A double-blind, placebo-controlled trial of abecarnil and diazepam in the treatment of patients with generalized anxiety disorder

Journal of Clinical Psychopharmacology

Volumn 20, Issue 1, 2000, Pages 12-18

  Rickels, Karl ^a   DeMartinis, Nicholas ^a   Aufdembrinke, Bernd ^b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b BAYER PHARMA AG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID RECEPTOR STIMULATING AGENT; ABECARNIL; DIAZEPAM; PLACEBO;

ADULT; ANXIETY NEUROSIS; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DROWSINESS; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; FATIGUE; FEMALE; HEADACHE; HUMAN; MAJOR CLINICAL STUDY; MALE; MOTOR DYSFUNCTION; MULTICENTER STUDY; NAUSEA; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SENSORY DYSFUNCTION; SEXUAL DYSFUNCTION; SINGLE BLIND PROCEDURE; VERTIGO;

ADOLESCENT; ADULT; AGED; ANALYSIS OF VARIANCE; ANTI-ANXIETY AGENTS; ANXIETY DISORDERS; CARBOLINES; DIAZEPAM; DOUBLE-BLIND METHOD; FEMALE; HUMANS; MALE; MIDDLE AGED; PLACEBOS;

EID: 0033984546     PISSN: 02710749     EISSN: None     Source Type: Journal    
DOI: 10.1097/00004714-200002000-00004     Document Type: Article

References (34)

