Abstract
Pregabalin has a multidimensional effect across a range of disorders that have of a pathogenesis involving a CNS response of abnormal hyperexcitability. The high-affinity binding of pregabalin at α2δ proteins and the subsequent reduction in excessive release of several excitatory neurotransmitters appears to be responsible for the clinical benefits of pregabalin in treating fibromyalgia, neurological pain and generalized anxiety disorder. The use of pregabalin in these complex and difficult-to-treat conditions is associated with rapid and durable clinically significant improvements in several outcome measures relating to core symptoms, including pain, anxiety and sleep, and improvements in overall health status and health-related quality-of-life. The most common adverse events associated with the drug are dizziness and somnolence, which are generally mild to moderate in intensity and are tolerated by many patients.
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References
Bellato E, Marini E, Castoldi F, et al. Fibromyalgia syndrome: etiology, pathogenesis, diagnosis, and treatment. Pain Res Treat. 2012;2012:426130.
Carville SF, Arendt-Nielsen S, Bliddal H, et al. EULAR evidence-based recommendations for the management of fibromyalgia syndrome. Ann Rheum Dis. 2008;67(4):536–41.
Attal N, Cruccu G, Baron R, et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. 2010;17(9):1113-e88.
Hurley RW, Adams MC, Benzon HT. Neuropathic pain: treatment guidelines and updates. Curr Opin Anaesthesiol. 2013;26(5):580–7.
Baldwin DS, Waldman S, Allgulander C. Evidence-based pharmacological treatment of generalized anxiety disorder. Int J Neuropsychopharmacol. 2011;14(5):697–710.
Bandelow B, Boerner JR, Kasper S, et al. The diagnosis and treatment of generalized anxiety disorder. Dtsch Arztebl Int. 2013;110(17):300–9.
Finnerup NB, Baastrup C. Spinal cord injury pain: mechanisms and management. Curr Pain Headache Rep. 2012;16(3):207–16.
Micó JA, Prieto R. Elucidating the mechanism of action of pregabalin: α2δ as a therapeutic target in anxiety. CNS Drugs. 2012;26(8):37–48.
Pregabalin capsules: Brazilian prescribing information [in Portuguese]. Guarulhos, Brazil: Aché Laboratórios Farmacêuticos S.A.; 2013.
Lyrica (pregabalin): summary of product characteristics. London: European Medicines Agency; 2013.
Lyrica (pregabalin): US prescribing information. New York (NY): Pfizer Inc.; 2013.
Crofford LJ, Rowbotham MC, Mease PJ, et al. Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2005;52(4):1264–73.
Mease PJ, Russell IJ, Arnold LM, et al. A randomized, double-blind, placebo-controlled, phase III trial of pregabalin in the treatment of patients with fibromyalgia. J Rheumatol. 2008;35(3):502–14.
Arnold LM, Russell IJ, Diri EW, et al. A 14-week, randomized, double-blinded, placebo-controlled monotherapy trial of pregabalin in patients with fibromyalgia. J Pain. 2008;9(9):792–805.
Pauer L, Winkelmann A, Arsenault P, et al. An international, randomized, double-blind, placebo-controlled, phase III trial of pregabalin monotherapy in treatment of patients with fibromyalgia. J Rheumatol. 2011;38(12):2643–52.
Russell IJ, Crofford LJ, Leon T, et al. The effects of pregabalin on sleep disturbance symptoms among individuals with fibromyalgia syndrome. Sleep Med. 2009;10(6):604–10.
Arnold LM, Leon T, Whalen E, et al. Relationships among pain and depressive and anxiety symptoms in clinical trials of pregabalin in fibromyalgia. Psychosomatics. 2010;51(6):489–97.
Crofford LJ, Mease PJ, Simpson SL, et al. Fibromyalgia relapse evaluation and efficacy for durability of meaningful relief (FREEDOM): a 6-month, double-blind, placebo-controlled trial with pregabalin. Pain. 2008;136(3):419–31.
Pauer L, Atkinson G, Murphy TK, et al. Long-term maintenance of response across multiple fibromyalgia symptom domains in a randomized withdrawal study of pregabalin. Clin J Pain. 2012;28(7):609–14.
Nüesch E, Häuser W, Bernardy K, et al. Comparative efficacy of pharmacological and non-pharmacological interventions in fibromyalgia syndrome: network meta-analysis. Ann Rheum Dis. 2013;72(6):955–62.
Choy E, Marshall D, Gabriel ZL, et al. A systematic review and mixed treatment comparison of the efficacy of pharmacological treatments for fibromyalgia. Semin Arthritis Rheum. 2011;41(3):335–45.
Wiffen PG, Derry S, Moore RA, et al. Antiepileptic drugs for neuropathic pain and fibromyalgia: an overview of Cochrane reviews. Cochrane Database Syst Rev. 2013;11:CD010567.
Uçeyler N, Sommer C, Walitt B, et al. Anticonvulsants for fibromyalgia. Cochrane Database Syst Rev. 2013;10:CD010782.
Freeman R, Durso-Decruze E, Emir B. Efficacy, safety, and tolerability of pregabalin treatment for painful diabetic peripheral neuropathy: findings from seven randomized, controlled trials across a range of doses. Diabetes Care. 2008;31(7):1448–54.
Raskin P, Huffman C, Toth C, et al. Pregabalin in patients with inadequately treated painful diabetic peripheral neuropathy: a randomized withdrawal trial. Clin J Pain. doi:10.1097/AJP.0b013e31829ea1a1. [Epub 24 Jul 2013].
