CNS Drugs

, Volume 23, Issue 2, pp 103–120 | Cite as

Current Considerations in the Treatment of Generalized Anxiety Disorder

  • Martin A. Katzman
Review Article


Generalized anxiety disorder (GAD) is a chronic disorder that frequently co-occurs with a variety of co-morbidities in patients with somatic conditions and other mental disorders. GAD is highly prevalent and is one of the most common anxiety disorders seen by primary care physicians. The individual and societal cost associated with GAD is high and the marked level of impairment experienced by patients with this disorder is equivalent in magnitude to that reported in patients with major depressive disorder. Furthermore, patients with GAD are at risk of suicide or suicide attempts, and are frequent users of healthcare services. Thus, GAD is a serious and chronic condition that requires appropriate long-term treatment.

The focus of acute treatment for patients with GAD is the improvement of symptoms, while the primary goal of long-term clinical management is remission, i.e. the complete resolution of both symptoms and functional impairment. The consensus across current treatment guidelines is that first-line treatment for patients with GAD should consist of an antidepressant, either a selective serotonin reuptake inhibitor (SSRI) such as sertraline, paroxetine or escitalopram, or a selective serotonin noradrenaline (norepinephrine) reuptake inhibitor (SNRI) such as venlafaxine or duloxetine. However, the SSRIs and SNRIs have efficacy limitations, such as lack of response in many patients, a 2- to 4-week delay before the onset of symptom relief, lack of full remission, and risk of relapse. In addition, there are troublesome adverse effects associated with both the SSRIs and SNRIs.

Evidence from early clinical studies of the atypical antipsychotics in the treatment of anxiety and GAD indicate that they may have a potential role in the treatment of GAD, either as monotherapy or as augmentation to standard treatment.


Major Depressive Disorder Anxiety Disorder Paroxetine Quetiapine Generalize Anxiety Disorder 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The author would like to thank Jocelyn Woodcock, MPhil, from Complete Medical Communications, who provided editorial assistance in the preparation of this review. An unrestricted educational grant was provided by AstraZeneca. Dr Martin Katzman has received grants from Lundbeck, Wyeth, GlaxoSmithKline, Eli Lilly, AstraZeneca, Solve, Genome Health and Pfizer. Dr Katzman has also consulted for GlaxoSmithKline, Wyeth, Lundbeck, AstraZeneca, Eli Lilly, Janssen, Bristol-Myers Squibb and Shire, and has received honoraria from Wyeth, GlaxoSmithKline, Lundbeck, AstraZeneca, Eli Lilly, Janssen, Solve, Bristol Myers-Squibb and Abbott.


  1. 1.
    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: 593–602PubMedCrossRefGoogle Scholar
  2. 2.
    Wittchen HU. Generalized anxiety disorder: prevalence, burden, and cost to society. Depress Anxiety 2002; 16: 162–71PubMedCrossRefGoogle Scholar
  3. 3.
    Riedel M, Muller N, Strassnig M, et al. Quetiapine has equivalent efficacy and superior tolerability to risperidone in the treatment of schizophrenia with predominantly negative symptoms. Eur Arch Psychiatry Clin Neurosci 2005; 255: 432–7PubMedCrossRefGoogle Scholar
  4. 4.
    Ansseau M, Fischler B, Dierick M, et al. Prevalence and impact of generalized anxiety disorder and major depression in primary care in Belgium and Luxemburg: the GADIS study. Eur Psychiatry 2005; 20: 229–35PubMedCrossRefGoogle Scholar
  5. 5.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd ed., revised. Washington, DC. American Psychiatric Association, 1987Google Scholar
  6. 6.
    Katon W, Von Korff M, Lin E, et al. Distressed high utilizers of medical care. DSM-III-R diagnoses and treatment needs. Gen Hosp Psychiatry 1990; 12: 355–62Google Scholar
  7. 7.
    Chartier M, Walker J, Kjernisted K. Health care utilization and anxiety disorders. Anxiety Disorders Association of America. 20th National Conference; 2000 Mar 23–26; Washington, DCGoogle Scholar
  8. 8.
    Keller MB. The long-term clinical course of generalized anxiety disorder. J Clin Psychiatry 2002; 63Suppl. 8: 11–6PubMedGoogle Scholar
  9. 9.
