Skip to main content

Advertisement

Log in

Generalised Anxiety Disorder

Treatment Options

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

In recent years generalised anxiety disorder (GAD) has become a much better defined disorder, with specific criteria distinguishing it from the other anxiety disorders; however, it still lacks the same public and scientific interests as some of the other anxiety disorders such as panic and social phobia. Nevertheless, refinement in the treatment of GAD is becoming more evident through the conduct of clinical trials.

Up until the mid-1980’s, treatment consisted primarily of benzodiazepines. However, as a result of growing characterisation of their abuse potential, other therapeutic options were explored. Benzodiazepines became seen as an effective short-term therapy, and buspirone and some of the newer antidepressants have become the treatment of choice for patients with GAD requiring long-term treatment.

Buspirone was the first available alternative to the benzodiazepines in the US; however, the initial excitement over this agent was somewhat dampened because of its mild efficacy combined with a slow onset of action. The antidepressants were seen as beneficial for the treatment of GAD because of the high comorbidity with depression, thus allowing a better outcome for these patients. The antidepressants that offer both a good adverse effect profile and efficacy are the selective serotonin reuptake inhibitors including paroxetine, and the serotonin-norepinephrine reuptake inhibitors such as venlafaxine. Clinicians should also consider the potential benefits of psychotherapy as an adjunct to medication.

There are a number of potentially new pharmacotherapies being investigated, including newer serotonin 5-HT1A receptor agonists, cholecystokinin receptor antagonists, neurokinin receptor antagonists, gabapentin and its analogues, and γ-aminobutyric acid (GABA)A receptor modulators. However, these compounds are all in the early stages of investigation, and there are no new therapies expected to be released in the near future. Nonetheless, in the search for the ideal anxiolytic, a more positive outlook is allowed by imminent future research for new treatment options in patients with GAD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. American Psychiatric Association. Diagnostic and statistical manuel of mental disorders. 4th rev. ed. Washington, DC, American Psychiatric Association, 2000: 472–76

    Google Scholar 

  2. Wittchen HU, Hoyer J. Generalized anxiety disorder: nature and course. J Clin Psychiatry 2001; 62 Suppl. 11: 15–9, discussion 20–1

    PubMed  Google Scholar 

  3. Rickels K, Schweizer E. The clinical course and long-term management of generalized anxiety disorder. J Clin Psychopharmacol 1990; 10: 101–10

    Article  Google Scholar 

  4. Salzman C. Behavioral side effects of benzodiazepines. In: Kane J, Lieberman J, editors. Adverse effects of psychotropic drugs.New York: Guilford, 1990: 139–52

    Google Scholar 

  5. Stahl SM. Mixed anxiety and depression: clinical implications. J Clin Psychiatry 1993; 54 Suppl. 1: 33–8

    PubMed  Google Scholar 

  6. Skinstad AD, Swain A. Comorbidity in a clinical sample of substance abuse. Am J Drug Alcohol Abuse 2001; 27(1): 45–64

    Article  PubMed  CAS  Google Scholar 

  7. Compton III WM, Cottier LB, Phelps D, et al. Am J Addict 2000; 9(2): 126–34

    Article  PubMed  Google Scholar 

  8. Blazer D, Hughes D, George LK. Stressful life events and the onset of generalized anxiety syndrome. Am J Psychiatry 1987; 144: 1178–83

    PubMed  CAS  Google Scholar 

  9. Keller MB. Long term course of generalized anxiety. Neuropsychopharmacology 1994; 10: 134S

    Google Scholar 

  10. Cutler NR, Sramek JJ, Kurtz NM. Anxiolytic compounds perspectives in drug development. West Sussex: John Wiley & Sons Ltd, 1996

    Google Scholar 

  11. Guy W. ECDEU assessment manual for psychopharmacology. Rev. 1976: 193–222. Rockville, MD: NIMH Publ. DHEW Publ No. (ADM.), 76–338

