the body clock (the circadian rhythm) is influential in mood disorders like depression. By mimicking the action of melatonin it helps to improve sleep, but a second action is an increase in levels of dopamine and noradrenaline to areas in the frontal cortex of the brain responsible for moods.

Reviews as to the therapeutic effects of Agomelatine are certainly mixed.   Some early randomized trials suggested it was no more effective than placebo although later controlled studies appeared to show it was as effective as the SSRI antidepressants paroxetine and sertraline, but not all antidepressants. The rights to market Agomelatine in the US were sold by Servier to Novartis in 2006 but the development phase was halted in 2011 when clinical trials suggested weak efficacy and an increase in the risk of liver damage if taken over longer periods.

Where Agomelatine is available it tends to be considered a possible alternative to SSRI medications if side effects have been especially problematic or where no response to SSRIs is seen. In the UK its use is not prevented but neither is it recommended by The National Institute for Health and Clinical Excellence (NICE) "because no evidence submission was received from the manufacturer or sponsor of the technology [but they will] review the position at any point if the manufacturer indicates that it wishes to make a full submission."


Kasper S, Hajak G, Wulff K, Hoogendijk WJ, Montejo AL, Smeraldi E, Rybakowski JK, Quera-Salva MA, Wirz-Justice AM, Picarel-Blanchot F, Baylé FJ (February 2010). "Efficacy of the novel antidepressant agomelatine on the circadian rest-activity cycle and depressive and anxiety symptoms in patients with major depressive disorder: a randomized, double-blind comparison with sertraline". J Clin Psychiatry 71 (2): 109-20.

NICE technology appraisal 231. Agomelatine for the treatment of major depressive episodes (terminated appraisal). July 2011. ISBN 978-1-84936-659-5