Abstract
Generalized anxiety disorder (GAD) is common in community and clinical settings. The individual and societal burden associated with GAD is substantial, but many of those who could benefit from treatment are not recognized or treated. Recent evidence-based guidelines for the pharmacological management of patients with GAD have recommended initial treatment with either a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI), on the basis of their proven efficacy and reasonable tolerability in randomized placebo-controlled trials. However, there is much room for improvement in both the efficacy and the tolerability of treatment. Response rates to first-line treatment can be disappointing and it is hard to predict reliably which patients will respond well and which will have only a limited treatment response. Many patients worry about becoming dependent on medication, a substantial proportion experience troublesome adverse effects, and these problems limit the effectiveness of pharmacological treatments in clinical practice. The relative lack of longitudinal studies of clinical outcomes in GAD, and the small number of placebo-controlled relapse prevention studies lead to uncertainty about the optimal duration of treatment after a satisfactory initial response. There have been few investigations of the further management of patients who have not responded to first-line treatment and there is a pressing need for further augmentation studies in patients who have not responded to an SSRI or SNRI, or to other initial pharmacological approaches. Future treatment guidelines for GAD will be influenced by emerging data for established and novel pharmacological approaches, and possibly through the more accurate identification of certain patient subgroups who are likely to respond preferentially to particular interventions.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Allgulander C (2008) Presented at 21st ECNP Congress, 31st August 2008, Barcelona, Spain
Allgulander C, Hackett D, Salinas E (2001) Venlafaxine extended release (ER) in the treatment of generalised anxiety disorder: twenty-four-week placebo-controlled dose-ranging study. Br J Psychiatry 179:15–22
Allgulander C, Dahl AA, Austin C et al (2004) Efficacy of sertraline in a 12-week trial for generalized anxiety disorder. Am J Psychiatry 161: 1642–1649
Allgulander C, Florea I, Huusom AK (2006) Prevention of relapse in generalized anxiety disorder by escitalopram treatment. Int J Neuropsychopharmacol 9:495–505
Angst J, Gamma A, Baldwin DS et al (2009) The generalized anxiety spectrum: prevalence, onset, course and outcome. Eur Arch Psychiatry Clin Neurosci 259: 37–45
Baldwin DS (2004) Sexual dysfunction associated with antidepressant drugs. Exp Opin Drug Safety 3:457–470
Baldwin DS, Ajel K (2007) The role of pregabalin in the treatment of generalized anxiety disorder. Neuropsychiatric Dis Treat 3:185–191
Baldwin DS, Polkinghorn C (2005) Evidence-based pharmacotherapy of generalized anxiety disorder. Int J Neuropsychopharmacol 8:293–302
Baldwin DS, Anderson IM, Nutt DJ et al (2005) Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British association for Psychopharmacology. J Psychopharmacol 19:567–596
Baldwin DS, Huusom AKT, Maehlum E (2006a) Escitalopram and paroxetine in the treatment of generalised anxiety disorder. Randomised, double-blind, placebo-controlled study. Br J Psychiatry 189:264–272
Baldwin DS, Bridgman K, Buis C (2006b) Resolution of sexual dysfunction during double-blind treatment of major depression with reboxetine or paroxetine. J Psychopharmacol 20:91–96
Baldwin DS, Reines EH, Guiton C et al (2007a) Escitalopram therapy for major depression and anxiety disorders. Ann Pharmacother 41:1583–1592
Baldwin DS, Montgomery SA, Nil R et al (2007b) Discontinuation symptoms in depression and anxiety disorders. Int J Neuropsychopharmacol 10:73–84
