Botox Injections and Side Effects

BOTOX AND SIDE EFFECTS

Botulinum toxin is derived from bacteria and is used in injection form that is available in different types. The subtypes of Botox are A, B, C1, D, E, F, and G. Clinically, toxins A and B are the ones used. Formulations of Botox types A include onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and prabotulinumtoxinA. The mechanism of action of Botox is that it inhibits acetylcholine release from peripheral nerve cells, which suppresses muscle contraction. Botox has been used in different cosmetic settings. This includes facial lines and wrinkles, forehead lines, crow's feet, frown lines, nasal flares, and gummy teeth. In addition, Botox A has also been approved to treat chronic migraines. It is injected into multiple sites on the head and neck, every 3 months. It has been approved for patients 18 years and older with migraine days for more than half the month (15 days or more). Botox type B, available as RimabotulinumtoxinB, is mainly used for cervical dystonia, which is involuntary neck muscle contractions. Evidence has also shown the effectiveness of Botox in the treatment of hyperhidrosis. Overactive bladder and urinary incontinence can also be treated with Botox. Once receiving the Botox injection, the results begin to show in one to three days. However, peak results occur one to four weeks post-injection. The duration of the injection depends on dose, formulation, and injection site, but it typically lasts for three or four months. After multiple injections at the same site, results can last for at least six months. If the desired outcome is not achieved with Botox alone, it can be combined with cosmetic fillers, lasering, micro-focused ultrasounds, or facial surgeries.

People who should not receive a Botox injection are those with an infection, psoriasis, or eczema on the site of desired infection and those with allergies to any of the ingredients inside Botox. People with cow's milk protein allergies should not be injected with AbobotulinumtoxinA but can receive injections of onabotulinumtoxinA, incobotulinumtoxinA, or rimabotulinumtoxinB. Patients with neurological disorders, such as myasthenia gravis or Eaton-Lambert syndrome, can experience severe muscle weakness. Increased muscle fatigue can be seen in patients taking gentamycin, amikacin, tobramycin, and neomycin. Pregnant women should not receive OnabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and rimabotulinumtoxinB injections, however, not enough evidence is available in regard to prabotulinumtoxinA. Side effects include pain and bruising from the injection site, which may be treated with ice or topical analgesics. After multiple injections, muscle atrophy, or muscle waste, can occur. If the facial Botox diffuses and spreads, it can cause brow and eye drooping, teary eyes, and double vision. Other symptoms that can be seen include facial paralysis, pneumonia, respiratory compromise, difficulty swallowing, and headaches. Botulism, which is bacterial food poisoning, can occur as well. Speaking with your doctor is the best way to see if Botox is right for you. Be sure to inform the doctor of allergies, disorders, medications, and if you are taking contraceptives or are pregnant.

Althawadi N, Ujam A, Visavadia B. Botox hidden dangers. Br Dent J. 2022 Feb;232(4):192-193. doi: 10.1038/s41415-022-4006-3. PMID: 35217725.

Botox for chronic migraine. Drug Ther Bull. 2011 Feb;49(2):22-4; quiz iii-iv. doi: 10.1136/dtb.2010.10.0008. PMID: 21304165.

Brin MF, Burstein R. Botox (onabotulinumtoxinA) mechanism of action. Medicine (Baltimore). 2023 Jul 1;102(S1):e32372. doi: 10.1097/MD.0000000000032372. PMID: 37499078; PMCID: PMC10374191.

Overactive bladder (OAB) is a common condition that affects millions of women worldwide. It is characterized by symptoms such as frequent urination, sudden urges to urinate, and involuntary leakage. While various treatment options exist, recent advancements have shown promising results in the use of Botox injections as an effective treatment for overactive bladder in women. 

Botox, also known as onabotulinumtoxin A, is a neurotoxin derived from the bacterium Clostridium botulinum. It works by temporarily paralyzing or relaxing the muscles where it is injected. In the case of OAB, Botox is administered directly into the bladder muscle. By inhibiting the release of acetylcholine, a neurotransmitter that stimulates muscle contractions, Botox helps to calm the overactive muscles of the bladder, reducing the frequency of urgency and incontinence episodes. The use of Botox for OAB in women has shown several significant benefits. Firstly, it provides long-lasting relief. Unlike oral medications that require daily intake, Botox injections provide relief for several months. This reduces the need for frequent medication management and enhances patient compliance. Additionally, Botox has been found to significantly reduce the number of daily voids, episodes of urgency, and incontinence episodes, leading to improved urinary control and overall quality of life. Numerous clinical trials and studies have demonstrated the efficacy and safety of Botox for OAB in women. One study published in The New England Journal of Medicine reported that Botox injections reduced daily voids by an average of three episodes, urgency episodes by 70%, and incontinence episodes by 50%. The treatment was well-tolerated, with only minimal side effects, including temporary urinary retention and urinary tract infections, which were easily managed. The impact of Botox treatment for OAB extends beyond symptom relief. Women who suffer from overactive bladder often experience a diminished quality of life, including social embarrassment, anxiety, and limitations in daily activities. Botox injections have been shown to improve these aspects significantly, allowing women to regain control over their bladder function and participate more fully in their personal and professional lives. Increased confidence and self-esteem are commonly reported benefits.