    Google Scholar 

  12. Cutler NR, Sramek JJ, Keppel-Hesselink JM, et al. A double-blind placebo controlled study comparing the efficacy and safety of ipsapirone versus lorazepam in patients with generalized anxiety disorder: a prospective multicenter trial. J. Clin Psychopharamcol 1993; 13: 429–37

    CAS  Google Scholar 

  13. Cutler NR, Sramek JJ, Wardle TS, et al. The safety and efficacy of ipsapirone vs lorazepam in outpatients with generalized anxiety disorder (GAD): single site findings from a multicenter trial. Psychopharmacol Bull 1993; 29: 303–8

    PubMed  CAS  Google Scholar 

  14. Piercy MA, Sramek JJ, Kurtz NM, et al. Placebo response in anxiety disorders. Ann Pharmaco 1996; 30: 1013–9

    CAS  Google Scholar 

  15. Shapiro AK, Shapiro E. Patient-provider relationships and the placebo effect. In: Metarazzo JD, Weiss Sm, Herd JA, Miller NE, editors. Behavioral health: a handbook of health enhancement and disease prevention. New York: Wiley-Interscience, 1984: 371–383

    Google Scholar 

  16. Loebel A, Hyde TS, Dunner DL. Early placebo response in anxious and depressed patients. J Clin Psychiatry 1986; 47: 230–2

    PubMed  CAS  Google Scholar 

  17. Rudorfer MC. Challenges in medication clinical trials. Psychopharmacol Bull 1993; 29: 35–44

    PubMed  CAS  Google Scholar 

  18. Sramek JJ, Frackeiwicz, EJ, et al. Adverse events in placebo treated patients with generalized anxiety disorder. Depress Anxiety. 1997; 5: 142–3

    Article  PubMed  CAS  Google Scholar 

  19. Cutler NR, Sramek JJ. Greenblatt DJ, et al. Defining the maximum tolerated dose: investigator, academic, industry and regulatory perspectives. J Clin Pharmacol 1997; 37: 767–83

    CAS  Google Scholar 

  20. Cutler NR, Sramek JJ. Scientific and ethical concerns in clinical trials in Alzheimer’s patients: the bridging study. Eur J Clin Pharmacol 1995; 48: 421–8

    Article  PubMed  CAS  Google Scholar 

  21. Cutler NR, Sramek JJ. Guidelines for conducting bridging studies in Alzheimer disease. Alzheimer Dis Assoc Disord 1998; 12(2): 88–92

    Article  PubMed  CAS  Google Scholar 

  22. Sramek JJ, Fresquet A, Marion-Landais G, et al. Establishing the maximum tolerated dose of lesopitron in patients with generalized anxiety disorder (GAD): a bridging study. J Clin Psychopharmacol 1996; 16: 454–8

    Article  PubMed  CAS  Google Scholar 

  23. Okuma T. Differential sensitivity to the effects of psychotropic drugs: psychotics vs normals; Asians vs Western populations. Folia Psychiatr Neurol Jpn 1981; 35: 79–87

    PubMed  CAS  Google Scholar 

  24. Miller AL, Maas JW, Contreras S, et al. Acute effects of neuroloeptics on unmedicated schizophrenic patients and controls. Biol Psychiatry 1993; 34: 178–87

    Article  PubMed  CAS  Google Scholar 

  25. Sramek JJ, Simpson GM. Pharmacodynamics of antipsychotic drugs in schizophrenia. In: Cutler NR, Sramek JJ Narang PK, editors. Pharmacodynamics and drug development: perspectives in clinical pharmacology. Chichester: John Wiley, 1994: 181–99

    Google Scholar 

  26. Grof P, Akhter MI, Campbell M. Clinical evaluation of psychotropic drugs for psychiatric disorders: principles and proposed guidelines. Seattle (WA): Hogrefe & Huber, 1993

