Botulinum toxin for glabellar lines: a review of the efficacy and safety of currently available products

Abstract

Facial rhytides represent a widespread aesthetic concern. In particular, glabellar lines are perceived as a sign of aging and may give an erroneous impression of negative emotions. The onset of glabellar lines is closely related to the movements of the underlying muscles. Botulinum toxins inhibit the release of acetylcholine into the synaptic cleft and therefore result in temporary muscle paralysis. The observation that botulinum toxin (BTX) smoothed facial lines when used therapeutically led researchers to study the toxin effect on glabellar lines. Nowadays, the use of BTX to smooth glabellar frown lines represents the leading procedure in aesthetic facial treatments and an increasing number of BTX formulations are becoming available. This article provides a comparative evaluation of currently available BTX options for the treatment of glabellar lines. Toxins have been divided into three groups, based on whether they have obtained approval for cosmetic use (approved treatments) or not (off-label treatments), or whether they are still under investigation (experimental treatments). We examine the basic similarities and differences between available botulinum toxins, and summarize the pharmacokinetics and dosing. All approved treatments consist of BTX type A (BTX-A) and differ in their molecular weight, as some formulations are made of a BTX-A complex of 900 kDa while the latest option on the market is a 150 kDa BTX-A that is free from complexing proteins. As for the dosage, the important aspect that emerges from this comparison is that even within a given serotype, such as BTX-A, formulations are not interchangeable as each possesses distinctive characteristics that are attributed to the unique toxin purification and manufacturing processes. There is a substantial body of published evidence on the use of these approved treatments for facial enhancement, proving efficacy and safety. We investigate the methods of evaluation used for each toxin and review the safety and efficacy data reported in the literature. Minor adverse effects, such as headache, blepharoptosis, and injection-site reactions, are relatively frequent but transient, whilst major adverse effects are rare. Some botulinum toxins, i.e. BTX type B, that are approved for therapeutic applications are used off-label for cosmetic indications, thus without the approval of the health regulatory committees and without sufficient published evidence on safety and efficacy. As for experimental treatments, a number of BTX products are currently in development or have been recently launched for aesthetic applications. These products have been specifically designed to overcome some of the limitations present in the older generation of products. However, some of these toxins may be easily purchased via the Internet, without having any license or approval for cosmetic or therapeutic indications; these products must be considered unsafe and are potentially a severe health risk for patients.