Expert Opinion: Exploring the Effectiveness and Tolerability of Capsaicin 179 mg Cutaneous Patch and Pregabalin in the Treatment of Peripheral Neuropathic Pain

Figures & data

Table 1 Summary of Key Guideline and Consensus Recommendations for Pharmacotherapy in Neuropathic Pain

Group/Author, year	Methodology	Condition(s)	Summary Recommendations
European Federation of Neurological Societies (EFNS) Task Force, 2010^Citation7	Literature review of RCTs since 2005, identified using the Cochrane Database and MEDLINE (lower class studies considered only when no RCTs available)	PHN	Level A rating: capsaicin 179 mg patch^a; gabapentin; gabapentin ER; lidocaine plasters, opioids; pregabalin, TCAs First line: gabapentin; pregabalin; TCAs; lidocaine plasters Second line: capsaicin; opioids
Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain, 2015^Citation4	Systematic review and meta-analysis of randomized, double-blind studies of oral and topical pharmacotherapy for neuropathic pain, with recommendations based on GRADE^Citation56,Citation57	All neuropathic pain, except trigeminal neuralgia	First line: gabapentin; gabapentin ER/enacarbil; pregabalin; SNRIs (duloxetine/venlafaxine); TCAs Second line: capsaicin 179 mg patches (PNP only); lidocaine patches (PNP only); tramadol Third line: botulinum toxin type A; strong opioids
Allegri et al, 2016^Citation3	Advisory board of pain specialists convened to develop a treatment guidance algorithm	Localized neuropathic pain	First line: topical treatment, ie lidocaine plasters (for PHN) or capsaicin patches Second and third lines: systemic medication (per first-line recommendations of the 2015 NeuPSIG guidelines)^Citation4 If no response after second systemic medication, refer to pain specialist
Deng et al, 2016^Citation58	Systematic review of 16 published clinical practice guidelines, assessed using the AGREE-II instrument^Citation59	All neuropathic pain	First/second line: anticonvulsants (gabapentin/pregabalin), low-dose TCAs; SNRIs (duloxetine/venlafaxine); topical lidocaine Second line: opioid analgesics Third line: opioid analgesics; anticonvulsants (carbamazepine, lamotrigine, oxcarbazepine); SSRIs (citalopram, paroxetine); mexiletine; NMDA receptor antagonists (dextromethorphan, memantine); topical capsaicin Fourth line: cannabinoids; SSRIs (citalopram, paroxetine); anticonvulsants (carbamazepine, lamotrigine, clonidine); mexiletine; methadone
NICE, 2017^Citation18	Committee review of the literature, economic analysis, lay member consultations	All neuropathic pain, except trigeminal neuralgia	Offer a choice of amitriptyline, duloxetine, gabapentin, or pregabalin as initial treatment for neuropathic pain If the initial treatment is not effective or is not tolerated, offer one of the remaining three drugs, and consider switching again if the second and third drugs tried are also not effective or not tolerated Consider tramadol only if acute rescue therapy is needed Consider capsaicin cream for people with localized neuropathic pain who wish to avoid, or who cannot tolerate, oral treatments Do not start the following to treat neuropathic pain in non-specialist settings, unless advised by a specialist to do so: cannabis sativa extract; capsaicin patch; lacosamide; lamotrigine; levetiracetam; morphine; oxcarbazepine; topiramate; long-term tramadol; venlafaxine

Note: ^aCapsaicin patch not available at the time of guideline development.

Abbreviations: AGREE-II, Appraisal of Guidelines Research and Evaluation II; ER, extended release; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; NICE, National Institute for Health and Care Excellence; NMDA, N-methyl-D-aspartate; PHN, post-herpetic neuralgia; PNP, peripheral neuropathic pain; RCT, randomized controlled trial; SNRI, serotonin and norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant.

Figure 1 Mechanism of action of capsaicin in treatment of localized peripheral neuropathic pain. Activation of transient receptor potential vanilloid-1 (TRPV1) by capsaicin results in sensory neuronal depolarization, and can induce local sensitization to activation by heat, acidosis, and endogenous agonists. Topical exposure to capsaicin leads to the sensations of heat, burning, stinging, or itching. High concentrations of capsaicin or repeated applications can produce a persistent local effect on cutaneous nociceptors, which is best described as “defunctionalization” and constituted by reduced spontaneous activity and a loss of responsiveness to a wide range of sensory stimuli. .Reproduced from Anand P, Bley K. Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentrationcapsaicin 8% patch. Br J Anaesth. 2011;107(4):490–502, Copyright 2011, with permission from Elsevier.¹⁹

Figure 2 BURDEN OF THERAPY™© in a peripheral neuropathic pain study. TEAE, treatment-emergent adverse event; TRPV1, transient receptor potential vanilloid-1. Reproduced from Abdulahad AK, Snijder RJ, Panni MK, Riaz FK, Karas AJ. A novelstandard to evaluate the impact of therapeutic agents on patientsafety – the BURDEN OF THERAPY™©. Contemp Clin Trials Commun. 2016;4:186–191, Copyright 2016, with permission from Elsevier.³³

Table 2 The Mean Changes of Pain Intensity Between 7 and 14 Days and 12 Weeks versus Baseline According to the Duration of Pre-Existing Neuropathic Pain in QUEPP

Pain Duration	n	Mean Reduction %	SEM
<6 months	105	36.6	4.6
6 months–2 years	311	25.1	1.9
>2 years–10 years	391	22.3	1.6
>10 years	99	19.2	2.6
No data	119	25.9	2.9
Total	1025	24.7	1.1

Abbreviation: SEM, standard error of mean.

Table 3 Reduction from Baseline to Weeks 2 and 8 in Mean NPRS Score According to PNP Duration in ASCEND

Quartile According to PNP Duration, Years	n	Reduction from Baseline to Weeks 2 and 8 in Mean NPRS Score, %	95% CI
0–0.72	101	36.3	30.0–42.6
0.72–2.1	104	23.6	17.1–30.1
>2.1–5.4	104	25.0	19.4–30.6
>5.4	103	21.8	16.4–27.2

Abbreviations: CI, confidence interval; NPRS, Numerical Pain Rating Scale; PNP, peripheral neuropathic pain.

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 PubMed Web of Science ®Google Scholar

Abdulahad AK, Snijder RJ, Panni MK, Riaz FK, Karas AJ. A novel standard to evaluate the impact of therapeutic agents on patient safety – the BURDEN OF THERAPY™©. Contemp Clin Trials Commun. 2016;4:186–191. doi:10.1016/j.conctc.2016.09.003

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