Zalospirone in major depression: a placebo-controlled multicenter study.
Compounds active at the serotonin (5-HT)1A receptor (mostly azapirones) have shown some evidence of antidepressant effect. We report here the results of an antidepressant trial with zalospirone, a novel cyclic imide with 5-HT1A partial agonist activity. Two hundred eighty-seven outpatients (mean age 44 years, 55% men, 45% nonfertile women) who met criteria for unipolar major depression with a minimum 21-item Hamilton Rating Scale for Depression (HAM-D) score of 20 were randomly assigned to receive 6 weeks of double-blind treatment with either placebo or one of three fixed doses of zalospirone (6, 15, or 45 mg/day), administered three times daily. The high dose (45 mg) of zalospirone produced a significant antidepressant effect compared with placebo from week 2 on with mean improvement (change from baseline) in HAM-D total score of 12.8 versus 8.4 (p < 0.05) at week 6. Clinical improvement with the high dose of zalospirone was consistent across all outcome measures, however, only in the observed cases and not the last-observation-carried-forward analyses. Improvement with the 6-mg or 15-mg doses was greater than that with placebo, but not significantly so, suggesting a dose-response effect. Although the 45-mg dose of zalospirone seemed to have significant antidepressant efficacy, it was not well tolerated. Dizziness and nausea were noted in almost half of the patients, and by week six, 51% of patients in the high-dose group had dropped out. Whether or not tolerance to this high dose might be improved by gradual drug titration, only future research can answer.
Rickels
K
K
Department of Psychiatry, University of Pennsylvania, Philadelphia.
Derivan
A
A
Kunz
N
N
Pallay
A
A
Schweizer
E
E
D000328:Adult; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy*; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D054833:Isoindoles; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*
D014151:Anti-Anxiety Agents; D054833:Isoindoles; D010879:Piperazines; D011743:Pyrimidines; C067729:zalospirone