Botox Doesn’t Work Like It Used To. Have I Developed Resistance?

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By Daebbang

“Botox used to work well for me, but this time it doesn’t seem to have done much. Have I already developed resistance?”

It’s possible. But one treatment with a weaker effect doesn’t automatically mean resistance. First, we need to look at how long it has been since treatment, whether muscle movement has decreased, and which wrinkles the treatment was intended to address. [1]

Today, let’s focus on Botox for expression lines between the eyebrows, on the forehead, and around the eyes. We’ll also look at the dose given in one session and questions about Xeomin. Here, I’m using “Botox” as a familiar term for botulinum toxin treatment. When discussing research on a particular product, I’ll name the formulation separately.

What do you mean when you say it isn’t working?

If it’s only been a few days and you see little change, it may still be too early to judge.

Botox for wrinkles doesn’t produce its final result immediately after injection. Experts recommend reviewing the result at around two weeks after a first treatment or treatment in a new area. If this result feels disappointing, I also recommend checking both muscle movement and changes in the wrinkles at that point. This doesn’t mean that two weeks is the time of maximum effect for every product and every person. [2]

If it worked well at first and movement returned a few months later, the effect may simply be wearing off gradually.

Botox doesn’t work permanently. As signaling between the nerves and muscles recovers over time, movement returns. Starting to move a little again doesn’t, by itself, mean you’ve developed resistance. [3]

If the muscle moves less but a wrinkle remains even when your face is at rest, that’s a different situation.

Botox softens expression lines by reducing excessive muscle contraction. It doesn’t erase every deeply etched skin crease in one treatment. A line can remain even when movement has decreased, so we need to distinguish a remaining wrinkle from a treatment that isn’t acting at all. [4]

On the other hand, if enough time has passed and the muscle movement itself has barely decreased, the actual dose, injection locations, and choice of muscles need to be reviewed. Two treatments described as “one area of Botox” aren’t necessarily the same treatment in practice. [1]

How does antibody-related resistance develop?

Botulinum toxin is a protein. The body can recognize it and produce antibodies. Those that interfere with the drug’s action are called neutralizing antibodies. By interfering with the drug’s action at nerve endings, they may weaken the effect or leave little effect at all. [3]

Put simply, the drug has a job to do, but antibodies made by the body can get in the way. However, not everyone with a weak response has neutralizing antibodies, and detecting neutralizing antibodies doesn’t necessarily mean the treatment will stop working. [1]

How common is Botox resistance?

In a pooled analysis published in 2023, neutralizing antibodies were detected after treatment in 27 of 5,876 evaluable patients, about 0.5%, who received onabotulinumtoxinA. This is the proportion in whom antibodies were found, not the proportion in whom Botox stopped working altogether. [5]

This analysis combined data from cosmetic treatment and several medical conditions, and examined clinical trials of one formulation. It was also supported by its manufacturer, AbbVie. The figure cannot be applied directly to every product or to the probability of resistance in someone receiving repeated treatment for decades.

There are also published reports of patients whose response declined after cosmetic treatment and who tested positive for neutralizing antibodies. Being uncommon in clinical trials is not the same as being impossible in practice. [6]

Will receiving 300 units or more at once cause resistance?

“I’ve heard you develop resistance if you receive 300 units or more of Botox.”

Looking at the prescribing information helps explain where this idea may have come from. But 300 units is not a universal resistance threshold for every botulinum toxin product.

The Korean prescribing information for BOTOX sets a dose limit of no more than 300 U in a single treatment for cervical dystonia, a condition involving abnormal contractions of the neck muscles. Its information on antibodies also describes reduced effectiveness due to antibodies in some patients with torticollis after repeated injections totaling 300 U or more within one month. One is a single-treatment dose limit for a particular condition; the other describes repeated administration over a short period. [12]

Does the same rule apply to other products? The Korean approved product information for Xeomin and Nabota also warns that high doses or frequent administration may increase the risk of antibody formation. However, it doesn’t set “300 U and above” as the point at which that risk begins. [13] [14]

So we can’t draw a line saying that below 300 U is safe and that resistance starts at or above it. That doesn’t mean it’s acceptable to exceed a product’s dose limits, either. The dose and interval appropriate to the product and treatment indication still need to be followed.

Does that mean dose has nothing to do with resistance?

