Evaluation of the safety and efficacy of pregabalin in older patients with neuropathic pain: results from a pooled analysis of 11 clinical studies

Abstract

BackgroundOlder patients are typically underrepresented in clinical trials of medications for chronic pain. A post hoc analysis of multiple clinical studies of pregabalin in patients with painful diabetic peripheral neuropathy (DPN) or postherpetic neuralgia (PHN) was conducted to evaluate the efficacy and safety of pregabalin in older patients.MethodsData from 11 double-blind, randomized, placebo-controlled clinical studies of pregabalin in patients with DPN or PHN were pooled. Efficacy outcomes included change in Daily Pain Rating Scale score, ≥30% and ≥50% responders, and endpoint pain score ≤3. Safety was based on adverse events (AEs). Primary efficacy was analyzed by analysis of covariance with terms for treatment, age category, protocol, baseline pain, and treatment-by-age category interaction.Results2516 patients (white, n = 2344 [93.2%]; men, n = 1347 [53.5%]; PHN, n = 1003 [39.9%]; pregabalin, n = 1595) were included in the analysis. Patients were grouped by age: 18 to 64 years (n = 1236), 65 to 74 years (n = 766), and ≥75 years (n = 514). Baseline mean pain and sleep interference scores were comparable across treatment and age groups. Significant improvements in endpoint mean pain were observed for all pregabalin dosages versus placebo in all age groups (p ≤ 0.0009), except for the lowest dosage (150 mg/day) in the youngest age group. Clinically meaningful pain relief, defined as ≥30% and ≥50% pain response, was observed in all age groups. The most common AEs were dizziness, somnolence, peripheral edema, asthenia, dry mouth, weight gain, and infections. The relative risks for these AEs increased with pregabalin dose, but did not appear related to older age or type of neuropathic pain.ConclusionsPregabalin (150-600 mg/day) significantly reduced pain in older patients (age ≥65 years) with neuropathic pain and improvements in pain were comparable to those observed in younger patients. Titration of pregabalin to the lowest effective dose should allow for effective pain relief while minimizing AEs in older patients with neuropathic pain. Given the common use of polypharmacy in older patients, the absence of known drug-drug interactions makes pregabalin an important treatment option for older patients with pain of neuropathic origin.

Comparative Efficacy of Pregabalin and Ultrasonography-guided Lateral Femoral Cutaneous Nerve Blockage for Meralgia Paresthetica

“…Frequently reported side effects include peripheral edema in 5-10% of patients and weight increase in 4-20%, but the mechanisms by which pregabalin induces these side effects have not been determined. An evaluation of the adverse effects of pregabalin in 11 clinical studies reported that central nervous system side effects included dizziness and somnolence (10%), whereas systemic side effects included peripheral edema, mouth dryness, weight gain, infection, increased appetite and constipation (26,27). Of the 19 patients in our study treated with 300 mg/day pregabalin, six (31.6%) experienced dizziness and somnolence and one (5.3%) showed pretibial edema, but none required drug discontinuation.…”

<i>Clostridium difficile</i> Infection Induced by Pregabalin-associated Agranulocytosis

“…Recent studies have also demonstrated the efficacy of this drug in the treatment of fibromyalgia (15), epilepsy (16), and general anxiety disorder (17). Pregabalin is usually well tolerated; however, adverse effects can include dizziness, somnolence, peripheral edema, asthenia, dry mouth, and weight gain (18). There have also been reports of heart failure (19), rashes (20), and increased liver enzyme levels (21).…”

Ion Channels as Drug Targets in Central Nervous System Disorders

“…It is a wellknown antiepileptic drug, exhibiting both anticonvulsant and analgesic activity in central and peripheral neuropathic pain. [130][131][132].…”