Dworkin RH, Corbin AE, Young JP Jr, et al. Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology. 2003;60(8):1274–83.
Sabatowski R, Gálvez R, Cherry DA, et al. Pregabalin reduces pain and improves sleep and mood disturbances in patients with postherpetic neuralgia: results of a randomised, placebo-controlled clinical trial. Pain. 2004;109(1–2):26–35.
van Seventer R, Feister HA, Young JP, et al. Efficacy and tolerability of twice-daily pregabalin for treating pain and related sleep interference in postherpetic neuralgia: a 13-week, randomized trial. Curr Med Res Opin. 2006;22(2):375–84.
Siddall PJ, Cousins MJ, Otte A, et al. Pregabalin in central neuropathic pain associated with spinal cord injury: a placebo-controlled trial. Neurology. 2006;67(10):1792–800.
Cardenas DD, Nieshoff ED, Suda K, et al. A randomized trial of pregabalin in patients with neuropathic pain due to spinal cord injury. Neurology. 2013;80(6):533–9.
Parsons B, Sanin L, Yang R, et al. Efficacy and safety of pregabalin in patients with spinal cord injury: a pooled analysis. Curr Med Res Opin. 2013;29(12):1675–83.
Tanenberg RJ, Irving GA, Risser RC, et al. Duloxetine, pregabalin, and duloxetine plus gabapentin for diabetic peripheral neuropathic pain management in patients with inadequate pain response to gabapentin: an open-label, randomized, noninferiority comparison. Mayo Clin Proc. 2011;86(7):615–26.
Quilici S, Chancellor J, Löthgren M, et al. Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain. BMC Neurol. 2009;10(9):6.
Rudroju N, Bansal D, Talakollula ST, et al. Comparative efficacy and safety of six antidepressants and anticonvulsants in painful diabetic neuropathy: a network meta-analysis. Pain Physician. 2013;16(6):E705–14.
Lydiard RB, Rickels K, Herman B, et al. Comparative efficacy of pregabalin and benzodiazepines in treating the psychic and somatic symptoms of generalized anxiety disorder. Int J Neuropsychopharmacol. 2010;13(2):229–41.
Kasper S, Herman B, Nivoli G, et al. Efficacy of pregabalin and venlafaxine-XR in generalized anxiety disorder: results of a double-blind, placebo-controlled 8-week trial. Int Clin Psychopharmacol. 2009;24(2):87–96.
Stein DJ, Baldwin DS, Baldinetti F, et al. Efficacy of pregabalin in depressive symptoms associated with generalized anxiety disorder: a pooled analysis of 6 studies. Eur Neuropsychopharmacol. 2008;18(6):422–30.
Holsboer-Trachsler E, Prieto R. Effects of pregabalin on sleep in generalized anxiety disorder. Int J Neuropsychopharmacol. 2013;16(4):925–36.
Montgomery SA, Herman BK, Schweizer E, et al. The efficacy of pregabalin and benzodiazepines in generalized anxiety disorder presenting with high levels of insomnia. Int Clin Psychopharmacol. 2009;24(4):214–22.
Stein DJ, Lydiard RB, Herman BK, et al. Impact of gastrointestinal symptoms on response to pregabalin in generalized anxiety disorder: results of a six-study combined analysis. Int Clin Psychopharmacol. 2009;24(3):126–32.
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.
Feltner D, Wittchen HU, Kavoussi R, et al. Long-term efficacy of pregabalin in generalized anxiety disorder. Clin Psychopharmacol. 2008;23(1):18–28.
Zaccara G, Perucca P, Gangemi PF. The adverse event profile of pregabalin across different disorders: a meta-analysis. Eur J Clin Pharmacol. 2012;68(6):903–12.
Arnold LM, Emir B, Murphy TK, et al. Safety profile and tolerability of up to 1 year of pregabalin treatment in 3 open-label extension studies in patients with fibromyalgia. Clin Ther. 2012;34(5):1092–102.
Montgomery S, Emir B, Haswell H, et al. Long-term treatment of anxiety disorders with pregabalin: a 1 year open-label study of safety and tolerability. Curr Med Res Opin. 2013;29(10):1223–30.
Freynhagen R, Serpell M, Emir B, et al. A comprehensive drug safety evaluation of pregabalin in peripheral neuropathic pain. Pain Pract. doi:10.1111/papr.12146. [Epub 27 Nov 2013].
Berger A, Mychaskiw M, Dukes E, et al. Magnitude of inappropriate prescribing in Germany among older patients with generalized anxiety disorder. BMC Geriatr. 2009;27(9):31.
Harden RN, Kaye AD, Kintanar T, et al. Evidence-based guidance for the management of postherpetic neuralgia in primary care. Postgrad Med. 2013;125(4):191–202.
Acknowledgments
The manuscript was reviewed by: C.P. Alderman, Repatriation General Hospital, Adelaide, SA, Australia, M. Hahn, Vitos Rheingau, Eltville, Germany.
Disclosure
The preparation of this review was not supported by any external funding. During the peer review process, a manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from comments received were made by the authors on the basis of scientific and editorial merit.
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Lyseng-Williamson, K.A. Pregabalin: a guide to its use in fibromyalgia, neuropathic pain and generalized anxiety disorder. Drugs Ther Perspect 30, 75–84 (2014). https://doi.org/10.1007/s40267-014-0107-7
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DOI: https://doi.org/10.1007/s40267-014-0107-7