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17 Articles in Volume 19, Issue #7
Analgesics of the Future: Inside the Potential of 3 Drug Delivery Systems
Balancing Pain Care - and Opioids - in the Aging Adult
Book Review: A Useful Guide for New Pain Practitioners
Correspondence: Opioid Tapering & Discontinuation
Effective Interventions for Post-Stroke Shoulder Subluxation and Pain
Family: Their Role and Impact on Pain Management
Introducing the "Phoenix Sign:" Improved Vascular Perfusion of the Dorsalis Pedis Artery after a Subanesthetic Dose of Lidocaine
Medication Management of Chronic Pain in Patients with Comorbid Cardiovascular Disease
Multisite Pain May Be Associated with Fractures in the Elderly
Reconciling the New HHS Opioid Tapering Guideline with CDC and State Policies
Research Insights: Impaired Motor Imagery in Chronic Pain Conditions
Tapentadol: A Real-World Look at Misuse, Abuse, and Diversion
Temporomandibular Disorders in Performance Artists (Part 2)
Thoracic Outlet Syndrome Presenting as an Acute Stroke Mimic
Untangling Chronic Pain and Hyperarousal with Heart Rate Variability: A Case Report
What topicals exist for post-herpetic neuralgia pain?
When to Keep Your License: Older Physicians and Boundary Issues

What topicals exist for post-herpetic neuralgia pain?

November/December 2019 Ask the Expert: More options for treating PHN.
Pages 16-17

Post-herpetic neuralgia (PHN) is the most common chronic complication of herpes zoster, defined as dermatomal pain lasting at least 90 days after the appearance of an acute herpes zoster rash. This complex neuropathic pain syndrome is caused by the reactivation of dormant varicella-zoster virus (VZV).1,2 Pain manifests as an acutely painful vesicular rash secondary to peripheral nerve damage sustained during the herpes zoster attack.2 In North America, more than 95% of young adults are seropositive for VZV and, thus, may be at risk for developing herpes zoster, with incidence of herpes zoster increasing significantly around 50 years of age.1

Treatment Options

FDA-approved treatment options for PHN are limited to the capsaicin patch, lidocaine patch, gabapentin, and pregabalin. Systemic and topical therapies are typically prescribed, including tricyclic antidepressants (amitriptyline, nortriptyline, desipramine) and anticonvulsants (gabapentin, pregabalin).1

Topical agents have been considered first- and second-line treatments, respectively, alone or in combination with other first-line treatments for mild to moderate pain associated with PHN.2,3 These agents provide patients with local pain relief while minimizing systemic absorption and adverse effects. For these reasons, topicals may be preferred in patients when effects of systemic medications are of concern (see also, prescribing for the elderly).1 Due to the uncertainty of long-term benefits and concern for abuse and overdose, opioids (morphine, oxycodone, tramadol) are considered third-line.4

Compounded topicals offer promising options for PHN treatment but more research is needed. (Image: iStock)

Current Research on Topicals

Compounded topical pain creams offer some promising options for PHN treatment as well, yet evidence supporting their use remains limited. Although available studies indicate that topical therapies may provide some pain relief when administered alone, it appears that maximum benefit is achieved when topical agents are used in combination with systemic therapy options. Current treatment options may provide an acceptable amount of pain relief for many PHN sufferers; however, patient specific factors (eg, adverse effects, cost, previously trialed therapies) could restrict the use of one product over another, further necessitating the study and development of alternative therapies. This article will focus on a review of available data to support some of the newer, non-FDA approved topical treatment options for PHN.

Topical Amitriptyline/Ketamine Cream

A compounded topical combination of low-dose amitriptyline (4%) and ketamine (2%) has been proposed and studied as a treatment option for PHN.5 One double-blind, placebo- controlled trial comparing topical amitriptyline/ketamine cream twice daily to an approved oral gabapentin dose (600 mg, three times daily) for the treatment of PHN was conducted over a 4-week period (n = 350). Pain was measured using the numeric pain rating scale (NPRS). Results between groups were similar concerning reduction in average pain score (P = 0.841). Compared to placebo, topical amitriptyline/ketamine produced significantly more pain relief (1.88 vs 2.42 reduction, respectively). Application site reactions were the most common reported adverse effects.5

A larger review of studies evaluating the efficacy of combined topical amitriptyline/ketamine cream in patients with PHN pain suggested that this treatment may actually have potential as a first-line therapy, either as a monotherapy, or as an adjunct to systemic therapies.5,6 Information available within the US government-based trial registry record (ClinicalTrials.gov) lacks presentation of key information, including baseline pain scores, previous therapies, and concomitant medications. The duration of assessment was limited to 28 days. Other evidence exists for the use of combination amitriptyline/ketamine in neuropathic pain and/or PHN.6,7

TV-45070 Ointment

In 2015, Teva Pharmaceuticals sponsored a Phase 2, placebo controlled, crossover trial involving TV-45070 ointment, a novel potent sodium channel inhibitor, evaluating its safety and efficacy for the treatment of PHN.8 Patients with pain lasting greater than 6 months post-appearance of herpes zoster rash were included. Subjects were permitted to continue concomitant systemic therapy, including acetaminophen rescue therapy, and remain on ≤ 2 stable doses of oral PHN medication (amitriptyline, duloxetine, gabapentin, pregabalin), defined as dose unchanged for four weeks prior to the start of the first placebo run-in period.

Patients with mean daily pain scores ≥ 4 (on an 11-point Numerical Rating Scale) for at least four days during the initial placebo seven-day run-in period were randomized to one of two treatment sequences (TV-45070/placebo or placebo/TV-45070) with a one-week washout period in between. In total, 35 patients were randomized to each treatment group.

A statistically significant change in reported pain scores from baseline to week 3 was not found (difference in change between treatments of 0.03, 95% CI, -0.38 to 0.43). However, a significant difference in response rates (≥ 50% improvement) during treatment with TV-45070 (n = 15; 26.8%) was observed at week 3 compared to placebo (n = 6; 10.7%).

Incidence of adverse effects experienced was similar between groups, with the most common reported adverse effects including application site pain and pruritus, each having a higher incidence in the placebo group (n = 10, 15.9% and n = 8, 12.7%, respectively) over the treatment group (n = 2, 3.2% for both). Eight patients discontinued treatment prior to final analysis (TV-45070: n = 3; placebo: n = 5) due to adverse events, the majority being local skin reactions (n = 7).

The small sample size randomized to each treatment group is a limitation of this study. Although no significant difference was found in pain scores between treatment groups, a difference was found in the response rate with TV-45070 as opposed to placebo, indicating some benefit for the use of this agent for the treatment of PHN.8 Although the results of this study may be promising, further research evaluating the efficacy and safety of TV-45070 ointment is needed to formally recommend it as a treatment option for PHN.

More on topicals for pain conditions.

Last updated on: December 9, 2019
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Emerging Treatments for Postherpetic Neuralgia
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