Efficacy and safety of pregabalin in generalised anxiety disorder: A critical review of the literature

Journal of Psychopharmacology

Volumn 29, Issue 10, 2015, Pages 1047-1060

  Baldwin, David S ^a,b   Den Boer, Johan A ^c,d   Lyndon, Gavin ^e   Emir, Birol ^f   Schweizer, Edward ^g   Haswell, Hannah ^e  

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^b UNIVERSITY OF CAPE TOWN   (South Africa)

^c PRA HEALTH SCIENCES   (United States)

^d UNIVERSITY OF GRONINGEN   (Netherlands)

^e PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

^f PFIZER INC   (United States)

^g Paladin Consulting Group   (United States)

Author keywords

efficacy; Generalised anxiety disorder; pregabalin; safety

Indexed keywords

ALPRAZOLAM; LORAZEPAM; PLACEBO; PREGABALIN; VENLAFAXINE; ANXIOLYTIC AGENT; SEROTONIN UPTAKE INHIBITOR;

ACCIDENTAL INJURY; AMBLYOPIA; ANXIETY; ASTHENIA; COGNITIVE DEFECT; CONSTIPATION; DEPRESSION; DIARRHEA; DISEASE SEVERITY; DIZZINESS; DRUG ABUSE; DRUG CLEARANCE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG EXCRETION; DRUG MEGADOSE; DRUG METABOLISM; DRUG POTENCY; DRUG SAFETY; DRUG SUBSTITUTION; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; FATIGUE; GENERALIZED ANXIETY DISORDER; HEADACHE; HUMAN; INFECTION; INSOMNIA; MEDICAL LITERATURE; MONOTHERAPY; NAUSEA; PHARYNGITIS; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIDE EFFECT; SOMNOLENCE; TREATMENT DURATION; TREATMENT RESPONSE; TREATMENT WITHDRAWAL; VERTIGO; WEIGHT GAIN; XEROSTOMIA; ANXIETY DISORDERS; DOUBLE BLIND PROCEDURE;

ANTI-ANXIETY AGENTS; ANXIETY DISORDERS; DOUBLE-BLIND METHOD; HUMANS; PREGABALIN; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SEROTONIN UPTAKE INHIBITORS;

EID: 84942100738     PISSN: 02698811     EISSN: 14617285     Source Type: Journal    
DOI: 10.1177/0269881115598411     Document Type: Review

References (90)

