Clinical use of
onabotulinumtoxinA evolved based on strategic, hypothesis-driven applications, as well as serendipitous observations by physicians and patients. The success of
onabotulinumtoxinA in
blepharospasm and
strabismus led to its study in other head and neck dystonias, followed by
limb dystonia,
tremor, and spasticity. The aesthetic use of
onabotulinumtoxinA followed initial reports from patients of improved facial lines after
injections for facial dystonias and
hemifacial spasm. Although patients with dystonias and spasticity regularly reported that their local
pain improved after
injections,
onabotulinumtoxinA was not systematically explored for chronic
migraine until patients began reporting
headache improvements following aesthetic
injections. Clinicians began assessing
onabotulinumtoxinA for facial sweating and
hyperhidrosis based on its inhibition of
acetylcholine from sympathetic
cholinergic nerves. Yet another line of research grew out of
injections for laryngeal
dystonia, whereby clinicians began to explore other sphincters in the gastrointestinal tract and eventually to treatment of pelvic sphincters; many of these sphincters are innervated by autonomic nerves. Additional investigations in other autonomically mediated conditions were conducted, including
overactive bladder and neurogenic detrusor overactivity,
achalasia,
obesity, and postoperative
atrial fibrillation. The study of
onabotulinumtoxinA for depression also grew out of the cosmetic experience and the observation that relaxing facial muscle contractions associated with negative emotions may improve mood. For approved indications, the safety profile of
onabotulinumtoxinA has been demonstrated in the formal development programs and post-marketing reports. Over time, evidence has accumulated suggesting clinical manifestations of systemic effects, albeit uncommon, particularly with high doses and in vulnerable populations. Although
onabotulinumtoxinA is approved for approximately 26 indications across multiple local regions, there are 15 primary indication uses that have been approved in most regions, including the United States, Europe, South America, and Asia. This review describes many uses for which AbbVie has not sought and/or received regulatory approval and are mentioned for historical context only.