Neuropathic pain responds better to increased doses of pregabalin: an in-depth analysis of flexible-dose clinical trials

Abstract

Background

Pregabalin is an effective treatment option for many patients with neuropathic pain. Higher doses of pregabalin have been shown to be more effective in improving pain outcomes but, in practice, failing to appropriately increase the dose can leave patients under-treated.

Methods

This was a pooled analysis of 6 flexible-dose clinical trials of pregabalin in patients with neuropathic pain (diabetic peripheral neuropathy, peripheral herpetic neuralgia, posttraumatic pain, or postsurgical pain). Patients were divided into “dose pathway” groups based on their weekly pregabalin dose from the start of their trial to the first week of their maintenance phase. These were: 150 mg/day only; 150 to 300 mg/day; 150 to 300 to 450 mg/day; 150 to 300 to 450 to 600 mg/day; 150 to 300 to 600 mg/day; 300 to 600 mg/day. Pain outcomes assessed for each group at each new dose were proportion of 30% and 50% responders (≥30% or ≥50% reduction in mean pain score from baseline) and mean change in pain score. Percent change in mean pain score from baseline was assessed using a marginal structural model.

Results

Seven hundred and sixty-one patients treated with flexible-dose pregabalin were included in the analysis. For each dose pathway group, there was a notably greater proportion of 30% and 50% responders and change in pain score, at each escalating dose. As assessed by the marginal structural model, higher doses of pregabalin were estimated to result in a significantly greater change in mean pain score at each week. This dose response with flexible-dose pregabalin was consistent with that previously observed with fixed-dose pregabalin.

Conclusion

Many patients who do not respond to lower doses of pregabalin will respond with notable improvements in pain outcomes when the dose is escalated. These data should encourage physicians treating patients with neuropathic pain to escalate pregabalin to the dose that delivers optimal analgesia and tolerable side effects.

Keywords:

• neuropathic pain
• pregabalin
• dosing

Acknowledgments

This study was sponsored by Pfizer. Michael Serpell has received honoraria from Astellas, Grünenthal, NAPP, and Pfizer for speaking at meetings. His institution has received research support in the past 5 years from commercial studies sponsored by Astellas, Grünenthal, and NAPP. Medical writing support was provided by Joshua Fink, PhD, of Engage Scientific Solutions, and funded by Pfizer.

Disclosure

Mark Latymer, Mary Almas, Marie Ortiz, Bruce Parsons, and Rita Prieto are employees of Pfizer and hold stock options with Pfizer. The authors report no other conflicts of interest in this work.