Once perceived as the deadliest substance known to man, botulinum toxin (BT) is now known for its role in improving patient quality of life in many aspects of health care. Clinical uses for botulinum toxin-A extend far beyond cosmetic procedures, such as smoothing facial lines, that it is best known for; BT’s ability to block neuromuscular transmission is used to manage hyperhidrosis, chronic migraine, urinary incontinence, cervical dystonia, and more.
Botulinum Toxin: a History
Produced from the gram-positive bacterium Clostridium botulinum, BT is the neurotoxin responsible for botulism. While there are 8 types of BT (A, B, C1, C2, D, E, F, and G), only serotypes A and B can cause illness and have clinical applications.1 Once researchers discovered BT’s toxicity, it was considered for use as a biological weapon during World War II.2 Modern use of BT as a medical treatment began in the early 1970s when clinicians began using the type A serotype to treat strabismus.3
The FDA approved onabotulinumtoxinA for various uses including strabismus, hemifacial spasm, and blepharospasm in 1989; 13 years later, the FDA approved BT for cosmetic purposes.3
Since BT causes weakness and paralysis of the implicated muscle, it can be useful in conditions where muscle hyperactivity is the root cause.1 The neuromuscular blocking cascade caused by BT occurs in 4 steps. Step 1 includes binding to nerve cells. Step 2 is the uptake of BT by endocytic vesicles via ATPase proton pumps. Step 3 occurs as the vesicular lumen becomes acidic, altering the structure, and translocating BT into the cytosol. Once in the cytosol, step 4 occurs when it is catalyzed. These steps all cause the inhibition of acetylcholine,2 an important player as an excitatory neurotransmitter located within neuromuscular junctions.4
Botulinum Toxin Preparations
Injecting BT can be done in an outpatient setting; when injected, BT takes approximately 2 to 3 days to take effect, and up to 2 weeks in some cases. The effects will last around 3 months depending on the patient, dosage, technique, and strength of the muscle. It is important that patients understand that BT injections are a temporary treatment.1
The most common preparations of BT — onabotulinumtoxinA, abobotulinumtoxinA, and incobotulinumtoxinA — can each be stored for up to 24 hours after they are reconstituted with 0.9% sodium chloride. While abobotulinumtoxinA is supplied in 300 or 500 unit vials,5 both onabotulinumtoxinA and incobotulinumtoxinA are distributed in 50, 100, or 200 units per vial.6,7
Treating Facial Lines With Botulinum Toxin
The most common areas to have lines and wrinkles include the forehead, glabella (frown lines), and around the eyes, all FDA approved indications. When BT is injected into the frontalis muscle, there is risk of temporary blepharoptosis and eyebrow ptosis; this risk decreases with improved technique from the injector.8
The lateral orbicularis oculi should be targeted to treat crows feet.8 Patients with dynamic wrinkles, meaning they are only present on muscle contraction, will benefit most from BT injections compared with those with wrinkles present at rest, who will require multiple treatments and maintenance for optimal results.9
Treating Primary Headaches With Botulinum Toxin
In Germany, there were case reports that injections of BT into muscles involving the neck and head to alleviate tension-type headaches.10 In 2010, BT was reported to be an effective agent in the management of chronic migraines via the Phase 3 Research Evaluative Migraine Prophylaxis Therapy trials.11
Botulinum toxin is injected in 5-unit increments in the glabellar, frontal, temporal, occipital, upper cervical, and trapezius areas.12 Extra BT can be injected into temporal, occipital, and trapezius areas to target specific locations of headaches.12
Evidence has shown that patients who receive BT for chronic migraine treatment earlier during their condition have increased likelihood for remission in the future.13
BT injections are often better tolerated by patients compared to oral migraine medications, and BT has also been tested in other headache conditions including trigeminal neuralgia, tension headaches, and headache from temporomandibular disorder.12
Treating Hyperhidrosis With Botulinum Toxin
Hyperhidrosis, an idiopathic condition which involves excess sweating, can be treated with BT. For treatment of hyperhidrosis, BT is administered intradermally in multiple injections. While treatment of axillary hyperhydrosis is an FDA-approved indication for BT, treatment of palmar or plantar hyperhidrosis are off-label uses. BT is a second-line treatment for patients with hyperhidrosis after topical treatments have been tried. BT blocks autonomic innervation of sweat glands; this effect lasts 3 to 6 months.14 In a study that followed up with patients treated with BT 5 years after treatment, patients had a significant improvement in quality-of-life outcomes.15
Treating Depression With Botulinum Toxin
Treating Urinary Incontinence With Botulinum Toxin
One of the first FDA-approved uses of BT was treating urinary incontinence. Botulism toxin can be used to cause chemical denervation to the detrusor muscle, responsible for contraction during urination, which pushes urine from the bladder into the urethra.18 Injections of BT into the detrusor muscle have been shown to decrease the frequency of urinary incontinence episodes.19 The benefits of BT may last up to 9 months, far longer than most BT injections. This treatment does however require a higher dosage when compared to other applications, around 200-300 units are necessary to see results.18
Treating Temporomandibular Dysfunction With Botulinum Toxin
Safety Considerations for Botulinum Toxin
Contraindications to BT include allergy, pregnancy, breastfeeding, body dysmorphic disorder, keloidal scarring, and neuromuscular disorders. The median lethal dose of BT is 1 to 3 nanograms per kilogram of body weight. Treatment for toxicity is antitoxin or vaccine. Although adverse effects are typically moderate, it is important for providers to be aware and provide education to patients receiving BT. Minor adverse effects include bruising, edema, and pain. Moderate adverse effects may include blepharoptosis or eyebrow ptosis lasting up to 3 months. Most adverse effects are dependent on the provider and their training. Allergic reactions are rare, but range from rashes to anaphylaxis.22
Key Takeaways on Clinical Uses for Botulinum Toxin
Olivia Jose BSN, RN, is affiliated with Brooks College of Health, University of North Florida in Jacksonville, Florida.
This article originally appeared on Clinical Advisor