While Botox injections for OAB in women have shown remarkable efficacy and safety, several considerations should be taken into account. Firstly, Botox treatment is typically recommended after conservative treatments, such as lifestyle modifications and oral medications, have proven ineffective. Secondly, as with any medical intervention, it is important to discuss potential risks and benefits with a healthcare professional to make an informed decision. Future directions for the use of Botox in OAB treatment involve optimizing injection techniques and dosages to maximize effectiveness while minimizing side effects. Research is also ongoing to explore the use of Botox for other bladder-related conditions, such as neurogenic bladder and interstitial cystitis, to further expand treatment options for women suffering from these conditions.

Botox injections have emerged as a game-changer in the treatment of overactive bladder in women. By targeting the overactive muscles of the bladder, Botox provides long-lasting relief and improves urinary control, leading to enhanced quality of life for women who have been burdened by OAB symptoms. With its proven efficacy and safety profile, Botox is still considered a last line agent and should not be the first route in treatment. We can aide in the decision making with patients by giving them the risks and benefits and hoping they can make an informed decision 

Resources 

“A Study of the Effectiveness of Transvaginal Administration of Botulinum-a Toxin for the Treatment of Women with over Active Bladder (OAB) Syndrome.” Mayo Clinic, 16 July 2022, www.mayo.edu/research/clinical-trials/cls-20359596.

Since BOTOX (onabotulinumtoxinA) was first approved by the FDA in 1989 for two rare eye muscle disorders - blepharospasm and strabismus in adults - new indications have been developed and approved. OnabotulinumtoxinA is now FDA-approved for 12 therapeutic indications, including chronic migraine, overactive bladder, leakage of urine (incontinence) due to overactive bladder caused by a neurologic condition in adults, cervical dystonia, adult and pediatric spasticity, severe underarm sweating (axillary hyperhidrosis), and pediatric detrusor overactivity associated with a neurologic condition.

On April 15, 2002, the FDA approved BOTOX® as a temporary cosmetic treatment for moderate to severe frown lines in adults and requested the product be marketed as BOTOX® Cosmetic to distinguish cosmetic from therapeutic uses. BOTOX Cosmetic is a prescription medicine that has 3 FDA-approved areas - moderate to severe forehead lines, lateral canthal lines, and/or glabellar lines. It was the first treatment of its kind and today is the only product FDA approved to make moderate to severe frown lines, crow’s feet, and forehead lines look better in adults.

In general, the clinical effects of botulinum toxin begin to appear in one to three days, peak in one to four weeks, and gradually decline after three to four months. However, the duration of response is dependent upon the injection site, dose, and specific formulation of botulinum toxin utilized. Some patients, particularly those who have received repeated injections in the same area, may experience benefits for six months or longer. This may be at least partially due to the development of muscle atrophy.

When patients are appropriately selected and proper dosing and injection techniques are utilized, the use of botulinum toxin for cosmetic indications appears to be relatively safe. Side effects are usually mild and transient and most commonly include swelling or bruising at the injection site, mild headache, or flu-like symptoms . Undesired impairment of muscle function may also occur, but is usually associated with poor injection technique or inappropriate patient selection. Because smaller doses are less likely to cause unintended adverse effects, a conservative approach to treatment is advisable.

Examination of the available data on botulinum toxin reveals an impressive safety record. The authors of a 2004 systematic review and meta-analysis of randomized trials (n = 1425) found no reports of serious adverse effects in patients treated with onabotulinumtoxinA for medical or cosmetic purposes. Serious adverse effects reported to the FDA have also been low in number; between 1989 and 2003, only 36 serious adverse effects associated with cosmetic use were reported. Examples of the serious adverse effects that were documented included injection site reactions, headache, focal facial paralysis, muscle weakness, flu-like symptoms, dysphagia, respiratory compromise, cardiac arrhythmia, seizure, ocular abnormalities, and allergic reactions. Of note, 13 of the patients who experienced serious adverse effects had underlying medical conditions that may have contributed to the observed event (eg, respiratory compromise in a patient with asthma and cardiac arrhythmia in a patient with a history of heart murmur).

Although the risk of serious adverse effects is low with cosmetic use, side effects such as aspiration, dysphagia, pneumonia, anaphylaxis, botulism, and death have been reported in association with the use of botulinum toxin. As a result, in 2009, the US FDA instituted a requirement for boxed warnings on product labels and a Risk Evaluation and Mitigation Strategy for all botulinum toxin products.

