Usefulness of a Double-Blind Placebo-Controlled Response Test to Demonstrate Rapid Onset Analgesia with Phenytoin 10% Cream in Polyneuropathy

David J Kopsky, Alexander F J E Vrancken, Jan M Keppel Hesselink, Ruben P A van Eijk, Nicolette C Notermans, David J Kopsky, Alexander F J E Vrancken, Jan M Keppel Hesselink, Ruben P A van Eijk, Nicolette C Notermans

Abstract

Purpose: Topical analgesics are an upcoming treatment option for neuropathic pain. In this observational study, we performed a double-blind placebo-controlled response test (DOBRET) in patients with polyneuropathy to determine the personalized analgesic effect of phenytoin 10% cream.

Patients and methods: In a double-blind fashion, 12 consecutive adult patients with symmetrical painful polyneuropathy and equal pain intensity of ≥4 on the 11-point numerical rating scale (NRS) applied phenytoin10% cream on one painful area and a placebo cream on the corresponding contralateral area. We defined responders as patients who experienced a pain reduction ≥2 NRS points from baseline and ≥1 NRS point difference in pain reduction in favour of phenytoin 10% cream compared with placebo cream within 30 minutes after application. We also evaluated the percentage of pain reduction and frequency of 30% and 50% pain relief from baseline.

Results: Six patients (50%) were responders. Compared with placebo cream, pain reduction was higher in phenytoin 10% cream-applied areas with mean difference in pain reduction of 1.3 (95% CI: 1.1 to 1.8; p<0.001) on the NRS and mean percentage difference in pain reduction of 22% (95% CI: 13% to 32%; p =0.03). All responders had at least 30% pain reduction, and 4 out of 6 had at least 50% pain reduction in the phenytoin 10% cream applied area. All non-responders had less than 30% pain reduction. No side effects were reported.

Conclusion: A DOBRET is easy to perform, quickly identifies an analgesic effect in responders and could be a useful tool to personalize neuropathic pain treatment with topical formulations.

Keywords: analgesics; neuropathic pain; neuropathy; topical administration; treatment.

Conflict of interest statement

DJK and JMKH are holders of two pending patents: (1) topical phenytoin for use in the treatment of peripheral neuropathic pain (WO2018106107); and (2) topical pharmaceutical composition containing phenytoin and a (co-)analgesic for the treatment of chronic pain (WO2018106108). The authors report no other conflicts of interest in this work.

© 2020 Kopsky et al.

Figures

Figure 1
Figure 1
Individual results of DOBRET. Abbreviation: NRS, 11-point numerical rating scale in which 0 is no pain and 10 worst pain ever.

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Source: PubMed

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