New approaches to the pharmacological management of generalized anxiety disorder

Expert Opinion on Pharmacotherapy

Volumn 14, Issue 2, 2013, Pages 175-184

  Buoli, Massimiliano ^a   Caldiroli, Alice ^a   Caletti, Elisabetta ^a   Paoli, Riccardo Augusto ^a   Altamura, Alfredo Carlo ^a  

^a UNIVERSITY OF MILAN   (Italy)

Author keywords

Antipsychotics; Atypical; Generalized anxiety disorder; Pharmacotherapy; Unmet needs

Indexed keywords

4 AMINOBUTYRIC ACID; AGOMELATINE; ANTICONVULSIVE AGENT; ANTIDEPRESSANT AGENT; ARIPIPRAZOLE; ATYPICAL ANTIPSYCHOTIC AGENT; BENZODIAZEPINE DERIVATIVE; CLONIDINE; ESCITALOPRAM; FLUOXETINE; GABAPENTIN; LAMOTRIGINE; MEMANTINE; MOOD STABILIZER; NORADRENALIN; NORQUETIAPINE; OLANZAPINE; ONDANSETRON; PAROXETINE; PLACEBO; QUETIAPINE; RILUZOLE; RISPERIDONE; SEROTONIN; SEROTONIN NORADRENALIN REUPTAKE INHIBITOR; SEROTONIN UPTAKE INHIBITOR; TIAGABINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROIC ACID; ZIPRASIDONE;

ADD ON THERAPY; ANXIETY; BRAIN NERVE CELL; BRAIN REGION; DATA BASE; DIZZINESS; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG SAFETY; EVIDENCE BASED MEDICINE; GENERALIZED ANXIETY DISORDER; HEADACHE; HUMAN; HYPOTENSION; LOW DRUG DOSE; NAUSEA; OFF LABEL DRUG USE; PATHOPHYSIOLOGY; PRACTICE GUIDELINE; REMISSION; REVIEW; SIDE EFFECT; SOMNOLENCE; TRANSCRANIAL MAGNETIC STIMULATION; TREATMENT RESPONSE;

ANTI-ANXIETY AGENTS; ANXIETY DISORDERS; EVIDENCE-BASED MEDICINE; HUMANS; MODELS, BIOLOGICAL; MOLECULAR TARGETED THERAPY; PRACTICE GUIDELINES AS TOPIC; TREATMENT OUTCOME;

EID: 84872714544     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1517/14656566.2013.759559     Document Type: Review

References (92)

