Venlafaxine extended-release - A review of its clinical potential in the management of generalised anxiety disorder

Venlafaxine inhibits presynaptic reuptake of both serotonin (5-hydroxytrypt amine: 5-HT) and noradrenaline (norepinephrine). Dysregulation of one or bo th of these neurotransmitters has been implicated in anxiety disorders, whi ch often co-exist with depressive disorders. Venlafaxine extended release (XR) formulation has been evaluated in patient s with generalised anxiety disorder (GAD) as defined in the DSM-IV without comorbid major depression. Ln randomised, double-blind, placebo-controlled, multi-centre studies, venlafaxine XR 75 to 225 mg/day produced greater imp rovements in Hamilton Rating Scale for Anxiety (HAM-A) total scores than pl acebo. A therapeutic effect was evident within 1 week of the initiation of treatment with venlafaxine XR and improvements were sustained over less tha n or equal to 28 weeks. In 2 long term (6 month) studies all dosages of ven lafaxine were significantly better than placebo. In an 8-week study venlafa xine XR 225 mg/day (but not lower dosages) was significantly better than pl acebo with respect to reductions in HAM-A total scores. Discontinuation bec ause of an unsatisfactory clinical response was consistently less common am ong recipients of venlafaxine XR than placebo in the long term studies. Venlafaxine XR 75 and 150 mg/day was at least as effective as buspirone 30 mg/day and diazepam 15 mg/day in 2 randomised, double-blind, placebo-contro lled multicentre trials. Reductions in HAM-A total scores in patients recei ving active treatment exceeded those in placebo recipients, but were not st atistically significant in either study. Adverse events pertaining to the digestive (nausea, dry mouth), nervous (in somnia, somnolence, dizziness) and urogenital systems (abnormal ejaculation ) were the most frequently reported adverse events: in venlafaxine recipien ts during 8 weeks of treatment in 2 randomised, double-blind, placebo-contr olled, multi-centre studies. In conclusion venlafaxine XR is the only antidepressant presently approved for, and shown to be effective, in the long term management (i.e. less than or equal to6 months) of GAD.