Tox Outside the Box: Off-Label Aesthetic Uses of Botulinum Toxin

The FDA approves drugs and devices based on scientific data to prove efficacy with an acceptable safety profile. Double blinded, placebo controlled studies are conducted by pharmaceutical companies and are the gold standard to gain commercial release of their drug. Such studies are very rigorous and defined, with no variation allowed between test study sites, patients, or physicians. In other words, no creativity is allowed. When the drug or device is ultimately released with FDA approval, it is for a specific indication and exact dosage with strict adherence to the “label”, which the company can promote to and educate physicians or advertise to patients via direct-to-consumer advertisements. Doctors, however, can legally recommend and utilize these approved and legally prescribed drugs and devices in any manner they deem safe and appropriate. Such use is called “off-label”. The FDA controls the pharmaceutical industry, but not the free practice of medicine in the United States by licensed physicians, and in some cases, lower level medical care providers. Many creative and talented physicians use these drugs and devices in many ways quite different from the FDA label.

When onobotulinumtoxinA was FDA approved in 2002 for glabellar frown line improvement, it was already being used for quite some time in an aesthetic “off-label” manner, since it was originally intended for blepharospasm and strabismus. The new package insert called for 5 very specific injection points into the corrugator and procerus muscles, injecting a total of 20 units using a 2.5cc sterile, non-preserved, normal saline reconstitution. Many experienced doctors were already using 1cc or 2cc reconstitution volumes with good success and felt no need to alter their formula and as such, became the first to use the toxin in a manner technically beyond the package insert. Countless other changes and variations were to follow as experienced injectors began to think outside the box provided by the FDA. Soon after, besides injection volume variations, it was noted that substitution of sterile preserved saline for reconstitution provided a decrease in pain with no change in efficacy.¹ This too was technically “off label”. The use of botulinum toxin in areas not approved for treatment led to the clinical trials that ultimately resulted in FDA approval for crow’s feet in 2013. The advantage to the sponsoring company was the ability of sales people to promote this new indication and the ability for company-sponsored trainings to include a second area for injection in the teaching sessions. Many physicians choose competing botulinum toxins (abobotulinumtoxinA, which was FDA approved for only glabellar use in 2009 and IncobotulinumtoxinA received glabellar clearance in 2011) for the treatment of their patients’ crow’s feet with success even though those products have not undergone the stringent FDA approval process for this second area.

The real artistry of facial rejuvenation with injectable neuromodulators involves so much more than softening crow’s feet and preventing frowning. Brow shaping, eyebrow lifting, opening the aperture of the eye, decreasing the mouth frown, defining a jaw line, increasing lip show, decreasing gummy smile, reducing the bar code lines around the mouth, lifting the nose tip, eliminating the “golf ball” chin, reducing platysma bands, and softening the squared, masculine jaw are all finesse treatments that turn us from aesthetic physicians into artists. To do this well, the physician needs to understand anatomy, the movement of muscles in isolation and in relation to other muscles, the concept of compensatory strengthening (as important sometimes as muscle weakening), and be observant evaluators of each individual patient’s presentation at rest as well as with normal and exaggerated animation. There is no painting by numbers when it comes to artistry with injections. Every face is unique. I don’t inject the same patient each time exactly the same, so the differences from patient to patient can be quite wide.

The brows are critical to the unspoken messages females send to others. Low medial brows, even without furrowed wrinkles, signal hostility and anger. Neurotoxin injection into the glabellar complex can have significant impact on brow height and position sometimes resulting in a pleasing look and sometimes not (Figures 1 and 2). ² This is why it is so critical to avoid the medial frontalis fibers that lie superficial to the corrugators when the frown complex is injected. Since I have been teaching toxin injections at Tulane since 1996, I can attest that this is the most common mistake novice injectors make. By the same token, lower lateral brows from injection of the lower lateral frontalis fibers (or by natural brow shape pattern) can signal uncertainty, concern, or distress. It is important for the female brow to be arced and arched in a feminine and