1. Lieb R, Becker E, Altamura AC. The epidemiology of generalized anxiety disorder. Eur Neuropsychopharmacol 2005;15:445-52
2. 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;79:161-6
3. Altamura AC, Buoli M, Albano A, Dell'Osso B. Age at onset and latency to treatment (duration of untreated illness) in patients with mood and anxiety disorders: a naturalistic study. Int Clin Psychopharmacol 2010;25:172-9
4. Altamura AC, Dell'osso B, D'Urso N, et al. Duration of untreated illness as a predictor of treatment response and clinical course in generalized anxiety disorder. CNS Spectr 2008;13:415-22
5. Nutt D, Argyropoulos S, Hood S, Potokar J. Generalized anxiety disorder: a comorbid disease. Eur Neuropsychopharmacol 2006;16:109-18
6. Kessler RC, Gruber M, Hettema JM, et al. Co-morbid major depression and generalized anxiety disorders in the National Comorbidity Survey follow-up. Psychol Med 2008;38:365-74
7. De Girolamo G, Dagani J, Purcell R, et al. Age of onset of mental disorders and use of mental health services: needs, opportunities and obstacles. Epidemiol Psychiatr Sci 2012;21:47-57
8. Beesdo K, Pine DS, Lieb R, Wittchen HU. Incidence and risk patterns of anxiety and depressive disorders and categorization of generalized anxiety disorder. Arch Gen Psychiatry 2010;67:47-57
9. Culpepper L. Generalized anxiety disorder in primary care: emerging issues in management and treatment. J Clin Psychiatry 2002;63:35-42
10. Bandelow B, Zohar J, Hollander E, et al. WFSBP task force on treatment guidelines for anxiety obsessive-compulsive posttraumatic stress disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders: first revision. World J Biol Psychiatry 2008;9:248-312
11. Bandelow B, Sher L, Bunevicius R, et al. WFSBP Task Force on Mental Disorders in Primary Care; WFSBP Task Force on Anxiety Disorders, OCD and PTSD. Guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder and posttraumatic stress disorder in primary care. Int J Psychiatry Clin Pract 2012;16:77-84
12. Dell'Osso B, Buoli M, Baldwin DS, Altamura AC. Serotonin norepinephrine reuptake inhibitors (SNRIs) in anxiety disorders: a comprehensive review of their clinical efficacy. Hum Psychopharmacol 2010;25:17-29
13. Dobrea C, Buoli M, Arici C, et al. Tolerability and use in co-administration of pregabalin in affective patients: a 6-month prospective naturalistic study. Expert Opin Drug Saf 2012;11:893-9
14. Reinhold JA, Mandos LA, Rickels K, Lohoff FW. Pharmacological treatment of generalized anxiety disorder. Expert Opin Pharmacother 2011;12:2457-67
15. 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(23):3082-8
16. 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(5):350-7
17. Zullino DF, Hattenschwiler J, Mattia M, et al. Pharmacotherapy of generalized anxiety disorder: state of the art. Praxis 2003;92(42):1775-9
18. Davidson JR, Feltner DE, Dugar A. Management of generalized anxiety disorder in primary care: identifying the challenges and unmet needs. Prim Care Companion J Clin Psychiatry 2010;12:pii PCC.09r00772
19. Schiepers OJ, Wichers MC, Maes M. Cytokines and major depression. Prog Neuropsychopharmacol Biol Psychiatry 2005;29:201-17
20. Duman RS. Neuronal damage and protection in the pathophysiology and treatment of psychiatric illness: stress and depression. Dialogues Clin Neurosci 2009;11:239-55
21. Gorman JM, Hirschfeld RM, Ninan PT. New developments in the neurobiological basis of anxiety disorders. Psychopharmacol Bull 2002;36:49-67
22. Jetty PV, Charney DS, Goddard AW. Neurobiology of generalized anxiety disorder. Psychiatr Clin North Am 2001;24:75-97
23. Engin E, Liu J, Rudolph U. Alpha2-containing GABA(A) receptors: a target for the development of novel treatment strategies for CNS disorders. Pharmacol Ther 2012;136:142-52
24. Costa B, Pozzo ED, Martini C. Translocator protein as a promising target for novel anxiolytics. Curr Top Med Chem 2012;12:270-85