1. Alonso J, Angermeyer MC, Bernert S, et al. (2004) 12-Month comorbidity patterns and associated factors in Europe: Results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand Suppl 420: 28-37.
2. American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Washington, DC: American Psychiatric Association.
3. Baldwin DS, Aitchison K, Bateson A, et al. (2013) Benzodiazepines: Risks and benefits. A reconsideration. J Psychopharmacol 27 (11): 967-971.
4. Baldwin DS, Anderson IM, Nutt DJ, et al. (2014). Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: A revision of the 2005 guidelines from the British Association for Psychopharmacology. J Psychopharmacol 28: 403-439.
5. Baldwin DS, Schweizer E, Xu Y, et al. (2012) Does early improvement predict endpoint response in patients with generalized anxiety disorder (GAD) treated with pregabalin or venlafaxine XR? Eur Neuropsychopharmacol 22: 137-142.
6. Bandelow B, Sher L, Bunevicius R, et al. (2012) Guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder and posttraumatic stress disorder in primary care. Int J Psychiatry Clin Pract 16: 77-84.
7. Bandelow B, Wedekind D, Leon T, (2007) Pregabalin for the treatment of generalized anxiety disorder: A novel pharmacologic intervention. Expert Rev Neurother 7: 769-781.
8. Barker MJ, Greenwood KM, Jackson M, et al. (2004) Cognitive effects of long-term benzodiazepine use: A meta-analysis. CNS Drugs 18: 37-48.
9. 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.
10. Boschen MJ, (2011) A meta-analysis of the efficacy of pregabalin in the treatment of generalized anxiety disorder. Can J Psychiatry 56: 558-566.
11. Boschen MJ, (2012) Pregabalin: Dose-response relationship in generalized anxiety disorder. Pharmacopsychiatry 45: 51-56.
12. Braga AJ, Chidley K, (2007) Self-poisoning with lamotrigine and pregabalin. Anaesthesia 62: 524-527.
13. Brodie MJ, Wilson EA, Wesche DL, et al. (2005) Pregabalin drug interaction studies: Lack of effect on the pharmacokinetics of carbamazepine, phenytoin, lamotrigine, and valproate in patients with partial epilepsy. Epilepsia 46: 1407-1413.
14. 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.
15. Cabrera J, Emir B, Dills D, et al. (2012) Characterizing and understanding body weight patterns in patients treated with pregabalin. Curr Med Res Opin 28: 1027-1037.
16. Carrasco MM, Baldinetti F, Leon T, (2007) Preliminary results evaluating cognitive function in elderly from double-blind, placebo-controlled trial of pregabalin in generalized anxiety disorder. 5th European Congress of Psychiatry. Madrid, Spain.
17. Citrome L, (2008) Compelling or irrelevant? Using number needed to treat can help decide. Acta Psychiatr Scand 117: 412-419.
18. Clayton PJ, Grove WM, Coryell W, et al. (1991) Follow-up and family study of anxious depression. Am J Psychiatry 148: 1512-1517.
19. Curran HV, Barrow S, Weingartner H, et al. (1995) Encoding, remembering and awareness in lorazepam-induced amnesia. Psychopharmacology (Berl) 122: 187-193.
20. De Beurs E, Beekman AT, van Balkom AJ, et al. (1999) Consequences of anxiety in older persons: Its effect on disability, well-being and use of health services. Psychol Med 29: 583-593.
21. Fawcett J, (1990) Targeting treatment in patients with mixed symptoms of anxiety and depression. J Clin Psychiatry 51: S40-S43.
22. Feltner D, Wittchen HU, Kavoussi R, et al. (2008) Long-term efficacy of pregabalin in generalized anxiety disorder. Int Clin Psychopharmacol 23: 18-28.
23. Feltner DE, 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.
24. Fergusson DM, Horwood LJ, Boden JM, (2006) Structure of internalising symptoms in early adulthood. Br J Psychiatry 189: 540-546.
25. Fieve RR, Sambunaris A, Trivedi MH, et al. (2004) Pregabalin€™s speed of onset in generalized anxiety disorder. Int J Neuropsychopharmacol 7 (Suppl. 1): S194.
26. Flint AJ, (1994) Epidemiology and comorbidity of anxiety disorders in the elderly. Am J Psychiatry 151: 640-649.
27. Frame B, Miller R, Hutmacher MM, (2009) Joint modeling of dizziness, drowsiness, and dropout associated with pregabalin and placebo treatment of generalized anxiety disorder. J Pharmacokinet Pharmacodyn 36: 565-584.
28. Frampton JE, Foster RH, (2006) Pregabalin: In the treatment of generalised anxiety disorder. CNS Drugs 20: 685-693; discussion 694-695.
29. Gould RL, Coulson MC, Patel N, et al. (2014) Interventions for reducing benzodiazepine use in older people: Meta-analysis of randomised controlled trials. Br J Psychiatry 204: 98-107.
30. Hadley SJ, Mandel FS, Schweizer E, (2012) Switching from long-term benzodiazepine therapy to pregabalin in patients with generalized anxiety disorder: A double-blind, placebo-controlled trial. J Psychopharmacol 26: 461-470.
31. Hamilton NA, Gallagher MW, Preacher KJ, et al. (2007) Insomnia and well-being. J Consult Clin Psychol 75: 939-946.
32. Hays RD, Martin SA, Sesti AM, et al. (2005) Psychometric properties of the Medical Outcomes Study Sleep measure. Sleep Med 6: 41-44.
