Treatment of glabellar lines with Botox (onabotulinumtoxinA): Development, insights, and impact

OnabotulinumtoxinA is an injectable medication that produces muscle relaxation through local chemical denervation at the neuromuscular junction. Discovery of onabotulinumtoxinA's aesthetic benefits occurred serendipitously in the 1980s at the intersection of several medical disciplines, including ophthalmology, neurology, otolaryngology, and dermatology. Patients receiving onabotulinumtoxinA for blepharospasm, hemifacial spasm, and dystonia noticed their periorbital wrinkles disappearing, particularly frown lines between the eyebrows called glabellar lines (GL). Aesthetic use of onabotulinumtoxinA necessitated rigorous training programs and vigilant monitoring by Allergan. Approval for the GL indication was based on 2 similarly designed, double-blind, randomized, multicenter clinical studies. Subjects with moderate to severe GL receiving onabotulinumtoxinA achieved significantly greater improvement in GL severity than those receiving placebo. In subsequent studies, more than 80% of subjects were satisfied with onabotulinumtoxinA treatment through day 60, and many reported looking approximately 4 years younger at weeks 4 and 12 than at baseline. OnabotulinumtoxinA has a rapid onset of action, and peak effect occurs between 30 and 60 days. The median duration of response for dynamic GL in the initial studies was 120 days and response progressively improved with subsequent treatments. OnabotulinumtoxinA was well tolerated, and the 2 most common adverse events, headache and blepharoptosis, tended to decrease in frequency with repeat treatment. The novel use of onabotulinumtoxinA for treating GL was an important step in addressing the clinical need for a noninvasive, straightforward, office-based procedure for facial lines that also left patients extremely satisfied with its treatment effects and represented the beginning of its widespread use for numerous aesthetic indications.