Baldwin DS, Stein DJ, Dolberg O et al (2009) How long should an initial treatment period be in patients with major depressive disorder, generalised anxiety disorder or social anxiety disorder? An exploration of the randomised controlled trial database. Hum Psychopharmacol 24:269–275
Baldwin DS, Moreno R, Briley M (2008) Resolution of sexual dysfunction during acute treatment of major depression with milnacipran. Hum Psychopharmacol 23:527–532
Ballenger JC (1999) Clinical guidelines for establishing remission in patients with depression and anxiety. J Clin Psychiatry 60(suppl 22):29–34
Bandelow B, Baldwin DS, Dolberg OT et al (2006) What is the threshold for symptomatic response and remission for major depressive disorder, panic disorder, social anxiety disorder, and generalized anxiety disorder? J Clin Psychiatry 67:1428–1434
Bandelow B, Bobes J, Ahokas A, et al (2007a) Results from a phase III study of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with generalised anxiety disorder. Int J Psychiatry Clin Pract 11:314–315 (abstract)
Bandelow B, Seidler-Brandler U, Becker A et al (2007b) Meta-analysis of randomized controlled comparisons of psychopharmacological and psychological treatments for anxiety disorders. World J Biol Psychiatr 8:175–187
Bech P (2007) Dose-response relationship of pregabalin in patients with generalized anxiety disorder. A pooled analysis of four placebo-controlled trials. Pharmacopsychiatry 40:163–168
Beekman AT, Bremmer MA, Deeg DJ et al (1998) Anxiety disorders in later life: a report from the longitudinal Aging Study Amsterdam. Int J Geriatr Psychiatry 13:717–726
Brawman-Mintzer O, Knapp RG, Nietert PJ (2005) Adjunctive risperidone in generalized anxiety disorder: a double-blind, placebo-controlled study. J Clin Psychiatry 66:1321–1325
Brawman-Mintzer O, Knapp RG, Rynn M et al (2006) Sertraline treatment for generalized anxiety disorder: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry 67:874–881
Bruce SE, Yonkers KA, Otto MW et al (2005) 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 162:1179–1187
Canadian Psychiatric Association (2006) Clinical practice guidelines. Management of anxiety disorders. Can J Psychiatr 51:9S–91S
Carney CE, Segal ZV, Edinger JD et al (2007) A comparison of rates of residual insomnia symptoms following pharmacotherapy or cognitive-behavioral therapy for major depressive disorder. J Clin Psychiatr 68:254–260
Cervena K, Matousek M, Prasko J et al (2005) Sleep disturbances in patients treated for panic disorder. Sleep Med 6:149–153
Chessick CA, Allen MH, Thase M et al (2006) Azapirones for generalized anxiety disorder. Cochrane Database Syst Rev 3:CD006115
Davidson JR, DuPont RL, Hedges D et al (1999) Efficacy, safety, and tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder. J Clin Psychiatry 60:528–535
Davidson JR, Bose A, Korotzer A et al (2004) Escitalopram in the treatment of generalized anxiety disorder: double-blind, placebo controlled, flexible-dose study. Depress Anxiety 19:234–240
Davidson JRT, Wittchen H-U, Llorca P-M et al (2008) Duloxetine treatment for relapse prevention in adults with generalized anxiety disorder: a double-blind placebo-controlled trial. Eur Neuropsychopharmacol 18:673–681
Downing RW, Rickels K (1985) Early treatment response in anxious outpatients treated with diazepam. Acta Psychiatr Scand 72:522–528
Feltner D, Crockatt JG, Dubovsky SJ et al (2003) A randomized, double-blind, placebo-controlled, fixed-dose, multicenter study of pregabalin in patients with generalized anxiety disorder. J Clin Psychopharmacol 23:240–249
Feltner D, Wittchen HU, Kavoussi R et al (2008) Long-term efficacy of pregabalin in generalized anxiety disorder. Int Clin Psychopharmacol 23:18–28
Ferguson JM (2001) SSRI antidepressant medications: adverse effects and tolerability. Prim Care J Clin Psychiatry 3:22–27
