My Botox Doesn’t Work Like It Used To
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I got Botox for the first time the year I turned 30. Have I aged in the six years since? Absolutely. Does it look like I have? That’s debatable. I’ve tried a plethora of facial aesthetic treatments (most with very favorable results), but none of them has had the impact of Botox for the way it smooths my fine lines—or at least, the way it used to. For about a year now, I’ve noticed Botox doesn’t unfurrow my brow as effectively or for as long as it once did.
Can you become less responsive to neuromodulators over time? The answer to that question is not a simple yes or no. There are many nuances that influence the effect that neuromodulators like Botox have on your muscles. (For the record, when we say Botox from here on out, we’re referring to the family of all five FDA-approved neurotoxins—also called neuromodulators—currently on the market, including Xeomin and Dysport.) And while there have been some initial clinical studies on the topic of so-called “Botox resistance” (the majority of which looked at onabotulinumtoxin A, also known as Botox), there’s still so much more that we have to learn.
To shed some light on what we do know about Botox resistance, I asked experts to weigh in on how common the phenomenon actually is, what factors can contribute to it, and what to do if you find that your muscles aren't responding to neuromodulators the way they used to.
Meet the experts:
David Shafer, MD, is a double board-certified plastic surgeon based in New York City and a trainer for Allergan Aesthetics.
Connie Yang, MD, is a board-certified dermatologist at PFRANKMD by Dr. Paul Jarrod Frank in New York City.
Mark Murphy, MD, is a board-certified facial plastic surgeon and founder of Palm Beach Facial Plastic Surgery in Florida.
Shari Marchbein, MD, is a board-certified dermatologist in New York City.
Ramtin Kassir, MD, is a board-certified facial plastic and reconstructive surgeon in New York City.
Shereene Idriss, MD, is a board-certified dermatologist in New York City.
In this story:
How do neuromodulators work?
Before we delve into the idea of Botox resistance, let’s refresh ourselves on how neuromodulators like Botox actually work. “Botox works on dynamic wrinkles,” says David Shafer, MD, a double board-certified plastic surgeon based in New York City and a trainer for Allergan Aesthetics, the makers of Botox. Those are the lines that appear when you express emotions and are invisible when your face is at rest. Neuromodulators inhibit the release of acetylcholine, a neurotransmitter that relays nerve signals to the muscle. As a result, “you get a temporary weakening or paralysis of the muscle,” says Connie Yang, MD, a board-certified dermatologist at PFRANKMD by Dr. Paul Jarrod Frank in New York City. “This effect is localized to the injected area, preventing the muscles there from fully contracting and forming wrinkles or lines.” Over time, the nerve signals gradually resume their normal function—and the lines return.
The same chemical reaction occurs in everyone after the needle penetrates your skin—but its effectiveness in terms of wrinkle-reduction lies in where the neuromodulator is placed and how much of it is used. No one’s facial anatomy is identical and an assessment of muscle movement by a highly skilled and experienced practitioner is essential to receiving the right treatment for you. (Allure recommends seeing a board-certified dermatologist or plastic surgeon for any treatments that go into or past the skin barrier, neuromodulators included.) “Every person is different in their anatomy and how they animate,” says Dr. Yang. “These are the factors that determine Botox dosing for each individual, not so much their age.”
When Dr. Yang evaluates a patient for neuromodulator injections (she most often uses Xeomin as she finds it produces the “most natural-looking” result) she looks at their facial movements and the strength of their muscle contractions. She takes note of any asymmetries and features like low-set brows. “The muscles on the face have opposing functions and there’s an art to facial balancing with neuromodulators,” she says.
Dr. Shafer notes that Allergan Aesthetics has recently worked with the FDA to update the injection pattern they recommend to providers to help them further individualize treatment for patients. This way, Allergan can “train providers on the nuances of each patient and [encourage a] less cookie-cutter approach to injecting,” he says. (Allergan Aesthetics declined to comment on this story, but put forth Dr. Shafer as an expert resource.)
You can typically expect to see the effects of neuromodulators kick in between two to seven days post-injection. They reach “peak strength” after 10 to 14 days but “look best—settled, loosened, and natural—around six to eight weeks,” says Mark Murphy, MD, a board-certified facial plastic surgeon and founder of Palm Beach Facial Plastic Surgery in Florida.
Of course, everyone is different—and there are a handful of people who seem to not respond to neuromodulators at all.
