When Botox starts to work and how long it lasts — the numbers verified area by area

This is the question we are asked most often. The prescribing information has written the answer down directly.

“In general, the initial doses of reconstituted Botox induce chemical denervation of the injected muscle one to two days after injection, increasing in intensity during the first week.” — the US FDA prescribing information

There is also material in which it was actually measured in a number of people. Rappl T et al., Clinical, Cosmetic and Investigational Dermatology 2013;6:211 — randomised · double-blind · 180 patients (60 per arm), glabellar lines.

To put it together, it runs like this. From day 1 to 2 something begins to change, around day 5 it becomes distinct, and as the first week passes it comes close to its maximum.

So we recommend seeing you once at about 2 weeks after the procedure. That is the point at which the effect has fully come up, so if there is an asymmetry or a place where a little is left over, judging it then is accurate. There are people who say on day 3 or 4 “it is still just the same”, but that point is not yet the time to judge.

The phrase “3 to 4 months” is written in the prescribing information just as it is.

“The duration of effect of Botox in glabellar lines is approximately 3-4 months.” — the US FDA prescribing information

Laying the measured material over this makes the picture clearer. These are the median durations from the 180-patient trial above.

This difference is not chance. In the same study sex was the main predictor of the duration, at p<0.0001. It is taken to be because the muscles of facial expression in men are thicker and stronger.

“The period in which it does not move at all” and “the period in which the effect remains” are different

Once you know this distinction, “3 to 4 months” makes far more sense. These are the numbers from a study on the forehead muscle that compared the left and right sides of the same person (Nestor MS & Ablon GR, Journal of Clinical and Aesthetic Dermatology 2011, randomised · double-blind · contralateral control, 20 patients).

That is, it is not that “the drug disappears”; it fades gradually. Feeling at about 2 months that “it seems to move a little” is normal, and that point is not the point at which the effect has ended.

The forehead study is of 20 patients. That said, being a design comparing the left and right sides of the same person, it has the advantage that individual variation is cancelled out.

This part is the most practical in this article. All three areas, glabellar lines · lateral canthal lines · forehead lines, are formally approved indications of the US FDA, and the dose and the number of sites are nailed down as numbers.

The forehead is meant to be treated together with the glabella

This point is scarcely mentioned in domestic material, but it is worth knowing. The forehead dosing in the prescribing information is “0.1 mL (4 Units) into each of 5 forehead line sites (20 Units) with 0.1 mL (4 Units) into each of 5 glabellar line sites (20 Units), for a recommended total of 40 Units”. That is, it was not approved as a way of treating the forehead on its own.

There is a reason. The frontalis is the muscle that raises the eyebrow, and the corrugator · procerus muscles of the glabella are the muscles that lower it. If only the raising side is made weak, the lowering side becomes relatively dominant. That is why handling the two muscles together is the approved way.

When someone in the consulting room says “I want the forehead only”, our recommending the glabella along with it is not for the sake of revenue but because that is what is written in the prescribing information.

The interval before re-treatment

The prescribing information writes down two things.

• “The safety and effectiveness of administration more frequently than every 3 months have not been clinically evaluated.”
• The cumulative total over 3 months should generally not exceed 360 Units.

Glabellar 20 + lateral canthal 24 + forehead 20 comes to 64 Units all told. For cosmetic purposes there is in practice no occasion to reach this ceiling. Still, it is better to know that “the effect seems to have dropped off, so again after a month” is outside the scope of the approval.

The glabella is the best-verified area in this field. These are the results of the phase 3 registration trials carried in the US FDA prescribing information.

Active 405 patients against placebo 132 patients — investigator-assessed responder rate at day 30 80% against 3% on placebo, patient self-assessment 89% against 7% on placebo.

That 80% against 3% comes out of a trial compared against a separate placebo arm is a size of difference uncommon in aesthetic medicine as a whole. It is a point that stands in contrast with the several procedures covered in earlier columns, where we had to write that “the evidence is thin”.

