Gepirone extended-release: new evidence for efficacy in the treatment of major depressive disorder.
OBJECTIVE
To assess the efficacy and tolerability of the 5-HT(1A) agonist gepirone in extended-release formulation (gepirone-ER) versus placebo in patients with major depressive disorder.


METHODS
Patients aged 18 to 70 years were eligible if they satisfied DSM-IV criteria for moderate-to-severe major depressive disorder and had a baseline 17-item Hamilton Rating Scale for Depression (HAM-D-17) score > or = 20. After a 4- to 7-day placebo washout period, patients were randomly assigned to receive either placebo (N = 106) or gepirone-ER (20-80 mg/day) (N = 103) for 56 days. Assessments were done at weeks 1-4, 6, and 8.


RESULTS
Mean change from baseline in HAM-D-17 score within the intent-to-treat group (gepirone, N = 101; placebo, N = 103) was significantly greater with gepirone-ER than placebo at weeks 3 (p =.013) and 8 (p =.018). Significantly (p <.05) more patients receiving gepirone-ER than placebo were HAM-D-17 responders at weeks 3 (33.7% vs. 18.8%, respectively) and 4 (38.6% vs. 24.8%, respectively) and HAM-D-17 remitters at weeks 6 (24.8% vs. 13.9%, respectively) and 8 (28.7% vs. 14.9%, respectively). Mean change from baseline for HAM-D-25 total score was significantly (p < pr =.05) greater with gepirone-ER at all assessments except week 6. The proportion of HAM-D-25 responders was significantly greater (p < or =.05) with gepirone-ER at weeks 3 and 8. Gepirone-ER was well tolerated: 9.8% of the gepirone-ER group and 2.8% of the placebo group discontinued due to adverse events. Common adverse events were considered mild and included dizziness, nausea, and insomnia. Gepirone-ER did not differ statistically compared with placebo in weight gain or sedation. Furthermore, preliminary evidence suggested that gepirone-ER may not be associated with sexual dysfunction. No serious adverse events occurred in gepirone-treated patients.


CONCLUSIONS
Gepirone-ER is effective for the short-term treatment of major depressive disorder and is well tolerated.
Feiger
Alan D
AD
Feiger Health Research Center, Wheat Ridge, CO 80033, USA. al@feigerresearch.com
Heiser
Jon F
JF
Shrivastava
Ram K
RK
Weiss
Kenneth J
KJ
Smith
Ward T
WT
Sitsen
J M A
JM
Gibertini
Michael
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D003692:Delayed-Action Preparations; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy*; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D006801:Humans; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D016896:Treatment Outcome
D003692:Delayed-Action Preparations; D010919:Placebos; D011743:Pyrimidines; D017366:Serotonin Receptor Agonists; C039979:gepirone