Food and Drug Administration [FDA] (2006) New controversial clinical trial design gives better long-term data. FDA Week
Geddes JR, Carney SM, Davies C et al (2003) Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet 361:653–661
Gelenberg AJ, Lydiard RB, Rudolph RL et al (2000) Efficacy of venlafaxine extended-release capsules in nondepressed outpatients with generalized anxiety disorder: A 6-month randomized controlled trial. JAMA, 283: 3082–3088
Goodman WK, Bose A, Wang Q (2005) Treatment of generalized anxiety disorder with escitalopram: pooled results from double-blind, placebo-controlled trials. J Affect Disord 87:161–167
Gould RA, Otto MW, Pollack MH et al (1997) Cognitive behavioural and pharmacological treatment of generalised anxiety disorder: a preliminary meta-analysis. Behav Ther 28:285–305
Guy W (1976) The clinical global impression severity and impression scales. In: ECDEU Assessment Manual for Psychopathology. Rockville, MD. US Dept Health, Education and Welfare, 218–222
Hamilton M (1959) The assessment of anxiety states by rating. Br J Med Psychol 32:50–55
Hartford J, Kornstein S, Liebowitz M et al (2007) Duloxetine as an SNRI treatment for generalized anxiety disorder: results from a placebo and active-controlled trial. Int Clin Psychopharmacol 22:167–174
Hidalgo RB, Tupler LA, Davidson JRT (2007) An effect-size analysis of pharmacologic treatments for generalized anxiety disorder. J Psychopharmacol 21:864–872
Judd LL, Kessler RC, Paulus MP et al (1998) Comorbidity as a fundamental feature of generalized anxiety disorders: results from the National Comorbidity Survey (NCS). Acta Psychiatr Scand 98(Suppl 393):6–11
Kasper S, Herman B, Nivoli G et al (2009). Efficacy of pregabalin and venlafaxine-XR in generalized anxiety disorder: results of a double-blind, placebo-controlled 8-week trial. Int Clin Psychopharmacol 2009. E-pub ahead of print. DOI: 10.1097/YIC.0b013e32831d7980
Katzman MA, Vermani M, Jacobs L et al (2008) Quetiapine as an adjunctive pharmacotherapy for the treatment of non-remitting generalized anxiety disorder: a flexible-dose, open-label pilot trial. J Anxiety Disord [Epub ahead of print]
Kessler RC, DuPont RL, Berglund (1999) Impairment in pure and comorbid generalized anxiety disorder and major depression at 12 months in two national surveys. Am J Psychiatry 156:1915–1923
Kinrys G, Vasconcelos e Sa D, Nery F (2007) Adjunctive zonisamide for treatment refractory anxiety. Int J Clin Pract 61:1050–1053
Laakmann G, Schüle C, Lorkowski G et al (1998) Buspirone and lorazepam in the treatment of generalized anxiety disorder in outpatients. Psychopharmacol 136:357–366
Lenox-Smith AJ, Reynolds A (2003) A double-blind, randomised, placebo controlled study of venlafaxine XL in patients with generalised anxiety disorder in primary care. Br J Gen Pract 53:772–777
Martin JLR, Sainz-Pardo M, Furukawa TA et al (2007) Benzodiazepines in generalized anxiety disorder: heterogeneity of outcomes based on a systematic review and meta-analysis of clinical trials. J Psychopharmacol 21:774–782
Mendels J, Krajewski TF, Huffer V et al (1986) Effective short-term treatment of generalized anxiety disorder with trifluoperazine. J Clin Psychiatry 47:170–174
Meredith C, Cutler A, Neijber A, She F, Eriksson H (2008) Efficacy and tolerability of extended release quetiapine fumarate monotherapy in the treatment of GAD. Eur Neuropsychopharmacol 18(suppl 4):S499–S450
Miceli JJ, Ramey TS, Weaver JJ et al (2009) Adjunctive pregabalin treatment after partial response in generalized anxiety disorder: results of a double-blind, placebo-controlled trial. Presented at the 162nd Annual Meeting of the American Psychiatric Association; May 16–21, 2009; San Francisco, CA
Mitte K, Noack P, Steil R, Hautzinger M (2005) A meta-analytic review of the efficacy of drug treatment in generalized anxiety disorder. J Clin Psychopharmacol 25:141–150