25. Wong DL, Tai TC, Wong-Faull DC, et al. Epinephrine: a short-and long-term regulator of stress and development of Illness: a potential new role for epinephrine in stress. Cell Mol Neurobiol 2012;32:737-48
26. Argyropoulos SV, Nutt DJ. Neurochemical aspects of anxiety. In: Anxiety disorders. Blackwell Science Ltd, Oxford,UK; 2003
27. Delgado LC, Guerra P, Perakakis P, et al. Psychophysiological correlates of chronic worry: cued versus non-cued fear reaction. Int J Psychophysiol 2009;74:280-7
28. Ohno Y. New insight into the therapeutic role of 5-HT1A receptors in central nervous system disorders. Cent Nerv Syst Agents Med Chem 2010;10:148-57
29. Katzman MA. Current considerations in the treatment of generalized anxiety disorder. CNS Drugs 2009;23:103-20
30. Murphy SE. Using functional neuroimaging to investigate the mechanisms of action of selective serotonin reuptake inhibitors (SSRIs). Curr Pharm Des 2010;16:1990-7
31. Buoli M, Dell'osso B, Bosi MF, Altamura C. Slow vs standard up-titration of paroxetine in the treatment of panic disorder: a prospective randomized trial. Psychiatry Clin Neurosci 2010;64:612-19
32. Marks DM, Shah MJ, Patkar AA, et al. Serotonin-norepinephrine reuptake inhibitors for pain control: premise and promise. Curr Neuropharmacol 2009;7:331-6
33. Dowben JS, Grant JS, Keltner NL. Clonidine: diverse use in pharmacologic management. Perspect Psychiatr Care 2011;47:105-8
34. Riaza Bermudo-Soriano C, Perez-Rodriguez MM, Vaquero-Lorenzo C, Baca-Garcia E. New perspectives in glutamate and anxiety. Pharmacol Biochem Behav 2012;100:752-74
35. Etkin A, Prater KE, Schatzberg AF, et al. Disrupted amygdalar subregion functional connectivity and evidence of a compensatory network in generalized anxiety disorder. Arch Gen Psychiatry 2009;66:1361-72
36. Kalin NH, Shelton SE, Davidson RJ. The role of the central nucleus of the amygdala in mediating fear and anxiety in the primate. J Neurosci 2004;16:5506-15
37. Stein MB. Neurobiology of generalized anxiety disorder. J Clin Psychiatry 2009;70:15-19
38. Monk CS, Telzer EH, Mogg K, et al. Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder. Arch Gen Psychiatry 2008;65:568-76
39. Mohlman J, Price RB, Eldreth DA, et al. The relation of worry to prefrontal cortex volume in older adults with and without generalized anxiety disorder. Psychiatry Res 2009;173:121-7
40. Schienle A, Ebner F, Schafer A. Localized gray matter volume abnormalities in generalized anxiety disorder. Eur Arch Psychiatry Clin Neurosci 2011;261:303-7
41. Brambilla P, Como G, Isola M, et al. White-matter abnormalities in the right posterior hemisphere in generalized anxiety disorder: a diffusion imaging study. Psychol Med 2011;25:1-8
42. Paulesu E, Sambugaro E, Torti T, et al. Neural correlates of worry in generalized anxiety disorder and in normal controls: a functional MRI study. Psychol Med 2010;40:117-24
43. La Via MF, Munno I, Lydiard RB, et al. The influence of stress intrusion on immunodepression in generalized anxiety disorder patients and controls. Psychosom Med 1996;58:138-42
44. Segal AB, Bruno S, Forte WC. Immune function in acute stress. Allergol Immunopathol (Madr) 2006;34:136-40
45. Altamura AC, Buoli M, Serati M. Duration of illness and duration of untreated illness in relation to drug response in psychiatric disorders. Neuropsychiatry 2011;1:81-90
46. Pollack MH. Refractory generalized anxiety disorder. J Clin Psychiatry 2009;70:32-8
47. Mula M, Pini S, Cassano GB. The role of anticonvulsant drugs in anxiety disorders: a critical review of the evidence. J Clin Psychopharmacol 2007;27:263-72
48. Wensel TM, Powe KW, Cates ME. Pregabalin for the treatment of generalized anxiety disorder. Ann Pharmacother 2012;46(3):424-9
