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Botulinum Toxin - Adult/Pediatric - Ambulatory

Botulinum Toxin - Adult/Pediatric - Ambulatory - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Clinical Practice Guidelines, Medications


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Botulinum Toxin – Adult/Pediatric –
Ambulatory Clinical Practice Guideline
Note: Active Table of Contents – Click to follow link
EXECUTIVE SUMMARY ...................................................................................................................... 3
SCOPE ............................................................................................................................................... 4
METHODOLOGY ................................................................................................................................ 4
INTRODUCTION................................................................................................................................. 5
RECOMMENDATIONS ........................................................................................................................ 7
UW HEALTH IMPLEMENTATION ...................................................................................................... 12
REFERENCES .................................................................................................................................... 15
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Contact for Content:
Name: Sara Shull, PharmD, MBA, BCPS
Phone Number: 262-1817
Email: ssmith-shull@uwhealth.org

Contact for Changes:
Name: Philip Trapskin, PharmD, BCPS
Phone Number: 265-0341
Email: ptrapskin@uwhealth.org

Guideline Author(s):
Updated by Heather LaRue, PharmD, February 2014
Updated by Sara Shull, PharmD, MBA, BCPS October 2016

Coordinating Team Members:
Sara Shull, PharmD, MBA, BCPS
MaryAnn Steiner, PharmD,

Review Individuals/Bodies:
Alaa Abd-Elsayed, MD- Anesthesia
Ahmed Afifi, MD – Plastic Surgery
Sheila Aton, PharmD- Pharmacy
Daniel Bennett, MD- Dermatology
Eric Berg, MD- Dermatology
Roland Brilla, MD- Neurology
Cat Burkat, MD- Ophthalmology
Wade Bushman, MD, PhD- Urology
Laura Buyan Dent- Neurology
Kristin Caldera, MD- Orthopedics/ Rehabilitation
Seth Dailey, MD- ENT/ Otolaryngology
Doug Dulli, MD- Neurology
Carin Endres, Pharm D BCPS; Pharmacy
Catherine Gallagher, MD- Neurology
James Leonard, DO, PT- Orthopedics/ Rehabilitation
Mark Lucarelli, MD- Ophthalmology
Christopher Luzzio, MD- Neurology
Deborah McLeish, MD- Orthopedics/ Rehabilitation
Jennifer Sandra, PharmD- Pharmacy
Susanne Seeger, MD- Neurology
MaryAnn Steiner, PharmD- Pharmacy
Michael Ward, MD- Orthopedics/ Rehabilitation
Bonnie Weigert, MD- Orthopedics/ Rehabilitation
Josh Vanderloo, PharmD- Pharmacy

Committee Approvals/Dates:
Clinic Administered Medications subcommittee: October 2016
P&T Committee: October 2016

Release Date: January 2017

Next Review Date: January 2020

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Executive Summary
Guideline Overview
This guideline provides recommendations for the therapeutic use of botulinum toxin to treat
several common conditions in the ambulatory setting. Individual clinician experience may
suggest stronger recommendations for some indications, however evidence based conclusions
are based on the currently available evidence.

Key Revisions (2017 Periodic Review)
1. Clinical information is emphasized while operational information has been removed.
2. All recommendations are have been ranked by strength and include the quality
ranking of the supporting evidence
3. Recommendations have been added for the management of: task-specific dystonia,
palatal myoclonus, orofacial dyskinesia due to temporomandibular joint disorder,
cricopharyngeal spasm, thyroid-associated orbitopathy, gustatory sweating, and
gustatory lacrimation,
4. Evidence now suggests botulinum toxin may be considered for the treatment of
essential hand tremor. Previously, insufficient evidence was available to recommend
botulinum toxin for this use.

Key Practice Recommendations
1. Botulinum toxin should be administered in the ambulatory setting whenever possible
2. Botulinum toxin should not be considered for indications when there is documented
lack of effect or available evidence is insufficient to support use.
3. Patients receiving botulinum toxin should be monitored regularly to ensure
achievement of adequate therapeutic response. If initial and/or continuing response
to the therapeutic effects of botulinum toxin is not documented, it should be
discontinued.

Companion Documents
1. Assessment and Treatment of Migraine- Adult- Emergency/ Ambulatory Setting:
https://uconnect.wisc.edu/clinical/cckm-
tools/content/?path=/content/cpg/neurology/name-97600-en.cckm


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Scope
Disease/Condition(s): Botulinum toxin is used to treat and prevent disorders from multiple
organ systems including cutaneous disorders, endocrine disorders; ear, nose, and throat
(ENT) disorders, gastroenterologic disorders, neurologic disorders, ophthalmologic disorders,
and urologic disorders.

Clinical Specialty: Dermatology, Endocrinology, ENT/ Otolaryngology, Gastroenterology,
Neurology, Nursing, Ophthalmology, Pharmacy, Physical Medicine and Rehabilitation, Primary
Care, Nursing, and Urology

Intended Users:
Physicians, Advanced Practice Providers, Nurses, Pharmacists, Technical Support, Medication
Prior Authorization

Objective(s): To provide evidence-based guidelines to assist clinicians in determining the
benefits of botulinum toxin use in patients with relevant disorders.

Target Population: All patients cared for within UW Health with a disorder for which botulinum
toxin may be appropriate treatment

Interventions and Practices Considered: Botulinum toxin is the sole clinical intervention
considered in the guideline, sometimes as a second or third line therapy

Major Outcomes Considered:
ξ Sustained relief or reversal of disorders addressed in the guideline.
ξ Avoidance/ delay of surgical or other invasive procedures
ξ Decrease in effect due to formation of antibodies to botulinum toxin after prolonged use
Methodology
Methods Used to Collect/Select the Evidence:
PUBMED searches were conducted by the guideline author(s) and workgroup members to
collect evidence for review. Expert opinion and clinical experience were also considered as a
valuable source of evidence.

Methods Used to Formulate the Recommendations:
Through a collaborative process, the workgroup members agreed to adopt recommendations a
consensus through discussion of the literature and expert experience. All recommendations
endorsed or developed by the guideline workgroup were reviewed and approved by other
stakeholders or committees.

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Methods Used to Assess the Quality of the Evidence/Strength of the Recommendations:
Internally developed recommendations, or those adopted from external sources without an
assigned evidence grade, were evaluated by the guideline workgroup using an algorithm
adapted from the Grading of Recommendations Assessment, Development and Evaluation
(GRADE) methodology (see Figure 1 in Appendix A).

Rating Scheme for the Strength of the Evidence/Recommendations:
See Appendix A for the rating scheme(s) used within this document.

Cost Analysis: The UW Health acquisition cost:
ξ OnabotulinumtoxinA 100 unit vial (Botox®)~$580
ξ RimabotulinumtoxinB 5000 unit vial (Myobloc®) ~ $530

Recognition of Potential Health Care Disparities: Botulinum toxin is a costly resource.
Therefore there may be barriers to consistent access depending on financial circumstances.

Introduction
Botulinum toxin (BoNT) is a potent neuroinhibitor that prevents the release of acetylcholine
within the neuromuscular junction.1,2 Two different formulations, BoNT type A (Botox®,
Dysport®, Xeomin®) and BoNT type B (Myobloc®), are FDA-approved. These formulations
vary in their activity and intracellular targets; therefore, they are not considered
interchangeable. Botulinum Toxin type A prevents acetylcholine release by cleavage of a
synaptosome-associated protein of 25,000 daltons.1 Botulinum neurotoxin type B has been
shown to inhibit neurotransmitter release by cleaving vesicle associated membrane
protein.2

Four botulinum toxin products are available on the US market:
ξ onabotulinumtoxinA (Botox®) – included on the UW Health formulary
ξ abobotulinum toxin A (Dysport®)- nonformulary
ξ incobotulinum toxin A (Xeomin®)- nonformulary
ξ rimabotulinum toxin B (Myobloc®)- included on the UW Health formulary

At this time, Botox® is the preferred formulary agent available at UW Health; however,
Myobloc® is also available. Patients may develop antibodies to BoNT type A, but due to
differing mechanisms of action may still respond to BoNT type B. One review by Yablon et
al.3 found the overall prevalence of BoNT type A antibodies to be 0.5% in 191 patients
treated for post-stroke spasticity. In these cases, it may be acceptable to treat patients with
BoNT type B.

Botulinum toxin is used in the treatment of many spastic conditions, movement, and
autonomic disorders. Since its’ FDA approval in the late 1980s, BoNT has been studied in
many disease states. The American Academy of Neurology has published reports and
recommendations that provide evidence and recommendations across a broad range of
clinical uses.4-7 This guideline offers evidence-based recommendations for use of BoNT at
UW Health.

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Botulinum toxin should be administered in the ambulatory setting whenever possible.
However, there are situations where it may be clinically appropriate to administer in the
inpatient setting. For additional details regarding inpatient use of botulinum toxin, please
refer to UWHC Policy 6.1.9 Restricted Primarily Ambulatory Administered Medications in
Hospitalized Patients. Botulinum toxin use requires pharmacy department review as
described in UWHC Policy 6.1.5 Formulary Restricted Clinic Administered Medication
Pharmacy Department Review and Use of Non-UW Health Supplied Medications
Administered in Clinics.


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Recommendations
1. Indications for Use of Botulinum Toxin
1.1. Movement Disorders
1.1.1. Cervical dystonia (spasmodic torticollis) defined as clonic and/or tonic involuntary contractions of
multiple neck muscles with sustained head torsion and/or tilt and limited range of motion in the neck
with duration of at least 6 months. There are several high quality placebo-controlled trials and other
evidence that support the use of BoNT for treatment of cervical dystonia1,2,8-24 and all four products
are FDA approved for this indication. BoNT should be offered to patients. (UW Health High quality
evidence; strong recommendation)

1.1.2. Spasticity –
1.1.2.1. Cerebral Palsy – High quality evidence supports the use of BoNT for treatment of
spasticity due to cerebral palsy.25-38 BoNT should be offered to patients in the setting of
cerebral palsy with spasticity or dystonia in addition to physical/occupational therapy,
conventional therapies (e.g.. baclofen), or splinting. (UW Health High quality evidence;
strong recommendation)

1.1.2.2. Upper and lower extremity spasticity –High quality evidence supports the use of BoNT for
treatment of upper and lower extremity spasticity.39-55 BoNT should be offered to treat
spasticity resulting from a stroke, traumatic or non-traumatic spinal cord injury, multiple
sclerosis or other demyelinating disease of the central nervous system, traumatic brain
injury or other central process with BoNT injections as a component of a documented
rehabilitation and strengthening program. (UW Health High quality evidence; strong
recommendation)

1.1.3. Hemifacial spasm- Moderate quality evidence supports the use of BoNT for treatment of hemifacial
spasm.56-67 BoNT is a reasonable treatment and should be considered for patients before
administration of oral medications. (UW Health Moderate quality evidence; strong recommendation)

1.1.4. Task specific dystonia- Moderate quality evidence supports the use of BoNT for treatment of task
specific dystonias,68-72 including writer’s and musician’s cramp. BoNT is a reasonable treatment
and should be considered as first line therapy. (UW Health Moderate quality evidence; strong
recommendation)

1.1.5. Essential hand tremor- Moderate quality evidence supports the use of BoNT for treatment of
essential hand tremor.73,74 Treatment with BoNT is reasonable and should be considered in
selected patients after oral medications are documented to be ineffective or when the patient is at
high risk of experiencing adverse effects. (UW Health Moderate quality evidence; strong
recommendation)

1.1.6. Facial synkinesia- Moderate quality evidence supports the use of BoNT for treatment of facial
synkinesia resulting from Bell’s palsy or injury.75-82 Treatment with BoNT is reasonable and should
be considered as part of a documented comprehensive plan for physical rehabilitation such as
occupational therapy. (UW Health Moderate quality evidence; strong recommendation)

1.1.7. Torsion dystonia – Low quality evidence supports the use of BoNT for treatment of torsion
dystonia.83-86 Treatment with BoNT may be considered after oral therapies are documented to be
ineffective or when the patient is documented to be at high risk for experiencing adverse effects.
(UW Health Low quality evidence; strong recommendation).

1.1.8. Congenital muscular torticollis- Low quality evidence supports the use of BoNT for treatment of
congenital muscular torticollis.87-92 Treatment with BoNT may be considered after conservative
treatment, including physical therapy or stretching, is documented to be ineffective. (UW Health
Low quality evidence; strong recommendation).

