A Double-Blind, Placebo-Controlled Study Comparing the Efficacy and Safety of Ipsapirone Versus Lorazepam in Patients With Generalized Anxiety Disorder
This multicenter, double-blind, placebo-controlled, randomized study compared 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 moderate or greater severity. A total of 317 outpatients with a primary diagnosis of GAD according to DSM-III criteria (at least 1 month's duration) 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 treatment period, and a 4-week extension period, followed by a 2-week, single-blind placebo withdrawal period. Efficacy was measured by changes in the HAM-A and Clinical Global Impression Scale and by evaluations of the Hamilton Rating Scale for Depression and Zung-Anxiety Self-Rating scale. The Raskin and Covi scales were performed at screening and baseline only. Withdrawal reactions were assessed during the withdrawal 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), and placebo (N = 87) groups. Both ipsapirone (mean daily dose, 18.0 mg) and lorazepam (mean daily dose, 3.5 mg) significantly (p & 0.05) reduced HAM-A and Clinical Global Impression scores during the acute treatment phase. Two hundred fifty-four patients completed the acute phase, and 16 patients dropped out of the study because of adverse events (ipsapirone, N = 7; lorazepam, N = 4; and placebo, N = 5) during this phase. Study medication was reduced for 87 patients because of adverse events during the acute phase (ipsapirone, N = 35; lorazepam, N = 35; and 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, performed at weeks 9 and 10, demonstrated greater withdrawal symptoms, such as rebound anxiety, in patients treated with lorazepam as compared with 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 more rational and selective therapy for GAD. (J Clin Psychopharmacol 1993;13:429–437)