Pharmacotherapy for generalized anxiety disorder in adults
- Alexander Bystritsky, MD, PhD
Alexander Bystritsky, MD, PhD
- Professor of Psychiatry and Biobehavioral Sciences Director,
- Anxiety Disorders Program, David Geffen School of Medicine, University of California, Los Angeles
Generalized anxiety disorder (GAD) is characterized by excessive worry and anxiety that are difficult to control, cause significant distress and impairment, and occur on more days than not for at least six months .
GAD is a relatively common disorder, most often with onset during adulthood and a chronic course [2-5]. GAD can lead to significant impairments in role functioning, diminished quality of life, and high healthcare costs [6,7]. The disorder can be effectively treated with medication, psychotherapy, or a combination of the two modalities.
This topic addresses pharmacotherapy for GAD. The epidemiology, pathogenesis, clinical manifestations, course, and diagnosis of GAD are described separately, as is psychotherapy for GAD. Anxiety disorders in children and adolescents is also described separately. (See "Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis" and "Psychotherapy for generalized anxiety disorder in adults" and "Anxiety disorders in children and adolescents: Epidemiology, pathogenesis, clinical manifestations, and course" and "Pharmacotherapy for anxiety disorders in children and adolescents" and "Psychotherapy for anxiety disorders in children and adolescents".)
Complementary and alternative treatments for anxiety symptoms and disorders are also discussed separately. (See "Complementary and alternative treatments for anxiety symptoms and disorders: Herbs and medications" and "Complementary and alternative treatments for anxiety symptoms and disorders: Physical, cognitive, and spiritual interventions".)
APPROACH TO TREATMENT
Our approach to selecting among treatments for generalized anxiety disorder, including the use of pharmacotherapy and psychotherapy, is discussed separately. (See "Approach to treating generalized anxiety disorder in adults".)
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington, VA 2013.
- Lieb R, Becker E, Altamura C. The epidemiology of generalized anxiety disorder in Europe. Eur Neuropsychopharmacol 2005; 15:445.
- Kessler RC, McGonagle KA, Zhao S, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 1994; 51:8.
- Kessler RC, Berglund P, Demler O, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005; 62:593.
- Bruce SE, Yonkers KA, Otto MW, et al. Influence of psychiatric comorbidity on recovery and recurrence in generalized anxiety disorder, social phobia, and panic disorder: a 12-year prospective study. Am J Psychiatry 2005; 162:1179.
- Kessler RC, Chiu WT, Demler O, et al. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005; 62:617.
- Bereza BG, Machado M, Einarson TR. Systematic review and quality assessment of economic evaluations and quality-of-life studies related to generalized anxiety disorder. Clin Ther 2009; 31:1279.
- Bielski RJ, Bose A, Chang CC. A double-blind comparison of escitalopram and paroxetine in the long-term treatment of generalized anxiety disorder. Ann Clin Psychiatry 2005; 17:65.
- Hidalgo RB, Tupler LA, Davidson JR. An effect-size analysis of pharmacologic treatments for generalized anxiety disorder. J Psychopharmacol 2007; 21:864.
- Mahe V, Balogh A. Long-term pharmacological treatment of generalized anxiety disorder. Int Clin Psychopharmacol 2000; 15:99.
- Rickels K, Zaninelli R, McCafferty J, et al. Paroxetine treatment of generalized anxiety disorder: a double-blind, placebo-controlled study. Am J Psychiatry 2003; 160:749.
- Stocchi F, Nordera G, Jokinen RH, et al. Efficacy and tolerability of paroxetine for the long-term treatment of generalized anxiety disorder. J Clin Psychiatry 2003; 64:250.
- Brawman-Mintzer O, Knapp RG, Rynn M, et al. Sertraline treatment for generalized anxiety disorder: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry 2006; 67:874.
- Dahl AA, Ravindran A, Allgulander C, et al. Sertraline in generalized anxiety disorder: efficacy in treating the psychic and somatic anxiety factors. Acta Psychiatr Scand 2005; 111:429.