    Wittchen HU, Zhao S, Kessler RC, et al. DSM-III-R generalized anxiety disorder in the National Comorbidity Survey. Arch Gen Psychiatry 1994; 51: 355–64PubMedCrossRefGoogle Scholar
  10. 10.
    Lieb R, Becker E, Altamura C. The epidemiology of generalized anxiety disorder in Europe. Eur Neuropsychopharmacol 2005; 15: 445–52PubMedCrossRefGoogle Scholar
  11. 11.
    Culpepper L. Generalized anxiety disorder in primary care: emerging issues in management and treatment. J Clin Psychiatry 2002; 63Suppl. 8: 35–42PubMedGoogle Scholar
  12. 12.
    Moffitt TE, Caspi A, Harrington H, et al. Generalized anxiety disorder and depression: childhood risk factors in a birth cohort followed to age 32. Psychol Med 2008; 37: 441–52CrossRefGoogle Scholar
  13. 13.
    Biederman J, Rosenbaum JF, Hirshfeld DR, et al. Psychiatric correlates of behavioral inhibition in young children of parents with and without psychiatric disorders. Arch Gen Psychiatry 1990; 47: 21–6PubMedCrossRefGoogle Scholar
  14. 14.
    Manassis K, Bradley S, Goldberg S, et al. Behavioural inhibition, attachment and anxiety in children of mothers with anxiety disorders. Can J Psychiatry 1995; 40: 87–92PubMedGoogle Scholar
  15. 15.
    Rosenbaum JF, Biederman J, Gersten M, et al. Behavioral inhibition in children of parents with panic disorder and agoraphobia: a controlled study. Arch Gen Psychiatry 1988; 45: 463–70PubMedCrossRefGoogle Scholar
  16. 16.
    Rosenbaum JF, Biederman J, Bolduc EA, et al. Comorbidity of parental anxiety disorders as risk for childhood-onset anxiety in inhibited children. Am J Psychiatry 1992; 149: 475–81PubMedGoogle Scholar
  17. 17.
    Schwartz CE, Snidman N, Kagan J. Adolescent social anxiety as an outcome of inhibited temperament in childhood. J Am Acad Child Adolesc Psychiatry 1999; 38: 1008–15PubMedCrossRefGoogle Scholar
  18. 18.
    Wittchen HU, Kessler RC, Pfister H, et al. Why do people with anxiety disorders become depressed? A prospective-longitudinal community study. Acta Psychiatr Scand Suppl 2000; 406: 14–23PubMedCrossRefGoogle Scholar
  19. 19.
    Wittchen HU, Beesdo K, Bittner A, et al. Depressive episodes: evidence for a causal role of primary anxiety disorders? Eur Psychiatry 2003; 18: 384–93PubMedCrossRefGoogle Scholar
  20. 20.
    Kessler RC, Andrade LH, Bijl RV, et al. The effects of comorbidity on the onset and persistence of generalized anxiety disorder in the ICPE surveys. International Consortium in Psychiatric Epidemiology. Psychol Med 2002; 32: 1213–25Google Scholar
  21. 21.
    Judd LL, Kessler RC, Paulus MP, et al. Comorbidity as a fundamental feature of generalized anxiety disorders: results from the National Comorbidity Study (NCS). Acta Psychiatr Scand Suppl 1998; 393: 6–11PubMedCrossRefGoogle Scholar
  22. 22.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994Google Scholar
  23. 23.
    Carter RM, Wittchen HU, Pfister H, et al. One-year prevalence of subthreshold and threshold DSM-IV generalized anxiety disorder in a nationally representative sample. Depress Anxiety 2001; 13: 78–88PubMedCrossRefGoogle Scholar
  24. 24.
    Hasler G, Pine DS, Gamma A, et al. The associations between psychopathology and being overweight: a 20-year prospective study. Psychol Med 2004; 34: 1047–57PubMedCrossRefGoogle Scholar
  25. 25.
    Stein DJ. Comorbidity in generalized anxiety disorder: impact and implications. J Clin Psychiatry 2001; 62Suppl. 11: 29–34PubMedGoogle Scholar
  26. 26.
