SAFETY OF IPSAPIRONE TREATMENT COMPARED WITH LORAZEPAM - DISCONTINUATION EFFECTS

Objective: To determine discontinuation effects of ipsapirone, a novel azapirone and partial 5-HT1A agonist that has anxiolytic effects clin ically and has not caused dependence or withdrawal symptoms in animals , and to compare these effects with those of the benzodiazepine loraze pam, owing to concern about dependence or withdrawal symptoms followin g use of these drugs. Design: Prospective, randomized, double-blind, p lacebo-controlled trial. Setting: Outpatient and inpatient treatment. Participants: Sixty-five healthy male volunteers who had experience wi th sedative-hypnotics or anxiolytics and did not meet DSM-III-R criter ia for abuse or dependence. Interventions: Participants were randomize d to receive ipsapirone 15 mg per day (n = 17), ipsapirone 22.5 mg per day (n = 16), lorazepam 3 mg per day (n = 16), or placebo (n = 16) as outpatients for 36 days (treatment) followed by single-blind placebo as inpatients for 3 days and as outpatients for 6 days (withdrawal). O utcome measures: Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depre ssion Scale (HAM-D), Spielberger State Anxiety Scale, Sleep Quality Qu estionnaire, General Symptom Checklist, self-rated intoxication, Clini cal Institute Withdrawal Assessment - Benzodiazepines (CIWA-Benzo), ps ychomotor testing and urine drug screen. Results: Only 45 subjects com pleted the study; discontinuation rates did not significantly differ a mong treatment groups. At day 39, fewer and less severe symptoms (e.g. , insomnia and fatigue) were found on the CIWA-Benzo scale after treat ment with ipsapirone or placebo than after treatment with lorazepam (p < 0.05). Subjects reported longer sleep latency and poorer sleep qual ity after receiving lorazepam than after receiving ipsapirone or place bo. Scores on the HAM-D, Spielberger State Anxiety and HAM-A scales di d not change from baseline. Conclusions: Withdrawal symptoms were dete cted after discontinuation of therapeutic doses of lorazepam. Signific antly fewer symptoms were observed after withdrawal from anxiolytic do ses of ipsapirone.