Agomelatine improves symptoms of generalised anxiety disorder.

ED FROM Stein DJ, Ahokas AA, de Bodinat C. Efficacy of agomelatine in generalized anxiety disorder: A randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol 2008;28:561– 6. Correspondence to: Dan J Stein, Department of Psychiatry, Groote Schuur Hospital, University of Cape Town, Anzio Road, Observatory, 7925, Cape Town, South Africa: [email protected] Source of funding: Servier, France. c Additional notes are published online only at http://ebmh.bmj.com/content/vol12/ issue2 C O M M EN TA R Y G eneralised anxiety disorder (GAD) is a common, typically persistent and burdensome condition, but many of those who might benefit from treatment are not recognised or treated. Evidence based guidelines for pharmacological management recommend initial treatment with either a selective serotonin reuptake inhibitor (SSRI) or a serotonin–noradrenaline reuptake inhibitor (SNRI). However, there is room for improvement in both the efficacy and tolerability of treatment; response rates can be disappointing, some patients will relapse despite continuing medication and many experience troublesome adverse effects. The exact mechanism of action underlying the antidepressant and anxiolytic efficacy of agomelatine is uncertain. Melatonin agonism alone is unlikely to be responsible, it being more probable that accompanying antagonism of 5-HT2C receptors, which enhances the release of noradrenaline and dopamine within the prefrontal cortex, combines with melatonergic effects to improve mood and correct disturbances of bodily rhythms. Antagonism of 5-HT2A/2C receptors has already been found to be efficacious in acute treatment in patients with GAD but this is the first evidence that agomelatine exerts anxiolytic effects in non-depressed patients. The decline in anxiety symptom severity and the proportion of patients meeting responder criteria is broadly similar to that seen with SSRIs or SNRIs, with a difference of approximately 3 points between agomelatine and placebo on the primary outcome measure at study endpoint, this difference being conventionally regarded as being clinically relevant. The relatively greater effects in relieving somatic (physical) anxiety symptoms when compared with placebo is intriguing, as antidepressant drugs are traditionally viewed as being more efficacious in reducing psychological symptoms. The sample size is probably insufficient to allow complete confidence here. More compelling is the evidence of good overall tolerability and absence of excess discontinuation symptoms after the withdrawal of double blind treatment; if these advantages are replicated, agomelatine could come to occupy an important role in wider practice. David S Baldwin, DM, FRPsych, Antonio T Lopes, MBBS, MRCPsych Clinical Neuroscience Division, School of Medicine, University of Southampton, Southampton, UK Competing interests: DSB has received personal honoraria from the manufacturers of agomelatine. ATL has no competing interests to declare. 1. Baldwin DS. Room for improvement in the pharmacological treatment of anxiety disorders. Curr Pharm Design 2008;14:3482–91. 2. Stahl S. Novel mechanism of antidepressant action: norepinephrine and dopamine disinhibition (NDDI) plus melatonergic agonism. Int J Neuropsychopharmacol 2007;10:575–8. 3. Naukkarinen H, Raassina R, Penttinen J, et al. Deramciclane in the treatment of generalized anxiety disorder: a placebo-controlled, double-blind, dosefinding study. Eur Neuropsychopharmacol 2005;15: 617–23. Therapeutics 54 EBMH May 2009 Vol 12 No 2 on 4 July 2009 ebmh.bmj.com Downloaded from