Montgomery SA, Sheehan DV, Meoni P et al (2002) Characterization of the longitudinal course of improvement in generalized anxiety disorder during long-term treatment with venlafaxine XR. J Psychiatr Res 36:209–217
Montgomery SA, Tobias K, Zornberg GL et al (2006) 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 67:771–782
Montgomery S, Chatamra K, Pauer L et al (2008) Efficacy and safety of pregabalin in elderly people with generalised anxiety disorder. Br J Psychiatry 193:389–394
Nutt DJ (2005) Overview of diagnosis and drug treatment of anxiety disorders. CNS Spectrums 10:49–56
Olatunji BO, Feldman G, Smits JAJ et al (2008) Examination of the decline in symptoms of anxiety and depression in generalized anxiety disorder: impact of anxiety sensitivity on response to pharmacotherapy. Depress Anx 25:167–171
Pande AC, Crockatt MA, Janney C et al (2000) Pregabalin treatment of GAD. Presented at: American Psychiatric Association 153rd Annual Meeting. May 13–18; Chicago, IL (Abstract NR244). Available at: http://www.psych.org/edu/other_res/lib_archives/archives/meetings/2000nra.pdf Accessed February 15, 2006
Pande AC, Crockatt JG, Feltner DE et al (2003) Pregabalin in generalized anxiety disorder: a placebo-controlled trial. Am J Psychiatry 160:533–540
Perugi G, Frare F, Toni C et al (2002) Open-label evaluation of venlafaxine sustained release in outpatients with generalized anxiety disorder with comorbid depression or dysthymia: effectiveness, tolerability and predictors of response. Neuropsychobiol 46:145–149
Pohl RB, Feltner DE, Fieve RR et al (2005) Efficacy of pregabalin in the treatment of generalized anxiety disorder: double-blind, placebo-controlled comparison of BID versus TID dosing. J Clin Psychopharmacol 25:151–158
Pollack MH, Zaninelli R, Goddard A et al (2001) Paroxetine in the treatment of generalized anxiety disorder: results of a placebo-controlled, flexible-dosage trial. J Clin Psychiatry 62:350–357
Pollack MH, Meoni P, Otto MW et al (2003) Predictors of outcome following venlafaxine extended-release treatment of DSM-IV generalized anxiety disorder: a pooled analysis of short- and long-term studies. J Clin Psychopharmacol 23:250–259
Pollack MH, Simon NM, Zalta AK et al (2006) Olanzapine augmentation of fluoxetine for refractory generalized anxiety disorder: a placebo controlled study. Biol Psychiatry 59:211–215
Pollack MH, Kornstein SG, Spann ME, et al (2008) Early improvement during duloxetine treatment of generalized anxiety disorder predicts response and remission at endpoint. J Psychiatr Res [Epub ahead of print]
Rickels K, Schweizer E, Csanalosi I et al (1988) Long-term treatment of anxiety and risk of withdrawal: prospective study of clorazepate and buspirone. Arch Gen Psychiatr 45:444–450
Rickels K, Pollack MH, Sheehan DV et al (2000) Efficacy of extended-release venlafaxine in nondepressed outpatients with generalized anxiety disorder. Am J Psychiatry 157:968–974
Rickels K, Zaninelli R, McCafferty J et al (2003) Paroxetine treatment of generalized anxiety disorder: a double-blind, placebo-controlled study. Am J Psychiatry 160:749–756
Rickels K, Pollack MH, Feltner DE et al (2005) Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam. Arch Gen Psychiatry 62:1022–1030
Rickels K, Rynn M, Iyengar M et al (2006) Remission of generalized anxiety disorder: a review of the paroxetine clinical trials database. J Clin Psychiatry 67:41–47
Rodriguez BF, Weisberg RB, Pagano ME et al (2006) Characteristics and predictors of full and partial recovery from generalized anxiety disorder in primary care patients. J Nerv Ment Dis 194:91–97
Rynn MA, Siqueland L, Rickels K (2001) Placebo-controlled trial of sertraline in the treatment of children with generalized anxiety disorder. Am J Psychiatry158:2008–2014
