A DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY COMPARING THE EFFICACY AND SAFETY OF IPSAPIRONE VERSUS LORAZEPAM IN PATIENTS WITH GENERALIZED ANXIETY DISORDER - A PROSPECTIVE MULTICENTER TRIAL

This multicenter, double-blind, placebo-controlled, randomized study c ompared the efficacy, safety, and tolerability of ipsapirone (an azapi rone anxiolytic) at daily dose levels of 10.0 to 30.0 mg with a daily dose of 2.0 to 6.0 mg of lorazepam (a benzodiazepine) or placebo when given to outpatients with generalized anxiety disorder (GAD) of modera te or greater severity. A total of 317 outpatients with a primary diag nosis of GAD according to DSM-III criteria (at least 1 month's duratio n) were randomized. Study entry criteria at the time of screening and at baseline included a Hamilton Rating Scale for Anxiety (HAM-A) score of 18 or more, a Covi Anxiety Scale score of 8 or more, and a Raskin Depression Scale score of 7 or less. The study design consisted of a 1 -week, single-blind placebo evaluation, a 4-week, double-blind acute t reatment period, and a 4-week extension period, followed by a 2-week, single-blind placebo withdrawal period. Efficacy was measured by chang es in the HAM-A and Clinical Global Impression Scale and by evaluation s of the Hamilton Rating Scale for Depression and Zung-Anxiety Self-Ra ting scale. The Raskin and Covi scales were performed at screening and baseline only. Withdrawal reactions were assessed during the withdraw al period by the Physician Withdrawal Checklist and by a patient self- rating checklist. Two-hundred sixty-three patients were valid for the analysis of efficacy in the ipsapirone (N = 87), lorazepam (N = 89), a nd placebo (N = 87) groups. Both ipsapirone (mean daily dose, 18.0 mg) and lorazepam (mean daily dose, 3.5 mg) significantly (p < 0.05) redu ced HAM-A and Clinical Global Impression scores during the acute treat ment phase. Two hundred fifty-four patients completed the acute phase, and 16 patients dropped out of the study because of adverse events (i psapirone, N = 7; lorazepam, N = 4; and placebo, N = 5) during this ph ase. Study medication was reduced for 87 patients because of adverse e vents during the acute phase (ipsapirone, N = 35; lorazepam, N = 35; a nd placebo, N = 17). A total of nine patients dropped out because of a lack of efficacy in the acute phase (ipsapirone, N = 2; lorazepam, N = 2; placebo, N = 5). The Physician Withdrawal Checklist ratings, perf ormed at weeks 9 and 10, demonstrated greater withdrawal symptoms, suc h as rebound anxiety, in patients treated with lorazepam as compared w ith patients on ipsapirone. Both lorazepam and ipsapirone demonstrated significantly more side effects than placebo. Ipsapirone was shown to be equally as effective as lorazepam in the management of GAD, and as a result of fewer withdrawal symptoms, ipsapirone may represent a mor e rational and selective therapy for GAD.