Escitalopram has demonstrated a robust and dose-dependent efficacy in the treatment of generalized anxiety disorder (GAD) for up to 3 months. In the present study, the efficacy and tolerability of escitalopram in the prevention of relapse in GAD was investigated. A total of 491 patients with a primary diagnosis of GAD and a Hamilton Anxiety (HAMA) total score>or=20 received 12 wk of open-label treatment with a fixed dose of escitalopram (20 mg/d). Of these, 375 patients responded (HAMA total score<or=10) and were randomized to double-blind treatment with 20 mg/d escitalopram (n=187) or placebo (n=188). Treatment was continued for 24-76 wk unless the patient relapsed or was withdrawn for other reasons. Relapse was defined as either an increase in HAMA total score to >or=15, or lack of efficacy, as judged by the investigator. The results of the primary analysis showed a clear beneficial effect of escitalopram relative to placebo on the time to relapse of GAD (log-rank test, p<0.001). The risk of relapse was 4.04 times higher for placebo-treated patients than for escitalopram-treated patients; the proportion of patients who relapsed was statistically significantly higher in the placebo group (56%) than in the escitalopram group (19%) (p<0.001). Escitalopram was well tolerated and 7% of the escitalopram-treated patients withdrew due to adverse events, vs. 8% of the placebo patients. The incidence of discontinuation symptoms with escitalopram during tapered withdrawal was low; the symptoms primarily being dizziness (10-12%), nervousness (2-6%), and insomnia (2-6%). Escitalopram 20 mg/d significantly reduced the risk of relapse and was well tolerated in patients with GAD.