    Simon NM, Otto MW, Wisniewski SR, et al. Anxiety disorder comorbidity in bipolar disorder patients: data from the first 500 participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Am J Psychiatry 2004; 161: 2222–9PubMedCrossRefGoogle Scholar
  27. 27.
    Henning ER, Turk CL, Mennin DS, et al. Impairment and quality of life in individuals with generalized anxiety disorder. Depress Anxiety 2007; 24: 342–9PubMedCrossRefGoogle Scholar
  28. 28.
    Frisch MB, Cornell J, Villaneuva M, et al. Clinical validation of the Quality of Life Inventory: a measure of life satisfaction for use in treatment planning and outcome assessment. Psychol Assess 1992; 4: 92–101CrossRefGoogle Scholar
  29. 29.
    Wittchen HU, Carter RM, Pfister H, et al. Disabilities and quality of life in pure and comorbid generalized anxiety disorder and major depression in a national survey. Int Clin Psychopharmacol 2000; 15: 319–28PubMedCrossRefGoogle Scholar
  30. 30.
    Wells KB, Stewart A, Hays RD, et al. The functioning and well-being of depressed patients: results from the Medical Outcomes Study. JAMA 1989; 262: 914–9PubMedCrossRefGoogle Scholar
  31. 31.
    Kessler RC, DuPont RL, Berglund P, et al. Impairment in pure and comorbid generalized anxiety disorder and major depression at 12 months in two national surveys. Am J Psychiatry 1999; 156: 1915–23PubMedGoogle Scholar
  32. 32.
    Hoffman DL, Dukes EM, Wittchen HU. Human and economic burden of generalized anxiety disorder. Depress Anxiety 2008; 25: 72–90PubMedCrossRefGoogle Scholar
  33. 33.
    Ware Jr JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Med Care 1992; 30: 473–83Google Scholar
  34. 34.
    Bernal M, Haro JM, Bernert S, et al. Risk factors for suicidality in Europe: Results from the ESEMED study. J Affect Disord 2006; 101: 27–34PubMedCrossRefGoogle Scholar
  35. 35.
    Bruce SE, Machan JT, Dyck I, et al. Infrequency of “pure” GAD: impact of psychiatric comorbidity on clinical course. Depress Anxiety 2001; 14: 219–25PubMedCrossRefGoogle Scholar
  36. 36.
    Hettema JM, Kuhn JW, Prescott CA, et al. The impact of generalized anxiety disorder and stressful life events on risk for major depressive episodes. Psychol Med 2006; 36: 789–95PubMedCrossRefGoogle Scholar
  37. 37.
    Nutt D, Argyropoulos S, Hood S, et al. Generalized anxiety disorder: a comorbid disease. Eur Neuropsycho-pharmacol 2006; 16Suppl. 2: S109–18CrossRefGoogle Scholar
  38. 38.
    Wittchen HU, Kessler RC, Beesdo K, et al. Generalized anxiety and depression in primary care: prevalence, recognition, and management. J Clin Psychiatry 2002; 63Suppl. 8: 24–34PubMedGoogle Scholar
  39. 39.
    Wittchen HU, Nelson CB, Lachner G. Prevalence of mental disorders and psychosocial impairments in adolescents and young adults. Psychol Med 1998; 28: 109–26PubMedCrossRefGoogle Scholar
  40. 40.
    Lim D, Sanderson K, Andrews G. Lost productivity among full-time workers with mental disorders. J Ment Health Policy Econ 2000; 3: 139–46PubMedCrossRefGoogle Scholar
  41. 41.
    Marciniak MD, Lage MJ, Dunayevich E, et al. The cost of treating anxiety: the medical and demographic correlates that impact total medical costs. Depress Anxiety 2005; 21: 178–84PubMedCrossRefGoogle Scholar
  42. 42.
    Smit F, Cuijpers P, Oostenbrink J, et al. Costs of nine common mental disorders: implications for curative and preventive psychiatry. J Ment Health Policy Econ 2006; 9: 193–200PubMedGoogle Scholar
  43. 43.
    Souetre E, Lozet H, Cimarosti I, et al. Cost of anxiety disorders: impact of comorbidity. J Psychosom Res 1994; 38Suppl. 1: 151–60PubMedCrossRefGoogle Scholar
  44. 44.
