Pregabalin in Seniors Confirmed Its Safety and Effectiveness

Introduction

The incidence of neuropathic pain in the European population is relatively high. Its prevalence increases exponentially with age. Managing chronic neuropathic pain in older patients can often be challenging, especially due to common comorbidities and polypharmacy, which complicate therapeutic decisions. Moreover, the representation of seniors in clinical studies on the treatment of neuropathic pain is usually low, making it difficult to draw comprehensive conclusions. The goal of the presented analysis was to evaluate the safety and effectiveness of pregabalin specifically in this under-researched age category.

Mechanism of Action and Pharmacological Properties of Pregabalin

Pregabalin is a gamma-aminobutyric acid analog - (S)-3-(aminomethyl)-5-methylhexanoic acid. It binds to the alpha₂δ subunit of voltage-gated calcium channels in the central nervous system. Its mechanism of action is very similar to gabapentin, but pregabalin shows higher efficacy, requiring a lower dose for the desired effect. Clinical studies have demonstrated the efficacy and safety of pregabalin in the therapy of peripheral neuropathy and postherpetic neuralgia in the adult population at doses of 150–600 mg/day. Pregabalin is mainly excreted unchanged in the urine and is negligibly metabolized in the human body. No drug interactions are known for pregabalin.

Analysis Methodology

This post-hoc analysis was based on data from 11 randomized double-blind placebo-controlled clinical studies involving a total of 2516 patients with diabetic polyneuropathy or postherpetic neuralgia. The safety and efficacy of pregabalin in the mentioned indications were assessed. Pain was evaluated primarily using the Daily Pain Rating Scale (DPRS), and safety was evaluated based on the occurrence of adverse effects. Pregabalin doses ranged between 150 and 600 mg/day. The pharmacokinetics of pregabalin are linear within the recommended daily dose range.

Findings

Of the 2516 adult patients included in the analysis, 1513 had diabetic polyneuropathy (type 1 or type 2 diabetes mellitus) for at least 3 months, and 1003 had postherpetic neuralgia, also for at least 3 months. Initial DPRS values did not differ across age categories. Males made up 53.5%. In terms of age composition, there were 1236 patients under 65, 766 patients aged 65–74, and 514 patients aged 75 and older.

All doses of pregabalin caused a significant reduction in pain compared to placebo across all age groups, except for the lowest dose (150 mg/day) in the youngest age group (< 65 years). The most common adverse effects included dizziness, drowsiness, peripheral edema, asthenia, dry mouth, weight gain, and infection. The relative risk of adverse effects increased with higher doses, but there was no link to age or type of neuropathic pain.

Conclusion

The results of this analysis indicate that pregabalin at doses of 150–600 mg/day significantly reduces neuropathic pain in patients aged 65 and older, comparable to the effect seen in younger populations. The safety profile observed in this age group did not significantly differ from that in younger patients. The most common adverse effects were fatigue, weight gain, dry mouth, asthenia, dizziness, peripheral edema, and infections. Titrating pregabalin from the lowest dose should allow for pain relief with the lowest possible occurrence of adverse effects. Additionally, due to the absence of known drug interactions, pregabalin is an ideal choice for seniors with polypharmacy.

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Source: Semel D., Murphy T. K., Zlateva G. et al. Evaluation of the safety and efficacy of pregabalin in older patients with neuropathic pain: results from a pooled analysis of 11 clinical studies. BMC Fam Pract 2010 Nov 5; 11: 85, doi: 10.1186/1471-2296-11-85.