49. Feltner D, Wittchen HU, Kavoussi R, et al. Long-term efficacy of pregabalin in generalized anxiety disorder. Int Clin Psychopharmacol 2008;23:18-28
50. Skopp G, Zimmer G. Pregabalin-a drug with abuse potential? Arch Kriminol 2012;229:44-54
51. Grosshans M, Mutschler J, Hermann D, et al. Pregabalin abuse, dependance and withdrawal: a case report. Am J Psychiatry 2010;167:7
52. Pollack MH, Matthews J, Scott EL. Gabapentin as a potential treatment for anxiety disorders. Am J Psychiatry 1998;155:992-3
53. Rosenthal M. Tiagabine for the treatment of generalized anxiety disorder: a randomized, open-label, clinical trial with paroxetine as a positive control. J Clin Psychiatry 2003;64:1245-9
54. 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;28:308-16
55. Schwartz TL, Azhar N, Husain J, et al. An open-label study of tiagabine as augmentation therapy for anxiety. Ann Clin Psychiatry 2005;17:167-72
56. Sepic-Grahovac D, Grahovac T, Ruzic-Barsic A, et al. Lamotrigine treatment of a patient affected by epilepsy and anxiety disorder. Psychiatr Danub 2011;23:111-13
57. Aliyev NA, Aliyev ZN. Valproate (depakine-chrono) in the acute treatment of outpatients with generalized anxiety disorder without psychiatric comorbidity: randomized, double-blind placebocontrolled study. Eur Psychiatry 2008;23:109-14
58. Maher AR, Maglione M, Bagley S, et al. Efficacy and comparative effectiveness of atypical antipsychotic medications for off-label uses in adults: a systematic review and meta-analysis. JAMA 2011;306:1359-69
59. Brawman-Mintzer O, Knapp RG, Nietert PJ. Adjunctive risperidone in generalized anxiety disorder: a double-blind, placebo-controlled study. J Clin Psychiatry 2005;66:1321-5
60. Pandina GJ, Canuso CM, Turkoz I, et al. Adjunctive risperidone in the treatment of generalized anxiety disorder: a double-blind, prospective, placebo-controlled, randomized trial. Psychopharmacol Bull 2007;40:41-57
61. Pollack MH, Simon NM, Zalta AK, et al. Olanzapine augmentation of fluoxetine for refractory generalized anxiety disorder: a placebo controlled study. Biol Psychiatry 2006;59:211-15
62. Bandelow B, Chouinard G, Bobes J, et al. Extended-release quetiapine fumarate (quetiapine XR): a once-daily monotherapy effective in generalized anxiety disorder. Data from a randomized, double-blind, placebo-and active-controlled study. Int J Neuropsychopharmacol 2010;13:305-20
63. Khan A, Joyce M, Atkinson S, et al. A randomized, double-blind study of once-daily extended release quetiapine fumarate (quetiapineXR) monotherapy in patients with generalized anxiety disorder. J Clin Psychopharmacol 2011;31:418-28
64. Merideth C, Cutler AJ, She F, Eriksson H. Efficacy and tolerability of extended release quetiapine fumarate monotherapy in the acute treatment of generalized anxiety disorder: a randomized, placebo controlled and active-controlled study. Int Clin Psychopharmacol 2012;27:40-54
65. Altamura AC, Serati M, Buoli M, Dell'Osso B. Augmentative quetiapine in partial/nonresponders with generalized anxiety disorder: a randomized, placebo-controlled study. Int Clin Psychopharmacol 2011;26(4):201-5
66. Gabriel A. The extended-release formulation of quetiapine fumarate (quetiapine XR) adjunctive treatment in partially responsive generalized anxiety disorder (GAD): an open label naturalistic study. Clin Ter 2011;162:113-18
67. Katzman MA, Vermani M, Jacobs L, et al. Quetiapine as an adjunctive pharmacotherapy for the treatment of non-remitting generalizedanxiety disorder: a flexible-dose, open-label pilot trial. J Anxiety Disord 2008;22:1480-6
68. Simon NM, Connor KM, LeBeau RT, et al. Quetiapine augmentation of paroxetine CR for the treatment of refractory generalized anxiety disorder: preliminary findings. Psychopharmacology (Berl) 2008;197:675-81