    Google Scholar 

  27. Sramek JJ, Sedman AF, Reece PA, et al. Safety and tolerability of CI-979 in patients with Alzheimer’s disease. Life Sci 1995; 57: 503–10

    Article  PubMed  CAS  Google Scholar 

  28. Sramek JJ, Hurley DJ, Wardle TS, et al. The safety and tolerance of xanomeline tartrate in patients with Alzheimer’s disease. J Clin Pharmacol 1995; 35: 800–6

    PubMed  CAS  Google Scholar 

  29. Sramek JJ, Block GA, Reines SA, et al. A multiple-dose safety trial of eptastigmine in Alzheimer’s disease with pharmacodynamic observations of red blood cell cholinesterase. Life Sci 1994; 56: 319–26

    Article  CAS  Google Scholar 

  30. Owen RT, Tyrer P. Benzodiazepine dependence: a review of the evidence. Drugs 1983; 25: 385–98

    Article  PubMed  CAS  Google Scholar 

  31. Puntillo KA, Casella V, Reid M. Opioid and benzodiazepine tolerance and dependence: application of theory to critical care practice. Heart Lung 1997; 26(4) Jul–Aug: 317–24

    Article  PubMed  CAS  Google Scholar 

  32. Greenblatt DJ, Shader RI, Abernethy DDR. Drug therapy: current status of benzodiazepines. N Engl J Med 1983; 309 (Pt 1): 354–8

    Article  PubMed  CAS  Google Scholar 

  33. Sussman N, Chou JCY Current issues in benzodiazepine use for anxiety disorders. Psychiatr Ann 1988; 18: 139–45

    Google Scholar 

  34. Ballinger JC. Current treatments of anxiety disorders in adults. Biol Psychiatry 1999; 46: 1579–94

    Article  Google Scholar 

  35. Rickels K, Case WG, Downing RW, et al. Long-term diazepam therapy and clinical outcome. JAMA 1983; 250: 767–71

    Article  PubMed  CAS  Google Scholar 

  36. Rickels K, Case WG, Downing RW, et al. One-year follow-up of anxious patients treated with diazepam. J Clin Psychopharmacol 1986 Feb; 6(1): 32–6

    Article  PubMed  CAS  Google Scholar 

  37. Dubovsky SL. Generalized anxiety disorder: new concepts and psychopharmacologic therapies. J Clin Psychiatry 1990; 51 Suppl. 1: 3–10

    Google Scholar 

  38. Griffiths RR, McLeod DR, Bigelow GE, et al. Relative abuse liability of diazepam and oxazepam: behavioral and subjective dose effects. Psychopharmacology 1984; 84(2): 147–54

    Article  PubMed  CAS  Google Scholar 

  39. Chan AW. Effects of combined alcohol and benzodiazepine: a review. Drug Alcohol Depend 1984 Jul; 13(4): 315–41

    Article  PubMed  CAS  Google Scholar 

  40. Piesiur-Strehlow B, Strehlow U, Poser W. Mortality of patients dependent on benzodiazepines. Acta Psychiatr Scand 1986 Mar; 73(3): 330–5

    Article  PubMed  CAS  Google Scholar 

  41. Van Der Bijl P, Roelofse JA. Disinhibitory reactions to benzodiazepines: a review. J Oral Maxillofac Surg 1991; 49(5): 519–23

    Article  PubMed  Google Scholar 

  42. Barbone F, McMahon AD, Davey PG, et al. Association of road-traffic accidents with benzodiazepine use. Lancet. 1998; 352: 1331–6

    Article  PubMed  CAS  Google Scholar 

  43. Woods JH, Katz JL, Winger G. Benzodiazepine: use, abuse and consequences. Pharmacol Rev 1992; 44: 151–347

    PubMed  CAS  Google Scholar 

  44. Gudex C. Adverse effects of benzodiazepines. Soc Sci Med 1991; 33: 587–96

    Article  PubMed  CAS  Google Scholar 

  45. Vgontzas AN, Kales A, Bixler EO. Benzodiazepine side effects: role of pharmacokinetics and pharmacodynamics. Pharmacology 1995; 51: 205–23

