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

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.

Posttraumatic stress disorder in male military veterans with comorbid overweight and obesity: psychotropic, antihypertensive, and metabolic medications.

UNLABELLED: Posttraumatic stress disorder (PTSD) is an important syndrome among military veterans. Little has been written about comorbid medical conditions of PTSD, particularly overweight and obesity. We focus on psychotropic and non-psychotropic drugs, their interactions, and metabolic issues most relevant to primary care physicians. METHOD: Data from the recently constituted PTSD program at the Department of Veterans Affairs Medical Center in Richmond, Va., were retrospectively reviewed to assess the prevalence and severity of comorbid overweight and obesity in male veterans with PTSD. Also, our database allowed us to correlate various drugs used to treat hypertension, diabetes mellitus, and dyslipidemia with body mass index (BMI). RESULTS: The mean BMI of 157 veterans with PTSD (DSM-IV criteria) in this sample was in the obese range (30.3 ± 5.6 kg/m²). The number of drugs a given patient was taking for treatment of hypertension, diabetes mellitus, and dyslipidemia correlated with BMI. Psychotropic drugs associated with weight gain did not explain our findings. CONCLUSIONS: Overweight and obesity among our male veterans with PTSD strikingly exceeded national findings. The administration of psychotropic drugs associated with weight gain did not explain these findings. The number of medications used to treat hypertension, diabetes mellitus, and dyslipidemia correlated significantly with BMI. Rather than these medications explaining the high prevalence of overweight and obesity in our study population, obesity probably worsened these components of the metabolic syndrome, necessitating more aggressive treatment reflected in the high number of drugs prescribed.