Venlafaxine inhibits presynaptic reuptake of both serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (norepinephrine). Dysregulation of one or both of these neurotransmitters has been implicated in anxiety disorders, which often co-exist with depressive disorders.Venlafaxine extended release (XR) formulation has been evaluated in patients with generalised anxiety disorder (GAD) as defined in the DSM-IV without comorbid major depression. In randomised, double-blind, placebo-controlled, multicentre studies, venlafaxine XR 75 to 225 mg/day produced greater improvements in Hamilton Rating Scale for Anxiety (HAM-A) total scores than placebo. A therapeutic effect was evident within 1 week of the initiation of treatment with venlafaxine XR and improvements were sustained over ≤28 weeks. In 2 long term (6 month) studies all dosages of venlafaxine were significantly better than placebo. In an 8-week study venlafaxine XR 225 mg/day (but not lower dosages) was significantly better than placebo with respect to reductions in HAM-A total scores. Discontinuation because of an unsatisfactory clinical response was consistently less common among 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-controlled multicentre trials. Reductions in HAM-A total scores in patients receiving active treatment exceeded those in placebo recipients, but were not statistically significant in either study.Adverse events pertaining to the digestive (nausea, dry mouth), nervous (insomnia, somnolence, dizziness) and urogenital systems (abnormal ejaculation) were the most frequently reported adverse events in venlafaxine recipients during 8 weeks of treatment in 2 randomised, double-blind, placebo-controlled, multicentre studies.In conclusionvenlafaxine XR is the only antidepressant presently approved for, and shown to be effective, in the long term management (i.e. ≤6 months) of GAD.