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1.1.9. Essential head tremor- Low quality evidence supports the use of BoNT for treatment of essential
head tremor.93 Treatment with BoNT may be considered in patients after oral medications are
documented to be ineffective or when the patient is documented to be at high risk for experiencing
adverse effects. (UW Health Low quality evidence; strong recommendation)

1.1.10. Palatal myoclonus- Low quality evidence supports the use of BoNT for treatment of palatal
myoclonus.94-100 Treatment with BoNT may be considered in this population. Benefit is modest;
however there are few treatment options for this disorder. (UW Health Low quality evidence;
weak/conditional recommendation)

1.1.11. Cervical or facial tic disorder (not including ocular tics)- Low quality evidence supports the use of
BoNT for treatment of tics.101-105 Treatment with BoNT may be considered for patients after oral
medications are documented to be ineffective or when patients are documented to be at high risk
for adverse effects. (UW Health Low quality evidence; strong recommendation)

1.1.12. Orofacial dyskinesia due to temporomandibular joint disorder- Low quality evidence supports the
use of BoNT for treatment of temporomandibular joint disorders.106-120 Treatment with BoNT may be
considered after splints, physical therapy, or orally administered medications are documented to be
ineffective or when patients are documented to be at high risk of adverse effects. (UW Health Low
quality evidence; strong recommendation)

1.2. Throat Disorders
1.2.1. Laryngeal spasm (spasmodic dysphonia/ voice tremor, refractory chronic cough, refractory
laryngospasm/paradoxical vocal fold motion [PVFM], refractory muscle tension dysphonia)-
Moderate quality evidence supports the use of BoNT for treatment of spasmodic dysphonia or voice
tremor.121-129 Treatment with BoNT is reasonable and should be considered for patients. There is a
distinct lack of alternative pharmacologic therapies established as effective for this indication. (UW
Health Moderate quality evidence; strong recommendation)

1.2.2. Cricopharyngeal spasm- Low quality evidence supports the use of BoNT for treatment of
cricopharyngeal spasm.130-144 Treatment with BoNT may be considered in selected patients who
wish to avoid mechanical dilation or surgery. (UW Health Low quality evidence; weak/conditional
recommendation)

1.3. Ophthalmic Disorders
1.3.1. Blepharospasm- High quality evidence supports the use of BoNT A for the treatment of
blepharospasm.145-158 It should be offered to patients especially when associated with dystonia. .
(UW Health High quality evidence; strong recommendation)

1.3.2. Strabismus- Low quality evidence supports the use of BoNT for the treatment of strabismus.1,159-162
A meta-analysis confirms that the majority of evidence is based on retrospective studies,
prospective cohorts, or case reviews. Randomized controlled trials show varying responses to
BoNT administration.159 Treatment with BoNT may be considered in these patients. (UW Health
Low quality evidence; weak/ conditional recommendation)

1.3.3. Thyroid associated orbitopathy- Low quality evidence supports the use of BoNT for the treatment
of orbitopathy associated with Grave’s Disease.163-167 Treatment with BoNT may be considered in
patients that wish to avoid surgery. (UW Health Low quality evidence; weak/conditional
recommendation)

1.4. Gastrointestinal Disorders
1.4.1. Esophageal achalasia- Moderate quality evidence supports the use of BoNT for the treatment of
esophageal achalasia.168-172 Although the initial esophageal relaxation success rate with BoNT is
high and comparable to surgical myotomy and pneumatic dilation, the effect is temporary and
requires repeated administration.168,173,174 Treatment with BoNT is reasonable and should be
considered for patients who are at high risk of adverse effects as a result of pneumatic balloon
dilation or surgical myotomy. (UW Health Moderate quality evidence; weak/ conditional
recommendation).
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1.4.2. Chronic anal fissures- Moderate quality evidence supports the use of BoNT for the treatment of
anal fissures.175-183 Lateral internal sphincterotomy has better long term results, however it
presents a risk of incontinence.177 Treatment with BoNT is reasonable and should be considered
for patients with documentation of therapeutic failure, contra-indication, or intolerance to
conventional therapy, including topical nitrates and calcium channel blockers, and who wish to avoid
surgery. (UW Health Moderate quality evidence; strong recommendation).

1.5. Hypersecretory Disorders-
1.5.1. Axillary hyperhydrosis - High quality evidence supports the use of BoNT for the treatment of
axillary hyperhydrosis in patients inadequately managed with topical antiperspirants.184-197
Treatment with BoNT should be offered to these patients. While BoTN is effective, only patients
with a documented failure of topical antiperspirants should receive it because topical antiperspirants
are readily available, inexpensive, and associated with few adverse effects. (UW Health High
quality evidence; strong recommendation)

1.5.2. Palmar/ plantar hyperhydrosis- Moderate quality evidence supports the use of BoNT for the
treatment of palmar/ plantar hyperhydrosis.198-211 Treatment with BoNT is reasonable and should be
considered for patients with documented therapeutic failure, contra-indication, or intolerance to
systemic (i.e. anticholinergics) or topical therapy. BoNT should also be considered for those
seeking an alternative to iontophoresis. Injections can be painful on the hands/ feet and there is risk
of temporary local muscle weakness. (UW Health Moderate quality evidence; strong
recommendation).

1.5.3. Sialorrhea- Moderate quality evidence supports the use of BoNT for the treatment of sialorrhea in
patients with Parkinson’s Disease, cerebral palsy, amyotrophic lateral sclerosis, and other motor
neuron disorders.212-235 Treatment with BoNT is reasonable and should be considered for patients
whose quality of life is significantly negatively impacted by sialorrhea. Caution should be used, as
BoNT may worsen symptoms of dysphagia. The efficacy of BoNT B is better supported by
evidence. (UW Health Moderate quality evidence; strong recommendation).

1.5.4. Gustatory sweating (Frey’s Syndrome)- Low quality evidence supports the use of BoNT for the
treatment of gustatory sweating.236 Treatment with BoNT may be considered for patients. (UW
Health Low quality evidence; weak/ conditional recommendation)

1.5.5. Gustatory lacrimation (crocodile tears)- Low quality evidence supports the use of BoNT for the
treatment of gustatory lacrimation.237-245 Treatment with BoNT may be considered as few treatment
options are available for this indication. (UW Health Low quality evidence; weak/ conditional
recommendation).

1.6. Urinary incontinence-

1.6.1. Neurogenic detrusor overactivity- High quality evidence supports the use of BoNT for the treatment
of neurogenic detrusor overactivity.246-256 Treatment with BoNT should be offered to patients who
use clean, intermittent catheterization and who have a documented therapeutic failure of behavior
modifications or physical therapy, Documentation of therapeutic failure, contra-indication, or
intolerance to anticholinergic medications is also required. (UW Health High quality evidence;
strong recommendation)

1.6.2. Overactive (idiopathic, non-neurogenic) bladder- High quality evidence supports the use of BoNT
for the treatment of idiopathic overactive bladder.257-275 Treatment with BoNT should be offered to
carefully selected patients who are documented to be refractory to first line (behavioral) and second
line (anticholinergic) overactive bladder therapies. Transient post void residual (PVR) may be high
after BoNT administration. Therefore patients should be willing to have the PVR monitored closely
and be willing and able to perform self-catheterization if necessary. (UW Health High quality
evidence; strong recommendation)

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1.6.3. Detrusor sphincter dyssynergia-Moderate quality evidence supports the use of BoNT for the
treatment of detrusor sphincter dyssynergia resulting from spinal cord injury.276-278 Treatment with
BoNT is reasonable and should be considered for these patients. (UW Health Moderate quality
evidence; strong recommendation)

Low quality evidence supports the use of BoNT for the treatment of detrusor sphincter dyssynergia
resulting from multiple sclerosis when confirmed by urodynamic testing. Treatment with
onabotulinumtoxin A may be considered as it may increase voiding volume, decrease detrusor
pressures, and/or improve bladder emptying in a population with few treatment options.279-281 (UW
Health low quality evidence; weak/ conditional recommendation)

1.7. Headache
1.7.1. Chronic migraine headache- High quality evidence supports the use of BoNT for the prevention of
chronic migraine headache.282-289 Treatment with BoNT should be offered to disabled (significantly
limited in ability to work, attend school, maintain household, or participate in social/ leisure
activities)290 patients who experience chronic migraine: headaches lasting at least 4 hours per day
at least 15 days per month for at least 3 months. Criteria for migraine must be met at least 8 days
out of the month. Patients should have documentation of therapeutic failure, contra-indication, or
intolerance to conventional migraine prophylactic medications such as beta adrenergic blockers
(propranolol) and tricyclic antidepressants (amitriptyline) or neuromodulators (divalproex). BoNT
should be prescribed by a headache specialist as part of a comprehensive headache management
plan to decrease the number of days the patient experiences migraine. Patient should report
improvements with successful use of BoNT, including less medication use, fewer visits to the
emergency department, urgent care center, clinic , or fewer work/school days missed. Currently
only onabotulinum toxin A is FDA approved for preventing chronic migraine headache. (UW Health
High quality evidence; strong recommendation)


2. Indications for Which Insufficient Data Exist to Warrant Use
Treatment with BoNT should not be considered when lack of effect is documented or available evidence is
insufficient to support use.

2.1. Benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) High quality evidence does
not support use of BoNT for this indication. Results of clinical studies do not provide adequate evidence
of clinical benefit.291-297 (UW Health high quality evidence; strong recommendation)

2.2. Chronic neck (cervicalgia)/ back pain: Moderate quality evidence does not support use of BoNT for
treatment of cervicalgia or low back pain. Results from clinical studies do not provide adequate evidence
of clinical benefit.298-307 (UW Health low quality evidence; strong recommendation)

2.3. Raynaud’s Disease- Low quality evidence does not support use of BoNT for the treatment of Raynaud’s
Disease. Results from clinical studies do not provide adequate evidence of clinical benefit.308-310 (UW
Health low quality evidence; strong recommendation)

2.4. Acute/ episodic migraine- High quality evidence does not support use of BoNT for the prophylaxis of
acute migraine. Results from clinical studies do not provide adequate evidence of clinical benefit.283,311-
313
(UW Health high quality evidence; strong recommendation)

2.5. Tension headache- Moderate quality evidence does not support use of BoNT for the prophylaxis of
tension headaches. Results from clinical studies do not provide adequate evidence of clinical
benefit.283,314-316 (UW Health moderate quality evidence; strong recommendation)

2.6. Restless leg syndrome- Low quality evidence does not support use of BoNT for the treatment of restless
leg syndrome. Results from clinical studies do not provide adequate evidence of clinical benefit.317-320
(UW Health low quality evidence; strong recommendation)

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11

3. Aesthetic/ Cosmetic Uses321-323
3.1. Glabellar lines
3.2. Horizontal facial rhytids
3.3. Crow’s feet
3.4. Bunny lines
3.5. Perioral area
3.6. Dimpled chin
3.7. Platysmal bands


4. Assessment for Allowance and Coverage
All patients will undergo insurance screening for coverage prior to receipt of botulinum toxin therapy.
Insurance company-specific prior authorization criteria will be reviewed, coverage will be verified, and
authorization will be documented in the EMR prior to receipt of the first dose of botulinum toxin therapy. Not all
insurance companies will cover botulinum toxin for all indications or doses, especially when the
recommendation strength is weak or conditional. For cosmetic uses, a payment plan is established prior to
administration of botulinum toxin. Additionally, continued coverage is reviewed prior to each subsequent
administration of botulinum toxin.

5. Usual Dosing
Dosing of BoNT is highly individualized based on condition, patient characteristics, affected muscle groups,
and patient response. It is recommended to use the lowest effective dose and to separate treatments by the
longest interval tolerated to avoid adverse effects and minimize antibody formation.324 Three months is
generally recommended between injections for spastic conditions.325 Various methods, such as
electromyography and electrical stimulation, are used to localize the involved muscle groups. The following
represent usual or starting doses of onabotulinumtoxin A (Botox®) 326for common conditions .Specific patient
doses may vary. Please note that insurers may not provide coverage for doses higher than those presented in
package inserts or generally recognized drug information databases.

5.1. Movement Disorders

5.1.1. Cervical dystonia326
5.1.1.1. Dose and location of injections should be individualized for each patient and is dependent
on previous exposure
5.1.1.2. Previously untreated: The mean dose should be less than 236 units.
5.1.1.3. Previously treated: dose is dependent on head/neck position, localization of pain, muscle
hypertrophy, patient response, and previous adverse reactions. The mean dose is 236
units divided among affected muscles

5.1.2. Spasticity and non-cervical dystonia in adult and pediatric patients327-329
5.1.2.1. 0.5 – 20 units/kg with a maximum dose of 400 – 600 units; initiate therapy at the lower
end of the dose range

5.1.3. Hemifacial spasm57
5.1.3.1. Mean dose per treatment session = 25 units divided (range = 7.5 – 100 units). Start at
low end of range and titrate based on effectiveness and adverse effects. Higher doses
are reserved for patients refractory to lower doses. The cumulative dose for treatment of
hemifacial spasm in a 30 day period should not exceed 200 units.

5.2. Throat Disorders

5.2.1. Laryngeal spasm (spasmodic dysphonia/tremor)330: 0.1-7.5 units

5.3. Ophthalmic Disorders

5.3.1. Blepharospasm326,331: typical initial dose is 2.5 units per injection in 5-6 sites around each eye.
Subsequent doses can be increased to 7.5-10 units per injection in six or more sites around each
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12

eye. The cumulative dose for treatment of blepharospasm in a 30-day period should not exceed
200 units.

5.3.2. Strabismus326: 1.25-5 units per muscle initially

5.4. Gastrointestinal Disorders

5.4.1. Esophageal achalasia332: 100 units divided in at least 4 quadrants (maximum dose = 100 units)

5.4.2. Chronic anal fissure179,333: 20-30 units

5.5. Hypersecretory Disorders

5.5.1. Axillary hyperhidrosis188,326: 50-75 units per axilla divided

5.5.2. Palmar hyperhidrosis199,211: 50-100 units per palm divided

5.5.3. Sialorrhea217: 10-50 units per gland

5.6. Urinary incontinence

5.6.1. Detrusor sphincter dyssynergia277,278: 100 units

5.6.2. Neurogenic detrusor overactivity252,326: 200-300 units

5.6.3. Nonneurogenic detrusor overactivity: 100 units administered no more frequently than every 12
weeks260,326,334

5.7. Migraine Headache286,326: 155 units divided into 31 sites administered every 12 weeks. Up to 40 units
may be added if necessary after the second administration (total should not exceed 195 units).

