Pregabalin(Lyrica): A novel GAAA in treatment of neuropathic pain, partial-onset

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

Pregabalin: A novel gamma-aminobutyric acid analogue in the

treatment of neuropathic pain, partial-onset seizures, and anxiety

disorders.

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

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 isobutylgaba, 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 </= 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 </= 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 </= 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 </= 0.01).

Across all the reviewed clinical trials, the most commonly reported

adverse effects (AEs) were those affecting the central nervous

system, including somnolence (</=50%), dizziness (</=49%), and

headache (</=29%). AEs resulted in withdrawal from the study in

</=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.