Deramciclane in the treatment of generalized anxiety disorder: a placebo-controlled, double-blind, dose-finding study.
Deramciclane, a camphor derivative, is a novel anxiolytic agent with a unique mechanism of action. It acts as a potent and specific antagonist at serotonin 5-HT2A/2C receptors, and exhibits anxiolytic efficacy in animal models. The aim of this double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy, safety, and tolerability of a range of doses of deramciclane in patients with generalized anxiety disorder (GAD). Adult patients with a diagnosis of GAD (DSM-IV) and a Hamilton Anxiety Rating Scale (HAM-A) total score >or=18; a score >or=2 for the HAM-A items 'Anxious Mood' and 'Tension'; a score >or=4 on the Clinical Global Impression of Severity of Illness (CGI-S) Scale; and a score <or=20 on the Montgomery-Asberg Depression Rating Scale (MADRS) were enrolled in the study. Following a 1-2 week placebo run-in period, patients were randomized to receive deramciclane (10, 30, or 60 mg/day in two divided doses) or placebo for 8 weeks, followed by a 2-week placebo wash-out period. The primary efficacy measure was change in HAM-A score from baseline to week 8. Adverse events were monitored throughout the study. Withdrawal reactions were assessed at the end of the study (week 8) and during the placebo wash-out period using the Physician's Withdrawal Checklist (34 items). In the intent-to-treat population (n=208), both the deramciclane 30 mg/day and 60 mg/day doses provided clinically relevant improvements in HAM-A total score after 8 weeks of treatment, reaching statistical significance compared with placebo in the 60 mg/day dose group (p=0.024) and a clear trend in the 30 mg/day group (p=0.059). On the HAM-A psychic anxiety factor, significant improvements were seen in patients in the deramciclane 30 mg/day and 60 mg/day treatment groups compared with those in the placebo group (p<0.05). Adverse events were reported at a similar frequency across all four treatment groups; the most commonly reported adverse event was headache. No withdrawal reactions were observed on abrupt discontinuation of deramciclane. In conclusion, deramciclane 60 mg/day showed significant evidence of efficacy for the treatment of GAD in adult patients. The efficacy for the 30 mg/day dose was close to the larger dose although not significant in the primary analysis, and there was no significant evidence of efficacy for the 10 mg/day dose. Deramciclane was safe and well-tolerated up to the 60 mg/day dose over an 8-week period.
Naukkarinen
Hannu
H
Department of Psychiatry, University of Helsinki, Box 320 (Lapinlahdentie), FIN-00180, HUCH, Helsinki, Finland. hannu.naukkarinen@hus.fi
Raassina
Roope
R
Penttinen
Jukka
J
Ahokas
Antti
A
Jokinen
Riitta
R
Koponen
Hannu
H
Lepola
Ulla
U
Kanerva
Harri
H
Lehtonen
Leena
L
Pohjalainen
Tiina
T
Partanen
Auli
A
Mäki-Ikola
Outi
O
Rouru
Juha
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000188:drug therapy*; D001892:Camphanes / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012008:Recurrence
D014151:Anti-Anxiety Agents; D001892:Camphanes; C060555:deramciclane