    Lothgren M. Economic evidence in anxiety disorders: a review. Eur J Health Econ 2004; 5Suppl. 1: S20–5PubMedCrossRefGoogle Scholar
  45. 45.
    Buhr K, Dugas MJ. The Intolerance of Uncertainty Scale: psychometric properties of the English version. Behav Res Ther 2002; 40: 931–45PubMedCrossRefGoogle Scholar
  46. 46.
    Dugas MJ, Marchand A, Ladouceur R. Further validation of a cognitive-behavioral model of generalized anxiety disorder: diagnostic and symptom specificity. J Anxiety Disord 2005; 19: 329–43PubMedCrossRefGoogle Scholar
  47. 47.
    Canadian Psychiatric Association. Management of anxiety disorders. Can J Psychiatry 2006; 51Suppl. 2: 1–93SGoogle Scholar
  48. 48.
    World Health Organization. International statistical classification of diseases. 10th rev. Vol. 3. Geneva: World Health Organization, 1992Google Scholar
  49. 49.
    World Health Organization. International statistical classification of diseases. 10th rev. Vol. 3, 2nd rev. Geneva: World Health Organization, 2005Google Scholar
  50. 50.
    Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol 1959; 32: 50–5PubMedCrossRefGoogle Scholar
  51. 51.
    Ruscio AM, Chiu WT, Roy-Byrne P, et al. Broadening the definition of generalized anxiety disorder: effects on prevalence and associations with other disorders in the National Comorbidity Survey Replication. J Anxiety Disord 2007; 21: 662–76PubMedCrossRefGoogle Scholar
  52. 52.
    Argyropoulos SV, Ploubidis GB, Wright T, et al. Development and validation of the Generalized Anxiety Disorder Inventory (GADI). J Psychopharmacol 2007; 21: 145–52PubMedCrossRefGoogle Scholar
  53. 53.
    Spitzer RL, Kroenke K, Williams JB, et al. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med 2006; 166: 1092–7PubMedCrossRefGoogle Scholar
  54. 54.
    Meyer TJ, Miller ML, Metzger RL, et al. Development and validation of the Penn State Worry Questionnaire. Behav Res Ther 1990; 28: 487–95PubMedCrossRefGoogle Scholar
  55. 55.
    Ballenger JC. Overview of different pharmacotherapies for attaining remission in generalized anxiety disorder. J Clin Psychiatry 2001; 62Suppl. 19: 11–9PubMedGoogle Scholar
  56. 56.
    Gorman JM, Hirschfeld RM, Ninan PT. New developments in the neurobiological basis of anxiety disorders. Psychopharmacol Bull 2002; 36Suppl. 2: 49–67PubMedGoogle Scholar
  57. 57.
    Weizman R, Tanne Z, Granek M, et al. Peripheral benzo-diazepine binding sites on platelet membranes are increased during diazepam treatment of anxious patients. Eur J Pharmacol 1987; 138: 289–92PubMedCrossRefGoogle Scholar
  58. 58.
    Rocca P, Beoni AM, Eva C, et al. Peripheral benzodiazepine receptor messenger RNA is decreased in lymphocytes of generalized anxiety disorder patients. Biol Psychiatry 1998; 43: 767–73PubMedCrossRefGoogle Scholar
  59. 59.
    Varnas K, Halldin C, Hall H. Autoradiographic distribution of serotonin transporters and receptor subtypes in human brain. Hum Brain Mapp 2004; 22: 246–60PubMedCrossRefGoogle Scholar
  60. 60.
    Nutt DJ. Antidepressants in panic disorder: clinical and preclinical mechanisms. J Clin Psychiatry 1998; 59Suppl. 8: 24–8PubMedGoogle Scholar
  61. 61.
    Scherrer JF, True WR, Xian H. Evidence for genetic influences common and specific to symptoms of generalized anxiety and panic. J Affect Disord 2000; 57: 25–35PubMedCrossRefGoogle Scholar
  62. 62.
    Hettema JM, Prescott CA, Kendler KS. A population-based twin study of generalized anxiety disorder in men and women. J Nerv Ment Dis 2001; 189: 413–20PubMedCrossRefGoogle Scholar
  63. 63.
