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.


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


CONCLUSIONS
YKP10A may have antidepressant activity at a daily dose range of 400-600 mg.
Amsterdam
Jay D
JD
Depression Research Unit, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. jamsterd@mail.med.upenn.edu
Brunswick
David J
DJ
Hundert
Miriam
M
D000284:Administration, Oral; D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001007:Anxiety / Q000139:chemically induced; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004064:Digestive System / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D010649:Phenylalanine / Q000008:administration & dosage / Q000009:adverse effects / Q000819:agonists* / Q000031:analogs & derivatives / Q000494:pharmacology*; D010919:Placebos; D012720:Severity of Illness Index; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D016896:Treatment Outcome
D000928:Antidepressive Agents; D010919:Placebos; C470510:YKP10A; D010649:Phenylalanine