UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

广泛性焦虑障碍的药物治疗

Author
Alexander Bystritsky, MD, PhD
Section Editor
Murray B Stein, MD, MPH
Deputy Editor
Richard Hermann, MD
Translators
王振, 副主任医师

引言

广泛性焦虑障碍(generalized anxiety disorder, GAD)的特征为难以控制的过度担心及焦虑，会给患者造成显著的劣性应激及功能受损，且出现在6个月或更久的大部分时间里[1]。

GAD是一种相对常见的障碍，最常起病于成年期，病程呈慢性[2-5]。GAD会导致患者角色功能显著受损、生活质量下降，并支付高昂的医疗保健费用[6,7]。药物治疗、心理治疗或两者联合都可以有效治疗GAD。

本专题将介绍GAD的药物治疗。其流行病学、发病机制、临床表现、病程和诊断及采用心理治疗治疗GAD将单独讨论。(参见“广泛性焦虑障碍：流行病学、发病机制、临床表现、病程、评估和诊断”和“广泛性焦虑障碍的心理治疗”)

一线药物

治疗GAD的一线药物是选择性5-羟色胺再摄取抑制剂(selective-serotonin reuptake inhibitor, SSRI)及5-羟色胺和去甲肾上腺素再摄取抑制剂(serotonin-norepinephrine reuptake inhibitor, SNRI)。相较于SNRI，我们更倾向使用SSRI，主要原因为在美国还没有的SNRI类非专利药物可用。(速释型文拉法辛可用，但这种剂型可能产生较大的副作用)。基于药物的副作用情况、药物相互作用或患者治疗史或偏好SNRI类药物更好，即可以用它们取代SSRI。

选择性5-羟色胺再摄取抑制剂 — 随机试验已显示SSRI可有效治疗GAD，这些药物包括帕罗西汀[8-10]、舍曲林[11,12]、西酞普兰及艾司西酞普兰[13-15]。非对照试验及我们的临床经验提示其他SSRI (如：氟西汀及氟伏沙明)也可有效治疗GAD。一项系统评价得出结论认为，要获得1例抗抑郁药物(而不是安慰剂)治疗有效的GAD患者至少需要治疗5例GAD患者[即：需治疗人数(number needed to treat, NNT)=5][16]。

                      

