Tags

Type your tag names separated by a space and hit enter

Deramciclane in the treatment of generalized anxiety disorder: a placebo-controlled, double-blind, dose-finding study.

Abstract

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.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Psychiatry, University of Helsinki, Box 320 (Lapinlahdentie), FIN-00180, HUCH, Helsinki, Finland. hannu.naukkarinen@hus.fi

    , , , , , , , , , , , ,

    Source

    MeSH

    Adolescent
    Adult
    Aged
    Anti-Anxiety Agents
    Anxiety Disorders
    Bornanes
    Double-Blind Method
    Female
    Humans
    Male
    Middle Aged
    Psychiatric Status Rating Scales
    Recurrence

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    15949921

    Citation

    Naukkarinen, Hannu, et al. "Deramciclane in the Treatment of Generalized Anxiety Disorder: a Placebo-controlled, Double-blind, Dose-finding Study." European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, vol. 15, no. 6, 2005, pp. 617-23.
    Naukkarinen H, Raassina R, Penttinen J, et al. Deramciclane in the treatment of generalized anxiety disorder: a placebo-controlled, double-blind, dose-finding study. Eur Neuropsychopharmacol. 2005;15(6):617-23.
    Naukkarinen, H., Raassina, R., Penttinen, J., Ahokas, A., Jokinen, R., Koponen, H., ... Rouru, J. (2005). Deramciclane in the treatment of generalized anxiety disorder: a placebo-controlled, double-blind, dose-finding study. European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, 15(6), pp. 617-23.
    Naukkarinen H, et al. Deramciclane in the Treatment of Generalized Anxiety Disorder: a Placebo-controlled, Double-blind, Dose-finding Study. Eur Neuropsychopharmacol. 2005;15(6):617-23. PubMed PMID: 15949921.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Deramciclane in the treatment of generalized anxiety disorder: a placebo-controlled, double-blind, dose-finding study. AU - Naukkarinen,Hannu, AU - Raassina,Roope, AU - Penttinen,Jukka, AU - Ahokas,Antti, AU - Jokinen,Riitta, AU - Koponen,Hannu, AU - Lepola,Ulla, AU - Kanerva,Harri, AU - Lehtonen,Leena, AU - Pohjalainen,Tiina, AU - Partanen,Auli, AU - Mäki-Ikola,Outi, AU - Rouru,Juha, AU - ,, Y1 - 2005/06/09/ PY - 2003/09/12/received PY - 2005/03/17/revised PY - 2005/03/17/accepted PY - 2005/6/14/pubmed PY - 2006/1/6/medline PY - 2005/6/14/entrez SP - 617 EP - 23 JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JO - Eur Neuropsychopharmacol VL - 15 IS - 6 N2 - 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. SN - 0924-977X UR - https://www.unboundmedicine.com/medline/citation/15949921/Deramciclane_in_the_treatment_of_generalized_anxiety_disorder:_a_placebo_controlled_double_blind_dose_finding_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-977X(05)00057-X DB - PRIME DP - Unbound Medicine ER -