    Kendler KS, Gardner CO, Gatz M, et al. The sources of co-morbidity between major depression and generalized anxiety disorder in a Swedish national twin sample. Psychol Med 2007; 37: 453–62PubMedCrossRefGoogle Scholar
  64. 64.
    Bandelow B, Zohar J, Hollander E, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders. World J Biol Psychiatry 2002; 3: 171–99PubMedCrossRefGoogle Scholar
  65. 65.
    Baldwin SH, Anderson IM, Nutt DJ, et al. Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2005; 19: 567–96PubMedCrossRefGoogle Scholar
  66. 66.
    NICE guidelines. Anxiety: management of anxiety (panic disorder, with or without agoraphobia, and generalised anxiety disorder) in adults in primary, secondary and community care. London: National Institute for Health and Clinical Excellence, 2004 DecGoogle Scholar
  67. 67.
    Rickels K, Rynn M, Iyengar M, et al. Remission of generalized anxiety disorder: a review of the paroxetine clinical trials database. J Clin Psychiatry 2006; 67: 41–7PubMedCrossRefGoogle Scholar
  68. 68.
    Guy W. Clinical global impressions. In: Guy W, editor. ECDEU assessment manual for psychopharmacology. Rockville (MD): US National Institute of Health, 1976: 218–22Google Scholar
  69. 69.
    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: 749–56PubMedCrossRefGoogle Scholar
  70. 70.
    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 2001; 62: 350–7PubMedCrossRefGoogle Scholar
  71. 71.
    Hewett K, Adams A, Bryson H, et al. Generalised anxiety disorder: efficacy of paroxetine [poster]. 7th World Congress of Biological Psychiatry; 2001 Jul 1–6; BerlinGoogle Scholar
  72. 72.
    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: 250–8PubMedCrossRefGoogle Scholar
  73. 73.
    Davidson JR, Bose A, Korotzer A, et al. Escitalopram in the treatment of generalized anxiety disorder: double-blind, placebo controlled, flexible-dose study. Depress Anxiety 2004; 19: 234–40PubMedCrossRefGoogle Scholar
  74. 74.
    Allgulander C, Florea I, Huusom AK. Prevention of relapse in generalized anxiety disorder by escitalopram treatment. Int J Neuropsychopharmacol 2006; 9: 495–505PubMedCrossRefGoogle Scholar
  75. 75.
    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: 874–81PubMedCrossRefGoogle Scholar
  76. 76.
    Allgulander C, Dahl AA, Austin C, et al. Efficacy of sertraline in a 12-week trial for generalized anxiety disorder. Am J Psychiatry 2004; 161: 1642–9PubMedCrossRefGoogle Scholar
  77. 77.
    Ball SG, Kuhn A, Wall D, et al. Selective serotonin reuptake inhibitor treatment for generalized anxiety disorder: a double-blind, prospective comparison between paroxetine and sertraline. J Clin Psychiatry 2005; 66: 94–9PubMedCrossRefGoogle Scholar
  78. 78.
    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: 3082–8PubMedCrossRefGoogle Scholar
  79. 79.
    Nimatoudis I, Zissis NP, Kogeorgos J, et al. Remission rates with venlafaxine extended release in Greek outpatients with generalized anxiety disorder: a double-blind, randomized, placebo controlled study. Int Clin Psychopharmacol 2004; 19: 331–6PubMedCrossRefGoogle Scholar
  80. 80.
    Lenox-Smith AJ, Reynolds A. A double-blind, randomised, placebo controlled study of venlafaxine XL in patients with generalised anxiety disorder in primary care. Br J Gen Pract 2003; 53: 772–7PubMedGoogle Scholar
  81. 81.
    Eli Lilly and Company. Study suggests Cymbalta® significantly reduces core anxiety symptoms of generalised anxiety disorder, 2006 Mar 24 [online]. Available from URL: [Accessed 2008 Nov 13]
  82. 82.
    Allgulander C, Hartford J, Russell J, et al. Pharmacotherapy of generalized anxiety disorder: results of duloxetine treatment from a pooled analysis of three clinical trials. Curr Med Res Opin 2007; 23(6): 1245–52PubMedCrossRefGoogle Scholar
  83. 83.
