ORLANDO – Two drugs that target ion channels in nerves are being used to quiet neurogenic itch.

The powerful anesthetic ketamine and the element strontium have both been formulated into topical compounds that do very well in quelling itches that have been stubbornly resistant to other therapies, Gil Yosipovitch, MD, said at the annual meeting of the American Academy of Dermatology.

Strontium is a calcimimetic that blocks calcium ion channels. It’s been formulated into a 4% gel, which performed very well in two studies, said Dr. Yosipovitch of the University of Miami. “Two double-blind, vehicle-controlled studies demonstrated a reduction in nonhistaminergic, cowhage-induced pruritus. Both showed that strontium 4% was superior to both 2% diphenhydramine and 1% hydrocortisone.”

Both studies employed a 4% strontium hydrogel that is available over the counter (TriCalm). The product is designed to alleviate skin irritation (itching, burning, or stinging sensations), according to the manufacturer’s website.

The first study, published in 2013, comprised 32 healthy subjects in whom itch was induced with cowhage before and after skin treatment with the strontium gel, a control vehicle, topical 1% hydrocortisone, and topical 2% diphenhydramine (Acta Derm Venereol. 2013 Sep 4;93[5]:520-6).

Strontium significantly reduced the peak intensity and duration of itch relative to all three of the comparators.

A confirmatory study was published in 2015. The vehicle-controlled, randomized, crossover study recorded cowhage-induced itch intensity and duration in 48 healthy subjects before and after skin treatment with TriCalm, 2% diphenhydramine, 1% hydrocortisone, and hydrogel vehicle (Clin Cosmet Investig Dermatol. 2015 Apr 24;8:223-9). The results were similar, Dr. Yosipovitch said.

TriCalm effectively reduced peak itch intensity by about 3 points on a visual analog scale – a 41% reduction. Itch duration was reduced by 40%. These results were both clinically and statistically significantly better than those achieved by the other active comparators and the vehicle control.

Dr. Yosipovitch said the gel is most effective on nonhistaminergic itches, including those with a neurogenic component, nummular eczema, and facial itch.

“The most powerful antipruritic we have seen in the last 3 years, however, is topical ketamine,” Dr. Yosipovitch said. Typically formulated in 2%-10% creams, the anesthetic is usually combined with amitriptyline and lidocaine. “I see this as the most effective topical antipruritic and antinociceptive we have been using.”

Ketamine is an antagonist of the n-methyl-D-aspartate (NMDA) glutamate receptor and an ion channel protein. Amitriptyline serves primarily as a voltage-gated sodium channel antagonist, and lidocaine as a local anesthetic.

Mark Davis, MD, professor of dermatology at the Mayo Clinic, Rochester, Minn., and associates initially investigated 0.5% ketamine in a topical combination with amitriptyline 1% in a cream. The compound was remarkably effective for a 41-year-old man with a recalcitrant case of brachioradial pruritus – a neuropathic condition characterized by upper-extremity itching (JAMA Dermatol. 2013;149[2]:148-50). The patient had already failed treatment with halobetasol propionate, pimecrolimus, capsaicin, doxepin hydrochloride creams, and oral hydroxyzine hydrochloride and desloratadine. However, he had complete resolution of the itch soon after using the combination cream two to three times daily. At last follow-up, 4 years later, he was still using it at least once daily and continued to obtain complete relief.

Dr. Yosipovitch said this case was followed by a retrospective study of 16 patients who had used the 0.5% ketamine cream with either 1% or 2% amitriptyline for recalcitrant pruritus. The etiologies included neurodermatitis, pruritus caused by postherpetic neuralgia, nostalgia paresthetica, anesthesia dolorosa, nasal pruritus, and diabetic neuropathy (J Am Acad Dermatol. 2013 Aug;69[2]:320-1).

They used the medication one to five times per day for a mean duration of 10 months. Of the 16 patients, two had complete relief; two had substantial relief; six had some relief; five had no relief; and one reported increased itching.

Most recently, Dr. Yosipovitch and associates reported the results of a retrospective case review of 96 patients with a variety of pruritic conditions. The most frequent indications were neuropathic conditions (29%) and prurigo nodularis (19%). Most patients got a compounded cream of 10% ketamine, 5% amitriptyline, and 2% lidocaine;16 patients got a compound with 5% ketamine. The medication worked quickly, providing itch relief within a median of about 4 minutes, with an average of about a 50% decrease in itch rating (J Am Acad Dermatol. 2017 Apr;76[4]:760-1).

Forty patients participated in a pharmacy-administered telephone survey that assessed medication tolerability and efficacy. Of these, 23 patients (58%) had relief “to a great extent” and 14 (35%) “to a moderate extent.”

There were mild side effects (burning and redness at the application site) in 16 patients. “We attributed this mainly to the lidocaine component,” Dr. Yosipovitch said. “Itch reduction lasted from 30 minutes to 7 hours, so we think this is quite a powerful tool. I now often use this topical for patients with severe intractable itch.”

He added that a case report of encephalopathy associated with the cream has recently surfaced. The patient was an elderly man with Parkinson’s disease who had been using 10% ketamine compounded with amitriptyline and lidocaine for 4 days. He gradually increased the use until he was applying it onto almost all of his upper body. The day after this extensive application, the patient presented to an emergency department with slurred speech, ataxia, and altered mental status (JAMA Dermatol. 2016;152[12]:1390-1).

“So a word of warning here: I don’t recommend using it all over the body,” Dr. Yosipovitch said.

Dr. Yosipovitch has financial relationships with numerous companies that are investigating antipruritic compounds, including strontium.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

Strontium, ketamine target troublesome itch