Usefulness of a Double-Blind Placebo-Controlled Response Test to Demonstrate Rapid Onset Analgesia with Phenytoin 10% Cream in Polyneuropathy
Received 23 December 2019
Accepted for publication 17 April 2020
Published 1 May 2020 Volume 2020:13 Pages 877—882
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr E Alfonso Romero-Sandoval
David J Kopsky,1 Alexander FJE Vrancken,2 Jan M Keppel Hesselink,3 Ruben PA van Eijk,2,4 Nicolette C Notermans2
1Institute for Neuropathic Pain, Amsterdam, the Netherlands; 2Department of Neurology, Brain Centre University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; 3Institute for Neuropathic Pain, Bosch En Duin, the Netherlands; 4Biostatistics & Research Support, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
Correspondence: David J Kopsky Tel +31 6 28671847
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: neuropathic pain, treatment, topical administration, analgesics, neuropathy
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