Rynn M, Khalid-Khan S, Garcia-Espana F (2006) Early response and 8-week treatment outcome in GAD. Depress Anx 23:461–465
Rynn MA, Riddle MA, Yeung PP et al (2007) Efficacy and safety of extended-release venlafaxine in the treatment of generalized anxiety disorder in children and adolescents: two placebo-controlled trials. Am J Psychiatry 164:290–300
Rynn M, Russell J, Erickson J et al (2008) Efficacy and safety of duloxetine in the treatment of generalized anxiety disorder: a flexible-dose, progressive-titration, placebo-controlled trial. Depress Anxiety 25:182–189
Simon NM, Zalta AK, Worthington JJ 3rd et al (2006) Preliminary support for gender differences in response to fluoxetine for generalized anxiety disorder. Depress Anx 23:373–376
Simon NM, Connor KM, LeBeau RT et al (2008) Quetiapine augmentation of paroxetine CR for the treatment of generalized anxiety disorder: preliminary findings. Psychopharmacol (Berl) 197:675–681
Stein DJ, Andersen HF, Goodman WK (2005) Escitalopram for the treatment of GAD: efficacy across different subgroups and outcomes. Ann Clin Psychiatry 17:71–75
Stein DJ, Baldwin DS, Dolberg OT et al (2006) Which factors predict placebo response in anxiety disorders and major depression? An analysis of placebo-controlled studies of escitalopram. J Clin Psychiatry 67:1741–1746
Stein DJ, Ahokas A, de Bodinat C (2008b) Efficacy of agomelatine in generalized anxiety disorder: a randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol 28:561–566
Stein DJ, Baldwin DS, Baldinetti F, Baldinetti F, Mandel F (2008a) Efficacy of pregabalin in depressive symptoms associated with generalized anxiety disorder: a pooled analysis of 6 studies. Eur Neuropsychopharmacol 18:422–430
Stocchi F, Nordera G, Jokinen RH et al (2003) Efficacy and tolerability of paroxetine for the long-term treatment of generalized anxiety disorder. J Clin Psychiatry 64:250–258
Tyrer P, Baldwin DS (2006) Generalised anxiety disorder. Lancet 368:2156–2166
Tyrer P, Owen R, Dawling S (1983) Gradual withdrawal of diazepam after long-term therapy. Lancet 321:1402–1406
Tyrer P, Seivewright H, Johnson T (2004) The Nottingham Study of Neurotic Disorder: predictors of 12 year outcome of dysthymic, panic and generalised anxiety disorder. Psychol Med 34:385–394
Weiller E, Bisserbe JC, Maier W et al (1998) Prevalence and recognition of anxiety syndromes in five European primary care settings. A report from the WHO Study on Psychological Problems in General Health Care. Br J Psychiatr 173(suppl 34):18–23
Wittchen H-U, Jacobi F (2005) Size and burden of mental disorders in Europe: a critical review and appraisal of 27 studies. Eur Neuropsychopharmacol 15:357–376
Wittchen H-U, Carter RM, Pfisster H, Montgomery SA et al (2000) Disabilities and quality of life in pure and comorbid generalized anxiety disorder and major depression in a national survey. Int Clin Psychopharmacol 15:319–328
Wittchen H-U, Kessler RC, Beesdo K et al (2002) Generalized anxiety disorder and depression in primary care: prevalence, recognition, and management. J Clin Psychiatry 63(suppl 8):24–34
Acknowledgments
This review is based upon a talk given at the 20th ECNP Congress, Vienna, Austria, the abstract for which was published as Baldwin DS, Ajel KI, Garner MJ (2007) Eur Neuropsychopharmacol 17(Suppl 4):S208.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Baldwin, D.S., Ajel, K.I., Garner, M. (2009). Pharmacological Treatment of Generalized Anxiety Disorder. In: Stein, M., Steckler, T. (eds) Behavioral Neurobiology of Anxiety and Its Treatment. Current Topics in Behavioral Neurosciences, vol 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2009_2
Download citation
DOI: https://doi.org/10.1007/7854_2009_2
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-02911-0
Online ISBN: 978-3-642-02912-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)