    Article  PubMed  CAS  Google Scholar 

  46. Salzman C. Benzodiazepine treatment of panic and agoraphobic symptoms: use, dependence, toxicity, abuse. J Psychiatr Res 1993; 27 Suppl. 1: 97–110

    Article  PubMed  Google Scholar 

  47. Michelini S, Cassano GB, Frare F, et al. Long term use of benzodiazepines: tolerance, dependence and clinical problems in anxiety and mood disorders. Pharmacopsychiatry 1996; 29(4): 127–34

    Article  PubMed  CAS  Google Scholar 

  48. Ladewig D, Grossenbacher H. Benzodiazepine abuse in patients of doctors in domiciliary practice in the Basle area. Pharmacopsychiatry 1988; 21: 104–8

    Article  PubMed  CAS  Google Scholar 

  49. Pecknold JC, McClure DJ, Fleuri D, et al. Benzodiazepines withdrawal effects. Prog Neuropsychopharmacol Biol Psychiatry 1982; 6: 517–22

    Article  PubMed  CAS  Google Scholar 

  50. Pecknold JC. Discontinuation reactions to alprazolam in panic disorder. J Psychiatr Res 1993; 27 Suppl. 1: 155–70

    Article  PubMed  Google Scholar 

  51. Noyes Jr R, Garvey MJ, Cook B, et al. Controlled discontinuation of benzodiazepine treatment for patients with panic disorder. Am J Psychiatry 1991; 148(4): 517–23

    PubMed  Google Scholar 

  52. Uhlenhuth EH, De Witt H, Balter MB, et al. Risks and benefits of long-term benzodiazepine use. J Clin Psychopharmacol 1988; 8: 161–7

    Article  PubMed  CAS  Google Scholar 

  53. Sramek JJ, Tansman M, Aswinder S, et al. Efficacy of buspirone in generalized anxiety disorder with coexsting mild depressive symptoms. J Clin Psychiatry 1996; 57: 287–91

    PubMed  CAS  Google Scholar 

  54. Sramek JJ, Hong WW, Hamid S, et al. Meta: analysis of the safety and tolerability of two dose regimens of buspirone in patients with persistent anxiety. Depress Anxiety 1999; 9: 131–4

    Article  PubMed  CAS  Google Scholar 

  55. Sramek JJ, Frackiewicz EJ, Cutler NR. Efficacy and safety of two dosing regimens of buspirone in the treatment of outpatients with persistent anxiety. Clin Ther 1997; 19(3): 498–506

    Article  PubMed  CAS  Google Scholar 

  56. Cutler NR, Sramek JJ, Shrotriya R, et al. Extended release (ER) formulation of buspirone in generalized anxiety disorder. [poster 235]. Biol Psychiatry 1994; 35: 680

    Google Scholar 

  57. Martin P. 1-(2-pyrimidinyl)-piperazine may alter the effects of the 5-HT1A agonist in the learned helplessness paradigm in rats. Psychopharmacol (Berl) 1991; 104(2): 275–8

    Article  CAS  Google Scholar 

  58. Amano M, Goto A, Sakai A, et al. Comparison of the anticonflict effect of buspirone and its major metabolite l-(2-pyrimidinyl)-piperazine (1-PP) in rats. Jpn J Pharmacol 1993 Apr; 61(4): 311–7

    Article  PubMed  CAS  Google Scholar 

  59. Cao BJ, Rodgers RJ. Comparative behavioral profiles of buspirone and its metabolites 1-(2-pyrimidinyl)-piperazine (1-PP) in the murine elevated plus-maze. Neuropharmcology 1997 Aug; 36(8): 1089–97