- Davidson JR, Bose A, Korotzer A, Zheng H. Escitalopram in the treatment of generalized anxiety disorder: double-blind, placebo controlled, flexible-dose study. Depress Anxiety 2004; 19:234.
- Davidson JR, Bose A, Wang Q. Safety and efficacy of escitalopram in the long-term treatment of generalized anxiety disorder. J Clin Psychiatry 2005; 66:1441.
- Goodman WK, Bose A, Wang Q. Treatment of generalized anxiety disorder with escitalopram: pooled results from double-blind, placebo-controlled trials. J Affect Disord 2005; 87:161.
- Kapczinski F, Lima MS, Souza JS, Schmitt R. Antidepressants for generalized anxiety disorder. Cochrane Database Syst Rev 2003; :CD003592.
- Rickels K, Rynn M, Iyengar M, Duff D. Remission of generalized anxiety disorder: a review of the paroxetine clinical trials database. J Clin Psychiatry 2006; 67:41.
- Lydiard RB. An overview of generalized anxiety disorder: disease state--appropriate therapy. Clin Ther 2000; 22 Suppl A:A3.
- Allgulander C, Bandelow B, Hollander E, et al. WCA recommendations for the long-term treatment of generalized anxiety disorder. CNS Spectr 2003; 8:53.
- Baldwin DS, Polkinghorn C. Evidence-based pharmacotherapy of Generalized Anxiety Disorder. Int J Neuropsychopharmacol 2005; 8:293.
- Carter NJ, McCormack PL. Duloxetine: a review of its use in the treatment of generalized anxiety disorder. CNS Drugs 2009; 23:523.
- Carter CS, Krug MK. The functional neuroanatomy of dread: Functional magnetic resonance imaging insights into generalized anxiety disorder and its treatment. Am J Psychiatry 2009; 166:263.
- Allgulander C, Hackett D, Salinas E. Venlafaxine extended release (ER) in the treatment of generalised anxiety disorder: twenty-four-week placebo-controlled dose-ranging study. Br J Psychiatry 2001; 179:15.
- Stahl SM, Ahmed S, Haudiquet V. Analysis of the rate of improvement of specific psychic and somatic symptoms of general anxiety disorder during long-term treatment with venlafaxine ER. CNS Spectr 2007; 12:703.
- Cunningham LA. Once-daily venlafaxine extended release (XR) and venlafaxine immediate release (IR) in outpatients with major depression. Venlafaxine XR 208 Study Group. Ann Clin Psychiatry 1997; 9:157.
- Chessick CA, Allen MH, Thase M, et al. Azapirones for generalized anxiety disorder. Cochrane Database Syst Rev 2006; :CD006115.
- Delle Chiaie R, Pancheri P, Casacchia M, et al. Assessment of the efficacy of buspirone in patients affected by generalized anxiety disorder, shifting to buspirone from prior treatment with lorazepam: a placebo-controlled, double-blind study. J Clin Psychopharmacol 1995; 15:12.
- 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.
- 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.
- 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 Psychiatry 2006; 67:771.
- Pande AC, Crockatt JG, Feltner DE, et al. Pregabalin in generalized anxiety disorder: a placebo-controlled trial. Am J Psychiatry 2003; 160:533.
- Pohl RB, Feltner DE, Fieve RR, Pande AC. 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.
- 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 Psychiatry 2005; 62:1022.
- Lydiard RB, Rickels K, Herman B, Feltner DE. Comparative efficacy of pregabalin and benzodiazepines in treating the psychic and somatic symptoms of generalized anxiety disorder. Int J Neuropsychopharmacol 2010; 13:229.
- Mula M, Pini S, Cassano GB. The role of anticonvulsant drugs in anxiety disorders: a critical review of the evidence. J Clin Psychopharmacol 2007; 27:263.
- Davidson JR. Pharmacotherapy of generalized anxiety disorder. J Clin Psychiatry 2001; 62 Suppl 11:46.
- Offidani E, Guidi J, Tomba E, Fava GA. Efficacy and tolerability of benzodiazepines versus antidepressants in anxiety disorders: a systematic review and meta-analysis. Psychother Psychosom 2013; 82:355.
