A Canadian multicenter study of three fixed doses of controlled-release ipsapirone in outpatients with moderate to severe major depression.
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.
Institute of Mental Health Research, Royal Ottawa Hospital, Ontario, Canada.
Y D
YD
Lapierre
P
P
Silverstone
R T
RT
Reesal
B
B
Saxena
P
P
Turner
D
D
Bakish
J
J
Plamondon
P M
PM
Vincent
R A
RA
Remick
C
C
Kroft
R
R
Payeur
D
D
Rosales
R
R
Lam
M
M
Bologa
D000293:Adolescent; D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D002170:Canada; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010555:Personality Inventory; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D003692:Delayed-Action Preparations; D011743:Pyrimidines; D017366:Serotonin Receptor Agonists; C043077:ipsapirone