Botulinum toxin (“Botox”) for expression lines

What botulinum toxin is and how it works

Botulinum toxins prevent nerve endings from releasing acetylcholine, the messenger that gives the muscle the signal to contract. The result is a temporary, partial paralysis of the injected muscle; in glands, the same mechanism dampens sweat production. Against lines, this works where facial expressions fold the skin again and again: between the eyebrows (glabellar or frown lines), at the outer corners of the eyes (crow’s feet) and on the forehead.

According to the US prescribing information, the effect sets in one to two days after the injection, increases during the first week and lasts about three to four months for frown lines. After that, the muscle contracts again as before. The products differ, and their units cannot be converted into one another. For anyone interested in skin ageing as a whole: other procedures target the skin structure itself, for example laser, microneedling and radiofrequency or tretinoin; botulinum toxin, by contrast, acts on the muscle beneath the line.

What the studies show

Guo 2015 — meta-analysis on frown lines

Seven randomized, placebo-controlled, double-blind trials from 2002 to 2014 with 1,474 participants, all with 20 units. The relative risk of a response as rated by the investigators was 33.54, for the lines at rest 5.88. In no trial did the frequency of side effects differ between treatment and placebo.

US approval trials — how long it works

Two identically designed double-blind trials with 405 treated and 132 placebo participants aged between 18 and 75. A responder was anyone whose frown line on frowning was only absent or mild. After 30 days this applied to 80 percent of those treated and 3 percent of the placebo group, after 90 days to 48 versus 2 percent, after 120 days to 25 versus 2 percent. People aged 65 and over responded less often than younger people.

Li 2023 — products compared

A network meta-analysis of randomized trials on onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, prabotulinumtoxinA and daxibotulinumtoxinA. All were far superior to placebo. DaxibotulinumtoxinA performed best for the proportion with at least one point of improvement; in side effects the products did not differ.

Binder 2006 — twins over 13 years

A case report on identical twin sisters: one was treated on the forehead and frown line two to three times a year for 13 years, the other only twice. In the regularly treated sister, no etched lines at rest were visible on the forehead and glabella, in the other they were; untreated facial regions aged equally in both. It is a single pair, without measurement and without blinding.

Schulze 2021 — mood and depression

The starting point is the idea that facial expression feeds back on mood. In five randomized trials, depressive symptoms improved more after injection into the frown line than after placebo injection, pooled effect size d equal to 0.98. The authors themselves name methodological limitations; botulinum toxin is not approved for this purpose.

Where the data stop

The studies measure whether a line is less visible after a treatment, and over weeks to months. What they do not answer: whether regular treatments from the mid-twenties, often called “prejuvenation” or “baby Botox”, slow skin ageing in the long term. For this there is no controlled long-term study, but the case report of a single pair of twins. Botulinum toxin is not intended for, and not studied for, facial ageing as a whole – volume, elasticity, pigment.

Safety over decades of repeated treatments has also hardly been recorded systematically; the FDA’s reporting data are incomplete because doctors do not report side effects completely, and many reports concerned uses outside the prescribing information, for example in dose, dilution or storage. The effect on mood is an interesting research question with small studies, not an established treatment.

Status, approval and legal

In Germany, botulinum toxin type A and B is prescription-only (German Ordinance on Prescription-Only Medicines, Annex 1). According to the Dear Doctor letter (Rote-Hand-Brief), agreed with the Federal Institute for Drugs and Medical Devices (BfArM), the products may only be used by physicians with appropriate experience. There are several approved products, some for neurological, some for cosmetic indications; which lines a product covers is stated in its prescribing information.

The US approval shows the range: cosmetically, onabotulinumtoxinA is approved for the temporary improvement of moderate to severe frown lines, crow’s feet, forehead lines and neck bands (platysma). For frown lines, 20 units are provided there, distributed over five injection sites; treatment more often than every three months has not been tested. Medically, it is approved among other things for overactive bladder, for the prevention of chronic migraine with at least 15 headache days a month, for spasticity, cervical dystonia, severe underarm sweating, eyelid spasm and squint. Aesthetic treatments are paid for out of pocket.

Safety

In the approval trials, the most common side effects were a drooping upper eyelid with frown lines (3 percent), eyelid swelling with crow’s feet (1 percent), and headache (9 percent) and a lowered eyebrow (2 percent) with forehead lines. In addition there are the usual consequences of an injection such as pain, redness and bruising. Treatment must not be given in case of allergy to any of the ingredients or an infection at the injection site.

All botulinum toxins carry a warning: very rarely the effect spreads beyond the injection site, with muscle weakness, difficulty swallowing, speaking or breathing, up to deaths. The risk is greatest with high doses in neurology and in people with pre-existing neurological conditions or swallowing disorders. Under cosmetic use, the FDA reported no deaths and 36 serious events up to 2003, 30 of which were known as a possible complication.

The greatest avoidable risk lies outside the doctor’s practice: in 2024, seven women in the USA fell ill after injections in non-medical settings, with drooping eyelids, difficulty swallowing and shortness of breath among other symptoms; four had to go to hospital, and at least four had probably received a counterfeit product.

Sources

• Guo et al., Plast Reconstr Surg 2015 (meta-analysis, glabellar lines)
• Li et al., Aesthetic Plast Surg 2023 (network meta-analysis of the products)
• FDA, prescribing information onabotulinumtoxinA cosmetic (DailyMed, as of 10/2024)
• FDA, prescribing information onabotulinumtoxinA medical (DailyMed, as of 02/2026)
• German Ordinance on Prescription-Only Medicines (AMVV), Annex 1 (Clostridium botulinum toxin)
• Dear Doctor letter (Rote-Hand-Brief) on botulinum toxin products, 2007 (AkdÄ archive)
• Coté et al., J Am Acad Dermatol 2005 (FDA reports of adverse events)
• Thomas et al., MMWR 2024 (counterfeit botulinum toxin, Tennessee and New York)
• Schulze et al., J Psychiatr Res 2021 (depression, meta-analysis)
• Binder, Arch Facial Plast Surg 2006 (twin case report)