    Article  CAS  Google Scholar 

  60. Kastenholz KV, Crismon ML. Buspirone, a novel non-benzodiazepine anxiolytic. Clin Pharm 1984; 3: 600–7

    PubMed  CAS  Google Scholar 

  61. Sussman N. Treatment of anxiety with buspirone. Psychiatr Ann 1987; 17: 114–20

    Google Scholar 

  62. Kessler RC. The epidemiology of psychiatric comorbidity. In: Tsuang M, Tohen M, Zahuer G, et al., editors. Textbook of psychiatric epidemiology. New York: John Wiley & Sons, 1995: 179–97

    Google Scholar 

  63. Feighner JP. Overview of antidepressants currently used to treat anxiety disorder. J Clin Psychiatry 1999; 60 Suppl. 22: 18–22

    PubMed  CAS  Google Scholar 

  64. Kahn RJ, Mcnair DM, Lipman RS, et al. Imipramine and chlordiazepoxide in depressive and anxiety disorders II: efficacy in anxious outpatients. Arch Gen Psychiatry 1988; 22 Suppl. 1: 7–31

    Google Scholar 

  65. Rickels K, Downing R, Schweizer E, et al. Antidepressants for the treatment of generalized anxiety disorder: a placebo-controlled comparison of imipramine, trazodone, and diazepam. Arch Gen Psychiatry 1993; 50: 884–95

    Article  PubMed  CAS  Google Scholar 

  66. Rocca P, Fonzo V, Scotta M, et al. Paroxetine efficacy in the treatment of generalized anxiety disorder. Acta Psychiatr Scand 1997; 95: 444–50

    Article  PubMed  CAS  Google Scholar 

  67. Pollack MH, Zaninelli R, Goddard A, et al. Paroxetine in the treatment of generalized anxiety disorder: results of a placebo-controlled flexible-dosage trial. J Clin Psychiatry May 2001; 62(5): 350–7

    Article  CAS  Google Scholar 

  68. Rudolph RL, Entsuah R, Chitra R. A meta-analysis of the effects of venlafaxine on anxiety associated with depression. J Clin Psychopharmacol 1998; 18: 136–44

    Article  PubMed  CAS  Google Scholar 

  69. Haskins T, Rudolph R, Pallay A, et al. Double-blind, placebo controlled study of once daily venlafaxine XR in outpatients with generalized anxiety disorder (GAD). Presented at the 21st meeting of the Collegium International Neuro-Psychopharmacologicum; 1998 Jul 12–16; Glasgow

  70. Davidson JRT, DuPont RL, Hedges D, et al. Efficacy, safety, and tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder. J Clin Psychiatry 1999; 60: 528–35

    Article  PubMed  CAS  Google Scholar 

  71. Haskins JT, Rudolph R, Aguiar L, et al. Venlafaxine XR is an efficacious short and long term treatment for generalized anxiety disorder. Presented at the 11th annual meeting of the European College of Neuropsychopharmacology; 1998 Oct 31–Nov 4; Paris

  72. Gelenberg AJ, Lydiard RB, Rudolph RL, et al. Efficacy of venlafaxine extended-release capsules in nondepressed outpatients with generalized anxiety disorder: a 6-month randomized controlled trial. JAMA 2000; 283: 3082–8

    Article  PubMed  CAS  Google Scholar 

  73. Falsetti SA, Davis J. The nonpharmacologic treatment of generalized anxiety disorder. Psychiatr Clin North Am 2001 Mar; 24(1): 99–117

    Article  PubMed  CAS  Google Scholar 

  74. Borkovec TD, Ayelet M, Ruscio MA. Psychotherapy for generalized anxiety disorder. J Clin Psychiatry 2001; 62 Suppl. 11: 37–42

    PubMed  Google Scholar 

  75. Lindsay WR, Gamsu CB, McLaughlin E, et al. A controlled trial of treatments for generalized anxiety. Br J Clin Psychol 1987; 26: 3–15