33. Hidalgo RB, Tupler LA, Davidson JR, (2007) An effect-size analysis of pharmacologic treatments for generalized anxiety disorder. J Psychopharmacol 21: 864-872.
34. Hindmarch I, Dawson J, Stanley N, (2005a) A double-blind study in healthy volunteers to assess the effects on sleep of pregabalin compared with alprazolam and placebo. Sleep 28: 187-193.
35. Hindmarch I, Trick L, Ridout F, (2005b) A double-blind, placebo- and positive-internal-controlled (alprazolam) investigation of the cognitive and psychomotor profile of pregabalin in healthy volunteers. Psychopharmacology (Berl) 183: 133-143.
36. Hoehn-Saric R, McLeod DR, Zimmerli WD, (1988) Differential effects of alprazolam and imipramine in generalized anxiety disorder: Somatic versus psychic symptoms. J Clin Psychiatry 49: 293-301.
37. Holsboer-Trachsler E, Prieto R, (2013) Effects of pregabalin on sleep in generalized anxiety disorder. Int J Neuropsychopharmacol 16: 925-936.
38. Kasper S, Brasser M, Schweizer E, et al. (2010) How well do randomized controlled trial data generalize to €real world€™ clinical practice settings? Comparison of 2 generalized anxiety disorder studies. Int J Psychiatry Clin Pract 14 (Suppl. 1): S25-S26.
39. 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 24: 87-96.
40. Kasper S, Iglesias-Garcia C, Schweizer E, et al. (2014) Pregabalin long-term treatment and assessment of discontinuation in patients with generalized anxiety disorder. Int J Neuropsychopharmacol 17: 685-695.
41. Kendler KS, Gardner CO, Gatz M, et al. (2007) The sources of co-morbidity between major depression and generalized anxiety disorder in a Swedish national twin sample. Psychol Med 37: 453-462.
42. Kessler RC, Wang PS, (2008) The descriptive epidemiology of commonly occurring mental disorders in the United States. Annu Rev Public Health 29: 115-129.
43. Kessler RC, Berglund P, Demler O, et al. (2005) Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 62: 593-602.
44. Kessler RC, DuPont RL, Berglund P, et al. (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.
45. Lauria-Horner BA, Pohl RB, (2003) Pregabalin: A new anxiolytic. Expert Opin Investig Drugs 12: 663-672.
46. LeBlanc M, Beaulieu-Bonneau S, Mérette C, et al. (2007) Psychological and health-related quality of life factors associated with insomnia in a population-based sample. J Psychosom Res 63: 157-166.
47. Lockwood P, Pauer L, Scavone J, et al. (2014) The pharmacokinetics of pregabalin in breast milk, plasma and urine of healthy postpartum women. Abstract for the annual meeting of the American Society of Clinical Pharmacology and Therapeutics (ASCPT), Atlanta, GA, 18-22 March 2010.
48. Lydiard RB, Rickels K, Herman B, et al. (2010) Comparative efficacy of pregabalin and benzodiazepines in treating the psychic and somatic symptoms of generalized anxiety disorder. Int J Neuropsychopharmacol 13: 229-241.
49. Madhusoodanan S, Bogunovic OJ, (2004) Safety of benzodiazepines in the geriatric population. Expert Opin Drug Saf 3: 485-493.
50. Martin EL, Nemeroff CB, (2010) The biology of generalized anxiety disorder and major depressive disorder: Commonalities and distinguishing features. In: Goldberg DP, (ed) Diagnostic Issues in Depression and Generalized Anxiety Disorder: Refining the Research Agenda for DSM-5. Washington DC: American Psychiatric Press, pp. 45-70.
51. Micó JA, Prieto R, (2012) Elucidating the mechanism of action of pregabalin: α2i as a therapeutic target in anxiety. CNS Drugs 26: 637-648.
52. Mitte K, Noack P, Steil R, et al. (2005) A meta-analytic review of the efficacy of drug treatment in generalized anxiety disorder. J Clin Psychopharmacol 25: 141-150.
53. Moffitt TE, Caspi A, Harrington H, et al. (2007) Generalized anxiety disorder and depression: Childhood risk factors in a birth cohort followed to age 32. Psychol Med 37: 441-452.
54. Moller H-J, Brasser M, Kasper S, et al. (2009) Wirksamkeit und Verträglichkeit von Pregabalin bei Patienten mit generalisierten Angststörungen in der täglichen Praxis. Psychopharmakotherapie 16: 211-217.
55. 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.
56. Montgomery S, Emir B, Haswell H, et al. (2013) Long-term treatment of anxiety disorders with pregabalin: A 1 year open-label study of safety and tolerability. Curr Med Res Opin 29: 1223-1230.
57. Montgomery S, Prieto R, Emir B, et al. (2012) Long-term study of pregabalin for the treatment of generalized anxiety disorder: A 1-year open-label extension. 20th European Congress of Psychiatry. Prague, Czech Republic, 3-6 March 2012. Available at: http://www.epa-congress.org/useful-links/previous-congresses#.VbIXXaNwaUk (. accessed 24 July 2015).
58. Montgomery SA, (2006) Pregabalin for the treatment of generalised anxiety disorder. Expert Opin Pharmacother 7: 2139-2154.
59. Montgomery SA, Kasper S, (2010) Pharmacotherapy update: Pregabalin in the treatment of generalized anxiety disorder. Clin Med Insights: Ther 2: 189-202.