What exactly is Botox resistance?
The medical community uses various terms—neurotoxin tolerance, Botox resistance, and the tongue-twisting Botox/neurotoxin nonresponders—to refer to what happens when a patient doesn’t respond to neurotoxin injections or does not respond to them in the same way that they used to. In the simplest terms, resistance is defined as full movement returning to the muscles before three to four months’ time, which is how long one neuromodulator treatment lasts on average. (Though Daxxify, the newest one on the block, may last as long as six months.)
“Botox resistance is a rare and not yet well-understood phenomenon that occurs when the body develops neutralizing antibodies,” explains Dr. Yang. The development of antibodies can be in response to either the active ingredient botulinum toxin or the supporting proteins in the given formula, adds Dr. Murphy. The idea is that over time and with repetitive injections your body is overexposed to the complex proteins that are bound to the neurotoxin. “With these repeated exposures, your body can develop an immune response to these foreign proteins and form neutralizing antibodies,” says Dr. Yang.
Botox resistance has been recorded in neurology literature, particularly during instances in which the drug is used to treat chronic conditions such as migraines, explains Shari Marchbein, MD, a board-certified dermatologist in New York City. (Botox was FDA-approved as a treatment for migraines in 2010.) That said, in therapeutic cases much higher doses of botulinum toxin are used than in cosmetic patients. For the treatment of migraines, upwards of over 100 units can be used at a time, compared to the 20 to 70 units used to immobilize muscle movement in the face, explains Dr. Marchbein. It’s thought that the significantly higher dosage used for therapeutic cases can place a patient at greater risk of developing Botox resistance.
Evidence of developing neutralizing antibodies as a result of aesthetic use of Botox is scarce: A recent analysis found that the occurrence hovers around 0.5%. “In my practice—and I’ve done hundreds of thousands of Botox injections—[Botox resistance] is extremely rare. I’ve maybe seen it one or two times in the last almost 30 years,” says Ramtin Kassir, MD, a board-certified facial plastic and reconstructive surgeon in New York City.
The jury is still out on what mechanisms in the body or individual traits (like the speed of your metabolism) can cause someone to develop neutralizing antibodies, if they do at all. The good news is that while neutralizing antibodies may impact how well your Botox “takes,” their development has not been shown to have other health impacts, says Dr. Yang.
What factors contribute to Botox resistance?
The consensus from the medical experts I spoke with was that too-frequent dosing, underdosing, and maybe even the COVID-19 vaccine (more on that in a minute) are all possible contributing factors to Botox resistance. Keep in mind, as with any scientific phenomenon, correlation does not mean causation.
If you’re the type to run back to your injector at the first signs of movement (something I’m guilty of, and perhaps the reason for my own resistance), this can increase your risk of developing Botox resistance. You should always wait at least three months between neuromodulator treatments. “It’s going really frequently [that] can increase the risk of developing neutralizing antibodies,” says Dr. Marchbein, who adds that of the thousands of patients she sees in her practice, a “handful” have become resistant to neuromodulators over time.
Dr. Marchbein also points to the rise of medspas as a possible reason for an uptick in Botox resistance. She explains that patients may be receiving “cookie-cutter” dosing—as in, a set number of units that does not account for the individual’s unique muscle movement or facial anatomy. She explains that in her experience, medspas tend to inject fewer units, which enables them to offer a lower price for services—and prompts clients to return for more injections more often. As someone who has visited medspas over the years, I can’t help but wonder if this, too, contributed to my own experience. Dr. Marchbein stresses the importance of making sure that you seek out a highly qualified injector and “really stick to that three-month mark, don’t do it sooner” even if you’re starting to see more movement than you’d like.
There may also be a correlation between the COVID-19 vaccine and the effectiveness of Botox—but before we say another word about it, let’s be clear that this is not a reason not to get vaccinated. In 2022, a small study of 45 patients found that muscle movement resumed about two weeks sooner among those who had gotten the COVID-19 vaccine versus those who had not yet received the vaccine. In another case, a patient under observation received Botox after getting the vaccine. Though the patient had been receiving Botox injections successfully for five years, this time she reported a lack of response. This case suggests that the introduction of foreign proteins via the vaccine (intended to help the body build an immune response against the virus) may have led to the development of neutralizing antibodies. But one case is far (extremely far) from a study from which we can draw conclusions.