5.8. Cosmetic use323,335
5.8.1. Glabellar lines: 20-30 units total for women and 30-40 total units for men
5.8.2. Horizontal forehead rhytids: 10-20 total units for women and 20-30 total units for men
5.8.3. Crow’s feet: 12-30 units total
5.8.4. Bunny lines: 2-5 units total
5.8.5. Perioral area: 4-10 units total
5.8.6. Dimpled chin: 2-6 units total for women and 2-8 units total for men
5.8.7. Platysmal bands: highly variable

6. Patient Monitoring
6.1. Patients should be monitored for efficacy and toxicity throughout treatment. Goals of therapy may vary
depending on condition and patient specific variables. However goals should be established prior to
initiation of treatment for all patients. After 6-12 months of treatment, if adequate response is not
achieved, consideration should be given to alternative treatments which may include use of a different
serotype or discontinuation of botulinum toxin.

7. Contraindications
7.1. If active infection is present at the site of injection, botulinum toxin is contraindicated.
7.2. If a patient has a known reaction or hypersensitivity to botulinum toxin or any ingredients use is
contraindicated.
UW Health Implementation
Potential Benefits: Botulinum toxin will be used in a consistent, evidence-based, cost-
effective manner throughout UW Health.

Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org


13

Potential Harms: Patients may experience adverse effects to botulinum toxin, even when
receiving it for an approved indication and at a recommended dose.

Pertinent UW Health Policies & Procedures
1. UW Health Policy 8.30: Management of Clinic Administered Medications with Internal
Pharmacy Prior Authorization
2. UW Health Policy 8.95: Restricted Clinic Administered Medications in Hospitalized
Patients.

Patient Resources
1. UW Health Botulinum Toxin Consent Form
2. Health Facts for You #6370 Trigger Point Injections
3. UW Health Facial Nerve Paralysis Questionnaire
4. Medication guides are available for each specific product. Health professionals should
urge patients, their families, and caregivers to review it carefully.
Onabotulinum toxin A (Botox): http://www.allergan.com/miscellaneous-pages/allergan-pdf-
files/botox_med_guide
Rimabotulinum toxin B (Myobloc): http://www.myobloc.com/myobloc/hcp/medguide/medguide.pdf
Abobotulinum toxin A (Dysport): https://www.dysport.com/pdfs/Dysport_Medication_Guide.pdf
Incobotulinum toxin A (Xeomin): http://www.xeomin.com/wp-content/uploads/xeomin-medication-
guide.pdf
Guideline Metrics
1. Periodic medication use evaluation of botulinum toxin

Implementation Plan/Clinical Tools:
The restriction of botulinum toxin to appropriate, evidence-based indications will be
operationalized by pharmacist review for appropriate indication. Applicable paper orders will
reflect current recommendations in the guideline. Prescribers, pharmacists, and nursing staff
will be educated about the guideline through electronic distribution.

Disclaimer: This Clinical Practice Guideline provides an evidence-based approach for the use
of botulinum toxin. It is understood that occasionally patients will not match the conditions
addressed in the guideline.


Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org


14



Appendix A. Evidence Grading Scheme(s)

Appendix A. GRADE Methodology adapted by UW Health







GRADE Ranking of Evidence
High We are confident that the effect in the study reflects the actual effect.
Moderate We are quite confident that the effect in the study is close to the true effect, but it is also
possible it is substantially different.
Low The true effect may differ significantly from the estimate.
Very Low The true effect is likely to be substantially different from the estimated effect.

GRADE Ratings for Recommendations For or Against Practice
Strong The net benefit of the treatment is clear, patient values and circumstances are
unlikely to affect the decision.
Weak/conditional Recommendation may be conditional upon patient values and preferences, the
resources available, or the setting in which the intervention will be implemented.

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Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org


15


References

1. Onabotulinumtoxin A (Botox®) [prescribing information]. Allergan Pharmaceuticals, Inc.; Irvine, CA. 2016.
2. Rimabotulinumtoxin B (Myobloc) [Prescribing information]. Solstice Neuroscienes, Inc.; South San
Fransisco, CA. 2010.
3. Yablon SA, Brashear A, Gordon MF, et al. Formation of neutralizing antibodies in patients receiving
botulinum toxin type A for treatment of poststroke spasticity: a pooled-data analysis of three clinical trials.
Clin Ther. 2007;29(4):683-690.
4. Naumann M, So Y, Argoff CE, et al. Assessment: Botulinum neurotoxin in the treatment of autonomic
disorders and pain (an evidence-based review): report of the Therapeutics and Technology Assessment
Subcommittee of the American Academy of Neurology. Neurology. 2008;70(19):1707-1714.
5. Simpson DM, Blitzer A, Brashear A, et al. Assessment: Botulinum neurotoxin for the treatment of
movement disorders (an evidence-based review): report of the Therapeutics and Technology Assessment
Subcommittee of the American Academy of Neurology. Neurology. 2008;70(19):1699-1706.
6. Simpson DM, Gracies JM, Graham HK, et al. Assessment: Botulinum neurotoxin for the treatment of
spasticity (an evidence-based review): report of the Therapeutics and Technology Assessment
Subcommittee of the American Academy of Neurology. Neurology. 2008;70(19):1691-1698.
7. Simpson DM, Hallett M, Ashman EJ, et al. Practice guideline update summary: Botulinum neurotoxin for
the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the
Guideline Development Subcommittee of the American Academy of Neurology. Neurology.
2016;86(19):1818-1826.
8. Truong D, Duane DD, Jankovic J, et al. Efficacy and safety of botulinum type A toxin (Dysport) in cervical
dystonia: results of the first US randomized, double-blind, placebo-controlled study. Mov Disord.
2005;20(7):783-791.
9. Truong D, Brodsky M, Lew M, et al. Long-term efficacy and safety of botulinum toxin type A (Dysport) in
cervical dystonia. Parkinsonism Relat Disord. 2010;16(5):316-323.
10. Brashear A, Lew MF, Dykstra DD, et al. Safety and efficacy of NeuroBloc (botulinum toxin type B) in type
A-responsive cervical dystonia. Neurology. 1999;53(7):1439-1446.
11. Brin MF, Lew MF, Adler CH, et al. Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-
resistant cervical dystonia. Neurology. 1999;53(7):1431-1438.
12. Lew MF, Adornato BT, Duane DD, et al. Botulinum toxin type B: a double-blind, placebo-controlled, safety
and efficacy study in cervical dystonia. Neurology. 1997;49(3):701-707.
13. Comella CL, Jankovic J, Truong DD, Hanschmann A, Grafe S, Group USXCDS. Efficacy and safety of
incobotulinumtoxinA (NT 201, XEOMIN(R), botulinum neurotoxin type A, without accessory proteins) in
patients with cervical dystonia. J Neurol Sci. 2011;308(1-2):103-109.
14. Odergren T, Hjaltason H, Kaakkola S, et al. A double blind, randomised, parallel group study to
investigate the dose equivalence of Dysport and Botox in the treatment of cervical dystonia. J Neurol
Neurosurg Psychiatry. 1998;64(1):6-12.
15. Brans JW, Lindeboom R, Snoek JW, et al. Botulinum toxin versus trihexyphenidyl in cervical dystonia: a
prospective, randomized, double-blind controlled trial. Neurology. 1996;46(4):1066-1072.
16. Benecke R, Jost WH, Kanovsky P, Ruzicka E, Comes G, Grafe S. A new botulinum toxin type A free of
complexing proteins for treatment of cervical dystonia. Neurology. 2005;64(11):1949-1951.
17. Pappert EJ, Germanson T, Myobloc/Neurobloc European Cervical Dystonia Study G. Botulinum toxin
type B vs. type A in toxin-naive patients with cervical dystonia: Randomized, double-blind, noninferiority
trial. Mov Disord. 2008;23(4):510-517.
18. Comella CL, Jankovic J, Shannon KM, et al. Comparison of botulinum toxin serotypes A and B for the
treatment of cervical dystonia. Neurology. 2005;65(9):1423-1429.
19. Yun JY, Kim JW, Kim HT, et al. Dysport and Botox at a ratio of 2.5:1 units in cervical dystonia: a double-
blind, randomized study. Mov Disord. 2015;30(2):206-213.
20. Fernandez HH, Pappert EJ, Comella CL, et al. Efficacy and Safety of IncobotulinumtoxinA in Subjects
Previously Treated with Botulinum Toxin Versus Toxin-Naive Subjects with Cervical Dystonia. Tremor
Other Hyperkinet Mov (N Y). 2013;3.
21. Charles D, Brashear A, Hauser RA, et al. Efficacy, tolerability, and immunogenicity of onabotulinumtoxina
in a randomized, double-blind, placebo-controlled trial for cervical dystonia. Clin Neuropharmacol.
2012;35(5):208-214.
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org


16

22. Brin MF, Comella CL, Jankovic J, Lai F, Naumann M, Group CDBS. Long-term treatment with botulinum
toxin type A in cervical dystonia has low immunogenicity by mouse protection assay. Mov Disord.
2008;23(10):1353-1360.
23. Jankovic J, Adler CH, Charles D, et al. Primary results from the cervical dystonia patient registry for
observation of onabotulinumtoxina efficacy (CD PROBE). J Neurol Sci. 2015;349(1-2):84-93.
24. Marques RE, Duarte GS, Rodrigues FB, et al. Botulinum toxin type B for cervical dystonia. Cochrane
Database Syst Rev. 2016(5):CD004315.
25. Bjornson K, Hays R, Graubert C, et al. Botulinum toxin for spasticity in children with cerebral palsy: a
comprehensive evaluation. Pediatrics. 2007;120(1):49-58.
26. Pieper C. Botulinum toxin type a neuromuscular blockade in the treatment of lower extremity spasticity in
cerebral palsy: a randomized, double-blind, placebo-controlled trial. Pediatr Phys Ther. 2006;13(2):92-94.
27. Speth LA, Leffers P, Janssen-Potten YJ, Vles JS. Botulinum toxin A and upper limb functional skills in
hemiparetic cerebral palsy: a randomized trial in children receiving intensive therapy. Dev Med Child
Neurol. 2005;47(7):468-473.
28. El O, Peker O, Kosay C, Iyilikci L, Bozan O, Berk H. Botulinum toxin A injection for spasticity in diplegic-
type cerebral palsy. J Child Neurol. 2006;21(12):1009-1012.
29. Koman LA, Mooney JF, 3rd, Smith BP, Walker F, Leon JM. Botulinum toxin type A neuromuscular
blockade in the treatment of lower extremity spasticity in cerebral palsy: a randomized, double-blind,
placebo-controlled trial. BOTOX Study Group. J Pediatr Orthop. 2000;20(1):108-115.
30. Autti-Rämö I, Larsen A, Taimo A, von Wendt L. Management of the upper limb with botulinum toxin type
A in children with spastic type cerebral palsy and acquired brain injury: clinical implications. Eur J Neurol.
2001;8 Suppl 5:136-144.
31. Bakheit AM, Severa S, Cosgrove A, et al. Safety profile and efficacy of botulinum toxin A (Dysport) in
children with muscle spasticity. Dev Med Child Neurol. 2001;43(4):234-238.
32. Corry IS, Cosgrove AP, Walsh EG, McClean D, Graham HK. Botulinum toxin A in the hemiplegic upper
limb: a double-blind trial. Dev Med Child Neurol. 1997;39(3):185-193.
33. Sutherland DH, Kaufman KR, Wyatt MP, Chambers HG, Mubarak SJ. Double-blind study of botulinum A
toxin injections into the gastrocnemius muscle in patients with cerebral palsy. Gait Posture. 1999;10(1):1-
9.
34. Ubhi T, Bhakta BB, Ives HL, Allgar V, Roussounis SH. Randomised double blind placebo controlled trial
of the effect of botulinum toxin on walking in cerebral palsy. Arch Dis Child. 2000;83(6):481-487.
35. Baker R, Jasinski M, Maciag-Tymecka I, et al. Botulinum toxin treatment of spasticity in diplegic cerebral
palsy: a randomized, double-blind, placebo-controlled, dose-ranging study. Dev Med Child Neurol.
2002;44(10):666-675.
36. Wissel J, Heinen F, Schenkel A, et al. Botulinum toxin A in the management of spastic gait disorders in
children and young adults with cerebral palsy: a randomized, double-blind study of "high-dose" versus
"low-dose" treatment. Neuropediatrics. 1999;30(3):120-124.
37. Polak F, Morton R, Ward C, Wallace WA, Doderlein L, Siebel A. Double-blind comparison study of two
doses of botulinum toxin A injected into calf muscles in children with hemiplegic cerebral palsy. Dev Med
Child Neurol. 2002;44(8):551-555.
38. Delgado MR, Hirtz D, Aisen M, et al. Practice parameter: pharmacologic treatment of spasticity in children
and adolescents with cerebral palsy (an evidence-based review): report of the Quality Standards
Subcommittee of the American Academy of Neurology and the Practice Committee of the Child
Neurology Society. Neurology. 2010;74(4):336-343.
39. Rosales RL, Chua-Yap AS. Evidence-based systematic review on the efficacy and safety of botulinum
toxin-A therapy in post-stroke spasticity. J Neural Transm. 2008;115(4):617-623.
40. Bakheit AM, Pittock S, Moore AP, et al. A randomized, double-blind, placebo-controlled study of the
efficacy and safety of botulinum toxin type A in upper limb spasticity in patients with stroke. Eur J Neurol.
2001;8(6):559-565.
41. Bakheit AM, Thilmann AF, Ward AB, et al. A randomized, double-blind, placebo-controlled, dose-ranging
study to compare the efficacy and safety of three doses of botulinum toxin type A (Dysport) with placebo
in upper limb spasticity after stroke. Stroke. 2000;31(10):2402-2406.
42. Smith SJ, Ellis E, White S, Moore AP. A double-blind placebo-controlled study of botulinum toxin in upper
limb spasticity after stroke or head injury. Clin Rehabil. 2000;14(1):5-13.
43. Marciniak C, Rader L, Gagnon C. The use of botulinum toxin for spasticity after spinal cord injury. Am J
Phys Med Rehabil. 2008;87(4):312-317; quiz 318-320, 329.
44. Yablon SA, Agana BT, Ivanhoe CB, Boake C. Botulinum toxin in severe upper extremity spasticity among
patients with traumatic brain injury: an open-labeled trial. Neurology. 1996;47(4):939-944.
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org