No. An older study of patients with dystonia found that those with antibodies had received higher doses per treatment and higher cumulative doses. Later research in patients receiving long-term treatment for neurological disorders also found associations between neutralizing antibodies and both the dose per treatment and cumulative dose. [15] [16]

But we can’t transfer those findings directly to facial wrinkle treatment and say that a certain number of units means a certain percentage risk of resistance. The conditions treated, products, and observation periods differed, and older studies used the formulations available at the time.

Recent research doesn’t all point neatly in one direction, either. In the 2023 analysis mentioned earlier, antibody formation was rare, and no clear relationship with dose could be established. In a 2025 meta-analysis, studies using higher average doses of onabotulinumtoxinA (BOTOX) had higher observed rates of antibody positivity, but the difference was not statistically significant. That meta-analysis combined studies of neurological conditions, excluded cosmetic treatments, and was supported by Merz. [5] [8]

Another point: units are not interchangeable across all products. You shouldn’t simply transfer the dose number for one product to another. [9]

So if you’re treating not just facial wrinkles but also the jaw or several areas of the body, I recommend reviewing which product you received, the total amount, and how often treatments were repeated. If you’ve had injections at different clinics, share those records too. It’s important to use enough to achieve the intended effect, while avoiding unnecessary dose increases or repeated additions at short intervals. [3]

Can frequent touch-ups cause resistance?

“It still moves a little. I’ll just get another injection.”

I wouldn’t recommend repeatedly adding injections at short intervals like this. Recommendations advise reducing unnecessary repeat injections and using the dose needed to achieve the desired effect. [3]

Reviewing the result at around two weeks and having another injection that day are separate decisions. Remaining movement and symmetry should be assessed, but any touch-up should be decided in light of the product’s approved instructions and your previous dosing record. Don’t think of every follow-up as an appointment for another injection. [2] [13]

For a full repeat treatment of expression lines, the usual advice is to allow an interval of at least about three months. However, three months is not a boundary that completely prevents resistance. Follow the product’s instructions and consider how long your actual result lasts. [7] [13]

Is it impossible to develop resistance to Xeomin?

“I’ve heard Xeomin is a Botox product that doesn’t cause resistance.”

It’s a product that can be considered when resistance risk matters, but it cannot be described as having zero possibility of resistance.

Xeomin is a formulation called incobotulinumtoxinA. Its complexing proteins—the proteins associated with the toxin—have been removed, reducing the bacterial protein load. But the active toxin itself is also a protein, and neutralizing antibodies can target this core toxin. The absence of complexing proteins doesn’t make antibody formation impossible. [10] [3]

There is evidence supporting low immunogenicity. A 2025 meta-analysis found no reported cases of persistent neutralizing-antibody positivity or antibody-related loss of treatment effect in patients who had used only Xeomin from the start. However, these were studies of neurological conditions, and follow-up periods and study conditions differed between products. They cannot establish superiority over other products in every cosmetic treatment or a lifetime without resistance. [8] [11]

In fact, a 2023 pooled analysis of Xeomin clinical trials did include positive neutralizing-antibody test results. These included patients who were already positive before treatment and those whose test results fluctuated. However, no cases of antibody-related loss of treatment effect were identified in that study. These were data from treatment of neurological conditions, supported by the manufacturer, Merz. Detecting antibodies and the drug actually failing to work need to be considered separately. [10]

The Korean approved product information for Xeomin also states that high doses and frequent administration carry a risk of antibody formation. Even if you choose Xeomin, you still need to follow appropriate dosing and treatment intervals. [13]

If neutralizing antibodies against type A toxin have already reduced the effect, simply switching to Xeomin cannot be guaranteed to solve the problem straight away. Choosing a product with resistance risk in mind and addressing resistance that has already developed are different issues. Instead of considering only whether a product is Korean or imported, or how much it costs, review your previous products, doses, intervals, and actual responses together. [1]

So when should you have a review, and when should you have another treatment?

For Botox treatment of expression lines, here’s the approach I recommend.

Have the result reviewed at around two weeks. This is a particularly useful point for a first treatment or treatment in a new area. If the effect is less than expected, compare actual movement and before-and-after photos taken with the same facial expression. A review doesn’t automatically mean another injection. [2]

Usually, consider a full repeat treatment after about three months, when movement and wrinkles start to bother you again. If the result is holding up well, there’s no need to rush into another treatment just to match the calendar. This is practical guidance based on expert recommendations; it varies with the product, treatment area, and previous response. [7]

If your response repeatedly declines despite appropriate treatment, have the cause assessed before booking the next injection. Rather than continually shortening the interval or increasing the dose, first review your previous records and consider possible causes, including antibody-related resistance. [3]

A few remaining lines on the forehead or between the eyebrows don’t all mean resistance. What matters is identifying which effect has decreased and planning the next treatment around the reason.