    Hartford J, Kornstein S, Liebowitz M, et al. Duloxetine as an SNRI treatment for generalized anxiety disorder: results from a placebo and active-controlled trial. Int Clin Psychopharmacol 2007; 22: 167–74PubMedCrossRefGoogle Scholar
  84. 84.
    Lauer D, Holzel L, Hornyak M. Generalized anxiety disorder with comorbidity: treatment with pregabalin [in German]. Nervenarzt 2006; 77(11): 1363–7PubMedCrossRefGoogle Scholar
  85. 85.
    Frampton JE, Foster RH. Pregabalin: in the treatment of generalised anxiety disorder. CNS Drugs 2006; 20: 685–93PubMedCrossRefGoogle Scholar
  86. 86.
    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: 771–82PubMedCrossRefGoogle Scholar
  87. 87.
    Chessick CA, Allen MH, Thase M, et al. Azapirones for generalized anxiety disorder. Cochrane Database Syst Rev 2006; (3): CD006115Google Scholar
  88. 88.
    Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand 1983; 67: 361–70PubMedCrossRefGoogle Scholar
  89. 89.
    Davidson JR, 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: 528–35PubMedCrossRefGoogle Scholar
  90. 90.
    Pollack MH, Worthington JJ, Manfro GG, et al. Abecarnil for the treatment of generalized anxiety disorder: a placebo-controlled comparison of two dosage ranges of abecarnil and buspirone. J Clin Psychiatry 1997; 58Suppl. 11: 19–23PubMedGoogle Scholar
  91. 91.
    Struzik L, Vermani M, Coonerty-Femiano A, et al. Treatments for generalized anxiety disorder. Expert Rev Neurother 2004; 4: 285–94PubMedCrossRefGoogle Scholar
  92. 92.
    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: 884–95PubMedCrossRefGoogle Scholar
  93. 93.
    Roerig JL. Diagnosis and management of generalized anxiety disorder. J Am Pharm Assoc 1999; 39: 811–21Google Scholar
  94. 94.
    Pollack MH. Optimizing pharmacotherapy of generalized anxiety disorder to achieve remission. J Clin Psychiatry 2001; 62Suppl. 19: 20–5PubMedGoogle Scholar
  95. 95.
    Kennedy SH, Lam RW, Cohen NL, et al. Clinical guidelines for the treatment of depressive disorders: IV. Medications and other biological treatments. Can J Psychiatry 2001; 46Suppl. 1: 38–58SGoogle Scholar
  96. 96.
    Gahimer J, Wernicke J, Yalcin I, et al. A retrospective pooled analysis of duloxetine safety in 23,983 subjects. Curr Med Res Opin 2007; 23: 175–84PubMedCrossRefGoogle Scholar
  97. 97.
    Thase ME. Treatment of anxiety disorders with venlafaxine XR. Expert Rev Neurother 2006; 6: 269–82PubMedCrossRefGoogle Scholar
  98. 98.
    Himei A, Okamura T. Discontinuation syndrome associated with paroxetine in depressed patients: a retrospective analysis of factors involved in the occurrence of the syndrome. CNS Drugs 2006; 20: 665–72PubMedCrossRefGoogle Scholar
  99. 99.
    Perahia DG, Kajdasz DK, Desaiah D, et al. Symptoms following abrupt discontinuation of duloxetine treatment in patients with major depressive disorder. J Affect Disord 2005; 89: 207–12PubMedCrossRefGoogle Scholar
  100. 100.
    Joint Formulary Committee. British national formulary. 52nd ed. London: British Medical Association and Royal Pharmaceutical Society of Great Britain, 2006Google Scholar
  101. 101.
    FDA Public Health Advisory. Suicidality in children and adolescents being treated with antidepressant medications, 2004 Oct 15 [online]. Available from URL: [Accessed 2008 Nov 13]
  102. 102.
    FDA. FDA proposes new warnings about suicidal thinking, behavior in young adults who take antidepressant medications [online]. Available from URL: [Accessed 2008 Sep 25]
  103. 103.
