A phase II multicenter dose-finding, efficacy and safety trial of ipsapirone in outpatients with generalized anxiety disorder.

Benzodiazepines have been prescribed for the treatment of Generalized Anxiety Disorder (GAD) for nearly three decades due to their proven anxiolytic efficacy, despite a considerable side effect and abuse liability profile. A new class of compounds, the azapirones, have been developed as an alternative to benzodiazepine treatment. Ipsapirone is a novel anxiolytic azapirone which has high specificity for the 5-HT1A receptor and which has the potential for offering certain advantages over buspirone. The present 5-week study investigated three doses of ipsapirone (2.5mg, 5.0mg and 7.5mg tid) versus placebo in 267 GAD outpatients. Efficacy was evaluated using the Hamilton Anxiety Rating Scale (HAM-A), Zung Anxiety Scale (Zung-A), and Clinical Global Impression (CGI). The study design consisted of a 1-week placebo run-in, a 4-week double-blind treatment period, and a 1-week placebo washout. The 5.0mg group demonstrated consistently superior improvement in all efficacy variables during the treatment period, with significant differences (p < 0.05) from placebo and, at times, the 2.5mg and 7.5mg groups. Incidence of adverse events, primarily dizziness, nausea, sedation, and asthenia, was found to be dose proportional, with significant increase in the 7.5mg group, which may account for the diminished effectiveness seen with this dose. Our results suggest that ipsapirone may represent a viable treatment for GAD.