Pregabalin for painful diabetic peripheral neuropathy: strategies for dosing, monotherapy vs. combination therapy, treatment-refractory patients, and adverse events

Objective: Primary care physicians face significant challenges when treating painful diabetic peripheral neuropathy (pDPN). The physician must determine the best dosing strategy, consider the use of combination therapy, and decide how best to treat patients who have responded poorly to other treatment options in the past. With a focus on these issues, this paper will review the use of pregabalin for the treatment of pDPN in order to provide physicians with clinical data needed to develop, in combination with real-world prescribing data, effective treatment strategies for this common but challenging type of pain. Research design and methods: A formal PubMed search, along with a search of unpublished data from the Pfizer clinical trial database, was used to identify papers describing results from clinical trials of pregabalin in patients with pDPN. Papers were selected for inclusion in the review if they addressed the use of pregabalin in the context of a head-to-head treatment comparison, use in refractory patients, or as part of combination therapy. A discussion of pregabalin dosing and adverse events is also presented. Conclusions: There is some difference with respect to the maximum approved dose of pregabalin for the treatment of pDPN in the United States (300 mg/day) and European Union (600 mg/day), though clinical data demonstrate that pregabalin doses >300 mg/day may be beneficial in some patients. Pregabalin has shown efficacy (and is approved) as a monotherapy for pDPN, although several guidelines recommend combination therapy for challenging cases. However, evidence to support combination therapy is sparse and the decision of monotherapy vs. combination therapy should be at the physician's discretion. There are data demonstrating the efficacy of pregabalin in some patients with pDPN who have not responded to other pharmacological treatments, including those unresponsive to treatment with gabapentin. Clinical guidelines acknowledge the paucity of head-to-head data among treatment options, but consistently recommend pregabalin as a first-tier treatment for pDPN.