Abstract
Pregabalin (Lyrica®), a well established anxiolytic agent, has been approved in the EU for the treatment of generalized anxiety disorder (GAD) in adults. It has a distinct mechanism of action relative to other anti-anxiety agents (α2δ binding at presynaptic voltage dependent calcium channels leading to inhibition of excitatory neurotransmission), a rapid onset of effect (typically ≤1 week) and broad spectrum activity against both the psychic and somatic symptoms of GAD. In long-term studies, pregabalin maintained improvements in anxiety symptoms that occurred in response to short-term treatment and delayed the time to relapse of GAD compared with placebo. Common comorbidities of GAD, such as insomnia, gastrointestinal symptoms and subsyndromal depression, have no effect on the anxiolytic efficacy of, and moreover are specifically improved by, pregabalin. Treatment with pregabalin is generally well tolerated; the drug has an adverse event profile that includes dizziness, somnolence and weight gain. The potential for abuse of pregabalin is low; the risk of withdrawal symptoms is generally low when the drug is discontinued gradually (over 1 week). Alongside selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs), pregabalin is considered a first-line agent for the long-term treatment of GAD by the World Federation of Societies of Biological Psychiatry. It should be stressed, however, that definitive head-to-head studies comparing pregabalin with SSRI/SNRIs, including in patients with GAD and co-morbid major depressive disorder, are currently lacking. Recently, a study of SSRI/SNRI augmentation with pregabalin yielded positive results, while another study of switching from long-term benzodiazepine therapy to pregabalin was inconclusive; further investigations on these topics are warranted.
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The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the authors on the basis of scientific and editorial merit. James Frampton is a salaried employee of Adis/Springer.
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The manuscript was reviewed by: M. J. Boschen, School of Applied Psychology and Griffith Health Institute, Griffith University, Southport, Australia; J. Carrasco, Department of Psychiatry, Hospital Clínico San Carlos, Madrid, Spain; S. Kasper, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; V. G. Masdrakis, Department of Psychiatry, Athens University Medical School, Athens, Greece; J. A. Micó, Department of Neuroscience, Pharmacology and Psychiatry, CIBER of Mental Health, CIBERSAM, Instituto de Salud Carlos III, University of Cádiz, Cádiz, Spain; S. A. Montgomery, Imperial College School of Medicine, University of London, London, UK; K. Rickels, Department of Psychiatry, Mood and Anxiety Disorders Section, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; G. Zaccara, Unit of Neurology, Department of Medicine, Florence Health Authority, Firenze, Italy.
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Frampton, J.E. Pregabalin: A Review of its Use in Adults with Generalized Anxiety Disorder. CNS Drugs 28, 835–854 (2014). https://doi.org/10.1007/s40263-014-0192-0
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DOI: https://doi.org/10.1007/s40263-014-0192-0