Research Papers and Approved Product Information

1. Kroumpouzos G, Silikovich F. (2025). Exploring Nonresponse to Botulinum Toxin in Aesthetics: Narrative Review of Key Trigger Factors and Effective Management Strategies. JMIR Dermatology, 8:e69960. DOI: 10.2196/69960.
2. Goodman GJ, et al. (2020). Facial aesthetic injections in clinical practice: Pretreatment and posttreatment consensus recommendations to minimise adverse outcomes. Australasian Journal of Dermatology, 61:217–225. DOI: 10.1111/ajd.13273.
3. Bellows S, Jankovic J. (2019). Immunogenicity Associated with Botulinum Toxin Treatment. Toxins, 11(9):491. DOI: 10.3390/toxins11090491.
4. Anido J, et al. (2017). Tailored botulinum toxin type A injections in aesthetic medicine: consensus panel recommendations for treating the forehead based on individual facial anatomy and muscle tone. Clinical, Cosmetic and Investigational Dermatology, 10:413–421. DOI: 10.2147/CCID.S138274.
5. Jankovic J, et al. (2023). Neutralizing Antibody Formation with OnabotulinumtoxinA (BOTOX®) Treatment from Global Registration Studies across Multiple Indications: A Meta-Analysis. Toxins, 15(5):342. DOI: 10.3390/toxins15050342.
6. Torres S, et al. (2014). Neutralizing antibodies to botulinum neurotoxin type A in aesthetic medicine: five case reports. Clinical, Cosmetic and Investigational Dermatology, 7:11–17. DOI: 10.2147/CCID.S51938.
7. Philipp-Dormston WG, et al. (2024). The Patient Journey in Facial Aesthetics: Findings from a European Consensus Meeting on Improving the Quality of Life for Patients Receiving Botulinum Toxin Injections. Clinical, Cosmetic and Investigational Dermatology, 17:329–337. DOI: 10.2147/CCID.S446891.
8. Walter U, et al. (2025). Systematic Review and Meta-Analysis of Secondary Treatment Failure and Immunogenicity With Botulinum Neurotoxin A in Multiple Indications. European Journal of Neurology, 32(8):e70289. DOI: 10.1111/ene.70289.
9. Brin MF, et al. (2024). Update on Non-Interchangeability of Botulinum Neurotoxin Products. Toxins, 16(6):266. DOI: 10.3390/toxins16060266.
10. Jost WH, et al. (2023). Pooled Safety Analysis of IncobotulinumtoxinA in the Treatment of Neurological Disorders in Adults. Toxins, 15(6):353. DOI: 10.3390/toxins15060353.
11. Magacho-Vieira FN. (2026). Systematic Review and Meta-Analysis of Secondary Treatment Failure and Immunogenicity with Botulinum Neurotoxin A in Multiple Indications—Comment on Recommending IncobotulinumtoxinA as First-Line to Prevent Secondary Treatment Failure [Letter]. European Journal of Neurology, 33(4):e70581. DOI: 10.1111/ene.70581.
12. AbbVie Korea. Korean prescribing information for BOTOX 100 U (2024.02.08). Cervical dystonia dosage and administration, p. 4; patient information on antibodies, p. 33.
13. Ministry of Food and Drug Safety, Republic of Korea. Korean approved product information for Xeomin. General precautions, section 5.3; precautions for administration, section 11. Accessed: 2026.10.24.
14. Ministry of Food and Drug Safety, Republic of Korea. Korean approved product information for Nabota 50 Units. Immunogenicity under general precautions. Accessed: 2026.10.24.
15. Jankovic J, Schwartz K. (1995). Response and immunoresistance to botulinum toxin injections. Neurology, 45:1743–1746. DOI: 10.1212/WNL.45.9.1743.
16. Albrecht P, et al. (2019). High prevalence of neutralizing antibodies after long-term botulinum neurotoxin therapy. Neurology, 92:e48–e54. DOI: 10.1212/WNL.0000000000006688.