Topical phenytoin for the treatment of neuropathic pain

Kopsky, David J; Hesselink, Jan M Keppel

doi:10.2147/jpr.s129749

Cited by 36 publications

(26 citation statements)

References 34 publications

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“…In modern times communication from medical researchers to the medical field should not be hampered by conservationism, as we have seen above in the reaction of both reviewers to our presentation of a non-randomized, non-controlled case series. We demonstrated by sharing our first observations the safety of topical phenytoin cream, our case collection was the first in the world of patients treated with topical phenytoin cream [7].…”

Section: Missed Opportunitiesmentioning

confidence: 83%

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Hesselink¹

2018

MSR

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Prestigious Journals such as the 'New England Journal of Medicine' are criticized by scientists for lack of objectivity in its peer review process [1]. Comparative Journals, such as 'Science', published fake data, without anyone noticing it [2]. Research misconduct cases, related to individual scientists falsifying data or manipulations within the science publishing community is a hot topic. In 2017 China's Ministry of Science and Technology found hundreds of scientists guilty of supporting in a peer-review fraud scam related to the nomination of fictitious peer reviewers. An Expert Group on Scientific Misconduct in Sweden, on request from the Karolinska Institute, analysed a case where the well-known and respected Journal 'The Scientist' was covering for years of fraudulent data produced by the surgeon Paolo Macchiarini. Evidence of scientific misconduct leading to the death of 3 patients was found by the expert group in all six of Macchiarini's publications it reviewed. Meanwhile, to counteract these critical aspects in science, at one of the universities of Amsterdam (The Netherlands), a special chair is created to address scientific integrity, leading to a number of important papers and congresses in this new emerging field [3,4]. In 2017, the holder of the chair, Professor Lex Bouter, organized the 5 th World Conference on Research Integrity in Amsterdam and subsequently became chair of the World Conferences on Research Integrity Foundation.

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Section: Missed Opportunitiesmentioning

confidence: 83%

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Hesselink¹

2018

MSR

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“…For instance, we have found that SFN pain patients, in which pathology resides mainly in the skin, are good responders to phenytoin cream. Elsewhere, we have outlined the pathogenesis of neuropathic pain syndromes related to the skin, pointing out the pathological triad of keratinocytes, immune-competent cells, and nociceptors targeted by topical creams containing sodium channel blockers such as phenytoin 22,23…”

Section: First Patent On Topical Formulations Containing Ketamine Andmentioning

confidence: 99%

Bottlenecks in the development of topical analgesics: molecule, formulation, dose-finding, and phase III design

Hesselink¹,

Kopsky²,

Stahl

2017

JPR

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Topical analgesics can be defined as topical formulations containing analgesics or co-analgesics. Since 2000, interest in such formulations has been on the rise. There are, however, four critical issues in the research and development phases of topical analgesics: 1) The selection of the active pharmaceutical ingredient. Analgesics and co-analgesics differ greatly in their mechanism of action, and it is required to find the most optimal fit between such mechanisms of action and the pathogenesis of the targeted (neuropathic) pain. 2) Issues concerning the optimized formulation. For relevant clinical efficacy, specific characteristics for the selected vehicle (eg, cream base or gel base) are required, depending on the physicochemical characteristics of the active pharmaceutical ingredient(s) to be delivered. 3) Well-designed phase II dose-finding studies are required, and, unfortunately, such trials are missing. In fact, we will demonstrate that underdosing is one of the major hurdles to detect meaningful and statistically relevant clinical effects of topical analgesics. 4) Selection of clinical end points and innovatively designed phase III trials. End point selection can make or break a trial. For instance, to include numbness together with tingling as a composite end point for neuropathic pain seems stretching the therapeutic impact of an analgesic too far. Given the fast onset of action of topical analgesics (usually within 30 minutes), enrichment designs might enhance the chances for success, as the placebo response might decrease. Topical analgesics may become promising inroads for the treatment of neuropathic pain, once sufficient attention is given to these four key aspects.

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“…Before we could use this cream in our clinic however, we had to solve a number of formulation issues, especially since phenytoin sodium leads to pH changes in the base cream. After this we found solutions in order for us to start testing the cream in a number of localized peripheral neuropathic disorders [24].…”

Section: Figurementioning

confidence: 99%

Topical Compounded Analgesic Treatment in Neuropathic Pain: 8 years of Experience

Hesselink¹,

Kopsky²

2017

Pain Manage Med

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In our tertiary referral centre, the Institute for Neuropathic Pain, we have treated many patients suffering from localized peripheral neuropathic pain since 2009. We have developed, together with a compounding pharmacist, a base cream as a topical formulation which has enabled us to compound creams based on amongst others amitriptyline, ketamine, clonidine, baclofen, and phenytoin. We have found that many patients profit from such topical formulations and we will describe our experiences using such creams over the last 8 years in this paper, since we first started exploring such topical treatments. We have analysed the efficacy and safety of these topicals, and based on literature, our own online data pool and the patients who had let us know that they benefited from the creams, found sufficient analgesia and positive effects impaired sleep, while the tolerability was excellent. Patients suffering from localized peripheral neuropathic pain, as in diabetic neuropathy, chronic idiopathic axonal polyneuropathy, chemotherapy induced polyneuropathy and small fiber neuropathy, as well as in complex regional pain syndrome, seem especially responsive to such topical approach. Meanwhile, more than 800 Dutch medical doctors have been prescribing one or more of our compounded creams, and patients and medical doctors from abroad frequently contact us to explore the therapeutic options for their patients based on these creams.

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Topical phenytoin for the treatment of neuropathic pain

Cited by 36 publications

References 34 publications

Exit Conservative Peer Review and Welcome to Predator Journals!

Exit Conservative Peer Review and Welcome to Predator Journals!

Bottlenecks in the development of topical analgesics: molecule, formulation, dose-finding, and phase III design

Topical Compounded Analgesic Treatment in Neuropathic Pain: 8 years of Experience

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