    Tiihonen J, Lonnqvist J, Wahlbeck K, et al. Anti-depressants and the risk of suicide, attempted suicide, and overall mortality in a nationwide cohort. Arch Gen Psychiatry 2006; 63: 1358–67PubMedCrossRefGoogle Scholar
  104. 104.
    Lang AJ. Treating generalized anxiety disorder with cognitive-behavioral therapy. J Clin Psychiatry 2004; 65Suppl. 13: 14–9PubMedGoogle Scholar
  105. 105.
    Hunot V, Churchill R, Silva DL, et al. Psychological therapies for generalised anxiety disorder. Cochrane Database Syst Rev 2007; (1): CD001848Google Scholar
  106. 106.
    Borkovec TD, Ruscio AM. Psychotherapy for generalized anxiety disorder. J Clin Psychiatry 2001; 62Suppl. 11: 37–42PubMedGoogle Scholar
  107. 107.
    Chambless DL, Gillis MM. Cognitive therapy of anxiety disorders. J Consult Clin Psychol 1993; 61: 248–60PubMedCrossRefGoogle Scholar
  108. 108.
    Borkovec TD, Whisman MA. Psychosocial treatment for generalized anxiety disorder. In: Mavissakalian MR, Prien RF, editors. Long-term treatments of anxiety disorders. Washington (DC): American Psychiatric Press, 1996: 171–99Google Scholar
  109. 109.
    Arntz A. Cognitive therapy versus applied relaxation as treatment of generalized anxiety disorder. Behav Res Ther 2003; 41: 633–46PubMedCrossRefGoogle Scholar
  110. 110.
    Stanley MA, Beck JG, Novy DM, et al. Cognitive-behavioral treatment of late-life generalized anxiety disorder. J Consult Clin Psychol 2003; 71: 309–19PubMedCrossRefGoogle Scholar
  111. 111.
    Mohlman J, Gorenstein EE, Kleber M, et al. Standard and enhanced cognitive-behavior therapy for late-life generalized anxiety disorder: two pilot investigations. Am J Geriatr Psychiatry 2003; 11: 24–32PubMedGoogle Scholar
  112. 112.
    Worthington III JJ, Kinrys G, Wygant LE, et al. Aripiprazole as an augmentor of selective serotonin reuptake inhibitors in depression and anxiety disorder patients. Int Clin Psychopharmacol 2005; 20: 9–11PubMedCrossRefGoogle Scholar
  113. 113.
    Galynker I, Khan A, Grebchenko Y, et al. Low-dose risperidone and quetiapine as monotherapy for comorbid anxiety and depression. J Clin Psychiatry 2005; 66: 544PubMedCrossRefGoogle Scholar
  114. 114.
    Brawman-Mintzer O, Knapp RG, Nietert PJ. Adjunctive risperidone in generalized anxiety disorder: a double-blind, placebo-controlled study. J Clin Psychiatry 2005; 66: 1321–5PubMedCrossRefGoogle Scholar
  115. 115.
    Pollack MH, Simon NM, Zalta AK, et al. Olanzapine augmentation of fluoxetine for refractory generalized anxiety disorder: a placebo controlled study. Biol Psychiatry 2006; 59: 211–5PubMedCrossRefGoogle Scholar
  116. 116.
    Brawman-Mintzer O, Nietert PJ, Rynn M, et al. Quetiapine monotherapy in patients with GAD [abstract no. NR634]. American Psychiatric Association 159th Annual Meeting; 2006 May 20–25; Toronto (ON)Google Scholar
  117. 117.
    Katzman M, Vermani M, Jacobs L, et al. The use of quetiapine as an adjunct in the pharmacotherapy of generalised anxiety disorder: a flexible-dose, open-label trial [poster]. 7th International Forum on Mood and Anxiety Disorders; 2007 Dec 5–7; BudapestGoogle Scholar
  118. 118.
    Snyderman SH, Rynn MA, Rickels K. Open-label pilot study of ziprasidone for refractory generalized anxiety disorder. J Clin Psychopharmacol 2005; 25: 497–9PubMedCrossRefGoogle Scholar
  119. 119.
    Crane DL. Ziprasidone as an augmenting agent in the treatment of anxiety-spectrum disorders. CNS Spectr 2005; 10: 176–9PubMedGoogle Scholar
  120. 120.