    Article  PubMed  Google Scholar 

  76. Power KG, Simpson RJ, Swanson V, et al. A controlled comparison of cognitive-behavior therapy, diazepam and placebo in the management of generalized anxiety. Behav Psychother 1989; 17: 1–14

    Article  Google Scholar 

  77. Power KG, Simpson RJ, Swanson V, et al. A controlled comparison of cognitive-behavior therapy, diazepam and placebo alone and in combination for the treatment of generalized anxiety disorder. J Anxiety Disord 1990; 4: 267–92

    Article  Google Scholar 

  78. Bradwejn J, deMontigny C. Benzodiazepines antagonize cholecystokinin-induced activation of rat hippocampal neurons. Nature 1984; 312: 263–364

    Article  Google Scholar 

  79. deMontigny C. Cholecystokinin tetrapeptide induces panic-like attacks in healthy volunteers: preliminary findings. Arch Gen Psychiatry 1989; 46: 511–7

    Article  PubMed  Google Scholar 

  80. Bradwejn J, Koszycki D, Shriqui C. Enhances sensitivity to cholecystokinin tetrapeptide in panic disorder. Arch Gen Psychiatry 1991; 48: 603–10

    Article  PubMed  CAS  Google Scholar 

  81. Adams JB, Pyke RE, Costa J, et al. A double blind placebo-controlled study of CCKB receptor antagonist CI-988, in patients with generalized anxiety disorder. J Clin Psychopharmacol 1995; 15: 428–34

    Article  PubMed  CAS  Google Scholar 

  82. Kramer MS, Cutler NR, Ballenger JC, et al. A placebo-controlled trial of L-365,260, a CCKB receptor antagonist, in panic disorder. Biol Psychiatry 1995; 37: 462–6

    Article  PubMed  CAS  Google Scholar 

  83. Sramek JJ, Costa JF, Adams JB, et al. Single-site findings in a study of the safety and efficacy of a CCKB receptor antagonist CI-988, in the treatment of generalized anxiety disorder. Anxiety 1995; 1: 242–3

    CAS  Google Scholar 

  84. Brodie MS, Dunwiddie TV. Cholecystokinin potentiates dopamine inhibition of mesencephalic dopamine neurons in vitro. Brain Research 1987; 425(1): 106–13

    Article  PubMed  CAS  Google Scholar 

  85. Nair NP, Lal S, Bloom DM. Cholecystokinin peptides, dopamine and schizophrenia: a review. Prog Neuropsychopharmacology Biol Psychiatry. 1985; 9(5-6): 515–24

    Article  CAS  Google Scholar 

  86. Schaub M, Vassout A, et al. CGP 49823, a novel NK-1 receptor antagonist: behavioral effect. Neuropeptides 1994; 26 Suppl. 1: 38

    Google Scholar 

  87. Vassout A, Veenstra S, Häuser K, et al. NKP608: a selective NK-1 receptor antagonist with anxiolytic-like effects in the social interaction and social exploration test in rats. Regul Pept 2000; 96: 7–16

    Article  PubMed  CAS  Google Scholar 

  88. Cutler M. Potential anxiolytic activity in gerbils from the substance P (SP receptor antagonist, CGP 49823 [abstract]. J Psychopharmacol 1994; 8: A22

    Article  Google Scholar 

  89. Walsh DM, Stratton SC, Harvey FJ, et al. The anxiolytic-like activity of GR159897, a non peptide NK-2 receptor antagonist, in rodent and primate models of anxiety. Psychopharmacology 1995; 121: 186–91

    Article  PubMed  CAS  Google Scholar 

  90. Kramer MS, Cutler NR, Feighner J, et al. Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science 1998 Sep; 281: 1640–5