- Salzman C, Goldenberg I, Bruce SE, Keller MB. Pharmacologic treatment of anxiety disorders in 1989 versus 1996: results from the Harvard/Brown anxiety disorders research program. J Clin Psychiatry 2001; 62:149.
- Pollack MH. Refractory generalized anxiety disorder. J Clin Psychiatry 2009; 70 Suppl 2:32.
- Sibille E, Pavlides C, Benke D, Toth M. Genetic inactivation of the Serotonin(1A) receptor in mice results in downregulation of major GABA(A) receptor alpha subunits, reduction of GABA(A) receptor binding, and benzodiazepine-resistant anxiety. J Neurosci 2000; 20:2758.
- Weiss M, Tikhonov D, Buldakova S. Effect of flumazenil on GABAA receptors in isolated rat hippocampal neurons. Neurochem Res 2002; 27:1605.
- Charney DS, Minic SJ, Harris RA. Hypnotics and sedatives. In: Goodman and Gilman's: The pharmacological basis of therapeutics, 10th ed, Hardman JG, Limbird LE (Eds), McGraw-Hill, New York 2001. p.399.
- Chouinard G, Lefko-Singh K, Teboul E. Metabolism of anxiolytics and hypnotics: benzodiazepines, buspirone, zoplicone, and zolpidem. Cell Mol Neurobiol 1999; 19:533.
- Abuse of benzodiazepines: The problems and the solutions. A report of a Committee of the Institute for Behavior and Health, Inc. Am J Drug Alcohol Abuse 1988; 14 (Suppl 1):1.
- Rickels K, Lucki I, Schweizer E, et al. Psychomotor performance of long-term benzodiazepine users before, during, and after benzodiazepine discontinuation. J Clin Psychopharmacol 1999; 19:107.
- Bystritsky A. Treatment-resistant anxiety disorders. Mol Psychiatry 2006; 11:805.
- Keller MB. The long-term clinical course of generalized anxiety disorder. J Clin Psychiatry 2002; 63 Suppl 8:11.
- Schatzberg AF. New indications for antidepressants. J Clin Psychiatry 2000; 61 Suppl 11:9.
- Hellerstein DJ, Flaxer J. Vilazodone for the treatment of major depressive disorder: an evidence-based review of its place in therapy. Core Evid 2015; 10:49.
- Gommoll C, Durgam S, Mathews M, et al. A double-blind, randomized, placebo-controlled, fixed-dose phase III study of vilazodone in patients with generalized anxiety disorder. Depress Anxiety 2015; 32:451.
- Gao K, Muzina D, Gajwani P, Calabrese JR. Efficacy of typical and atypical antipsychotics for primary and comorbid anxiety symptoms or disorders: a review. J Clin Psychiatry 2006; 67:1327.
- Pollack MH, Tiller J, Xie F, Trivedi MH. Tiagabine in adult patients with generalized anxiety disorder: results from 3 randomized, double-blind, placebo-controlled, parallel-group studies. J Clin Psychopharmacol 2008; 28:308.
- Guaiana G, Barbui C, Cipriani A. Hydroxyzine for generalised anxiety disorder. Cochrane Database Syst Rev 2010; :CD006815.
- Pollack M, Kinrys G, Krystal A, et al. Eszopiclone coadministered with escitalopram in patients with insomnia and comorbid generalized anxiety disorder. Arch Gen Psychiatry 2008; 65:551.
- 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.
- Rickels K, Etemad B, Khalid-Khan S, et al. Time to relapse after 6 and 12 months' treatment of generalized anxiety disorder with venlafaxine extended release. Arch Gen Psychiatry 2010; 67:1274.
- APPROACH TO TREATMENT
- SEROTONERGIC REUPTAKE INHIBITORS (SRI)
- Efficacy and side effects
- - SSRIs
- - SNRIs
- Efficacy and side effects
- OTHER MEDICATIONS
- Other antidepressants
- Antipsychotic medications
- DURATION OF PHARMACOTHERAPY
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS