Contemplating tear trough injections? Considering a Botox brow lift? The latest data suggests that 73% of aesthetically-conscious consumers "expect to spend money on a physician-administered aesthetic treatment in the next year," so by virtue of the fact that you're on this site and reading this article, it stands to reason that you've probably thought about it.
If you've reached the research phase, it also stands to reason that you've come across one little hyphenated word over and over again: "off-label."
Many of today's most popular injectable offerings — the aforementioned tear trough fillers and Botox brow lifts, along with "liquid rhinoplasties," jawline reshaping and more — are classified as "off-label," meaning they haven't been through clinical trials and aren't technically approved by the Food and Drug Administration. Instead, these techniques were pioneered by independent injectors who, with raw materials in hand, went rogue.
Welcome to the wild, wild West of aesthetics.
To be fair, science isn't static. Medicine is constantly evolving, and cutting-edge innovations — from anti-inflammatories to fillers — are often built on uncharted territory. "Imagine the first person who ever injected Botox," muses Dr. Anna Guanche, a board-certified dermatologist and celebrity beauty expert based in Calabasas, Calif. "It's a toxin, it's a poison. It was 1971 and somebody injected freakin' poison into someone and we slowly, slowly got used to the idea that it's a purified toxin, and it's not going to give you botulism."
She tells Fashionista that "every new frontier has its terrifying stage," which is more or less true. But considering the fact that the "terrifying stage" of injectable experimentation takes place on your face, you should be fully aware of the risks (and rewards) before you go off-label.
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What Treatments Are Approved By The FDA?
On-label use is otherwise known as "approved treatment area" use. "An 'approved treatment area' means that a product has been evaluated and approved by the FDA to help a specific indication for that area," a representative for Allergan, the maker of Botox Cosmetic and Juvéderm, tells Fashionista. "In order for a treatment to receive FDA approval, it needs to prove its efficacy by meeting certain criteria defined within clinical trials."
Clinical trials can take years and cost millions of dollars — even billions, according to Dr. Guanche — so it's no surprise that there are fewer approved treatment areas than there are off-label options.
Botox Cosmetic and other neurotoxins are FDA-approved for the crow's feet, frown lines and forehead lines. Dermal fillers, including Juvéderm in its many forms — Ultra XC, Volbella XC, Voluma XC, et al. — have been cleared for use on the lips, nasolabial folds, cheeks and "moderate to severe facial wrinkles and folds," according to Allergan. Kybella, an injectable that destroys fat cells, is only approved for use under the chin.
Approved treatments still come with potential complications, which are thoroughly outlined in ads and on the pharmaceutical companies' websites. "The risks of Botox include droopiness, asymmetry, infection at the injection site, bruising and allergic reaction," Dr. Guanche summarizes. "The risks of filler include infection, bruising, allergic reaction, redness and swelling, vessel occlusion or blockage and poor cosmetic result." Most unfavorable outcomes involving fillers can be reversed by dissolving the filler with an enzyme treatment, if caught in time.
What Treatments Are Considered Off-Label?
"Off-label means the FDA hasn't approved the injectable for human use, but the doctor has determined it's OK to use it on a different area of the body, based on their knowledge of anatomy," Dr. Guanche explains. Essentially, once a pharmaceutical has been cleared for human use in any capacity, licensed medical practitioners have the right to determine the best way to employ said pharmaceutical based on the patient's needs.
This kind of carte blanche power is a holdover from a time long before injectables were a thing. "We've been doing this for many years; for example, antihistamines are approved for seasonal allergies, but we use them for eczema," Dr. Guanche says. "Tetracycline is approved for infectious diseases. Rosacea is not infectious, it's inflammatory, but we use it for that."
The dermatologist notes that since doctors go through at least eight years of medical training, they're deeply aware of the anatomy of the face — what nerves are where, what areas to avoid and so on. Based on this knowledge, it's common for doctors to extrapolate information from one clinical trial and apply it to a new use scenario. "As far as injectables, Kybella is for the double chin area and it's been studied extensively for faces — but we know it can get rid of little bulges of bra fat," Dr. Guanche says. "In this particular case, understanding there are more sensitive nerves in the chin and neck area, and Kybella is approved for that area, we can extrapolate and know it's OK for use in [a less-risky] area."
That's not exactly how most off-label experimentation works, though. Considering the common use of fillers in the tear troughs (right under the eyes) and liquid rhinoplasties (in the nose), it could be argued that the majority of off-label innovations, uh, swing the other way: They take clinical trial findings from one area of the face and apply that information to an area with significantly more risk.
Some popular off-label treatments include: Tear trough fillers; nose reshaping with fillers; the "Botox brow lift;" fillers around the jawline; neurotoxins around the jawline; "Baby Botox," a shallow injection of the material aimed at millennials; chin reshaping (with anything other than Kybella); Botox on the neck; the "Botox Lip Flip" and "skin Botox," an injection of Botox into the pores to tighten and create an air-brushed look. Basically, anything you need for an Instagram Face.
"Allergan does not promote or teach off-label uses of our products," the company says in a statement to Fashionista.
How Do Off-Label Treatments Start?
While the makers of substances like Botox and Juvéderm train doctors on how to administer these materials, they are legally only allowed to educate on the approved treatment areas.
When I heard this, I had a lot of questions: How do dermatologists come up with these new injectable creations, then? How do they know it’s going to work? Who do they experiment on? How does it all happen??
Dr. Guanche pauses. "Hmm, how does it happen?" She eventually explains that skilled injectors have an innate knowledge of both injectables and the anatomy, and trying something new isn't the terrifying process of trial-and-error I'm imagining. "I've been injecting for 16 years," she says. "I think I've injected 9,000 syringes of Juvéderm alone and I've probably done about 25,000 injectable procedures. All day, every day I’m injecting. I think it's a natural progression."
The board-certified dermatologist — who is Olivia Culpo's go-to dermatologist, by the way — is something of an innovator in the space. Besides offering an array of common off-label procedures in her practice, she's pioneered (and trademarked) the "GuancheLift," a technique she now independently teaches to other dermatologists. It involves injecting an off-label mix of Botox and Juvéderm around the lower face and neck and into the hairline, to "redistribute the jowls" and fake the effect of a face lift in about 30 minutes.
The idea materialized after her own consultation for a surgical face lift. The cost ($72,000) and the recovery time (six weeks) were far from ideal. "I thought, why don't we put fillers in some of those places and see if we can get the skin to lift?" she says. She revisited anatomy texts, analyzing the risks of injecting around the temples and above the mastoid bone. She found no history of vessel occlusion — the most serious risk of fillers — in those areas. "So I tried it on myself, and I was very happy," she says. Yup, Dr. Guanche is her own "patient zero," and doesn't offer anything to clients that she hasn't first attempted on herself.
Needless to say, this isn't how procedures are typically invented and tested. Off-label use is unregulated, and thus, so is off-label innovation. How injectors experiment, who they experiment on and how much of their experience — or lack thereof — with the procedure they disclose to the patient is left to their discretion.
"Ethics is something that's not mandated, and we see unethical behavior all over medicine," Dr. Marcelo Antunes, a double board certified facial plastic surgeon with The Piazza Center in Austin, Texas, tells Fashionista. "But if you're practicing on the edge, you're going to end up with unhappy patients."
Dr. Antunes notes that being up-front with patients about experience level and potential complications is the best policy (although not always the most common policy). "I can tell a patient, 'Hey, I've done this treatment only five times, but I really feel confident, I know this anatomy, these are the risks, and I think we can make an improvement here,'" he says. "People appreciate when you're honest and up-front."
The Risks of Off-Label Injectables
Dr. Guanche asserts that the risks of neuromodulators and fillers are pretty much the same no matter where you put them, which is true, if not a little misleading. Take vascular occlusion, for example, which is a fancy way to say "blocked blood vessel."
"If the injector pierces the blood vessel, or even if they don't go through and they put it next to the blood vessel and it 'kinks,' it could interrupt the blood flow," Dr. Antunes explains. "That could happen in a lot of areas." Juvéderm is approved for use on the lips, and "when you go into the lip and you occlude a blood vessel, the blood vessel on the other side basically goes in and supplies the area, because the blood vessels in the lips have this circular arcade, so to speak." Basically, even if a vascular occlusion does occur, the lips will be more or less fine. "But in certain areas, such as the nose and around the eyes, the stakes are very high due to the risk of blindness," Dr. Antunes says.
Vascular occlusion in these areas — a concern with tear trough fillers and liquid rhinoplasties — carries unique consequences. "The nose is an interesting area, because the blood supply to the nose doesn't have a big arcade, meaning if you interrupt a blood vessel in the nose, it's very possible the area has no blood supply, it's not going to get picked up by other areas," says Dr. Antunes. "If we're doing a nasal augmentation and we get into the blood vessel, that can really cause a problem for the skin that you wouldn’t get in other areas."
He notes that an occluded blood vessel in the nose area can prevent oxygen from getting through, which causes "death of the skin," or necrosis. The skin in the area could turn purplish or black, or develop a permanent divot or scar. "On the nose, this is a real tragedy, because it's not going to heal well," Dr. Antunes says. "We'd have to treat that with lasers or some sort of reconstructive procedure."
In rare and extreme cases, there's also the risk of blindness. This happens when blood flow to the eye is interrupted by an occlusion.
If the injector immediately notices that something doesn't seem right — say, the skin starts turning red or swelling — it can be reversed with the use of an enzyme to dissolve the filler. (Although in cases where blood flow to the eye is concerned, it is recommended for injectors to refer patients to an on-call ophthalmologist ASAP.) "Using an enzyme is also off-label, since it’s not medically approved for dissolving filler — it's for opening up the tissue so antibiotics can get in better," adds Dr. Guanche.
Luckily, these outcomes are exceedingly rare. One ten-year study published in 2014 showed that only 0.05% of filler treatments resulted in vascular occlusion. Dr. Guanche says she's seen "a true vessel occlusion" around once a year, and in her own practice, she's only seen blanching, an early sign of vessel occlusion twice in 15 years.
When it comes to the off-label use of Botox and other neuromodulators, the biggest risks include "over-freezing" a particular muscle or freezing a muscle you didn't want frozen. Here, poor outcomes can't be dissolved away like they can with filler, but they are, at least, temporary.
"The risks of neurotoxins are basically an excessive paralysis of the muscle, and all of a sudden you have an unwanted result," Dr. Antunes explains. "Meaning, you put Botox in your forehead and all of your sudden your brows get droopy. That could be either from oversensitivity or overdosing from the practitioner."
The other thing that can happen — which "is not very frequent" — is that the neurotoxin can be injected in the wrong place. "That could lead to paralysis of muscles that were not intended to be paralyzed," he says. The most common iteration of this is the accidental injection of the eyelid, leading to a droopy eye.
"There are two muscles that keep our eyelids open, and sometimes if the Botox is placed too close to the eyebrow [like with a 'Botox brow lift'] and a little seeps inside the eye, it affects that muscle," according to Dr. Antunes. "It's disconcerting, because it looks terrible, kind of like they had a stroke." He says that this can happen to even the best injectors, simply due to the nuances of individual anatomy, and sees it "maybe once a year" in his own practice.
More often, Dr. Antunes finds himself "fixing" poor injectable outcomes from local medispas. "We had a patient we saw that came in, and she had double vision — and the truth is, we were not even convinced the double vision was caused by the Botox," he shares. "I discussed it with my colleagues, and we agree it was more of a fluke or a coincidence." According to this scientific paper, only three cases of Botox-induced double vision have been reported.
"Botox, Dysport, they're incredibly safe, honestly," Dr. Antunes says. "It's almost impossible to create a problem that's a serious problem. But worst case, it isn't permanent anyway." Unintended muscle paralysis wears off in three to six months.
According to both dermatologists, the reason off-label injectables are such big business is precisely because they are so safe. "The market regulates that," says Dr. Antunes. "Let's say Botox had a very high risk of complications, you wouldn't see every other medispa doing Botox. When things are safe to do, then everybody jumps on board — because the truth is, there's very little they can do to mess it up."
What to Ask Before Getting an Off-Label Treatment
Dermatologists agree that although the risks associated with off-label offerings are pretty rare, you can further mitigate that risk by following a few safety guidelines.
First: Please, do not get your injectables done at a medispa. And definitely don't get them done at a party. "If you're at a medispa or somebody's party, they don't necessarily have the infrastructure in place to address [complications]," Dr. Guanche says, noting that a doctor's office should always have dissolving enzymes and other solutions on hand to treat poor outcomes ASAP.
Next, thoroughly research injectors in your area. You can learn a lot from Instagram comments and Yelp reviews, says Dr. Antunes. "Even with all of that information, I think the best thing is a face-to-face consultation," he adds. "Make sure you feel comfortable."
During the consultation, don't be hesitant to ask questions. Doctors do not legally have to disclose to you that they've never done a particular off-label injection before, or if you'd be their first — so be direct. After discussing the treatment plan, ask: Is this off-label? How often do you perform this procedure? Am I your first patient for this specific treatment? What measures do you have in place in case of complications? Oh, and you're a licensed injector, right?
"There should be warnings out there that off-label is higher-risk," Dr. Guanche says. "But when it's done in the hands of someone who's fully trained and has years and years of experience, it's less risky."