    Article  PubMed  CAS  Google Scholar 

  91. Koek W, Patoiseau JF, Assie MB, et al. F 11440, a potent, selective high efficacy 5-HT1A receptor agonist with marked anxiolytic and antidepressant potential. J Pharmacol Exp Ther 1998; 287: 266–83

    PubMed  CAS  Google Scholar 

  92. Robinson DS, Rickels K, Feighner J, et al. Clinical effects of the 5-HT1A partial agonists in depression: a composite analysis of buspirone in the treatment of depression. J Clin Psychopharmacol 1990 Jun; 10 Suppl. 3: 67S–76S

    Article  PubMed  CAS  Google Scholar 

  93. Becker HC. Comparison of the effects of the benzodiazepine midazolam and three serotonin antagonists on a consummatory conflict paradigm. Pharmacol Biochem Behav 1986; 42: 1057–64

    Article  Google Scholar 

  94. Sramek JJ, Robinson RE, Aswinder S, et al. Efficacy trial of the 5-ht2 antagonist MDL 11,939 in patients with generalized anxiety disorder. J Clin Psychopharmacol 1995; 15: 20–2

    Article  PubMed  CAS  Google Scholar 

  95. Pande AC, Pollack MH, Crockatt J, et al. Placebo-controlled study of gabapentin treatment of panic disorder. J Clin Psychopharmacol 2000; 20: 467–71

    Article  PubMed  CAS  Google Scholar 

  96. Gee NS, Brown JP, Dissanayake VUK, et al. The novel anticonvulsant drug, Gabapenitn (neurontin), binds to the α2δ subunit of a calcium channel. J Biol Chem 1996; 271: 5868–876

    Google Scholar 

  97. Field MJ, Ryszard JO, Lakhbir S. Pregabalin may represent a novel class of anxiolytic agents with a broad spectrum of activity. Br J Pharmacol 2001; 132: 1–4

    Article  PubMed  CAS  Google Scholar 

  98. Musch B, Mallard F. Zopiclone, the third generation hypnotic: a clinical overview. Int Clin Psychopharmacol 1990; 5: 147–58

    PubMed  Google Scholar 

  99. Julou L, Blanchard JC, Dreyfus JF. Pharmacological and clinical studies of cyclopyrrolones: zopiclone and suriclone. Pharmacol Biochem Behav 1985; 23: 653–9

    Article  PubMed  CAS  Google Scholar 

  100. Ansseau M, Eolie JP, Von Frenckell R, et al. Controlled comparison of the efficacy and safety of four doses of suriclone, diazepam, and placebo in generalized anxiety disorder. Psychopharmacololgy 1991; 104(4): 439–43

    Article  CAS  Google Scholar 

  101. Cox ED, Diaz-Aruzo H, Huang Q, et al. Synthesis and evaluation of analogues of the partial agnosit 6-(propyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (6-PBC) and the full agonist 6-(benzyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (ZK 93423) at wild type and recombinant GABAA receptors. J Med Chem 1998 Jul 2; 41(4): 2537–52

    Article  PubMed  CAS  Google Scholar 

  102. Jacobsen EJ, TenBrink RE, Stelzer LS, et al. High-affinity partial agonist imidazo[1,5,-a]quinoxaline amides, carbamate and ureas at the gamma-aminobutyric acid A/benzodiazepine receptor complex. J Med Chem 1996 Jan 5; 39(1): 158–75

    Article  PubMed  CAS  Google Scholar 

  103. Jacobsen EJ, TenBrink RE, Belonga KL, et al. Piperazine imidazo[1,5]quinoxaline ureas as high-affinity GABA A ligands of dual functionality. J Med Chem 1999 Apr 8; 42(7): 1123–44

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this manuscript; and the authors have no potential conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to John J. Sramek.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sramek, J.J., Zarotsky, V. & Cutler, N.R. Generalised Anxiety Disorder. Drugs 62, 1635–1648 (2002). https://doi.org/10.2165/00003495-200262110-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200262110-00005

Keywords

Navigation