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: 2017-07 . | This topic last updated: 2016-04-25.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington, VA 2013.
  2. Lieb R, Becker E, Altamura C. The epidemiology of generalized anxiety disorder in Europe. Eur Neuropsychopharmacol 2005; 15:445.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. Mahe V, Balogh A. Long-term pharmacological treatment of generalized anxiety disorder. Int Clin Psychopharmacol 2000; 15:99.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. Kapczinski F, Lima MS, Souza JS, Schmitt R. Antidepressants for generalized anxiety disorder. Cochrane Database Syst Rev 2003; :CD003592.
  17. 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.
  18. 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.
  19. Hidalgo RB, Tupler LA, Davidson JR. An effect-size analysis of pharmacologic treatments for generalized anxiety disorder. J Psychopharmacol 2007; 21:864.
  20. Lydiard RB. An overview of generalized anxiety disorder: disease state--appropriate therapy. Clin Ther 2000; 22 Suppl A:A3.
  21. Allgulander C, Bandelow B, Hollander E, et al. WCA recommendations for the long-term treatment of generalized anxiety disorder. CNS Spectr 2003; 8:53.
  22. Baldwin DS, Polkinghorn C. Evidence-based pharmacotherapy of Generalized Anxiety Disorder. Int J Neuropsychopharmacol 2005; 8:293.
  23. Carter NJ, McCormack PL. Duloxetine: a review of its use in the treatment of generalized anxiety disorder. CNS Drugs 2009; 23:523.
  24. 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.
  25. 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.
  26. 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.
  27. 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.
  28. Keller MB. The long-term clinical course of generalized anxiety disorder. J Clin Psychiatry 2002; 63 Suppl 8:11.
  29. Davidson JR. Pharmacotherapy of generalized anxiety disorder. J Clin Psychiatry 2001; 62 Suppl 11:46.
  30. 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.
  31. Pollack MH. Refractory generalized anxiety disorder. J Clin Psychiatry 2009; 70 Suppl 2:32.
  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.
  33. Weiss M, Tikhonov D, Buldakova S. Effect of flumazenil on GABAA receptors in isolated rat hippocampal neurons. Neurochem Res 2002; 27:1605.
  34. 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.
  35. Chouinard G, Lefko-Singh K, Teboul E. Metabolism of anxiolytics and hypnotics: benzodiazepines, buspirone, zoplicone, and zolpidem. Cell Mol Neurobiol 1999; 19:533.
  36. 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.
  37. 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.
  38. Chessick CA, Allen MH, Thase M, et al. Azapirones for generalized anxiety disorder. Cochrane Database Syst Rev 2006; :CD006115.
  39. 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.
  40. 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.
  41. Bystritsky A. Treatment-resistant anxiety disorders. Mol Psychiatry 2006; 11:805.
  42. Schatzberg AF. New indications for antidepressants. J Clin Psychiatry 2000; 61 Suppl 11:9.
  43. 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.
  44. 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.
  45. Guaiana G, Barbui C, Cipriani A. Hydroxyzine for generalised anxiety disorder. Cochrane Database Syst Rev 2010; :CD006815.
  46. 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.
  47. Roy-Byrne PP, Bystritsky A, Russo J, et al. Use of herbal medicine in primary care patients with mood and anxiety disorders. Psychosomatics 2005; 46:117.
  48. Bressler R. Herb-drug interactions: interactions between kava and prescription medications. Geriatrics 2005; 60:24.
  49. Sarris J, Kavanagh DJ. Kava and St. John's Wort: current evidence for use in mood and anxiety disorders. J Altern Complement Med 2009; 15:827.
  50. Lakhan SE, Vieira KF. Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review. Nutr J 2010; 9:42.
  51. Whitton PA, Lau A, Salisbury A, et al. Kava lactones and the kava-kava controversy. Phytochemistry 2003; 64:673.
  52. Pilkington K, Kirkwood G, Rampes H, et al. Acupuncture for anxiety and anxiety disorders--a systematic literature review. Acupunct Med 2007; 25:1.
  53. Broman-Fulks JJ, Berman ME, Rabian BA, Webster MJ. Effects of aerobic exercise on anxiety sensitivity. Behav Res Ther 2004; 42:125.
  54. 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.
  55. 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.
  56. Hunot V, Churchill R, Silva de Lima M, Teixeira V. Psychological therapies for generalised anxiety disorder. Cochrane Database Syst Rev 2007; :CD001848.
  57. Hendriks GJ, Oude Voshaar RC, Keijsers GP, et al. Cognitive-behavioural therapy for late-life anxiety disorders: a systematic review and meta-analysis. Acta Psychiatr Scand 2008; 117:403.
  58. Mitte K. Meta-analysis of cognitive-behavioral treatments for generalized anxiety disorder: a comparison with pharmacotherapy. Psychol Bull 2005; 131:785.
  59. Power KG, Simpson RJ, Swanson V, Wallace LA. A controlled comparison of cognitive-behaviour therapy, diazepam, and placebo, alone and in combination, for the treatment of generalised anxiety disorder. J Anxiety Disord 1990; 4:267.
  60. Power KG, Simpson RJ, Swanson V, Wallace LA. Controlled comparison of pharmacological and psychological treatment of generalized anxiety disorder in primary care. Br J Gen Pract 1990; 40:289.
  61. Walkup JT, Albano AM, Piacentini J, et al. Cognitive behavioral therapy, sertraline, or a combination in childhood anxiety. N Engl J Med 2008; 359:2753.