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Abecarnil, a new beta-carboline, in the treatment of anxiety disorders

Published online by Cambridge University Press:  06 August 2018

Abstract

Background Abecarnil, a novel anxiolytic beta-carboline, was investigated in five four-week double-blind, European multicentre studies. Overall, 451 patients with generalised anxiety disorder were randomised to abecarnil, 461 to placebo and 464 to active controls.

Method Data includes inferential statistics based on individual studies and descriptive analysis of 323 patients in open-label abecarnil longterm continuation up to 52 weeks.

Results Abecarnil was safe, the most frequent adverse event being drowsiness. Onset of effect was at week I. At week 4 the Hamilton Anxiety Scale score had improved by 12–13 points on average. Due to notably large and variable placebo effects abecarnil was not consistently superior to placebo. No rebound or withdrawal symptoms were observed after fast-tapered discontinuation. Safety, extent of efficacy and incidence of rebound or withdrawal did not change during longterm treatment.

Conclusions Abecarnil is safe and effective. Further research into its therapeutic potential seems warranted.

Type
Research Article
Copyright
Copyright © The Royal College of Psychiatrists, 1998 

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References

American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised) (DSM–III–R), pp. 235253 Washington, DC: APA.Google Scholar
American Psychiatric Association (1991) Benzodiazepine Dependence Toxicity, and Abuse: A Task Force Report of the APA. Washington, DC: APA.Google Scholar
Ballenger, J. C., McDonald, S., Noyes, R., et al (1991) The first double-blind placebo-controlled trial of a partial BZD agonist abecarnil (ZK-112–119) in generalised anxiety disorder. Psychopharmacology Bulletin, 27, 171179.Google Scholar
Boulenger, J. R. (1995) Le traitement de l'anxiété généralisée: approches pharmacologiques nouvelles. L'Encéphale, 21, 459466.Google Scholar
Brown, T. A., Barlow, D. H. & Liebowitz, M. R. (1994) The empirical basis of generalised anxiety disorder. American Journal of Psychiatry, 151, 12721280.Google Scholar
Covi, L. & Lipman, R. S. (1984) Primary depression or primary anxiety? A possible psychometric approach to a diagnostic dilemma. Clinical Neuropharmacology, 7 (suppl. 1), 501.Google Scholar
De Jonghe, F., Swinkels, J., Tuynman-Qua, H., et al (1989) A comparative study of suriclone, lorazepam and placebo in anxiety disorder. Pharmacopsychiatry, 22, 266271.Google Scholar
Dorow, R., Duka, T., Höller, L., et al (1987) Clinical perspectives of β-carbolines from first studies in humans. Brain Research Bulletin, 19, 319326.Google Scholar
Duka, T., Schutt, B., Krause, W., et al (1993) Human studies on abecarnil, a new β-carboline anxiolytic: safety, tolerability and preliminary pharmacological profile. British Journal of Clinical Pharmacology, 35, 386394.Google Scholar
Fontaine, R., Chouinard, G. & Annable, L. (1984) Rebound anxiety in anxious patients after abrupt withdrawal of BZD treatment. American Journal of Psychiatry, 141, 848852.Google Scholar
Fossey, M. D. & Lydiard, R. B. (1990) Placebo response in patients with anxiety disorders. In Handbook of Anxiety, Vol. 4 (eds Roth, M., Noyes, R. & Burrows, G. D.), pp. 2756. Amsterdam: Elsevier Science.Google Scholar
Hallfors, D. D. & Saxe, L. (1993) The dependence potential of short half-life benzodiazepines: A meta-analysis. American Journal of Public Health, 83, 13001304.CrossRefGoogle ScholarPubMed
Hamilton, M. (1959) The assessment of anxiety states by rating. British Journal of Medical Psychology, 32, 5055.Google Scholar
Lader, M. (1991) BZDs and novel anxiolytics: clinical pharmacology, dependence and withdrawal. In 5-HTIA Agonists, 5-HT3 Agonists, and BZDs: Their Comparative Behavioural Pharmacology (eds R.J. Rodgers & S.J. Cooper), pp. 343363. Chichester: Wiley.Google Scholar
Lader, M. (1994) Benzodiazepines: a risk-benefit profile. CNS Drugs, 1, 377387.Google Scholar
Lemoine, P., Guillet, P. & Pilate, C. (1992) Multicenter double-blind trial comparing 3 doses of suriclone to bromazepam and placebo in generalised anxiety treated by general practitioners. Clinical Neuropharmacology, 15 (suppl. 1), 171B.Google Scholar