69. Katzman MA, Brawman-Mintzer O, Reyes EB, et al. Extended release quetiapine fumarate (quetiapine XR) monotherapy as maintenance treatment forgeneralized anxiety disorder: a long-term, randomized, placebo-controlled trial. Int Clin Psychopharmacol 2011;26:11-24
70. Yargic I, Caferov C. Quetiapine dependence and withdrawal: a case report. Subst Abus 2011;32:168-9
71. Kim DR, Staab JP. Quetiapine discontinuation syndrome. Am J Psychiatry 2005;162:1020
72. Menza MA, Dobkin RD, Marin H. An open-label trial of aripiprazole augmentation for treatment-resistant generalized anxiety disorder. J Clin Psychopharmacol 2007;27:207-10
73. Hoge EA, Worthington JJ III, Kaufman RE, et al. Aripiprazole as augmentation treatment of refractory generalized anxiety disorder and panic disorder. CNS Spectr 2008;13:522-7
74. Snyderman SH, Rynn MA, Rickels K. Open-label pilot study of ziprasidone for refractory generalized anxiety disorder. J Clin Psychopharmacol 2005;25:497-9
75. Lohoff FW, Etemad B, Mandos LA, et al. Ziprasidone treatment of refractory generalized anxiety disorder: a placebo-controlled, double-blind study. J Clin Psychopharmacol 2010;30:185-9
76. Stein DJ, Ahokas AA, de Bodinat C. Efficacy of agomelatine in generalized anxiety disorder: a randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol 2008;28:561-6
77. Stein DJ, Ahokas A, Albarran C, et al. Agomelatine prevents relapse in generalized anxiety disorder: a 6-month randomized, double-blind, placebo-controlled discontinuation study. J Clin Psychiatry 2012;73:1002-8
78. Feusner JD, Kerwin L, Saxena S, Bystritsky A. Differential efficacy of memantine for obsessive-compulsive disorder vs. generalized anxiety disorder: an open-label trial. Psychopharmacol Bull 2009;42:81-93
79. Swartz CM. Betaxolol in anxiety disorders. Ann Clin Psychiatry 1998;10:9-14
80. Peet M, Ali S. Propranolol and atenolol in the treatment of anxiety. Int Clin Psychopharmacol 1986;1:314-19
81. Hoehn-Saric R, Merchant AF, Keyser ML, Smith VK. Effects of clonidine on anxiety disorders. Arch Gen Psychiatry 1981;38:1278-82
82. Kalk NJ, Melichar J, Holmes RB, et al. Central noradrenergic responsiveness to a clonidine challenge in generalized anxiety disorder: a single photon emission computed tomography study. J Psychopharmacol 2012;26:452-60
83. Freeman AM III, Westphal JR, Norris GT, et al. Efficacy of ondansetron in the treatment of generalized anxiety disorder. Depress Anxiety 1997;5:140-1
84. Mathew SJ, Amiel JM, Coplan JD, et al. Open-label trial of riluzole in generalized anxiety disorder. Am J Psychiatry 2005;162:2379-81
85. Mathew SJ, Price RB, Mao X, et al. Hippocampal N-acetylaspartate concentration and response to riluzole in generalized anxiety disorder. Biol Psychiatry 2008;63:891-8
86. Dell'Osso B, Mundo E, D'Urso N, et al. Augmentative repetitive navigated transcranial magnetic stimulation (rTMS) in drug-resistant bipolar depression. Bipolar Disord 2009;11:76-81
87. Bystritsky A, Kaplan JT, Feusner JD, et al. A preliminary study of fMRI-guided rTMS in the treatment of generalized anxiety disorder. J Clin Psychiatry 2008;69(7):1092-8
88. Labbate LA, Johnson MR, Lydiard RB, et al. Sleep Deprivation in social phobia and generalized anxiety disorder. Biol Psychiatry 1998;43(11):840-2
89. Bienvenu OJ, Wuyek LA, Stein MB. Anxiety disorders diagnosis: some history and controversies. Curr Top Behav Neurosci 2010;2:3-19
90. Tromp do PM, Grupe DW, Oathes DJ, et al. Reduced structural connectivity of a major frontolimbic pathway in generalized anxiety disorder. Arch Gen Psychiatry 2012;69:925-34
91. Newcomer JW. Comparing the safety and efficacy of atypical antipsychotics in psychiatric patients with comorbid medical illnesses. J Clin Psychiatry 2009;70:30-6
92. Rickels K, Shiovitz TM, Ramey TS, et al. Adjunctive therapy with pregabalin in generalized anxiety disorder patients with partial response to SSRI or SNRI treatment. Int Clin Psychopharmacol 2012;27(3):142-50