17

45. McCrory P, Turner-Stokes L, Baguley IJ, et al. Botulinum toxin A for treatment of upper limb spasticity
following stroke: a multi-centre randomized placebo-controlled study of the effects on quality of life and
other person-centred outcomes. J Rehabil Med. 2009;41(7):536-544.
46. Shaw LC, Price CI, van Wijck FM, et al. Botulinum Toxin for the Upper Limb after Stroke (BoTULS) Trial:
effect on impairment, activity limitation, and pain. Stroke. 2011;42(5):1371-1379.
47. Rosales RL, Kong KH, Goh KJ, et al. Botulinum toxin injection for hypertonicity of the upper extremity
within 12 weeks after stroke: a randomized controlled trial. Neurorehabil Neural Repair. 2012;26(7):812-
821.
48. Gracies JM, Bayle N, Goldberg S, Simpson DM. Botulinum toxin type B in the spastic arm: a randomized,
double-blind, placebo-controlled, preliminary study. Arch Phys Med Rehabil. 2014;95(7):1303-1311.
49. Lam K, Lau KK, So KK, et al. Can botulinum toxin decrease carer burden in long term care residents with
upper limb spasticity? A randomized controlled study. J Am Med Dir Assoc. 2012;13(5):477-484.
50. Simpson DM, Gracies JM, Yablon SA, Barbano R, Brashear A, Bo NTTZDST. Botulinum neurotoxin
versus tizanidine in upper limb spasticity: a placebo-controlled study. J Neurol Neurosurg Psychiatry.
2009;80(4):380-385.
51. Kaji R, Osako Y, Suyama K, et al. Botulinum toxin type A in post-stroke lower limb spasticity: a
multicenter, double-blind, placebo-controlled trial. J Neurol. 2010;257(8):1330-1337.
52. Marciniak CM, Harvey RL, Gagnon CM, et al. Does botulinum toxin type A decrease pain and lessen
disability in hemiplegic survivors of stroke with shoulder pain and spasticity?: a randomized, double-blind,
placebo-controlled trial. Am J Phys Med Rehabil. 2012;91(12):1007-1019.
53. Jahangir AW, Tan HJ, Norlinah MI, et al. Intramuscular injection of botulinum toxin for the treatment of
wrist and finger spasticity after stroke. Med J Malaysia. 2007;62(4):319-322.
54. Kanovský P, Slawek J, Denes Z, et al. Efficacy and safety of botulinum neurotoxin NT 201 in poststroke
upper limb spasticity. Clin Neuropharmacol. 2009;32(5):259-265.
55. Ward AB, Wissel J, Borg J, et al. Functional goal achievement in post-stroke spasticity patients: the
BOTOX(R) Economic Spasticity Trial (BEST). J Rehabil Med. 2014;46(6):504-513.
56. Trosch RM, Adler CH, Pappert EJ. Botulinum toxin type B (Myobloc) in subjects with hemifacial spasm:
results from an open-label, dose-escalation safety study. Mov Disord. 2007;22(9):1258-1264.
57. Defazio G, Abbruzzese G, Girlanda P, et al. Botulinum toxin A treatment for primary hemifacial spasm: a
10-year multicenter study. Arch Neurol. 2002;59(3):418-420.
58. Jitpimolmard S, Tiamkao S, Laopaiboon M. Long term results of botulinum toxin type A (Dysport) in the
treatment of hemifacial spasm: a report of 175 cases. J Neurol Neurosurg Psychiatry. 1998;64(6):751-
757.
59. Sampaio C, Ferreira JJ, Simões F, et al. DYSBOT: a single-blind, randomized parallel study to determine
whether any differences can be detected in the efficacy and tolerability of two formulations of botulinum
toxin type A--Dysport and Botox--assuming a ratio of 4:1. Mov Disord. 1997;12(6):1013-1018.
60. Mauriello JA, Leone T, Dhillon S, Pakeman B, Mostafavi R, Yepez MC. Treatment choices of 119 patients
with hemifacial spasm over 11 years. Clin Neurol Neurosurg. 1996;98(3):213-216.
61. Cuevas C, Madrazo I, Magallón E, Zamorano C, Neri G, Reyes E. Botulinum toxin-A for the treatment of
hemifacial spasm. Arch Med Res. 1995;26(4):405-408.
62. Price J, O'Day J. Efficacy and side effects of botulinum toxin treatment for blepharospasm and hemifacial
spasm. Aust N Z J Ophthalmol. 1994;22(4):255-260.
63. Park YC, Lim JK, Lee DK, Yi SD. Botulinum a toxin treatment of hemifacial spasm and blepharospasm. J
Korean Med Sci. 1993;8(5):334-340.
64. Flanders M, Chin D, Boghen D. Botulinum toxin: preferred treatment for hemifacial spasm. Eur Neurol.
1993;33(4):316-319.
65. Berardelli A, Formica A, Mercuri B, et al. Botulinum toxin treatment in patients with focal dystonia and
hemifacial spasm. A multicenter study of the Italian Movement Disorder Group. Ital J Neurol Sci.
1993;14(5):361-367.
66. Yoshimura DM, Aminoff MJ, Tami TA, Scott AB. Treatment of hemifacial spasm with botulinum toxin.
Muscle Nerve. 1992;15(9):1045-1049.
67. Elston JS. The management of blepharospasm and hemifacial spasm. J Neurol. 1992;239(1):5-8.
68. Kruisdijk JJ, Koelman JH, Ongerboer de Visser BW, de Haan RJ, Speelman JD. Botulinum toxin for
writer's cramp: a randomised, placebo-controlled trial and 1-year follow-up. J Neurol Neurosurg
Psychiatry. 2007;78(3):264-270.
69. Contarino MF, Kruisdijk JJ, Koster L, Ongerboer de Visser BW, Speelman JD, Koelman JH. Sensory
integration in writer's cramp: comparison with controls and evaluation of botulinum toxin effect. Clin
Neurophysiol. 2007;118(10):2195-2206.
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org


18

70. Cole R, Hallett M, Cohen LG. Double-blind trial of botulinum toxin for treatment of focal hand dystonia.
Mov Disord. 1995;10(4):466-471.
71. Tsui JK, Bhatt M, Calne S, Calne DB. Botulinum toxin in the treatment of writer's cramp: a double-blind
study. Neurology. 1993;43(1):183-185.
72. Yoshimura DM, Aminoff MJ, Olney RK. Botulinum toxin therapy for limb dystonias. Neurology. 1992;42(3
Pt 1):627-630.
73. Brin MF, Lyons KE, Doucette J, et al. A randomized, double masked, controlled trial of botulinum toxin
type A in essential hand tremor. Neurology. 2001;56(11):1523-1528.
74. Jankovic J, Schwartz K, Clemence W, Aswad A, Mordaunt J. A randomized, double-blind, placebo-
controlled study to evaluate botulinum toxin type A in essential hand tremor. Mov Disord. 1996;11(3):250-
256.
75. Borodic G, Bartley M, Slattery W, et al. Botulinum toxin for aberrant facial nerve regeneration: double-
blind, placebo-controlled trial using subjective endpoints. Plast Reconstr Surg. 2005;116(1):36-43.
76. Monini S, De Carlo A, Biagini M, et al. Combined protocol for treatment of secondary effects from facial
nerve palsy. Acta Otolaryngol. 2011;131(8):882-886.
77. Choi KH, Rho SH, Lee JM, Jeon JH, Park SY, Kim J. Botulinum toxin injection of both sides of the face to
treat post-paralytic facial synkinesis. J Plast Reconstr Aesthet Surg. 2013;66(8):1058-1063.
78. Azuma T, Nakamura K, Takahashi M, et al. Mirror biofeedback rehabilitation after administration of single-
dose botulinum toxin for treatment of facial synkinesis. Otolaryngol Head Neck Surg. 2012;146(1):40-45.
79. Ito H, Nakano S, Kusaka H. Low-dose subcutaneous injection of botulinum toxin type A for facial
synkinesis and hyperlacrimation. Acta Neurol Scand. 2007;115(4):271-274.
80. Chua CN, Quhill F, Jones E, Voon LW, Ahad M, Rowson N. Treatment of aberrant facial nerve
regeneration with botulinum toxin A. Orbit. 2004;23(4):213-218.
81. Armstrong MW, Mountain RE, Murray JA. Treatment of facial synkinesis and facial asymmetry with
botulinum toxin type A following facial nerve palsy. Clin Otolaryngol Allied Sci. 1996;21(1):15-20.
82. Roggenkamper P, Laskawi R, Damenz W, Schroder M, Nussgens Z. Orbicular synkinesis after facial
paralysis: treatment with botulinum toxin. Doc Ophthalmol. 1994;86(4):395-402.
83. Jankovic J, Schwartz K, Donovan DT. Botulinum toxin treatment of cranial-cervical dystonia, spasmodic
dysphonia, other focal dystonias and hemifacial spasm. J Neurol Neurosurg Psychiatry. 1990;53(8):633-
639.
84. Jankovic J. Treatment of dystonia. Lancet Neurol. 2006;5(10):864-872.
85. Hinson VK, Goetz CG. Torsion Dystonia in Children. Curr Treat Options Neurol. 2003;5(4):291-297.
86. Kamm C. Early onset torsion dystonia (Oppenheim's dystonia). Orphanet J Rare Dis. 2006;1:48.
87. Sinn CN, Rinaldi RJ. Treatment with Botulinum Toxin Type A in Infants with Refractory Congenital
Muscular Torticollis: A 10-Year Retrospective Study. Pm r. 2016;8(9s):S152-s153.
88. Bouchard M, Chouinard S, Suchowersky O. Adult cases of congenital muscular torticollis successfully
treated with botulinum toxin. Mov Disord. 2010;25(14):2453-2456.
89. Joyce MB, de Chalain TM. Treatment of recalcitrant idiopathic muscular torticollis in infants with botulinum
toxin type a. J Craniofac Surg. 2005;16(2):321-327.
90. Gunduz A, Korkmaz B, Kiziltan ME. Effective treatment of congenital muscular torticollis using botulinum
toxin. J Craniofac Surg. 2014;25(5):1935.
91. Collins A, Jankovic J. Botulinum toxin injection for congenital muscular torticollis presenting in children
and adults. Neurology. 2006;67(6):1083-1085.
92. Oleszek JL, Chang N, Apkon SD, Wilson PE. Botulinum toxin type a in the treatment of children with
congenital muscular torticollis. Am J Phys Med Rehabil. 2005;84(10):813-816.
93. Pahwa R, Busenbark K, Swanson-Hyland EF, et al. Botulinum toxin treatment of essential head tremor.
Neurology. 1995;45(4):822-824.
94. Krause E, Leunig A, Klopstock T, Gurkov R. Treatment of essential palatal myoclonus in a 10-year-old girl
with botulinum neurotoxin. Otol Neurotol. 2006;27(5):672-675.
95. Eryilmaz A, Basal Y, Gunel C, Ozkul A, Tosun A. Successful Treatment of Essential Palatal Tremor
Lasting Over a Long Term with a Rare Application of Botulinum Toxin in a Child. Iran J Child Neurol.
2015;9(4):75-77.
96. Cho JW, Chu K, Jeon BS. Case of essential palatal tremor: atypical features and remarkable benefit from
botulinum toxin injection. Mov Disord. 2001;16(4):779-782.
97. Bryce GE, Morrison MD. Botulinum toxin treatment of essential palatal myoclonus tinnitus. J Otolaryngol.
1998;27(4):213-216.
98. Varney SM, Demetroulakos JL, Fletcher MH, McQueen WJ, Hamilton MK. Palatal myoclonus: treatment
with Clostridium botulinum toxin injection. Otolaryngol Head Neck Surg. 1996;114(2):317-320.
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org