What can you do to prevent Botox resistance?
If you’re finding that you’re not responding to neuromodulators as well as you used to, there are a few tactics you can try.
Visit a highly experienced injector
The expertise of your injector plays a key role in how your muscles respond to any neurotoxin since they’re the ones who determine placement and dosing. It’s also important to choose an injector who will be able to see you for a follow-up about two weeks after the initial appointment to make sure you’ve received the correct number of units to achieve your desired result, explains Dr. Marchbein. After assessing how your neuromodulator has settled, they can add a little more here or there “to make sure that you’re optimally treated for the next three months,” she says.
Switch up your neuromodulator
You can also consider trying a different brand than you used before. Each of the five FDA-approved botulinum toxins has a slightly different formulation with varying proteins and you can become resistant to any one of them, explains Dr. Murphy. Xeomin has the least amount of proteins and therefore the least opportunity for potential resistance, he says.
Allow your toxin to run its course
After your initial appointment and touch-up, you should not be back in your injector’s chair before three months. And if you can wait longer, that’s even better. “Give your muscles a chance to allow movement to come back before getting injected again,” says Shereene Idriss, MD, a board-certified dermatologist in New York City.
Dr. Murphy agrees: “For most people, I recommend getting Botox treatments every four months. Typically, movement may return between two to three months. However, I would recommend waiting for full, baseline range of motion to return to avoid increasing the risk of resistance.” He adds that you need to avoid getting what he refers to as “booster” treatments if possible—meaning, after the initial touch-up, no injections of smaller units before your neurotoxin has run its course.
Consider zinc supplementation
“Consider” being the operative word. Whether you’re zinc deficient or not, taking a zinc supplement may help prolong the effectiveness of your neuromodulator of choice, but the supporting data is scarce and more studies are needed, explains Dr. Idriss.
If you want to give it a go, the recommended daily supplemental amount of zinc is 50 mg. “It should be taken for four to five days prior to Botox injections and on the day of injection, as zinc affects how the toxin binds to its target [neurotransmitter]. Once bound, the function of zinc is no longer relevant, [so] there is no need to continue the supplementation until a few days prior to your next treatment,” says Dr. Yang. There are possible side effects with taking excessive amounts of zinc; the most common are nausea, vomiting, and diarrhea. “However, 50 mg. daily for a few days is unlikely to cause these symptoms,” says Dr. Yang.
What happens if you stop responding to neuromodulators altogether?
If for some reason you have stopped responding to any brand of neuromodulator (just as a reminder, this is exceedingly rare), you may be classified as what Dr. Marchbein calls a “nonresponder.” The first thing she recommends is taking a “holiday” from neurotoxin injections to allow your body to clear itself of any neutralizing antibodies you may have developed. “The recommended break is somewhere between 6 and 18 months to see if you can potentially rid yourself of the neutralizing antibodies and become a responder again,” explains Dr. Marchbein.
Another option for nonresponders is switching to a different serotype or strain of neurotoxin, like Myobloc (the brand name for RimabotulinumtoxinB or botulinum toxin type B), which is more commonly used by neurologists to treat muscle spasms. Dr. Yang says that some cosmetic patients have had success switching to Myobloc, but it’s expensive, exceedingly difficult to find, and its duration of effectiveness is very short. “On average, [it lasts] two-thirds of the time of Botox,” says Dr. Idriss.
But the best option may be yet to come: “There are new neurotoxins in development as we speak,” says Dr. Yang, citing a neurotoxin called RelabotulinumtoxinA that’s currently being developed by the pharmaceutical company Galderma. The most recent trials show promising results in terms of quicker onset and potentially greater longevity than existing neurotoxins, she says. And perhaps most interestingly to those who feel their neuromodulator injections are no longer “working,” RelabotulinumtoxinA doesn’t contain the proteins that may cause resistance to develop.
As for me, after a year of experiencing resistance, I switched neuromodulators—I had only ever used Botox-brand Botox—and tried Daxxify. Not only did Daxxify work for me, it ended up lasting about two months longer than my Botox once did, and gave me a very natural-looking appearance. (Though, as Allure has previously reported, Daxxify also comes at a much higher price point than other neuromodulators.) I may try going back to Botox in the future, but for now, I’m heeding Dr. Marchbein’s advice and taking a break for at least a year.
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Originally Appeared on Allure