60. Montgomery SA, Herman BK, Schweizer E, et al. (2009) The efficacy of pregabalin and benzodiazepines in generalized anxiety disorder presenting with high levels of insomnia. Int Clin Psychopharmacol 24: 214-222.
61. 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.
62. Ormel J, VonKorff M, Ustun TB, et al. (1994) Common mental disorders and disability across cultures. Results from the WHO Collaborative Study on Psychological Problems in General Health Care. JAMA 272: 1741-1748.
63. Owen RT, (2007) Pregabalin: Its efficacy, safety and tolerability profile in generalized anxiety. Drugs Today (Barc) 43: 601-610.
64. Pande AC, Crockatt JG, Feltner DE, et al. (2003) Pregabalin in generalized anxiety disorder: A placebo-controlled trial. Am J Psychiatry 160: 533-540.
65. Pfizer Inc. (2013) LYRICA® EU product information. Available at: http://www.emea.europa.eu/docs/en-GB/document-library/EPAR-Product-Information/human/000546/WC500046602.pdf (first published 23 2009, last updated 6 2013,. accessed 3 April 2013).
66. 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.
67. Randinitis EJ, Posvar EL, Alvey CW, et al. (2003) Pharmacokinetics of pregabalin in subjects with various degrees of renal function. J Clin Pharmacol 43: 277-283.
68. Rapaport MH, Judd LL, Schettler PJ, et al. (2002) A descriptive analysis of minor depression. Am J Psychiatry 159: 637-643.
69. Reimers A, Brodtkorb E, (2012) Second-generation antiepileptic drugs and pregnancy: A guide for clinicians. Expert Rev Neurother 12: 707-717.
70. Rickels K, Downing R, Schweizer E, et al. (1993) Antidepressants for the treatment of generalized anxiety disorder. A placebo-controlled comparison of imipramine, trazodone, and diazepam. Arch Gen Psychiatry 50: 884-895.
71. 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.
72. Rickels K, Shiovitz TM, Ramey TS, et al. (2012) Adjunctive therapy with pregabalin in generalized anxiety disorder patients with partial response to SSRI or SNRI treatment. Int Clin Psychopharmacol 27: 142-150.
73. Rubio G, Bobes J, Cervera G, et al. (2011) Effects of pregabalin on subjective sleep disturbance symptoms during withdrawal from long-term benzodiazepine use. Eur Addict Res 17: 262-270.
74. Rynn MA, Brawman-Mintzer O, (2004) Generalized anxiety disorder: Acute and chronic treatment. CNS Spectr 9: 716-723.
75. Samuel M, Zimovetz EA, Gabriel Z, et al. (2011) Efficacy and safety of treatments for refractory generalized anxiety disorder: A systematic review. Int Clin Psychopharmacol 26: 63-68.
76. Schoevers RA, Beekman AT, Deeg DJ, et al. (2003) Comorbidity and risk-patterns of depression, generalised anxiety disorder and mixed anxiety-depression in later life: Results from the AMSTEL study. Int J Geriatr Psychiatry 18: 994-1001.
77. Schweizer E, Rickels K, (1998) Benzodiazepine dependence and withdrawal: A review of the syndrome and its clinical management. Acta Psychiatr Scand Suppl 393: 95-101.
78. Shear KM, (2012) Generalized anxiety disorder in ICD-11. World Psychiatry 11: 82-88.
79. Silverstone PH, Salinas E, (2001) Efficacy of venlafaxine extended release in patients with major depressive disorder and comorbid generalized anxiety disorder. J Clin Psychiatry 62: 523-529.
80. Spiller HA, Bratcher R, Griffith JR, (2008) Pregabalin overdose with benign outcome. Clin Toxicol (Phila) 46: 917.
81. Stein DJ, Mandel FS, Szczypa P, (2009) Tension in generalized anxiety disorder: A relatively neglected treatment target. 162nd Annual Meeting of the American Psychiatric Association. San Francisco, CA, 16-21 May 2009. Available at: http://www.psychiatry.org/File%20Library/Learn/Archives/am-syllabus-2009.pdf (. accessed 24 July 2015).
82. Toth C, (2014) Pregabalin: Latest safety evidence and clinical implications for the management of neuropathic pain. Ther Adv Drug Saf 5: 38-56.
83. Vgontzas AN, Kales A, Bixler EO,. (1995) Benzodiazepine side effects: Role of pharmacokinetics and pharmacodynamics. Pharmacology 51: 205-223.
84. Wensel TM, Powe KW, Cates ME, (2012) Pregabalin for the treatment of generalized anxiety disorder. Ann Pharmacother 46: 424-429.
85. Wittchen HU, Jacobi F, (2005) Size and burden of mental disorders in Europe-a critical review and appraisal of 27 studies. Eur Neuropsychopharmacol 15: 357-376.
86. Wittchen HU, Jacobi F, Rehm J, et al. (2011) The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 21: 655-679.
87. Wittchen HU, Kessler RC, Beesdo K, et al. (2002) Generalized anxiety and depression in primary care: Prevalence, recognition, and management. J Clin Psychiatry 63: S24-S34.
88. Wood DM, Berry DJ, Glover G, et al. (2010) Significant pregabalin toxicity managed with supportive care alone. J Med Toxicol 6: 435-437.
89. World Health Organization (1992) The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. Geneva: World Health Organisation.
90. Zaccara G, Perucca P, Gangemi PF, (2012) The adverse event profile of pregabalin across different disorders: A meta-analysis. Eur J Clin Pharmacol 68: 903-912.