19

99. Awaad Y, Tayem H, Elgamal A, Coyne MF. Treatment of childhood myoclonus with botulinum toxin type
A. J Child Neurol. 1999;14(12):781-786.
100. Anis MM, Pollak N. Treatment of palatal myoclonus with botulinum toxin injection. Case Rep Otolaryngol.
2013;2013:231505.
101. Marras C, Andrews D, Sime E, Lang AE. Botulinum toxin for simple motor tics: a randomized, double-
blind, controlled clinical trial. Neurology. 2001;56(5):605-610.
102. Kwak CH, Hanna PA, Jankovic J. Botulinum toxin in the treatment of tics. Arch Neurol. 2000;57(8):1190-
1193.
103. Aguirregomozcorta M, Pagonabarraga J, Diaz-Manera J, Pascual-Sedano B, Gironell A, Kulisevsky J.
Efficacy of botulinum toxin in severe Tourette syndrome with dystonic tics involving the neck.
Parkinsonism Relat Disord. 2008;14(5):443-445.
104. Jankovic J. Botulinum toxin in the treatment of dystonic tics. Mov Disord. 1994;9(3):347-349.
105. Porta M, Maggioni G, Ottaviani F, Schindler A. Treatment of phonic tics in patients with Tourette's
syndrome using botulinum toxin type A. Neurol Sci. 2004;24(6):420-423.
106. Guarda-Nardini L, Manfredini D, Salamone M, Salmaso L, Tonello S, Ferronato G. Efficacy of botulinum
toxin in treating myofascial pain in bruxers: a controlled placebo pilot study. Cranio. 2008;26(2):126-135.
107. Guarda-Nardini L, Stecco A, Stecco C, Masiero S, Manfredini D. Myofascial pain of the jaw muscles:
comparison of short-term effectiveness of botulinum toxin injections and fascial manipulation technique.
Cranio. 2012;30(2):95-102.
108. Ernberg M, Hedenberg-Magnusson B, List T, Svensson P. Efficacy of botulinum toxin type A for treatment
of persistent myofascial TMD pain: a randomized, controlled, double-blind multicenter study. Pain.
2011;152(9):1988-1996.
109. Kurtoglu C, Gur OH, Kurkcu M, Sertdemir Y, Guler-Uysal F, Uysal H. Effect of botulinum toxin-A in
myofascial pain patients with or without functional disc displacement. J Oral Maxillofac Surg.
2008;66(8):1644-1651.
110. von Lindern JJ, Niederhagen B, Berge S, Appel T. Type A botulinum toxin in the treatment of chronic
facial pain associated with masticatory hyperactivity. J Oral Maxillofac Surg. 2003;61(7):774-778.
111. Nixdorf DR, Heo G, Major PW. Randomized controlled trial of botulinum toxin A for chronic myogenous
orofacial pain. Pain. 2002;99(3):465-473.
112. Freund B, Schwartz M, Symington JM. Botulinum toxin: new treatment for temporomandibular disorders.
Br J Oral Maxillofac Surg. 2000;38(5):466-471.
113. Karacalar A, Yilmaz N, Bilgici A, Baş B, Akan H. Botulinum toxin for the treatment of temporomandibular
joint disk disfigurement: clinical experience. J Craniofac Surg. 2005;16(3):476-481.
114. Bakke M, Møller E, Werdelin LM, Dalager T, Kitai N, Kreiborg S. Treatment of severe temporomandibular
joint clicking with botulinum toxin in the lateral pterygoid muscle in two cases of anterior disc
displacement. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100(6):693-700.
115. Aquilina P, Vickers R, McKellar G. Reduction of a chronic bilateral temporomandibular joint dislocation
with intermaxillary fixation and botulinum toxin A. Br J Oral Maxillofac Surg. 2004;42(3):272-273.
116. Martínez-Pérez D, García Ruiz-Espiga P. Recurrent temporomandibular joint dislocation treated with
botulinum toxin: report of 3 cases. J Oral Maxillofac Surg. 2004;62(2):244-246.
117. Ziegler CM, Haag C, Mühling J. Treatment of recurrent temporomandibular joint dislocation with
intramuscular botulinum toxin injection. Clin Oral Investig. 2003;7(1):52-55.
118. Daelen B, Thorwirth V, Koch A. Treatment of recurrent dislocation of the temporomandibular joint with
type A botulinum toxin. Int J Oral Maxillofac Surg. 1997;26(6):458-460.
119. Vázquez Bouso O, Forteza González G, Mommsen J, Grau VG, Rodríguez Fernández J, Mateos Micas
M. Neurogenic temporomandibular joint dislocation treated with botulinum toxin: report of 4 cases. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(3):e33-37.
120. Fu KY, Chen HM, Sun ZP, Zhang ZK, Ma XC. Long-term efficacy of botulinum toxin type A for the
treatment of habitual dislocation of the temporomandibular joint. Br J Oral Maxillofac Surg.
2010;48(4):281-284.
121. Troung DD, Rontal M, Rolnick M, Aronson AE, Mistura K. Double-blind controlled study of botulinum toxin
in adductor spasmodic dysphonia. Laryngoscope. 1991;101(6 Pt 1):630-634.
122. Justicz N, Hapner ER, Josephs JS, Boone BC, Jinnah HA, Johns MM, 3rd. Comparative effectiveness of
propranolol and botulinum for the treatment of essential voice tremor. Laryngoscope. 2016;126(1):113-
117.
123. Novakovic D, Waters HH, D'Elia JB, Blitzer A. Botulinum toxin treatment of adductor spasmodic
dysphonia: longitudinal functional outcomes. Laryngoscope. 2011;121(3):606-612.
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org


20

124. Cannito MP, Woodson GE, Murry T, Bender B. Perceptual analyses of spasmodic dysphonia before and
after treatment. Arch Otolaryngol Head Neck Surg. 2004;130(12):1393-1399.
125. Adler CH, Bansberg SF, Hentz JG, et al. Botulinum toxin type A for treating voice tremor. Arch Neurol.
2004;61(9):1416-1420.
126. Bielamowicz S, Squire S, Bidus K, Ludlow CL. Assessment of posterior cricoarytenoid botulinum toxin
injections in patients with abductor spasmodic dysphonia. Ann Otol Rhinol Laryngol. 2001;110(5 Pt
1):406-412.
127. Courey MS, Garrett CG, Billante CR, et al. Outcomes assessment following treatment of spasmodic
dysphonia with botulinum toxin. Ann Otol Rhinol Laryngol. 2000;109(9):819-822.
128. Blitzer A, Brin MF, Stewart CF. Botulinum toxin management of spasmodic dysphonia (laryngeal
dystonia): a 12-year experience in more than 900 patients. Laryngoscope. 1998;108(10):1435-1441.
129. Boutsen F, Cannito MP, Taylor M, Bender B. Botox treatment in adductor spasmodic dysphonia: a meta-
analysis. J Speech Lang Hear Res. 2002;45(3):469-481.
130. Kocdor P, Siegel ER, Tulunay-Ugur OE. Cricopharyngeal dysfunction: A systematic review comparing
outcomes of dilatation, botulinum toxin injection, and myotomy. Laryngoscope. 2016;126(1):135-141.
131. Sewell RK, Bauman NM. Congenital cricopharyngeal achalasia: management with botulinum toxin before
myotomy. Arch Otolaryngol Head Neck Surg. 2005;131(5):451-453.
132. Moerman M, Callier Y, Dick C, Vermeersch H. Botulinum toxin for dysphagia due to cricopharyngeal
dysfunction. Eur Arch Otorhinolaryngol. 2002;259(1):1-3.
133. Chiu MJ, Chang YC, Hsiao TY. Prolonged effect of botulinum toxin injection in the treatment of
cricopharyngeal dysphagia: case report and literature review. Dysphagia. 2004;19(1):52-57.
134. Parameswaran MS, Soliman AM. Endoscopic botulinum toxin injection for cricopharyngeal dysphagia.
Ann Otol Rhinol Laryngol. 2002;111(10):871-874.
135. Restivo DA, Palmeri A, Marchese-Ragona R. Botulinum toxin for cricopharyngeal dysfunction in
Parkinson's disease. N Engl J Med. 2002;346(15):1174-1175.
136. Schneider I, Thumfart WF, Pototschnig C, Eckel HE. Treatment of dysfunction of the cricopharyngeal
muscle with botulinum A toxin: introduction of a new, noninvasive method. Ann Otol Rhinol Laryngol.
1994;103(1):31-35.
137. Atkinson SI, Rees J. Botulinum toxin for cricopharyngeal dysphagia: case reports of CT-guided injection.
J Otolaryngol. 1997;26(4):273-276.
138. Blitzer A, Brin MF. Use of botulinum toxin for diagnosis and management of cricopharyngeal achalasia.
Otolaryngol Head Neck Surg. 1997;116(3):328-330.
139. Haapaniemi JJ, Laurikainen EA, Pulkkinen J, Marttila RJ. Botulinum toxin in the treatment of
cricopharyngeal dysphagia. Dysphagia. 2001;16(3):171-175.
140. Shaw GY, Searl JP. Botulinum toxin treatment for cricopharyngeal dysfunction. Dysphagia.
2001;16(3):161-167.
141. Alberty J, Oelerich M, Ludwig K, Hartmann S, Stoll W. Efficacy of botulinum toxin A for treatment of upper
esophageal sphincter dysfunction. Laryngoscope. 2000;110(7):1151-1156.
142. Murry T, Wasserman T, Carrau RL, Castillo B. Injection of botulinum toxin A for the treatment of
dysfunction of the upper esophageal sphincter. Am J Otolaryngol. 2005;26(3):157-162.
143. Krause E, Schirra J, Gürkov R. Botulinum toxin a treatment of cricopharyngeal dysphagia after
subarachnoid hemorrhage. Dysphagia. 2008;23(4):406-410.
144. Zaninotto G, Marchese Ragona R, Briani C, et al. The role of botulinum toxin injection and upper
esophageal sphincter myotomy in treating oropharyngeal dysphagia. J Gastrointest Surg. 2004;8(8):997-
1006.
145. Jankovic J, Comella C, Hanschmann A, Grafe S. Efficacy and safety of incobotulinumtoxinA (NT 201,
Xeomin) in the treatment of blepharospasm-a randomized trial. Mov Disord. 2011;26(8):1521-1528.
146. Truong D, Comella C, Fernandez HH, Ondo WG, Dysport Benign Essential Blepharospasm Study G.
Efficacy and safety of purified botulinum toxin type A (Dysport) for the treatment of benign essential
blepharospasm: a randomized, placebo-controlled, phase II trial. Parkinsonism Relat Disord.
2008;14(5):407-414.
147. Girlanda P, Quartarone A, Sinicropi S, Nicolosi C, Messina C. Unilateral injection of botulinum toxin in
blepharospasm: single fiber electromyography and blink reflex study. Mov Disord. 1996;11(1):27-31.
148. Wabbels B, Reichel G, Fulford-Smith A, Wright N, Roggenkamper P. Double-blind, randomised, parallel
group pilot study comparing two botulinum toxin type A products for the treatment of blepharospasm. J
Neural Transm (Vienna). 2011;118(2):233-239.
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org


21

149. Roggenkamper P, Jost WH, Bihari K, Comes G, Grafe S, Team NTBS. Efficacy and safety of a new
Botulinum Toxin Type A free of complexing proteins in the treatment of blepharospasm. J Neural Transm
(Vienna). 2006;113(3):303-312.
150. Nussgens Z, Roggenkamper P. Comparison of two botulinum-toxin preparations in the treatment of
essential blepharospasm. Graefes Arch Clin Exp Ophthalmol. 1997;235(4):197-199.
151. Saad J, Gourdeau A. A direct comparison of onabotulinumtoxina (Botox) and IncobotulinumtoxinA
(Xeomin) in the treatment of benign essential blepharospasm: a split-face technique. J Neuroophthalmol.
2014;34(3):233-236.
152. Bentivoglio AR, Fasano A, Ialongo T, Soleti F, Lo Fermo S, Albanese A. Fifteen-year experience in
treating blepharospasm with Botox or Dysport: same toxin, two drugs. Neurotox Res. 2009;15(3):224-
231.
153. Cillino S, Raimondi G, Guepratte N, et al. Long-term efficacy of botulinum toxin A for treatment of
blepharospasm, hemifacial spasm, and spastic entropion: a multicentre study using two drug-dose
escalation indexes. Eye (Lond). 2010;24(4):600-607.
154. Truong DD, Gollomp SM, Jankovic J, et al. Sustained efficacy and safety of repeated incobotulinumtoxinA
(Xeomin((R))) injections in blepharospasm. J Neural Transm (Vienna). 2013;120(9):1345-1353.
155. Kollewe K, Mohammadi B, Kohler S, Pickenbrock H, Dengler R, Dressler D. Blepharospasm: long-term
treatment with either Botox(R), Xeomin(R) or Dysport(R). J Neural Transm (Vienna). 2015;122(3):427-
431.
156. Jankovic J, Orman J. Botulinum A toxin for cranial-cervical dystonia: a double-blind, placebo-controlled
study. Neurology. 1987;37(4):616-623.
157. Dutton JJ, White JJ, Richard MJ. Myobloc for the treatment of benign essential blepharospasm in patients
refractory to botox. Ophthal Plast Reconstr Surg. 2006;22(3):173-177.
158. Colosimo C, Chianese M, Giovannelli M, Contarino MF, Bentivoglio AR. Botulinum toxin type B in
blepharospasm and hemifacial spasm. J Neurol Neurosurg Psychiatry. 2003;74(5):687.
159. Rowe FJ, Noonan CP. Botulinum toxin for the treatment of strabismus. Cochrane Database Syst Rev.
2012(2):CD006499.
160. de Alba Campomanes AG, Binenbaum G, Campomanes Eguiarte G. Comparison of botulinum toxin with
surgery as primary treatment for infantile esotropia. J AAPOS. 2010;14(2):111-116.
161. Gursoy H, Basmak H, Sahin A, Yildirim N, Aydin Y, Colak E. Long-term follow-up of bilateral botulinum
toxin injections versus bilateral recessions of the medial rectus muscles for treatment of infantile
esotropia. J AAPOS. 2012;16(3):269-273.
162. Lueder GT, Galli M, Tychsen L, Yildirim C, Pegado V. Long-term results of botulinum toxin-augmented
medial rectus recessions for large-angle infantile esotropia. Am J Ophthalmol. 2012;153(3):560-563.
163. Akbari MR, Ameri A, Keshtkar Jaafari AR, Mirmohammadsadeghi A. Botulinum toxin injection for
restrictive myopathy of thyroid-associated orbitopathy: success rate and predictive factors. J AAPOS.
2016;20(2):126-130.e121.
164. Melcescu E, Horton WB, Kim D, et al. Graves orbitopathy: update on diagnosis and therapy. South Med
J. 2014;107(1):34-43.
165. Costa PG, Saraiva FP, Pereira IC, Monteiro ML, Matayoshi S. Comparative study of Botox injection
treatment for upper eyelid retraction with 6-month follow-up in patients with thyroid eye disease in the
congestive or fibrotic stage. Eye (Lond). 2009;23(4):767-773.
166. Kikkawa DO, Cruz RC, Jr., Christian WK, et al. Botulinum A toxin injection for restrictive myopathy of
thyroid-related orbitopathy: effects on intraocular pressure. Am J Ophthalmol. 2003;135(4):427-431.
167. Korn BS, Seo SW, Levi L, Granet DB, Kikkawa DO. Optic neuropathy associated with botulinum A toxin in
thyroid-related orbitopathy. Ophthal Plast Reconstr Surg. 2007;23(2):109-114.
168. Leyden JE, Moss AC, MacMathuna P. Endoscopic pneumatic dilation versus botulinum toxin injection in
the management of primary achalasia. Cochrane Database Syst Rev. 2014(12):CD005046.
169. Pasricha PJ, Ravich WJ, Hendrix TR, Sostre S, Jones B, Kalloo AN. Intrasphincteric botulinum toxin for
the treatment of achalasia. N Engl J Med. 1995;332(12):774-778.
170. Zaninotto G, Annese V, Costantini M, et al. Randomized controlled trial of botulinum toxin versus
laparoscopic heller myotomy for esophageal achalasia. Ann Surg. 2004;239(3):364-370.
171. Gordon JM, Eaker EY. Prospective study of esophageal botulinum toxin injection in high-risk achalasia
patients. Am J Gastroenterol. 1997;92(10):1812-1817.
172. Fishman VM, Parkman HP, Schiano TD, et al. Symptomatic improvement in achalasia after botulinum
toxin injection of the lower esophageal sphincter. Am J Gastroenterol. 1996;91(9):1724-1730.
173. Pasricha PJ, Rai R, Ravich WJ, Hendrix TR, Kalloo AN. Botulinum toxin for achalasia: long-term outcome
and predictors of response. Gastroenterology. 1996;110(5):1410-1415.
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org


