Epinephrine may prolong neuromodulator results

Las Vegas - Mixing neuromodulators with epinephrine may give patients the longer-lasting results they seek, according to an expert at Cosmetic Surgery Forum, held here. This combination, however, may not prove beneficial for everyone.

The efficacy and prices patients pay for the three neuromodulators approved by the Food and Drug Administration are roughly equivalent, says Mark G. Rubin, M.D., a dermatologist in private practice in Beverly Hills, Calif. As such, he says, durability of results could provide a trump card.

“Anybody who comes out with a longer-lasting neuromodulator will take over the market, because that’s what our patients complain about.” Although filler results last six to eight months and sometimes longer, he says, “Patients have to come back every three months or so for their neuromodulators, so they start to get frustrated with that.”

The concept of adding epinephrine to neuromodulators to achieve better and longer-lasting results first appeared in 2007 (Hantash BM, Gladstone HB. Dermatol Surg. 2007;33(4):461-468). “It’s easy to do, and there’s actually some very good science behind it.”

Neuromodulators with epinephrine

Very few dermatologists and dermatology residents, however, are aware of the publication, according to Dr. Rubin. In this study, investigators injected the periorbital rhytids on one side of 14 patients’ faces with onabotulinumtoxinA (12 units, single injection site). They injected the other side with 12 units of onabotulinumtoxinA plus epinephrine (one part per 100,000). At all follow-up points through 90 days, the neuromodulator/epinephrine side showed better efficacy.

After the publication appeared, “I remember we started doing this for a while. And it worked. Then Dysport (abobotulinumtoxinA, Medicis) came out,” Dr. Rubin says.

At the time, Dr. Rubin used epinephrine only in patients who did not respond normally to neuromodulators.

“I tell patients, if your results are lasting around three months, that’s pretty much what you should be getting. If they last six weeks, something’s wrong.” Such patients generally did much better with the addition of epinephrine, he says.

“But when Dysport came out, we tried switching them to Dysport, and many of those patients responded. Now when I see patients who don’t respond to Dysport or Botox (onabotulinumtoxinA, Allergan), I try Xeomin (incobotulinumtoxinA, Merz) as well. So I forgot about the adrenaline approach” until seeing two recent publications, Dr. Rubin says.

In the 2007 trial investigators injected only one site, which is uncommon in critical practice, Dr. Rubin says. However, a new 40-patient study involving crows’ feet found that injecting one site (36 units abobotulinum) per side of the face yields no statistical difference in results versus injecting three sites per side (12 units each) through 120 days of follow-up (Fabi SG, Sundaram H, Guiha I, Goldman MP. J Drugs Dermatol. 2013;12(8):932-937).

Adding lidocaine to the mix

In another study, investigators gave injections of onabotulinum toxin mixed with lidocaine and epinephrine to 181 patients who previously had been treated with onabotulinumtoxinA diluted with saline. Treatment sites included the glabella, the perioral and the periorbital areas.

“Wherever patients were being treated before, they were treated again, the only difference being the addition of lidocaine and epinephrine,” Dr. Rubin says. Three months post-treatment, 58 percent of patients rated the combination treatment as superior (Kim A, Jung J, Pak A. Cutis. 2013;Suppl:13-18).

“It’s always challenging when you retrospectively ask patients, ‘How did you do with this last treatment?’ There’s a tendency for patients to like the last thing they had,” he says. However, the study’s large population at least suggests a trend toward better results with the combination.

“Intriguingly, 86 percent of patients thought the combination was better because they experienced immediate improvement due to the lidocaine, and the muscle paralysis associated with it,” Dr. Rubin says. “Only 50.5 percent thought it lasted longer.”

Future research should help to clarify what patients think of the treatment, according to Dr. Rubin.

Positive value

Based on current evidence, he says, the combination of neuromodulators and epinephrine appears to provide positive value.

“So why aren’t we all doing this? One reason is that it’s one more thing to do - we’re juggling three neuromodulators, and how do you keep them separated?” he says. “Our office uses color-coded syringes.”

Additionally, “Some patients don’t do well with epinephrine - they develop palpitations and anxiety after injection.”

Patients with ruddy complexions often develop significant vasoconstriction at treatment sites, resulting in the appearance of temporary white blotches, Dr. Rubin says. Additionally, the combination injection stings a little more than a traditional neuromodulator injection.

“In our experience, it worked really well in some patients and modestly well in others,” he says. “It’s easy to mix - just take 0.1 cc of 1:1000 epinephrine solution, inject it into 10 cc of saline and use that as your reconstituting solution.”

Disclosures: Dr. Rubin is a consultant for Allergan and Merz and has performed clinical research for Medicis.