A single-site, double-blind, placebo-controlled, dose-ranging study of YKP10A--a putative, new antidepressant.

Background: YKP10A is a novel, new antidepressant that may affect dopamine neurotransmission. We present results from the first Phase II clinical trial of YKP10A antidepressant activity in patients with major depression.

Methods: This was a single-site, placebo-controlled, dose-ranging study. Patients with major depression were randomly assigned to one of four double-blind treatment conditions: YKP10A 100-300 mg/day, YKP10A 400-600 mg/day, YKP10A 700-900 mg/day, or placebo for 8 weeks.

Results: 43 patients were screened and 35 were randomized. Nineteen patients (54.3%) completed the entire 8-week study. Five YKP10A-treated patients (19%) discontinued treatment for adverse events. Thirty-eight percent of patients in the medium dose YKP10A group had a reduction in baseline HAM-D17 score > or = 50% compared with the low-dose (13%), high-dose (13%), and placebo (29%) groups. A similar nonsignificant 'signal' for therapeutic activity was also seen in the medium-dose YKP10A group on the HAM-D28 and the Montgomery-Asberg Depression Rating Scale (MADRS). Headaches, nervousness, agitation, insomnia, and gastrointestinal complaints were the most commonly reported side effects. Two cases of hypomania were observed.

Limitations: This preliminary, single-site study was not powered to detect a statistically significant difference from placebo among treatment groups.

Conclusion: YKP10A may have antidepressant activity at a daily dose range of 400-600 mg.