Botulinum toxin injection

Botulinum toxin, or botulinum neurotoxin (commonly called botox), is a neurotoxic protein produced by the bacterium Clostridium botulinum and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction, thus causing flaccid paralysis. This toxin causes the disease botulism, and is also used commercially for medical and cosmetic purposes. New types are occasionally found.

Botulinum toxins are among the most potent toxins known to science. A little goes a long way.

Botulinum Toxin Info Dump

Cosmetic Uses

Botulinum toxin injected in the face:

In cosmetic applications, botulinum toxin is considered relatively safe and effective for reduction of facial wrinkles, especially in the uppermost third of the face.

Commercial forms are marketed under the brand names Botox Cosmetic/Vistabel from Allergan, Dysport/Azzalure from Galderma and Ipsen, Xeomin/Bocouture from Merz, Jeuveau/Nuceiva from Evolus, manufactured by Daewoong in South Korea.

The effects of botulinum toxin injections for glabellar lines ('11's lines' between the eyes) typically last two to four months and in some cases, product-dependent, with some patients experiencing a longer duration of effect of up to six months or longer.

Injection of botulinum toxin into the muscles under facial wrinkles causes relaxation of those muscles, resulting in the smoothing of the overlying skin.

Smoothing of wrinkles is usually visible three to five days after injection, with maximum effect typically a week following injection.

Muscles can be treated repeatedly to maintain the smoothed appearance.

Daxxify Studies

DaxibotulinumtoxinA (Daxxify) was approved for medical use in the United States in September 2022. It is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines (wrinkles between the eyebrows). DaxibotulinumtoxinA is an acetylcholine release inhibitor and neuromuscular blocking agent. The FDA approved daxibotulinumtoxinA based on evidence from two clinical trials (Studies GL-1 and GL-2), of 609 adults with moderate to severe glabellar lines. The trials were conducted at 30 sites in the United States and Canada. Both trials enrolled participants 18 to 75 years old with moderate to severe glabellar lines. Participants received a single intramuscular injection of daxibotulinumtoxinA or placebo at five sites within the muscles between the eyebrows. The most common side effects of daxibotulinumtoxinA are headache, drooping eyelids, and weakness of facial muscles.

Letybo Studies

LetibotulinumtoxinA (Letybo) was approved for medical use in the United States in February 2024. It is indicated to temporarily improve the appearance of moderate-to-severe glabellar lines. The FDA approved letibotulinumtoxinA based on evidence from three clinical trials (BLESS I [NCT02677298], BLESS II [NCT02677805], and BLESS III [NCT03985982]) of 1,271 participants with moderate to severe wrinkles between the eyebrows for efficacy and safety assessment. These trials were conducted at 31 sites in the United States and the European Union. All three trials enrolled participants 18 to 75 years old with moderate to severe glabellar lines (wrinkles between the eyebrows). Participants received a single intramuscular injection of letibotulinumtoxinA or placebo at five sites within the muscles between the eyebrows. The most common side effects of letibotulinumtoxinA are headache, drooping of eyelid and brow, and twitching eyelid.

Economics

In 2020, 4,401,536 botulinum toxin Type A procedures were administered. In 2019 the botulinum toxin market made US$3.19 billion.

Botox cost is generally determined by the number of units administered (avg. $10–30 per unit) or by the area ($200–1000) and depends on expertise of a physician, clinic location, number of units, and treatment complexity

The history of botulinum toxin for cosmetic uses

The effect of botulinum toxin type-A on reducing and eliminating forehead wrinkles was first described and published by Richard Clark, MD, a plastic surgeon from Sacramento, California. In 1987 Clark was challenged with eliminating the disfigurement caused by only the right side of the forehead muscles functioning after the left side of the forehead was paralyzed during a facelift procedure. This patient had desired to look better from her facelift, but was experiencing bizarre unilateral right forehead eyebrow elevation while the left eyebrow drooped and she emoted with deep expressive right forehead wrinkles while the left side was perfectly smooth due to the paralysis. Clark was aware that botulinum toxin was safely being used to treat babies with strabismus and he requested and was granted FDA approval to experiment with botulinum toxin to paralyze the moving and wrinkling normal functioning right forehead muscles to make both sides of the forehead appear the same. This study and case report on the cosmetic use of botulinum toxin to treat a cosmetic complication of a cosmetic surgery was the first report on the specific treatment of wrinkles and was published in the journal Plastic and Reconstructive Surgery in 1989. Editors of the journal of the American Society of Plastic Surgeons have clearly stated "the first described use of the toxin in aesthetic circumstances was by Clark and Berris in 1989."

J. D. and J. A. Carruthers also studied and reported in 1992 the use of botulinum toxin type-A as a cosmetic treatment. They conducted a study of participants whose only concern was their glabellar forehead wrinkle or furrow. Study participants were otherwise normal. Sixteen of seventeen participants available for follow-up demonstrated a cosmetic improvement. This study was reported at a meeting in 1991. The study for the treatment of glabellar frown lines was published in 1992. This result was subsequently confirmed by other groups (Brin, and the Columbia University group under Monte Keen). The FDA announced regulatory approval of botulinum toxin type A (Botox Cosmetic) to temporarily improve the appearance of moderate-to-severe frown lines between the eyebrows (glabellar lines) in 2002 after extensive clinical trials. Well before this, the cosmetic use of botulinum toxin type A became widespread. The results of Botox Cosmetic can last up to four months and may vary with each patient. The US Food and Drug Administration (FDA) approved an alternative product-safety testing method in response to increasing public concern that LD50 testing was required for each batch sold in the market.

Botulinum toxin type-A has also been used in the treatment of gummy smiles; the material is injected into the hyperactive muscles of upper lip, which causes a reduction in the upward movement of lip thus resulting in a smile with a less exposure of gingiva. Botox is usually injected in the three lip elevator muscles that converge on the lateral side of the ala of the nose; the levator labii superioris (LLS), the levator labii superioris alaeque nasi muscle (LLSAN), and the zygomaticus minor (ZMi).

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