Löscher, W., Hónack, D., Scherki, R., et al (1990) Pharmacokinetics, anticonvulsant efficacy and adverse effects of the β-carboline abecarnil, a novel ligand for BZD receptors, after acute and chronic administration in dogs. Journal of Pharmacology and Experimental Therapeutics, 355, 541548.Google Scholar
Lydiard, R. B., Ballenger, J. C. & Rickels, K. (1997) A double-blind evaluation of the safety and efficacy of abecarnil, alprazolam, and placebo in outpatients with generalized anxiety disorder. Journal of Clinical Psychiatry, 58 (suppl. 11), 1119.Google Scholar
Mumford, G. K., Rush, C. & Griffiths, R. (1995) Abecarnil and alprazolam in humans: behavioural, subjective and reinforcing effects. Journal of Pharmacology and Experimental Therapeutics, 272, 570580.Google ScholarPubMed
Murphy, S. M., Owen, R. & Tyrer, P. (1989) Comparative assessment of efficacy and withdrawal symptoms after 6 and 12 weeks’ treatment witfi diazepam or buspirone. British journal of Psychiatry, 154, 529534.CrossRefGoogle ScholarPubMed
National Institute of Mental Health (1976) 028 CGI. Clinical global impressions. In ECDEU Assessment for Psychopharmacology (ed. W. Guy) (rev. edn), pp. 217222. Rockville, MD: NIMH.Google Scholar
Petersen, E. N., Jensen, L. H., Honore, T., et al (1984) ZK 91296. A partial agonist at benzodiazepine receptors. Psychopharmacology, 83, 240248.CrossRefGoogle ScholarPubMed
Pribilla, I., Neuhaus, R., Huba, R., et al (1993) Abecarnil is a full agonist at some and a partial agonist at other recombinant GABA A receptor subtypes. In Anxiolytic β-carbolines: From Molecular Biology to the Clinic (ed. Stephens, D. N.), pp. 5061. New York: Springer Verlag.Google Scholar
Pollack, M. H., Worthington, J. H., Manfro, G. G., et al (1997) Abecarnil for the treatment of generalised anxiety disorder: a placebo-controlled comparison of two dose ranges of abecarnil and buspirone. Journal of Clinical Psychiatry, 58 (suppl. 11), 1923.Google Scholar
Raskin, A., Schulterbrandt, J., Reatig, N., et al (1969) Replication of factors of psychopathology in interview, ward behaviour and self report ratings of hospitalised depressives. Journal of Nervous and Mental Disease, 148, 8798.Google Scholar
Rickels, K. (1983) Benzodiazepines in the treatment of anxiety: North American experiences. In The Benzodiazepines: From Molecular Biology to Clinical Practice (ed. Costa, E.), pp. 295310. New York: Raven.Google Scholar
Rickels, K., Schweizer, E. & Case, G. (1990) Long-term therapeutic use of BZDs. I: Effects of abrupt discontinuation. Archives of General Psychiatry, 47, 899907.CrossRefGoogle Scholar
Schweizer, E. & Rickels, K. (1997) Placebo response in generalized anxiety: Its effect on the outcome of clinical trials. Journal of Clinical Psychiatry, 58 (suppl. 11), 3038.Google Scholar
Small, G. W. & Bystritsky, A. (1997) Double-blind placebo-controlled trial of two doses of abecarnil for geriatric anxiety. Journal of Clinical Psychiatry, 58 (suppl. 11), 2429.Google Scholar
Spencer, C. M. & Benfield, P. (1995) Abecarnil in generalized anxiety disorder. An initial appraisal of its clinical potential. CNS Drugs, 3, 6982.Google Scholar
Spitzer, R. L., Williams, J. B. W., Gibbon, M., et al (1990) User's Guide for the Structured Clinical Interview for DSM–III–R, SCID. Washington, DC: American Psychiatric Press.Google Scholar
Stephens, D. N., Turski, L., Jones, G. H., et al (1993) Abecarnil: a novel anxiolytic with mixed full agonist/partial agonist properties in animal models of anxiety and sedation. In Anxiolytic β-carbolines. From Molecular Biology to the Clinic in Anxiolytic β-carbolines. From Molecular Biology to the Clinic (ed. Stephens, D. N.), pp. 7995. New York: Springer Verlag.Google Scholar
Stephens, D. N., Schneider, H. H., Kehr, W., et al (1990) Abecarnil, a metabolically stable anxioselective β-carboline acting at benzodiazepine receptors. Journal of Pharmacology and Experimental Therapeutics, 253, 334343.Google Scholar
Stephens, D. N., Schneider, H. H. (1985) β-carbolines can enhance or antagonize the effects of punishment in mice. Psychopharmacology, 85, 143174.Google Scholar
Turski, L., Stephens, D. M., Jensen, L. H., et al (1990) Anticonvulsant action of the β-carboline abecarnil studies in rodents and baboon, Papio papio. Journal of Pharmacology and Experimental Therapeutics, 253, 344352.Google ScholarPubMed
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