1. Hollister LE, Muller-Oerlinghausen B, Rickels K, Shader RI. Clinical uses of benzodiazepines. J Clin Psychopharmacol 1993;13 [suppl 1]:1S-169S.
2. Greenblatt DJ, Shader RI, Abernathy DR. Current status of benzodiazepines (parts I and II). N Engl J Med 1983;309:354-416.
3. American Psychiatric Association. Benzodiazepines: dependence, toxicity and abuse a task force report of the American Psychiatric Association. Washington, DC: Amencan Psychiatric Association, 1991.
4. Fontaine R, Chouinard G, Annable L. Rebound anxiety in anxious patients after abrupt withdrawal of benzodiazepine treatment. Am J Psychiatry 1984;141:848-52.
5. Rickels K, Fox IL, Greenblatt DJ, Sandler KR, Schless A. Clorazepate and lorazepam: clinical improvement and rebound anxiety. Am J Psychiatry 1988;145:312-7.
6. Schweizer E, Rickels K, Case G, Greenblatt DJ. Long-term therapeutic use of benzodiazepines. II. Effects of gradual taper. Arch Gen Psychiatry 1990;47:908-15.
7. Rickels K, Schweizer E, Case G, Greenblatt DJ. Long-term therapeutic use of benzodiazepines. I: Effects of abrupt discontinuation. Arch Gen Psychiatry 1990;47:899-907.
8. Rickels K, Schweizer E, Csanalosi I, Case WG, Chung H. Long-term treatment of anxiety and risk of withdrawal: prospective comparison of clorazepate and buspirone. Arch Gen Psychiatry 1988;45:444-50.
9. Kahn RJ, McNair DM, Lipman RS, Covi L, Rickels K, Downing R, Fisher S, Frankenthaler LM. Imipramine and chlordiazepoxide in depressive and anxiety disorders. II. Efficacy in anxious outpatients. Arch Gen Psychiatry 1986;43:79-85.
10. Rickels K, Downing R, Schweizer E, Hassman H. Antidepressants for the treatment of generalized anxiety disorder: a placebo-controlled comparison of imipramine, trazodone and diazepam. Arch Gen Psychiatry 1993;50:884-95.
11. Barrett JE, Vanover KE. 5-HT receptors as targets for the development of novel anxiolytic drugs: models, mechanisms, and future directions. Psychopharmacology (Berl) 1993;112:1-12.
12. Breier A, Paul SM. Anxiety and the benzodiazepine-GABA receptor complex. In: Roth M, Noyes R, Burrows GD, eds. Handbook of anxiety, vol 4. Amsterdam: Elsevier Science Publishers, 1990:193-212.
13. Giusti P, Arban R. Physiological and pharmacological bases for the diverse properties of benzodiazepines and their congeners. Pharmacol Res 1993;27:210-5.
14. Pribilla I, Neushaus R, Huba R. Abecarnil is a full agonist at some and a partial agonist at other recombinant GABA receptor subtypes. In: Stephens DN, ed. Anxiolytic β-carbolines: from molecular biology to the clinic. New York: Springer-Verlag, 1993;50-61.
15. Stephens DN, Terski L, Jones GH, Steppuhn KG, Schneider HH. Abecarnil: a novel anxiolytic with mixed full agonist/partial agonist properties in animal models of anxiety and sedation. In: Stephens DN, ed. Anxiolytic β-carbolines: from molecular biology to the clinic. New York: Springer-Verlag, 1993:79-95.
16. Loscher W, Honack D, Scherki R, Hashem A, Frey H-H. Pharmacokinetics, anticonvulsant efficacy and adverse effects of the β-carboline abecarnil, a novel ligand for benzodiazepine receptors, after acute and chronic administration in dogs. J Pharmacol Exp Ther 1990;355:541-8.
17. Steppuhn KG, Schneider HH, Terski L, Stephens DN. Long-term treatment with abecarnil does not induce diazepam-like dependence in mice. J Pharmacol Exp Ther 1993;264:1395-400.
18. Serra M, Ghiani CA, Motzo C, Porceddu ML, Bioggio G. Long-term treatment with abecarnil fails to induce tolerance in mice. Eur J Pharmacol 1994;259:1-6.
19. Serra M, Ghiani CA, Foddi MC, Galici R, Motzo C, Biggio G. Failure of flumazenil to precipitate a withdrawal syndrome in cats chronically treated with the new anxioselective β-carboline derivative abecarnil. Behav Pharmacol 1993;4:529-33.
20. Ballenger JC, McDonald S, Noyes R, Rickels K, Sussman N, Woods S, Patin J, Singer J. The first double-blind, placebo-controlled trial of a partial benzodiazepine agonist abecarnil (ZK-112-119) in generalized anxiety disorder. Psychopharmacol Bull 1991;27:171-9.
21. Lydiard RB, Ballenger JC, Rickels K. A double-blind evaluation of the safety and efficacy of abecarnil, alprazolam, and placebo in outpatients with generalized anxiety disorder. J Clin Psychiatry 1997;58[suppl 11]:11-8.
22. Spitzer R, Williams JBW, Gibbon M, First MB. Structured Clinical Interview for DSM-III-R, Sandoz version, revised. New York: Biometrics Research Department, New York State Psychiatric Institute, 1989.
23. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol 1959;32:50-5.
24. Raskin A, Schulterbrandt JG, Reatig N, McKeon JJ. Differential response to chlorpromazine, imipramine, and placebo. Arch Gen Psychiatry 1970;23:164-73.
25. Lipman RS, Covi L, Downing RW, Fisher S, Kahn RJ, McNair DM, Rickels K, Smith VK. Pharmacotherapy of anxiety and depression: rationale and study design. Psychopharmacol Bull 1981;17:91-4.
26. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62.
27. Guy W. ECDEU assessment manual for psychopharmacology (DHEW Publication No. [ADM] 76-338). Rockville, MD: US Department of Health, Education and Welfare, 1976.
28. Mantel N, Haenszel LW. Statistical aspects of the analysis of data from retrospective studies of disease. J Am Stat Assoc 1959;58: 690-700.
29. Lepine JP, Lellouch J. Classification and epidemiology of anxiety disorders. In: Darcourt G, et al., eds. Current therapeutic approaches to panic and other anxiety disorders. Basel, Switzerland: Karger, 1994:1-14.
30. Rein W, Morselli PL. Patient sampling in anxiety studies: factors influencing response rate. Eur Psychiatry 1994;9:137-9.
31. Schweizer E, Rickels K. Placebo response in generalized anxiety: its effect on the outcome of clinical trials. J Clin Psychiatry 1997;58[suppl 11]:30-8.
32. Pollack MH, Worthington JJ, Manfro GG, Otto MW, Zucker BG. Abecarnil for the treatment of generalized anxiety disorder: a placebo-controlled comparison of two dosage ranges of abecarnil and buspirone. J Clin Psychiatry 1997;58[suppl 11]:19-23.
33. Rickels K, Schweizer E. Clinical presentation of generalized anxiety in primary-care settings: practical concepts of classification and management. J Clin Psychiatry 1997;58[suppl 11]:4-10.
34. Rickels K, Schweizer E. Spectrum of generalised anxiety in clinical practice: the role of short-term, intermittent treatment. Br J Psychiatry 1998;173[suppl 34]:49-54.