Since the effect of botulinum toxin is temporary, patients require additional treatment to maintain improvement. The safety of repetitive treatment with botulinum toxin was evaluated in a retrospective study of more than 4000 treatments in 945 patients treated for lines in the upper face. Patients had to have received a minimum of three consecutive treatment cycles. Only mild to moderate adverse effects were detected; bruising and ptosis were most common. In addition, the incidence of side effects decreased with repeated injections, a finding that has been reported in studies of the medical use of botulinum toxin type A. Repeat injections with abobotulinumtoxinA have also been well tolerated in large open label studies.

References:

1. BOTOX® Cosmetic (Boe-tox) (onabotulinumtoxinA) for Injection. (2021, February). U.S. Food and Drug Administration. Retrieved from https://www.rxabbvie.com/pdf/botox_medguide.pdf

2. Carruthers, J. (2022, November 8). Overview of botulinum toxin for cosmetic indications. UpToDate. Retrieved from uptodate.com/contents/overview-of-botulinum-toxin-for-cosmetic-indications#H522914

3. Naumann M, Jankovic J. Safety of botulinum toxin type A: a systematic review and meta-analysis. Curr Med Res Opin 2004; 20:981.

4. Rzany B, Dill-Müller D, Grablowitz D, et al. Repeated botulinum toxin A injections for the treatment of lines in the upper face: a retrospective study of 4,103 treatments in 945 patients. Dermatol Surg 2007; 33:S18.

Botox Injections and Side Effects

Botulinum toxin, commonly known as botox, is commonly used for the treatment of facial wrinkles. Frown lines, crows feet, and horizontal forehead lines are commonly treated with botox in the United States. Botulinum toxin is derived from the Clostridium botulinum bacterium. Injection into muscles inhibits the release of acetylcholine at the neuromuscular junction which blocks contraction of muscle. This process is called chemical denervation. Repetitive contraction of facial muscles leads to wrinkle formation. Botulinum toxin relaxes the facial muscles and smooths the skin. Most muscles in the body have bony attachments to the skin, so the skin does not move upon contraction. The skin on the face is attached to muscle through soft tissue allowing for movement upon contraction. Patients with wrinkles upon movement are the best candidates for botox treatment. Results are less dramatic for patients with wrinkles upon rest as it may take a few consecutive botulinum toxin treatments to see improvement.

Botulinum toxin type A is used for cosmetic procedures while Botulinum toxin type B is used for conditions like dystonia. FDA approved botulinum toxin serotype A products include: onabotulinumtoxinA (Botox), abobotulinumtoxinA (Dysport), and incobotulinumtoxinA (Xeomin). IncobotulinumtoxinA does not contain complexing proteins which may reduce its antigenicity and formation of antibodies in the body. Further research must be done to confirm this.

Doses are usually 1 mL or less with one injection in the procerus muscle and two injections in each of the corrugator supercilii muscles (Small R.). Results should be seen within 3 days and maximum results should be visible at 2 weeks after treatment. Results should last for about 3 to 4 months and treatment should be given again when there is visible muscle movement. Injection reactions include anxiety, erythema, headache, infection, or pain. Bruising and redness are common. NSAIDs can be used for treatment of headaches. Botulinum toxin side effects include allergic reaction, spreading from the injection site, eyebrow ptosis, or facial asymmetry.

The amount of procedures using botulinum toxin A is expanding. Studies have shown that botulinum toxin A can have an effect on hypertrophic scars. It can inhibit fibroblast proliferation and downregulate expression of actin and myosin II proteins. It may also inhibit TGF-B1 and connective tissue growth factor. The effect of botulinum toxin on vascular endothelial growth factor (VEGF) to promote new vessels for wound healing is not known, but it may be possible. There has not been as much promise for the treatment of keloids as there is for facial hypertrophic scars. The use of botulinum toxin A and dermal fillers together may enhance the effect. Fillers have a longer duration of action than botulinum toxin which may help to extend the duration of the effect. They may assist each other in improving the smoothness of the skin. Furthermore, using a skincare regimen that consists of a retinoid helps to protect the patient from photodamage. The use of botulinum toxin intradermally is another area of focus for research. There are current studies researching its effect for bruxism, psoriasis, pain, and rosacea. Botulinum toxin may help with rosacea by inhibiting acetylcholine which is responsible for redness and flushing. It may help acne by blocking acetylcholine in sebocytes. Many other skin diseases are caused by hyperhidrosis which can be treated with botulinum toxin A. Botulinum toxin is a powerful substance requiring further research for all of its possible uses.

Schlessinger, J., Gilbert, E., Cohen, J. L., & Kaufman, J. (2017). New Uses of AbobotulinumtoxinA in Aesthetics. Aesthetic surgery journal, 37(suppl_1), S45–S58. https://doi.org/10.1093/asj/sjx005

Small R. (2014). Botulinum toxin injection for facial wrinkles. American family physician, 90(3), 168–175.