22

174. Allescher HD, Storr M, Seige M, et al. Treatment of achalasia: botulinum toxin injection vs. pneumatic
balloon dilation. A prospective study with long-term follow-Up. Endoscopy. 2001;33(12):1007-1017.
175. Nelson RL, Thomas K, Morgan J, Jones A. Non surgical therapy for anal fissure. Cochrane Database
Syst Rev. 2012(2):Cd003431.
176. Yiannakopoulou E. Botulinum toxin and anal fissure: efficacy and safety systematic review. Int J
Colorectal Dis. 2012;27(1):1-9.
177. Chen HL, Woo XB, Wang HS, et al. Botulinum toxin injection versus lateral internal sphincterotomy for
chronic anal fissure: a meta-analysis of randomized control trials. Tech Coloproctol. 2014;18(8):693-698.
178. Berkel AE, Rosman C, Koop R, van Duijvendijk P, van der Palen J, Klaase JM. Isosorbide dinitrate
ointment vs botulinum toxin A (Dysport) as the primary treatment for chronic anal fissure: a randomized
multicentre study. Colorectal Dis. 2014;16(10):O360-366.
179. Samim M, Twigt B, Stoker L, Pronk A. Topical diltiazem cream versus botulinum toxin a for the treatment
of chronic anal fissure: a double-blind randomized clinical trial. Ann Surg. 2012;255(1):18-22.
180. Valizadeh N, Jalaly NY, Hassanzadeh M, et al. Botulinum toxin injection versus lateral internal
sphincterotomy for the treatment of chronic anal fissure: randomized prospective controlled trial.
Langenbecks Arch Surg. 2012;397(7):1093-1098.
181. Nasr M, Ezzat H, Elsebae M. Botulinum toxin injection versus lateral internal sphincterotomy in the
treatment of chronic anal fissure: a randomized controlled trial. World J Surg. 2010;34(11):2730-2734.
182. Arroyo A, Pérez F, Serrano P, Candela F, Lacueva J, Calpena R. Surgical versus chemical (botulinum
toxin) sphincterotomy for chronic anal fissure: long-term results of a prospective randomized clinical and
manometric study. Am J Surg. 2005;189(4):429-434.
183. Maria G, Cassetta E, Gui D, Brisinda G, Bentivoglio AR, Albanese A. A comparison of botulinum toxin
and saline for the treatment of chronic anal fissure. N Engl J Med. 1998;338(4):217-220.
184. Glaser DA, Pariser DM, Hebert AA, et al. A Prospective, Nonrandomized, Open-Label Study of the
Efficacy and Safety of OnabotulinumtoxinA in Adolescents with Primary Axillary Hyperhidrosis. Pediatr
Dermatol. 2015;32(5):609-617.
185. An JS, Hyun Won C, Si Han J, Park HS, Seo KK. Comparison of onabotulinumtoxinA and
rimabotulinumtoxinB for the treatment of axillary hyperhidrosis. Dermatol Surg. 2015;41(8):960-967.
186. Heckmann M, Ceballos-Baumann AO, Plewig G. Botulinum toxin A for axillary hyperhidrosis (excessive
sweating). N Engl J Med. 2001;344(7):488-493.
187. Naumann M, Lowe NJ. Botulinum toxin type A in treatment of bilateral primary axillary hyperhidrosis:
randomised, parallel group, double blind, placebo controlled trial. BMJ. 2001;323(7313):596-599.
188. Lowe NJ, Glaser DA, Eadie N, et al. Botulinum toxin type A in the treatment of primary axillary
hyperhidrosis: a 52-week multicenter double-blind, randomized, placebo-controlled study of efficacy and
safety. J Am Acad Dermatol. 2007;56(4):604-611.
189. Odderson IR. Long-term quantitative benefits of botulinum toxin type A in the treatment of axillary
hyperhidrosis. Dermatol Surg. 2002;28(6):480-483.
190. Baumann L, Slezinger A, Halem M, et al. Pilot study of the safety and efficacy of Myobloc (botulinum toxin
type B) for treatment of axillary hyperhidrosis. Int J Dermatol. 2005;44(5):418-424.
191. Dressler D. Comparing Botox and Xeomin for axillar hyperhidrosis. J Neural Transm (Vienna).
2010;117(3):317-319.
192. Talarico-Filho S, Mendonca DONM, Sperandeo DEMF, C DESP. A double-blind, randomized,
comparative study of two type A botulinum toxins in the treatment of primary axillary hyperhidrosis.
Dermatol Surg. 2007;33(1 Spec No.):S44-50.
193. Schnider P, Binder M, Kittler H, et al. A randomized, double-blind, placebo-controlled trial of botulinum A
toxin for severe axillary hyperhidrosis. Br J Dermatol. 1999;140(4):677-680.
194. Doft MA, Kasten JL, Ascherman JA. Treatment of axillary hyperhidrosis with botulinum toxin: a single
surgeon's experience with 53 consecutive patients. Aesthetic Plast Surg. 2011;35(6):1079-1086.
195. Absar MS, Onwudike M. Efficacy of botulinum toxin type A in the treatment of focal axillary hyperhidrosis.
Dermatol Surg. 2008;34(6):751-755.
196. Connor KM, Cook JL, Davidson JR. Botulinum toxin treatment of social anxiety disorder with
hyperhidrosis: a placebo-controlled double-blind trial. J Clin Psychiatry. 2006;67(1):30-36.
197. Salmanpoor R, Rahmanian MJ. Treatment of axillary hyperhidrosis with botulinum-A toxin. Int J Dermatol.
2002;41(7):428-430.
198. Schnider P, Binder M, Auff E, Kittler H, Berger T, Wolff K. Double-blind trial of botulinum A toxin for the
treatment of focal hyperhidrosis of the palms. Br J Dermatol. 1997;136(4):548-552.
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org


23

199. Lowe NJ, Yamauchi PS, Lask GP, Patnaik R, Iyer S. Efficacy and safety of botulinum toxin type a in the
treatment of palmar hyperhidrosis: a double-blind, randomized, placebo-controlled study. Dermatol Surg.
2002;28(9):822-827.
200. Baumann L, Slezinger A, Halem M, et al. Double-blind, randomized, placebo-controlled pilot study of the
safety and efficacy of Myobloc (botulinum toxin type B) for the treatment of palmar hyperhidrosis.
Dermatol Surg. 2005;31(3):263-270.
201. Simonetta Moreau M, Cauhepe C, Magues JP, Senard JM. A double-blind, randomized, comparative
study of Dysport vs. Botox in primary palmar hyperhidrosis. Br J Dermatol. 2003;149(5):1041-1045.
202. Basciani M, Di Rienzo F, Bizzarrini M, Zanchi M, Copetti M, Intiso D. Efficacy of botulinum toxin type B for
the treatment of primary palmar hyperhidrosis: a prospective, open, single-blind, multi-centre study. Arch
Dermatol Res. 2014;306(5):497-503.
203. Campanati A, Giuliodori K, Martina E, Giuliano A, Ganzetti G, Offidani A. Onabotulinumtoxin type A
(Botox((R))) versus Incobotulinumtoxin type A (Xeomin((R))) in the treatment of focal idiopathic palmar
hyperhidrosis: results of a comparative double-blind clinical trial. J Neural Transm (Vienna).
2014;121(1):21-26.
204. Kouris A, Vavouli C, Markantoni V, Kontochristopoulos G. Muscle weakness in treatment of palmar
hyperhidrosis with botulinum toxin type a: can it be prevented? J Drugs Dermatol. 2014;13(11):1315-
1316.
205. Naver H, Swartling C, Aquilonius SM. Palmar and axillary hyperhidrosis treated with botulinum toxin: one-
year clinical follow-up. Eur J Neurol. 2000;7(1):55-62.
206. Naumann M, Hofmann U, Bergmann I, Hamm H, Toyka KV, Reiners K. Focal hyperhidrosis: effective
treatment with intracutaneous botulinum toxin. Arch Dermatol. 1998;134(3):301-304.
207. Chow A, Wilder-Smith EP. Effect of transdermal botulinum toxin on sweat secretion in subjects with
idiopathic palmar hyperhidrosis. Br J Dermatol. 2009;160(3):721-722.
208. Yamashita N, Shimizu H, Kawada M, et al. Local injection of botulinum toxin A for palmar hyperhidrosis:
usefulness and efficacy in relation to severity. J Dermatol. 2008;35(6):325-329.
209. Galadari I, Alkaabi J. Botulinum toxin in the treatment of axillary hyperhidrosis. Skinmed. 2003;2(4):209-
211.
210. Sevim S, Dogu O, Kaleagasi H. Botulinum toxin-A therapy for palmar and plantar hyperhidrosis. Acta
Neurol Belg. 2002;102(4):167-170.
211. Saadia D, Voustianiouk A, Wang AK, Kaufmann H. Botulinum toxin type A in primary palmar
hyperhidrosis: randomized, single-blind, two-dose study. Neurology. 2001;57(11):2095-2099.
212. Jackson CE, Gronseth G, Rosenfeld J, et al. Randomized double-blind study of botulinum toxin type B for
sialorrhea in ALS patients. Muscle Nerve. 2009;39(2):137-143.
213. Lipp A, Trottenberg T, Schink T, Kupsch A, Arnold G. A randomized trial of botulinum toxin A for
treatment of drooling. Neurology. 2003;61(9):1279-1281.
214. Mancini F, Zangaglia R, Cristina S, et al. Double-blind, placebo-controlled study to evaluate the efficacy
and safety of botulinum toxin type A in the treatment of drooling in parkinsonism. Mov Disord.
2003;18(6):685-688.
215. Lagalla G, Millevolte M, Capecci M, Provinciali L, Ceravolo MG. Botulinum toxin type A for drooling in
Parkinson's disease: a double-blind, randomized, placebo-controlled study. Mov Disord. 2006;21(5):704-
707.
216. Ondo WG, Hunter C, Moore W. A double-blind placebo-controlled trial of botulinum toxin B for sialorrhea
in Parkinson's disease. Neurology. 2004;62(1):37-40.
217. Vashishta R, Nguyen SA, White DR, Gillespie MB. Botulinum toxin for the treatment of sialorrhea: a meta-
analysis. Otolaryngol Head Neck Surg. 2013;148(2):191-196.
218. Young CA, Ellis C, Johnson J, Sathasivam S, Pih N. Treatment for sialorrhea (excessive saliva) in people
with motor neuron disease/amyotrophic lateral sclerosis. Cochrane Database Syst Rev.
2011(5):Cd006981.
219. Alrefai AH, Aburahma SK, Khader YS. Treatment of sialorrhea in children with cerebral palsy: a double-
blind placebo controlled trial. Clin Neurol Neurosurg. 2009;111(1):79-82.
220. Banerjee KJ, Glasson C, O'Flaherty SJ. Parotid and submandibular botulinum toxin A injections for
sialorrhoea in children with cerebral palsy. Dev Med Child Neurol. 2006;48(11):883-887.
221. Basciani M, Di Rienzo F, Fontana A, Copetti M, Pellegrini F, Intiso D. Botulinum toxin type B for
sialorrhoea in children with cerebral palsy: a randomized trial comparing three doses. Dev Med Child
Neurol. 2011;53(6):559-564.
222. Bothwell JE, Clarke K, Dooley JM, et al. Botulinum toxin A as a treatment for excessive drooling in
children. Pediatr Neurol. 2002;27(1):18-22.
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org


