Pharmacopsychiatry 2012; 45(02): 51-56
DOI: 10.1055/s-0031-1291176
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Pregabalin: Dose-Response Relationship in Generalized Anxiety Disorder

M. J. Boschen
1   School of Psychology and Griffith Health Institute, Griffith University, Southport, Queensland, Australia
› Author Affiliations
Further Information

Publication History

received 06 June 2011
revised 24 July 2011

accepted 06 September 2011

Publication Date:
15 November 2011 (online)

Abstract

Introduction:

Pregabalin is a structural analogue of the inhibitory neurotransmitter GABA. Although pregabalin has demonstrated efficacy in the treatment of generalized anxiety disorder (GAD) in a number of randomized controlled trials, there is little published data on the optimal dose for treating this condition. The objective of the current study was to examine the dose-response relationship for treatment of GAD with pregabalin.

Method:

The current study pools results from previous fixed-dose treatment trials of GAD with pregabalin and uses curve-fitting statistical procedures to generate curvilinear regression lines as a synthesis of previous dose-response information.

Results:

Peak reduction in anxiety symptoms was observed to occur at a dose of approximately 450 mg/day, with a small reduction in treatment effect beyond this dose. Treatment effect on psychic anxiety symptoms reached a peak at approximately 400 mg, with a reduction in efficacy beyond this dose. Somatic anxiety symptoms showed continued increase in therapeutic effect up to the maximum dose of 600 mg/day.

Discussion:

Implications for psychiatric practice, limitations of the methodology and avenues for future research are discussed.

 
  • References

  • 1 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. text rev. Washington, DC: American Psychiatric Press; 2000
  • 2 Somers JM, Goldner EM, Waraich P et al. Prevalence and incidence studies of anxiety disorders: A systematic review of the literature. Can J Psychiatry 2006; 51: 100-113
  • 3 Barrera TL, Norton PJ. Quality of life impairment in generalized anxiety disorder, social phobia, and panic disorder. J Anxiety Disord 2009; 23: 1086-1090
  • 4 Stein MB, Heimberg RG. Well-being and life satisfaction in generalized anxiety disorder: Comparison to major depressive disorder in a community sample. J Affect Disord 2004; 79: 161-166
  • 5 Kroenke K, Spitzer RL, Williams JBW et al. Anxiety disorders in primary care: Prevalence, impairment, comorbidity, and detection. Ann Intern Med 2007; 146: 317-325
  • 6 Jones GN, Ames SC, Jeffries SK et al. Utilization of medical services and quality of life among low-income patients with generalized anxiety disorder attending primary care clinics. Int J Psychiatry Med 2001; 21: 183-198
  • 7 Boschen MJ. Publication trends in individual anxiety disorders: 1980–2005. J Anxiety Disord 2008; 22: 570-575
  • 8 Boschen MJ, Neumann DL, Waters AM. Relapse of successfully treated anxiety and fear: Theoretical issues and recommendations for clinical practice. Aust N Z J Psychiatry 2009; 43: 89-100
  • 9 Yonkers KA, Bruce SE, Dyck IR et al. Chronicity, relapse, and illness-course of panic disorder, social phobia, and generalized anxiety disorder: Findings in men and women from 8 years of follow-up. Depress Anxiety 2003; 17: 173-179
  • 10 Baldwin DS, Ajel K. Role of pregabalin in the treatment of generalized anxiety disorder. Neuropsychiatr Dis Treat 2007; 3: 185-191
  • 11 Boschen MJ. Generalized anxiety disorder in adults: Focus on pregabalin. Clin Med Insights: Psychiat 2011; 4: 17-35
  • 12 Czuczwar SJ, Patsalos PM. The new generation of GABA enhancers: Potential in the treatment of epilepsy. CNS Drugs 2001; 15: 339-350
  • 13 Stahl S. Anticonvulsants as anxiolytics, part 2: Pregabalin and gabapentin as α2δ ligands at voltage-gated calcium channels. J Clin Psychiat 2004; 65: 460-461
  • 14 Stahl S. Mechanism of action of α2δ ligands: Voltage sensitive calcium channel (VSCC) modulators. J Clin Psychiat 2004; 65: 1033-1034
  • 15 Feltner DE, Crockatt JG, Dubovsky SJ et al. A randomized, double-blind, placebo-controlled, fixed-dose, multicenter study of pregabalin in patients with generalized anxiety disorder. J Clin Psychopharmacol 2003; 23: 240-249
  • 16 Pande AC, Crockatt JG, Feltner DE et al. Pregabalin in generalized anxiety disorder: A placebo-controlled trial. Am J Psychiat 2003; 160: 533-540
  • 17 Rickels K, Pollack MH, Feltner DE et al. Pregabalin for treatment of generalized anxiety disorder: A 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam. Arch Gen Psychiat 2005; 62: 1022-1030
  • 18 Pohl RB, Feltner DE, Fieve RR et al. Efficacy of pregabalin in the treatment of generalized anxiety disorder: Double-blind, placebo-controlled comparison of BID versus TID dosing. J Clin Psychopharmacol 2005; 25: 151-158
  • 19 Montgomery SA, Tobias K, Zornberg GL et al. Efficacy and safety of pregabalin in the treatment of generalized anxiety disorder: A 6-week, multicenter, randomized, double-blind, placebo-controlled comparison of pregabalin and venlafaxine. J Clin Psychiat 2006; 67: 771-782
  • 20 Montgomery SA, Chatamra K, Pauer L et al. Efficacy and safety of pregabalin in elderly people with generalized anxiety disorder. Br J Psychiat 2008; 193: 389-394
  • 21 Kasper S, Herman B, Nivoli G et al. Efficacy of pregabalin and venlafaxine-XR in generalized anxiety disorder: Results of a double-blind, placebo-controlled 8-week trial. Int Clin Psychopharmacol 2009; 24: 87-96
  • 22 Feltner D, Wittchen H-U, Kavoussi R et al. Long-term efficacy of pregabalin in generalized anxiety disorder. Int Clin Psychopharmacol 2008; 23: 18-28
  • 23 Boschen MJ. A meta-analysis of the efficacy of pregabalin in the treatment of generalized anxiety disorder. Can J Psychiatry 2011; 56: 558-566
  • 24 Bech P. Dose-response relationship of pregabalin in patients with generalized anxiety disorder: A pooled analysis of four placebo-controlled trials. Pharmacopsychiatry 2007; 40: 163-168
  • 25 Lydiard RB, Rickels K, Herman B et al. Comparative efficacy of pregabalin and benzodiazepines in treating the psychic and somatic symptoms of generalized anxiety disorder. Int J Neuropsychopharmacol 2010; 13: 229-241
  • 26 SPSS Inc. SPSS for Windows, Release 17.0. Chicago: SPSS Inc; 2008
  • 27 Montgomery SA, Kasper S. Pharmacotherapy update: Pregabalin in the treatment of generalized anxiety disorder. Clin Med Insights: Therapeutics 2010; 2: 189-202
  • 28 Frame B, Miller R, Hutmacher MM. Joint modeling of dizziness, drowsiness, and dropout associated with pregabalin and placebo treatment of generalized anxiety disorder. J Pharmacokinet Pharmacodyn 2009; 36: 565-584