Stein D, Márquez MS, Höschl C, Ahokas A, Oh KS, Jarema M, Avedisova A, Vavrusova L, Olivier V. Efficacy and tolerability of agomelatine in generalized anxiety disorder (GAD): A randomised double-blind, placebo-controlled trial with escitalopram as validator. P-04-019, 28th CINP World Congress of Neuropsychopharmacology. Stockholm, 3-7 June 2012

6. 6. 2012


Objective
Agomelatine, a MT1/MT2 receptor agonist and 5-HT2C receptor antagonist, has demonstrated efficacy in GAD. This 12 weeks multi-centre, randomised, double-blind, parallel group study in GAD aimed to confirm the superiority of agomelatine (25-50mg/day) vs placebo, using escitalopram (10-20mg/day) as a validator, on the Hamilton Anxiety Rating Scale (HAMA) total score.

Methods
412 patients with a DSM-IV diagnosis of GAD were randomised to receive agomelatine (139), placebo (131) or escitalopram (142). The HAMA total scores at baseline in the Full Analysis Set (FAS) (n=409) were respectively: 28.6; 28.2 and 28.6.

Results
At last value, the HAMA total score decreased significantly more with agomelatine -15.6(p<.0001) and with escitalopram –15.6(p<.0001) compared to placebo -10.6. In patients with more severe GAD symptoms (HAMA total score >= 25 and CGI-S>= 5 at baseline), the between group difference vs placebo was 5.61 for agomelatine (SE=1.49, p<0.001) and 4.08 for escitalopram (SE=1.50, p=0.007).

Significant improvement of patients’ functioning was clearly shown on the Sheehan Disability Scale (SDS) for agomelatine and escitalopram compared to placebo at the last value with a SDS work score between group difference vs placebo of 1.69 for agomelatine and 1.55 for escitalopram (SE=0.35, p<0.0001 for both comparisons). Similar results were observed on both the SDS social and family life scores (unplanned analyses).

The proportion of patients reporting at least one Emergent Adverse Event (EAE) was 47.5% with agomelatine, 48.2% with escitalopram and 44.3% with placebo. Fewer patients discontinued the treatment for EAE with agomelatine (2.2%) and placebo (3.5%) than with escitalopram (8.5%). The most commonly reported EAEs were headache, nasopharyngitis, diarrhoea, and nausea.

Conclusion
This study confirms that agomelatine is efficacious and well tolerated in the treatment of GAD.

Policy of full disclosure
Pr. STEIN has received research grants and/or consultancy honoraria from Abbott, Astrazeneca, Eli-Lilly, GlaxoSmithKline, Jazz Pharmaceuticals, Johnson & Johnson, Lundbeck, Orion, Pfizer, Pharmacia, Roche, Servier, Solvay, Sumitomo, Takeda, Tikvah, and Wyeth.