24

223. Chinnapongse R, Gullo K, Nemeth P, Zhang Y, Griggs L. Safety and efficacy of botulinum toxin type B for
treatment of sialorrhea in Parkinson's disease: a prospective double-blind trial. Mov Disord.
2012;27(2):219-226.
224. Ellies M, Laskawi R, Rohrbach-Volland S, Arglebe C, Beuche W. Botulinum toxin to reduce saliva flow:
selected indications for ultrasound-guided toxin application into salivary glands. Laryngoscope.
2002;112(1):82-86.
225. Ellies M, Rohrbach-Volland S, Arglebe C, Wilken B, Laskawi R, Hanefeld F. Successful management of
drooling with botulinum toxin A in neurologically disabled children. Neuropediatrics. 2002;33(6):327-330.
226. Giess R, Naumann M, Werner E, et al. Injections of botulinum toxin A into the salivary glands improve
sialorrhoea in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2000;69(1):121-123.
227. Guidubaldi A, Fasano A, Ialongo T, et al. Botulinum toxin A versus B in sialorrhea: a prospective,
randomized, double-blind, crossover pilot study in patients with amyotrophic lateral sclerosis or
Parkinson's disease. Mov Disord. 2011;26(2):313-319.
228. Jongerius PH, van den Hoogen FJ, van Limbeek J, Gabreels FJ, van Hulst K, Rotteveel JJ. Effect of
botulinum toxin in the treatment of drooling: a controlled clinical trial. Pediatrics. 2004;114(3):620-627.
229. Lagalla G, Millevolte M, Capecci M, Provinciali L, Ceravolo MG. Long-lasting benefits of botulinum toxin
type B in Parkinson's disease-related drooling. J Neurol. 2009;256(4):563-567.
230. Porta M, Gamba M, Bertacchi G, Vaj P. Treatment of sialorrhoea with ultrasound guided botulinum toxin
type A injection in patients with neurological disorders. J Neurol Neurosurg Psychiatry. 2001;70(4):538-
540.
231. Racette BA, Good L, Sagitto S, Perlmutter JS. Botulinum toxin B reduces sialorrhea in parkinsonism. Mov
Disord. 2003;18(9):1059-1061.
232. Reid SM, Johnstone BR, Westbury C, Rawicki B, Reddihough DS. Randomized trial of botulinum toxin
injections into the salivary glands to reduce drooling in children with neurological disorders. Dev Med
Child Neurol. 2008;50(2):123-128.
233. Savarese R, Diamond M, Elovic E, Millis SR. Intraparotid injection of botulinum toxin A as a treatment to
control sialorrhea in children with cerebral palsy. Am J Phys Med Rehabil. 2004;83(4):304-311; quiz 312-
304, 336.
234. Schroeder AS, Kling T, Huss K, et al. Botulinum toxin type A and B for the reduction of hypersalivation in
children with neurological disorders: a focus on effectiveness and therapy adherence. Neuropediatrics.
2012;43(1):27-36.
235. Wilken B, Aslami B, Backes H. Successful treatment of drooling in children with neurological disorders
with botulinum toxin A or B. Neuropediatrics. 2008;39(4):200-204.
236. Xie S, Wang K, Xu T, Guo XS, Shan XF, Cai ZG. Efficacy and safety of botulinum toxin type A for
treatment of Frey's syndrome: evidence from 22 published articles. Cancer Med. 2015;4(11):1639-1650.
237. Montoya FJ, Riddell CE, Caesar R, Hague S. Treatment of gustatory hyperlacrimation (crocodile tears)
with injection of botulinum toxin into the lacrimal gland. Eye (Lond). 2002;16(6):705-709.
238. Baranano DE, Miller NR. Long term efficacy and safety of botulinum toxin A injection for crocodile tears
syndrome. Br J Ophthalmol. 2004;88(4):588-589.
239. Yavuzer R, Basterzi Y, Akata F. Botulinum toxin A for the treatment of crocodile tears. Plast Reconstr
Surg. 2002;110(1):369-370.
240. Salles AG, Zampieri LA, Moraes LB, Remigio AF, Costa EF, Gemperli R. Development of a Protocol for
Treatment of Crocodile Tears Syndrome with Botulinum Toxin. Plast Reconstr Surg. 2015;136(4
Suppl):146.
241. Keegan DJ, Geerling G, Lee JP, Blake G, Collin JR, Plant GT. Botulinum toxin treatment for
hyperlacrimation secondary to aberrant regenerated seventh nerve palsy or salivary gland
transplantation. Br J Ophthalmol. 2002;86(1):43-46.
242. Nava-Castaneda A, Tovilla-Canales JL, Boullosa V, et al. Duration of botulinum toxin effect in the
treatment of crocodile tears. Ophthal Plast Reconstr Surg. 2006;22(6):453-456.
243. Riemann R, Pfennigsdorf S, Riemann E, Naumann M. Successful treatment of crocodile tears by injection
of botulinum toxin into the lacrimal gland: a case report. Ophthalmology. 1999;106(12):2322-2324.
244. Hofmann RJ. Treatment of Frey's syndrome (gustatory sweating) and 'crocodile tears' (gustatory
epiphora) with purified botulinum toxin. Ophthal Plast Reconstr Surg. 2000;16(4):289-291.
245. Kyrmizakis DE, Pangalos A, Papadakis CE, Logothetis J, Maroudias NJ, Helidonis ES. The use of
botulinum toxin type A in the treatment of Frey and crocodile tears syndromes. J Oral Maxillofac Surg.
2004;62(7):840-844.
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org


25

246. Ginsberg D, Cruz F, Herschorn S, et al. OnabotulinumtoxinA is effective in patients with urinary
incontinence due to neurogenic detrusor overactivity [corrected] regardless of concomitant anticholinergic
use or neurologic etiology. Adv Ther. 2013;30(9):819-833.
247. Ginsberg D, Gousse A, Keppenne V, et al. Phase 3 efficacy and tolerability study of onabotulinumtoxinA
for urinary incontinence from neurogenic detrusor overactivity. J Urol. 2012;187(6):2131-2139.
248. Herschorn S, Gajewski J, Ethans K, et al. Efficacy of botulinum toxin A injection for neurogenic detrusor
overactivity and urinary incontinence: a randomized, double-blind trial. J Urol. 2011;185(6):2229-2235.
249. Cruz F, Herschorn S, Aliotta P, et al. Efficacy and safety of onabotulinumtoxinA in patients with urinary
incontinence due to neurogenic detrusor overactivity: a randomised, double-blind, placebo-controlled trial.
Eur Urol. 2011;60(4):742-750.
250. Grise P, Ruffion A, Denys P, Egon G, Chartier Kastler E. Efficacy and tolerability of botulinum toxin type A
in patients with neurogenic detrusor overactivity and without concomitant anticholinergic therapy:
comparison of two doses. Eur Urol. 2010;58(5):759-766.
251. Ehren I, Volz D, Farrelly E, et al. Efficacy and impact of botulinum toxin A on quality of life in patients with
neurogenic detrusor overactivity: a randomised, placebo-controlled, double-blind study. Scand J Urol
Nephrol. 2007;41(4):335-340.
252. Schurch B, de Seze M, Denys P, et al. Botulinum toxin type a is a safe and effective treatment for
neurogenic urinary incontinence: results of a single treatment, randomized, placebo controlled 6-month
study. J Urol. 2005;174(1):196-200.
253. Del Popolo G, Filocamo MT, Li Marzi V, et al. Neurogenic detrusor overactivity treated with english
botulinum toxin a: 8-year experience of one single centre. Eur Urol. 2008;53(5):1013-1019.
254. Akbar M, Abel R, Seyler TM, et al. Repeated botulinum-A toxin injections in the treatment of
myelodysplastic children and patients with spinal cord injuries with neurogenic bladder dysfunction. BJU
Int. 2007;100(3):639-645.
255. Grosse J, Kramer G, Stöhrer M. Success of repeat detrusor injections of botulinum a toxin in patients with
severe neurogenic detrusor overactivity and incontinence. Eur Urol. 2005;47(5):653-659.
256. Schulte-Baukloh H, Michael T, Stürzebecher B, Knispel HH. Botulinum-a toxin detrusor injection as a
novel approach in the treatment of bladder spasticity in children with neurogenic bladder. Eur Urol.
2003;44(1):139-143.
257. Amundsen CL, Richter HE, Menefee SA, et al. OnabotulinumtoxinA vs Sacral Neuromodulation on
Refractory Urgency Urinary Incontinence in Women: A Randomized Clinical Trial. Jama.
2016;316(13):1366-1374.
258. Sun Y, Luo D, Tang C, Yang L, Shen H. The safety and efficiency of onabotulinumtoxinA for the
treatment of overactive bladder: a systematic review and meta-analysis. Int Urol Nephrol.
2015;47(11):1779-1788.
259. Cui Y, Zhou X, Zong H, Yan H, Zhang Y. The efficacy and safety of onabotulinumtoxinA in treating
idiopathic OAB: A systematic review and meta-analysis. Neurourol Urodyn. 2015;34(5):413-419.
260. Nitti VW, Dmochowski R, Herschorn S, et al. OnabotulinumtoxinA for the Treatment of Patients with
Overactive Bladder and Urinary Incontinence: Results of a Phase 3, Randomized, Placebo Controlled
Trial. The Journal of Urology. 2013;189(6):2186-2193.
261. Jabs C, Carleton E. Efficacy of botulinum toxin a intradetrusor injections for non-neurogenic urinary urge
incontinence: a randomized double-blind controlled trial. J Obstet Gynaecol Can. 2013;35(1):53-60.
262. Chapple C, Sievert KD, MacDiarmid S, et al. OnabotulinumtoxinA 100 U significantly improves all
idiopathic overactive bladder symptoms and quality of life in patients with overactive bladder and urinary
incontinence: a randomised, double-blind, placebo-controlled trial. Eur Urol. 2013;64(2):249-256.
263. Visco AG, Brubaker L, Richter HE, et al. Anticholinergic Therapy vs. OnabotulinumtoxinA for Urgency
Urinary Incontinence. New England Journal of Medicine. 2012;367(19):1803-1813.
264. Denys P, Le Normand L, Ghout I, et al. Efficacy and safety of low doses of onabotulinumtoxinA for the
treatment of refractory idiopathic overactive bladder: a multicentre, double-blind, randomised, placebo-
controlled dose-ranging study. Eur Urol. 2012;61(3):520-529.
265. Tincello DG, Kenyon S, Abrams KR, et al. Botulinum toxin a versus placebo for refractory detrusor
overactivity in women: a randomised blinded placebo-controlled trial of 240 women (the RELAX study).
Eur Urol. 2012;62(3):507-514.
266. Dowson C, Sahai A, Watkins J, Dasgupta P, Khan MS. The safety and efficacy of botulinum toxin-A in the
management of bladder oversensitivity: a randomised double-blind placebo-controlled trial. Int J Clin
Pract. 2011;65(6):698-704.
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org


