Pregabalin: a novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders.

Clin Ther. 2007 Jan;29(1):26-48.

Tassone DM, Boyce E, Guyer J, Nuzum D.

Wingate University School of Pharmacy, Wingate, North Carolina 28174, USA. dtassone@wingate.edu

BACKGROUND: The US Food and Drug Administration (FDA) approved pregabalin in December 2004 for the treatment of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. Pregabalin is the first drug approved in the United States and in Europe for both conditions. In June 2005, pregabalin was approved as an adjunctive treatment in adults with partial-onset seizures. The FDA currently is considering the approval of pregabalin as adjunctive therapy in adults with generalized anxiety disorder (GAD) or social anxiety disorder (SAD). OBJECTIVES: The goals of this review were to summarize the pharmacology, pharmacokinetics, efficacy, and tolerability of pregabalin; review its approved uses in the management of neuropathic pain and refractory partial-onset seizures; and investigate its potential use in patients with GAD or SAD. METHODS: Relevant English-language literature was identified through a search of MEDLINE (1993-June 2006) and International Pharmaceutical Abstracts (2000-June 2006). The search terms included pregabalin, Lyrica, S-(+)-3 isobutyl-gaba, PN, DPN, diabetic peripheral neuropathy, PHN, postherpetic neuralgia, partial seizures, epilepsy, generalized anxiety disorder, and CI-1008. RESULTS: In 4 clinical trials in a total of 1068 patients with diabetic peripheral neuropathy, the patients receiving pregabalin 300 to 600 mg/d had significantly greater improvement in mean pain scores than placebo recipients (P < or = 0.01). Patients with postherpetic neuralgia receiving pregabalin 450 to 600 mg/d had significantly greater improvement in relief of pain and pain-related sleep interference than placebo recipients (P < or = 0.002). Patients with refractory partial-onset seizures who received pregabalin 150 to 600 mg/d (divided into 2 or 3 doses) concomitantly with antiepileptic drugs had significantly fewer seizures than placebo recipients (P < or = 0.001). In the 3 studies that evaluated the efficacy of pregabalin in patients with GAD or SAD, the patients receiving pregabalin 200 to 600 mg/d (divided into 2 or 3 daily doses) had a significantly greater reduction in mean pain scores on the Hamilton Anxiety Scale than placebo recipients (P < or = 0.01). Across all the reviewed clinical trials, the most commonly reported adverse effects (AEs) were those affecting the central nervous system, including somnolence (< or =50%), dizziness (< or =49%), and headache (< or =29%). AEs resulted in withdrawal from the study in < or =32% of patients.
CONCLUSIONS: Pregabalin appears to be an effective therapy in patients with diabetic peripheral neuropathy, postherpetic neuralgia, and adults with refractory partial-onset seizures. The available data suggest that pregabalin may be beneficial as an adjunctive therapy in adult patients with GAD or SAD.

Publication Types:
Review

PMID: 17379045 [PubMed - indexed for MEDLINE]
Address correspondence to: Daniel M. Tassone, PharmD, Wingate University School of Pharmacy, Campus Box 3087, Wingate, NC 28174.

Depression and anxiety associated with three pain conditions: results from a nationally representative sample.

Pain. 2004 Sep;111(1-2):77-83.

McWilliams LA, Goodwin RD, Cox BJ.

Department of Psychology, PZ-430 PsycHealth Centre, University of Manitoba, 771 Bannatyne Avenue, Winnipeg, Man. R3E 3N4, Canada. UMMCWIL1@cc.umanitoba.ca

Investigations of the relationship between pain conditions and psychopathology have largely focused on depression and have been limited by the use of non-representative samples (e.g. clinical samples). The present study utilized data from the Midlife Development in the United States Survey (MIDUS) to investigate associations between three pain conditions and three common psychiatric disorders in a large sample (N = 3,032) representative of adults aged 25-74 in the United States population. MIDUS participants provided reports regarding medical conditions experienced over the past year including arthritis, migraine, and back pain. Participants also completed several diagnostic-specific measures from the Composite International Diagnostic Interview-Short Form [Int. J. Methods Psychiatr. Res. 7 (1998) 171], which was based on the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders [American Psychiatric Association 1987]. The diagnoses included were depression, panic attacks, and generalized anxiety disorder. Logistic regression analyses revealed significant positive associations between each pain condition and the psychiatric disorders (Odds Ratios ranged from 1.48 to 3.86). The majority of these associations remained statistically significant after adjusting for demographic variables, the other pain conditions, and other medical conditions. Given the emphasis on depression in the pain literature, it was noteworthy that the associations between the pain conditions and the anxiety disorders were generally larger than those between the pain conditions and depression. These findings add to a growing body of evidence indicating that anxiety disorders warrant further attention in relation to pain. The clinical and research implications of these findings are discussed.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

PMID: 15327811 [PubMed - indexed for MEDLINE]