Gepirone extended-release in the treatment of adult outpatients with major depressive disorder: a double-blind, randomized, placebo-controlled, parallel-group study.
OBJECTIVE
To evaluate the efficacy and tolerability of extended-release gepirone (gepirone-ER), a 5-HT(1A) agonist, versus placebo in the treatment of adult outpatients with major depressive disorder (MDD).


METHODS
A double-blind, randomized, placebo-controlled, parallel-group, 8-week study was conducted from October 2003 to August 2004 in outpatients 18 to 64 years old with moderate-to-severe MDD, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), and a baseline Hamilton Rating Scale for Depression (HAM-D(17)) total score > or = 20. Patients were titrated from 20 to 80 mg/day of gepirone-ER or placebo (most patients received gepirone-ER 60 or 80 mg/day by week 3). The primary outcome measure was baseline-to-endpoint mean change in HAM-D(17) total score. Secondary outcome measures included the 28-item version of the HAM-D, HAM-D depressed mood (item 1), Bech Six-Item Scale, Montgomery-Asberg Depression Rating Scale, and Clinical Global Impressions scale.


RESULTS
Significantly greater reductions in HAM-D(17) total scores occurred in gepirone-ER-treated patients compared with placebo-treated patients by week 4 (p = .004) and continued through weeks 6 (p = .006) and 8 (p = .032). Secondary outcomes also improved significantly at multiple timepoints, including at endpoint. The most frequently reported adverse events in the gepirone-ER versus placebo groups were dizziness (45% vs. 10%), nausea (36% vs. 13%), and headache (24% vs. 16%). Dizziness occurred most frequently during initial dosing and up-titration.


CONCLUSIONS
Gepirone-ER significantly reduced depression symptoms and illness severity in MDD outpatients through the end of the study and was generally well tolerated, confirming previous findings.
Bielski
Robert J
RJ
Summit Research Network, Inc., Okemos, Mich 48864, USA. rbielski@summitnetwork.com
Cunningham
Lynn
L
Horrigan
Joseph P
JP
Londborg
Peter D
PD
Smith
Ward T
WT
Weiss
Kenneth
K
D000293:Adolescent; D000328:Adult; D000553:Ambulatory Care; D003692:Delayed-Action Preparations; D003710:Demography; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires
D003692:Delayed-Action Preparations; D011743:Pyrimidines; D017366:Serotonin Receptor Agonists; C039979:gepirone