For the lateral canthal lines and the forehead too, an effect significant against placebo is carried in the prescribing information. However, the responder-rate figures for the three areas must not be set side by side and compared — the criterion for judging a “response” is designed differently for each area, so comparing the numbers alone reads them wrongly. That is why only the glabellar figures are written in this article.

This part is of particular significance for Korean patients.

The cosmetic indications approved by the US FDA are the three of glabellar lines · lateral canthal lines · forehead lines only, and the masseter (square jaw) is not included. Yet in Korea, on 25 August 2023, a domestic product received MFDS approval for “benign masseteric hypertrophy” — the first in the world for this indication.

So square jaw Botox in Korea is not an “off-label use” but a formally approved indication. However, it differs from product to product — there are products that hold this indication and products that do not. We tell you before the procedure which product we are using.

The masseter has a different time curve

Unlike facial lines, for the masseter it takes time for the muscle volume to decrease. These are the curves measured in a small prospective study (8 patients).

• The reduction is greatest at week 11 — 31.1% on clenching, 25.8% at rest (p<0.05)
• At week 15 it was still significant at 28.8% / 24.6%
• At week 25 it was 20.1% / 15.6% and the significance was gone

That is, the square jaw is not a procedure to be judged 2 to 3 weeks after the injection. Months 2 to 3 are when it is at its best, and so we take the photographs again at that point.

This time-curve material is of 8 patients. The direction is consistent across several sources, but the sample is small for applying the exact percentages to an individual as they stand.

Botulinum toxin preparations receive MFDS product approval in Korea as prescription drugs. They are not cosmetics or medical devices — they are a category requiring a doctor's prescription and a doctor's procedure.

For one domestic product the approved indications are verified as five.

1. Glabellar lines (20 to 65 years), moderate to severe
2. Crow's feet · lateral canthal lines (18 to 65 years), moderate to severe
3. Benign masseteric hypertrophy (18 to 65 years)
4. Post-stroke upper limb spasticity (18 years and over)
5. Benign blepharospasm (18 years and over)

In the domestic dosing, glabellar 20 Units over 5 sites and lateral canthal 24 Units over 6 sites are identical to the US FDA prescribing information. It means the same numbers are in use even in different countries, and it is by that much a signal that this dose is well established.

The approval number and the approved indications can be looked up by anyone at the MFDS drug information portal (nedrug.mfds.go.kr). The place where one looks them up is different from the one for medical devices.

What we verified is the approved product information of one domestic product. The indications of the other domestic products we were not able to verify in the original — since the approved indications can differ from product to product, if you are curious, ask before the procedure and we will check for you. How the approval number and the review number differ is written up in What the approval number in a clinic's material means, and how to look one up yourself in Jeheo · suheo · certification.

These are figures with a clear denominator, from the registration trials. The number in brackets is the size of the active group; the placebo group is a different size in each area, so for placebo we have given the percentage only.

Of the three areas the lateral canthal lines are on the safer side — the only adverse event carried in the table of the prescribing information is eyelid edema at 1%.

What Botox does is to block signal transmission at the nerve ending temporarily, and the wording of the approved indication is itself “temporary improvement”. It is not a procedure that removes muscle or cuts a nerve.

Material presenting the time to recovery when eyelid ptosis occurs as a figure with a denominator we were not able to verify. That number is not in the prescribing information either. So we do not state it as a certainty that “it comes back in a few days”. What matters, though, if this happens, is that you contact us straight away — there are measures that help.

What we do in the consulting room is four things.

1. We look first at which muscles you use and how much. We look at you both when you tense and when you relax, and we look at the balance of the forehead and the glabella together
2. We start from the approved dose and sites. The numbers in the table above are the starting point
3. We see you once 2 weeks later. That is the point at which a judgement can be made
4. We tell you which product we are using. The approved indications differ from product to product

How men and women differ in dose and duration is written up further in What is different about lifting for men, and when you should begin to judge after a procedure in When things start to improve after a procedure.

Written and reviewed by Lee Chi-Hak, MD, medical director of Miso Clinic in Daegu, South Korea. Every study cited above is given together with its design, its size and the limitations the authors themselves recorded, and where we could not find data, we have said that we could not find any.