A Canadian Multicenter Study of Three Fixed Doses of Controlled-Release Ipsapirone in Outpatients With Moderate to Severe Major Depression

Abstract

Ipsapirone, an azapirone with 5-hydroxytryptamine (5-HT1A) partial agonist activity, has been shown in preliminary studies to be effective in 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 severe major depression (Hamilton Rating Scale for Depression [HAM-D] score > or = 20). The 10-mg ipsapirone treatment arm was discontinued early in the study. A total of 390 patients were eligible for evaluation in the intent-to-treat sample. The primary efficacy variable was the change in HAM-D total score from baseline to visit 8. There was no significant difference in efficacy in the two treatment groups versus the placebo group. The overall treatment response, defined as a 50% decrease in the HAM-D total score from baseline, was 43% with ipsapirone 50 mg given once daily, 34% with ipsapirone 30 mg given once daily, and 35% with placebo. In subanalyses, ipsapirone 50 mg given once daily was superior to placebo according to the HAM-D Core Depression (mood, guilt, interest, psychomotor activity) subtotal (p = 0.0453) and Melancholic item (p = 0.0225). Ipsapirone 30 mg given once daily was superior to placebo only in patients with moderate depression (baseline HAM-D total score < or = 25; p = 0.0100). The most common adverse effect in all groups was headache. The only dose-dependent adverse effects were dizziness and nausea.

Synergistic Action of 5-HT2A Antagonists and Selective Serotonin Reuptake Inhibitors in Neuropsychiatric Disorders

“…Furthermore, no positive double-blind placebo-controlled reports of antidepressant activity in depressed patients have been reported for the 5-HT 1A partial agonists tandospirone and flesinoxan. A large multicenter, double-blind, placebo-controlled trial for ipsapirone failed to observe a significant antidepressant response, despite a placebo response rate of only 35% (Lapierre et al, 1998). Finally, it should be noted that no 5-HT 1A partial agonists have been approved by the FDA for the treatment of major depression.…”

Looking in the wrong place? The search for an ideal migraine preventative

“…Furthermore, drugs that decrease the discharge rate of NRM neurons such as ipsapirone [Fornal et al, 1994], MCPP [Sprouse and Aghajanian, 1988] and 5-methoxydimethyltryptamine [Fornal et al, 1985] precipitate migraine-like headaches with a high degree of reliability [Fozard and Gray, 1989;Lapierre et al, 1998;Yu et al, 1991]. Conversely, drugs like methiothepin, methysergide, and cyproheptadine, which increase the discharge rate of raphe neurons [Blier et al, 1993] have been used to prevent migraine.…”

Monoaminergic‐based Pharmacotherapy for Depression

“…Other newer 5HT1A agonists are also being developed; ipsapirone (Stahl et al, 1998) and zalospirone (Rickels et al, 1996) are reported to have greater effectiveness than placebo in controlled trials, while a second trial of iprapirone showed greater efficacy over placebo only for core depressive symptoms (Lapierre et al, 1998). For the serotonin 5HT1A partial agonist flesinoxan, only a small open trial in patients with treatment-resistant depression has been reported (Grof et al, 1993).…”