Inside a Rare Case of Botox Resistance

Over the past few years, there's been increased conversation around Botox resistance, where a person develops antibodies to the neurotoxin that block it from taking effect. Fifty-year-old Michelle Grant*, a front-office manager at Skin Wellness Dermatology in Birmingham, Alabama, considers herself "toxin resistant" after her routine neurotoxin injections stopped taking effect. "I'm just not freezing like I used to," she says.

Grant's dermatologist, Corey L. Hartman, MD, FAAD, says this happens sometimes — a routine Botox user develops resistance to Botox or another form of botulinum toxin A — but it's very rare and hard to diagnose without bloodwork.

"I have three patients like that, where the forehead just does not hold," Dr. Hartman says (including Grant). While resistance to Botox can happen, what's much more likely is that someone assumes they're "Botox resistant" when their lack of effect may not be verifiably antibody-related. More commonly, their dose, specific toxin, or placement just needs a little tweaking. To learn more about why this "conundrum" sometimes occurs, keep reading.

Experts Featured in This Article

Corey L. Hartman, MD, FAAD, is a board-certified dermatologist and the founder of Skin Wellness Dermatology in Birmingham, Alabama.

Robert M. Schwarcz, MD, is a board-certified reconstructive and cosmetic surgeon based in New York City.

What Is Botox Resistance?

Botox resistance is the body's resistance to the neurotoxin. "Botox resistance is when your body develops antibodies for the toxin," says cosmetic surgeon Robert M. Schwarcz, MD. "So your body develops a resistance or a blocker to it. That can happen with pretty much any foreign body or drug." In the case of Botox resistance, the toxin does not take effect or produce the desired aesthetic result. "It just stops paralyzing the muscle, so movement doesn't fully stop," says Dr. Schwarcz.

This was Grant's experience. When she started getting Botox injections in 2015 — 20 units of Botox Cosmetic in her forehead — she had a great experience. "My forehead was tight; it was wonderful," Grant says. However, six years later, in 2021, the same injections were not taking effect the same way. "It just didn't really take like it used to," Grant says, adding she had full movement. "My forehead was not smooth. And it felt different because I was able to move my forehead."

What Causes Botox Resistance?

Dr. Hartman considers Botox resistance "a real conundrum" because we don't know exactly what causes it from person to person. "You see these people with a resistance or a lack of effect and it doesn't correlate to antibodies," says Dr. Hartman. Grant has never had any bloodwork done to confirm elevated antibodies, as she's never experienced any other symptoms beyond toxin resistance.

Some anecdotal evidence connects neurotoxin resistance to the COVID-19 vaccine. Coincidentally, Grant's resistance started shortly after she received the Pfizer vaccine. "It started to really be a 'thing' during the pandemic," says Dr. Hartman. "That's when I started to see it most and I also started to hear more of my colleagues talking about it in our derm groups." In 2022, the Journal of Cosmetic Dermatology published a study showing that "botulinum toxin A might be less effective after COVID-19 vaccination." But it was a small case study and there's been little published evidence verifying the connection. "I don't know if [the vaccine] has anything to do with it," Dr. Hartman says. Dr. Schwartz is similarly reluctant to make any causal claims between vaccine and resistance, as none of his thousands of vaccinated patients have neurotoxin resistance.

Dr. Schwartz says more often, what's perceived as Botox or neurotoxin resistance is a miscommunication between the patient and their injector. "More commonly the area was undertreated," Dr. Schwartz says. "Let's say [the patient] needed 30 units of [Botox,] but they only got 15, there's still going to be movement. The movement will be dulled, but it won't be frozen."

The patient may require a higher dose of a toxin to achieve their desired result, especially if the lack of effect is in their strong forehead muscle. "Anyone who injects will tell you that the forehead is the hardest [area] to get right," Dr. Hartman says. "That's the [area] where patients are more aware if it doesn't feel good. That's the one where if you knock out all the expressions, they're going to look the weirdest, but you also want to duration. My approach is always to be conservative. Inevitably, patients are going to come in complaining that their forehead is not lasting as long. But that's a dosing issue."

What's important to keep in mind is that neurotoxin injections naturally taper off. "Botox is not an on-off switch," Dr. Hartman says. "If it lasts four months, in that last month it's going to taper down." What might present as resistance or a lack of efficacy might be a change in one's tolerance to the natural taper. "Perception drift can happen," Dr. Hartman says. "That movement you were OK with before, you don't like it anymore so you start to perceive that [the neurotoxin] doesn't last as long or work as well."

Another possibility is that the patient assumes that their neurotoxin will take effect on a particular part of their face that was not fully treated or not treated at all. "They'll say, 'Look, I can still move my forehead,'" says Dr. Schwartz. "I'll look and see that they didn't get their forehead injected, they got their 11 lines injected. If that's the case, it's just a miscommunication about the area that was treated."

How to Avoid Botox Resistance

It's impossible to avoid Botox or neurotoxin resistance. "It's hard to tell the body to stop protecting itself and that's essentially what it's doing," says Dr. Schwartz. But if you do develop a non-response to the toxin you're using, your provider should first address the dose. "The first thing I would do is address the strength."

If upping the dose doesn't work, your provider might consider switching to a different neurotoxin. "The beauty is that there are so many available to us now," says Dr. Schwartz. For example, if you show little to no response to Botox Cosmetic, consider trying Xeomin, which lacks the protein structure present in Botox Cosmetic. "I've had some people do better when they were switched to Xeomin," says Dr. Hartman. "But I always advise that they do nothing for six to 12 months. Then start it fresh with Xeomin."

Grant has tried upping her dose of Botox Cosmetic from her routine of 20 units to 50 units. She's tried Dysport, Jeuveau, Xeomin, and Daxxify. "I've tried everything and nothing works," she says. But she hasn't fully given up on neurotoxins altogether. "I keep trying," she says. "I think a little bit helps." Plus, as a perk of working in a dermatology office, Grant has access to other skin treatments to address the expression lines on her forehead. "I've also tried microneedling," she says. "It helps a little."

— *Name has been changed.

Megan Decker is a freelance writer and editor based in New York City. Formerly the beauty editor at Refinery29, Megan has worked in editorial for over seven years, frequently covering emerging trends and profiling celebrities.