A CANADIAN MULTICENTER STUDY OF 3 FIXED DOSES OF CONTROLLED-RELEASE IPSAPIRONE IN OUTPATIENTS WITH MODERATE TO SEVERE MAJOR DEPRESSION

Ipsapirone, an azapirone with B-hydroxytryptamine (5-HT1A) partial ago nist activity, has been shown in preliminary studies to be effective i n the treatment of major depressive disorder. This 8-week, randomized, double-blind study compared the efficacy, safety, and tolerability of three fixed doses of controlled-release ipsapirone (10-, 30-, and 50- mg dose once daily) with placebo in 410 patients with moderate to seve re major depression (Hamilton Rating Scale for Depression [HAM-D] scor e greater than or equal to 20). The 10-mg ipsapirone treatment arm was discontinued early in the study. A total of 390 patients were eligibl e for evaluation in the intent-to-treat sample. The primary efficacy v ariable was the change in HAM-D total score from baseline to visit 8. There was no significant difference in efficacy in the two treatment g roups versus the placebo group. The overall treatment response, define d as a 50% decrease in the HAM-D total score from baseline, was 43% wi th ipsapirone 50 mg given once daily, 34% with ipsapirone 30 mg given once daily, and 35% with placebo. In sub-analyses, ipsapirone 50 mg gi ven once daily was superior to placebo according to the HAM-D Core Dep ression (mood, guilt, interest, psychomotor activity) subtotal (p = 0. 0453) and Melancholic item (p = 0.0225). Ipsapirone 30 mg given once d aily was superior to placebo only in patients with moderate depression (baseline HAM-D total score less than or equal to 25; p = 0.0100). Th e most common adverse effect in all groups was headache. The only dose -dependent adverse effects were dizziness and nausea.