    Simon NM, Hoge EA, Fischmann D, et al. An open-label trial of risperidone augmentation for refractory anxiety disorders. J Clin Psychiatry 2006; 67: 381–5PubMedCrossRefGoogle Scholar
  121. 121.
    Reiss S, Peterson RA, Gursky M, et al. Anxiety sensitivity, anxiety frequency and the prediction of fearfulness. Behav Res Ther 1986; 24: 1–8PubMedCrossRefGoogle Scholar
  122. 122.
    Morin CM. Insomnia: psychological assessment and management. New York (NY): Guilford, 1993Google Scholar
  123. 123.
    Hedlund JL, Viewig BW. Hamilton rating scale for depression: a comprehensive review. J Oper Psychiatry 1979; 10: 149–65Google Scholar
  124. 124.
    Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979; 134: 382–9PubMedCrossRefGoogle Scholar
  125. 125.
    Buysse DJ, Reynolds III CF, Monk TH, et al. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989; 28: 193–213PubMedCrossRefGoogle Scholar
  126. 126.
    Endicott J, Nee J, Harrison W, et al. Quality of Life Enjoyment and Satisfaction Questionnaire: a new measure. Psychopharmacol Bull 1993; 29: 321–6PubMedGoogle Scholar
  127. 127.
    Sheehan DV. The anxiety disease. New York (NY): Charles Scribner’s Sons, 1983Google Scholar
  128. 128.
    Leon AC, Shear MK, Portera L, et al. Assessing impairment in patients with panic disorder: the Sheehan Disability Scale. Soc Psychiatry Epidemiol 1992; 27: 78–82CrossRefGoogle Scholar
  129. 129.
    Calabrese JR, Keck Jr PE, Macfadden W, et al. A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry 2005; 162: 1351–60PubMedCrossRefGoogle Scholar
  130. 130.
    Thase M, MacFadden W, McCoy R, et al. Efficacy of quetiapine monotherapy in bipolar depression: a confirmatory double-blind, placebo-controlled study (the BOLDER II Study). Int J Neuropsychopharmacol 2006; 9: S237Google Scholar
  131. 131.
    Carson WH, Kitagawa H, Nemeroff CB. Drug development for anxiety disorders: new roles for atypical anti-psychotics. Psychopharmacol Bull 2004; 38Suppl. 1: 38–45Google Scholar
  132. 132.
    Masand PS, Narasimhan M. Improving adherence to anti-psychotic pharmacotherapy. Curr Clin Pharmacol 2006; 1:47–56PubMedCrossRefGoogle Scholar
  133. 133.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd ed. Washington, DC: American Psychiatric Association, 1980Google Scholar
  134. 134.
    Bremner JD. Traumatic stress: effects on the brain. Dialogues Clin Neurosci 2006; 8: 445–61PubMedGoogle Scholar
  135. 135.
    Bremner JD. Stress and brain atrophy. CNS Neurol Disord Drug Targets 2006; 5: 503–12PubMedCrossRefGoogle Scholar
  136. 136.
    Zhang L, Zhou R, Li X, et al. Stress-induced change of mitochondria membrane potential regulated by genomic and non-genomic GR signaling: a possible mechanism for hippocampus atrophy in PTSD. Med Hypotheses 2006; 66: 1205–8PubMedCrossRefGoogle Scholar
  137. 137.
    Kalisch R, Schubert M, Jacob W, et al. Anxiety and hippocampus volume in the rat. Neuropsychopharmacology 2006; 31: 925–32PubMedCrossRefGoogle Scholar
  138. 138.
    Ballenger JC. Treatment of anxiety disorders to remission. J Clin Psychiatry 2001; 62Suppl. 12: 5–9PubMedGoogle Scholar
  139. 139.
    Rector NA, Szacun-Shimizu K, Leybman M. Anxiety sensitivity within the anxiety disorders: disorder-specific sensitivities and depression comorbidity. Behav Res Ther 2007; 45(8): 1967–75PubMedCrossRefGoogle Scholar

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© Adis Data Information BV 2009

Authors and Affiliations

  1. 1.START (Stress, Trauma, Anxiety, Rehabilitation, and Treatment) Clinic for Mood and Anxiety DisordersTorontoCanada

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