26

267. Rovner E, Kennelly M, Schulte-Baukloh H, Zhou J, Haag-Molkenteller C, Dasgupta P. Urodynamic results
and clinical outcomes with intradetrusor injections of onabotulinumtoxinA in a randomized, placebo-
controlled dose-finding study in idiopathic overactive bladder. Neurourol Urodyn. 2011;30(4):556-562.
268. Dmochowski R, Chapple C, Nitti VW, et al. Efficacy and safety of onabotulinumtoxinA for idiopathic
overactive bladder: a double-blind, placebo controlled, randomized, dose ranging trial. J Urol.
2010;184(6):2416-2422.
269. Cohen BL, Barboglio P, Rodriguez D, Gousse AE. Preliminary results of a dose-finding study for
botulinum toxin-A in patients with idiopathic overactive bladder: 100 versus 150 units. Neurourol Urodyn.
2009;28(3):205-208.
270. Flynn MK, Amundsen CL, Perevich M, Liu F, Webster GD. Outcome of a randomized, double-blind,
placebo controlled trial of botulinum A toxin for refractory overactive bladder. J Urol. 2009;181(6):2608-
2615.
271. Sahai A, Dowson C, Khan MS, Dasgupta P. Improvement in quality of life after botulinum toxin-A
injections for idiopathic detrusor overactivity: results from a randomized double-blind placebo-controlled
trial. BJU Int. 2009;103(11):1509-1515.
272. Brubaker L, Richter HE, Visco A, et al. Refractory idiopathic urge urinary incontinence and botulinum A
injection. J Urol. 2008;180(1):217-222.
273. White WM, Pickens RB, Doggweiler R, Klein FA. Short-term efficacy of botulinum toxin a for refractory
overactive bladder in the elderly population. J Urol. 2008;180(6):2522-2526.
274. Sahai A, Khan MS, Dasgupta P. Efficacy of botulinum toxin-A for treating idiopathic detrusor overactivity:
results from a single center, randomized, double-blind, placebo controlled trial. J Urol. 2007;177(6):2231-
2236.
275. Ghei M, Maraj BH, Miller R, et al. Effects of botulinum toxin B on refractory detrusor overactivity: a
randomized, double-blind, placebo controlled, crossover trial. J Urol. 2005;174(5):1873-1877; discussion
1877.
276. Dykstra DD, Sidi AA, Scott AB, Pagel JM, Goldish GD. Effects of botulinum A toxin on detrusor-sphincter
dyssynergia in spinal cord injury patients. J Urol. 1988;139(5):919-922.
277. de Seze M, Petit H, Gallien P, et al. Botulinum a toxin and detrusor sphincter dyssynergia: a double-blind
lidocaine-controlled study in 13 patients with spinal cord disease. Eur Urol. 2002;42(1):56-62.
278. Chen SL, Bih LI, Huang YH, Tsai SJ, Lin TB, Kao YL. Effect of single botulinum toxin A injection to the
external urethral sphincter for treating detrusor external sphincter dyssynergia in spinal cord injury. J
Rehabil Med. 2008;40(9):744-748.
279. Gallien P, Reymann JM, Amarenco G, Nicolas B, de Seze M, Bellissant E. Placebo controlled,
randomised, double blind study of the effects of botulinum A toxin on detrusor sphincter dyssynergia in
multiple sclerosis patients. J Neurol Neurosurg Psychiatry. 2005;76(12):1670-1676.
280. Utomo E, Groen J, Blok BF. Surgical management of functional bladder outlet obstruction in adults with
neurogenic bladder dysfunction. Cochrane Database Syst Rev. 2014(5):CD004927.
281. Moore DC, Cohn JA, Dmochowski RR. Use of Botulinum Toxin A in the Treatment of Lower Urinary Tract
Disorders: A Review of the Literature. Toxins (Basel). 2016;8(4):88.
282. Aurora SK, Dodick DW, Diener HC, et al. OnabotulinumtoxinA for chronic migraine: efficacy, safety, and
tolerability in patients who received all five treatment cycles in the PREEMPT clinical program. Acta
Neurol Scand. 2014;129(1):61-70.
283. Jackson JL, Kuriyama A, Hayashino Y. Botulinum toxin A for prophylactic treatment of migraine and
tension headaches in adults: a meta-analysis. Jama. 2012;307(16):1736-1745.
284. Lipton RB, Varon SF, Grosberg B, et al. OnabotulinumtoxinA improves quality of life and reduces impact
of chronic migraine. Neurology. 2011;77(15):1465-1472.
285. Cady RK, Schreiber CP, Porter JA, Blumenfeld AM, Farmer KU. A multi-center double-blind pilot
comparison of onabotulinumtoxinA and topiramate for the prophylactic treatment of chronic migraine.
Headache. 2011;51(1):21-32.
286. Aurora SK, Dodick DW, Turkel CC, et al. OnabotulinumtoxinA for treatment of chronic migraine: results
from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia.
2010;30(7):793-803.
287. Diener HC, Dodick DW, Aurora SK, et al. OnabotulinumtoxinA for treatment of chronic migraine: results
from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia.
2010;30(7):804-814.
288. Dodick DW, Turkel CC, DeGryse RE, et al. OnabotulinumtoxinA for treatment of chronic migraine: pooled
results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program.
Headache. 2010;50(6):921-936.
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org


27

289. Cady R, Schreiber C. Botulinum toxin type A as migraine preventive treatment in patients previously
failing oral prophylactic treatment due to compliance issues. Headache. 2007;48(6):900-913.
290. Stewart WF, Lipton RB, Dowson AJ, Sawyer J. Development and testing of the Migraine Disability
Assessment (MIDAS) Questionnaire to assess headache-related disability. Neurology. 2001;56(6 Suppl
1):S20-28.
291. Shim SR, Cho YJ, Shin IS, Kim JH. Efficacy and safety of botulinum toxin injection for benign prostatic
hyperplasia: a systematic review and meta-analysis. Int Urol Nephrol. 2016;48(1):19-30.
292. Marberger M, Chartier-Kastler E, Egerdie B, et al. A randomized double-blind placebo-controlled phase 2
dose-ranging study of onabotulinumtoxinA in men with benign prostatic hyperplasia. Eur Urol.
2013;63(3):496-503.
293. McVary KT, Roehrborn CG, Chartier-Kastler E, et al. A multicenter, randomized, double-blind, placebo
controlled study of onabotulinumtoxinA 200 U to treat lower urinary tract symptoms in men with benign
prostatic hyperplasia. J Urol. 2014;192(1):150-156.
294. Arnouk R, Suzuki Bellucci CH, Benatuil Stull R, de Bessa J, Jr., Malave CA, Mendes Gomes C. Botulinum
neurotoxin type A for the treatment of benign prostatic hyperplasia: randomized study comparing two
doses. ScientificWorldJournal. 2012;2012:463574.
295. Crawford ED, Hirst K, Kusek JW, et al. Effects of 100 and 300 units of onabotulinum toxin A on lower
urinary tract symptoms of benign prostatic hyperplasia: a phase II randomized clinical trial. J Urol.
2011;186(3):965-970.
296. Maria G, Brisinda G, Civello IM, Bentivoglio AR, Sganga G, Albanese A. Relief by botulinum toxin of
voiding dysfunction due to benign prostatic hyperplasia: results of a randomized, placebo-controlled
study. Urology. 2003;62(2):259-264; discussion 264-255.
297. Kuo HC, Liu HT. Therapeutic effects of add-on botulinum toxin A on patients with large benign prostatic
hyperplasia and unsatisfactory response to combined medical therapy. Scand J Urol Nephrol.
2009;43(3):206-211.
298. Langevin P, Lowcock J, Weber J, et al. Botulinum toxin intramuscular injections for neck pain: a
systematic review and metaanalysis. J Rheumatol. 2011;38(2):203-214.
299. Nicol AL, Wu, II, Ferrante FM. Botulinum toxin type a injections for cervical and shoulder girdle myofascial
pain using an enriched protocol design. Anesth Analg. 2014;118(6):1326-1335.
300. Miller D, Richardson D, Eisa M, Bajwa RJ, Jabbari B. Botulinum neurotoxin-A for treatment of refractory
neck pain: a randomized, double-blind study. Pain Med. 2009;10(6):1012-1017.
301. Lew HL, Lee EH, Castaneda A, Klima R, Date E. Therapeutic use of botulinum toxin type A in treating
neck and upper-back pain of myofascial origin: a pilot study. Arch Phys Med Rehabil. 2008;89(1):75-80.
302. Ojala T, Arokoski JP, Partanen J. The effect of small doses of botulinum toxin a on neck-shoulder
myofascial pain syndrome: a double-blind, randomized, and controlled crossover trial. Clin J Pain.
2006;22(1):90-96.
303. Zhang T, Adatia A, Zarin W, et al. The efficacy of botulinum toxin type A in managing chronic
musculoskeletal pain: a systematic review and meta analysis. Inflammopharmacology. 2011;19(1):21-34.
304. De Andres J, Adsuara VM, Palmisani S, Villanueva V, Lopez-Alarcon MD. A double-blind, controlled,
randomized trial to evaluate the efficacy of botulinum toxin for the treatment of lumbar myofascial pain in
humans. Reg Anesth Pain Med. 2010;35(3):255-260.
305. Göbel H, Heinze A, Reichel G, Hefter H, Benecke R, group Dmps. Efficacy and safety of a single
botulinum type A toxin complex treatment (Dysport) for the relief of upper back myofascial pain syndrome:
results from a randomized double-blind placebo-controlled multicentre study. Pain. 2006;125(1-2):82-88.
306. Ney JP, Difazio M, Sichani A, Monacci W, Foster L, Jabbari B. Treatment of chronic low back pain with
successive injections of botulinum toxin a over 6 months: a prospective trial of 60 patients. Clin J Pain.
2006;22(4):363-369.
307. Foster L, Clapp L, Erickson M, Jabbari B. Botulinum toxin A and chronic low back pain: a randomized,
double-blind study. Neurology. 2001;56(10):1290-1293.
308. Zebryk P, Puszczewicz MJ. Botulinum toxin A in the treatment of Raynaud's phenomenon: a systematic
review. Arch Med Sci. 2016;12(4):864-870.
309. Jenkins SN, Neyman KM, Veledar E, Chen SC. A pilot study evaluating the efficacy of botulinum toxin A
in the treatment of Raynaud phenomenon. J Am Acad Dermatol. 2013;69(5):834-835.
310. Neumeister MW. Botulinum toxin type A in the treatment of Raynaud's phenomenon. J Hand Surg Am.
2010;35(12):2085-2092.
311. Aurora SK, Gawel M, Brandes JL, Pokta S, Vandenburgh AM. Botulinum toxin type a prophylactic
treatment of episodic migraine: a randomized, double-blind, placebo-controlled exploratory study.
Headache. 2007;47(4):486-499.
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org


28

312. Relja M, Poole AC, Schoenen J, Pascual J, Lei X, Thompson C. A multicentre, double-blind, randomized,
placebo-controlled, parallel group study of multiple treatments of botulinum toxin type A (BoNTA) for the
prophylaxis of episodic migraine headaches. Cephalalgia. 2007;27(6):492-503.
313. Elkind AH, O'Carroll P, Blumenfeld A, DeGryse R, Dimitrova R, Group B---S. A series of three sequential,
randomized, controlled studies of repeated treatments with botulinum toxin type A for migraine
prophylaxis. J Pain. 2006;7(10):688-696.
314. Silberstein SD, Göbel H, Jensen R, et al. Botulinum toxin type A in the prophylactic treatment of chronic
tension-type headache: a multicentre, double-blind, randomized, placebo-controlled, parallel-group study.
Cephalalgia. 2006;26(7):790-800.
315. Padberg M, de Bruijn SF, de Haan RJ, Tavy DL. Treatment of chronic tension-type headache with
botulinum toxin: a double-blind, placebo-controlled clinical trial. Cephalalgia. 2004;24(8):675-680.
316. Schulte-Mattler WJ, Krack P, Bo NSG. Treatment of chronic tension-type headache with botulinum toxin
A: a randomized, double-blind, placebo-controlled multicenter study. Pain. 2004;109(1-2):110-114.
317. Ghorayeb I, Benard A, Vivot A, Tison F, Burbaud P. A phase II, open-label, non-comparative study of
Botulinum toxin in Restless Legs Syndrome. Sleep Med. 2012;13(10):1313-1316.
318. Agarwal P, Sia C, Vaish N, Roy-Faderman I. Pilot trial of onabotulinumtoxina (Botox) in moderate to
severe restless legs syndrome. Int J Neurosci. 2011;121(11):622-625.
319. Ghorayeb I, Burbaud P. Failure of botulinum toxin A to relieve restless legs syndrome. Sleep Med.
2009;10(3):394-395.
320. Nahab FB, Peckham EL, Hallett M. Double-blind, placebo-controlled, pilot trial of botulinum toxin A in
restless legs syndrome. Neurology. 2008;71(12):950-951.
321. Bonaparte JP, Ellis D, Quinn JG, Rabski J, Hutton B. A Comparative Assessment of Three Formulations
of Botulinum Toxin Type A for Facial Rhytides: A Systematic Review with Meta-Analyses. Plast Reconstr
Surg. 2016;137(4):1125-1140.
322. Sundaram H, Signorini M, Liew S, et al. Global Aesthetics Consensus: Botulinum Toxin Type A--
Evidence-Based Review, Emerging Concepts, and Consensus Recommendations for Aesthetic Use,
Including Updates on Complications. Plast Reconstr Surg. 2016;137(3):518e-529e.
323. Onabotulinumtoxin A (Botox Cosmetic®) [prescribing information]. Allergan Pharmacuticals, Inc.; Irvine,
CA 2016.
324. Atassi MZ. Basic immunological aspects of botulinum toxin therapy. Mov Disord. 2004;19 Suppl 8:S68-
84.
325. LCD for Botulinum Toxins Type A and Type B (R2) (L26841). 2008;
http://www.cms.hhs.gov/mcd/viewlcd.asp?lcd_id=26841&lcd_version=15&show=all.
326. Lexicomp Online: Clinical Drug Information Wolters Kluwer; 2016. Accessed October 7, 2016.
327. Alter K, Wilson N. Botulinum Neurotoxin Injection Manual. New York, NY: Demos Medical Publishing
2014.
328. Heinen F, Desloovere K, Schroeder AS, et al. The updated European Consensus 2009 on the use of
Botulinum toxin for children with cerebral palsy. Eur J Paediatr Neurol. 2010;14(1):45-66.
329. Goldstein EM. Safety of high-dose botulinum toxin type A therapy for the treatment of pediatric spasticity.
J Child Neurol. 2006;21(3):189-192.
330. Holden PK, Vokes DE, Taylor MB, Till JA, Crumley RL. Long-term botulinum toxin dose consistency for
treatment of adductor spasmodic dysphonia. Ann Otol Rhinol Laryngol. 2007;116(12):891-896.
331. Broadbent TJ, Wesley RE, Mawn LA. A Survey of Current Blepharospasm Treatment Patterns Among
Oculoplastic Surgeons. Ophthal Plast Reconstr Surg. 2016;32(1):24-27.
332. Vaezi MF, Pandolfino JE, Vela MF. ACG clinical guideline: diagnosis and management of achalasia. Am
J Gastroenterol. 2013;108(8):1238-1249; quiz 1250.
333. Arroyo A, Perez F, Serrano P, Candela F, Lacueva J, Calpena R. Surgical versus chemical (botulinum
toxin) sphincterotomy for chronic anal fissure: long-term results of a prospective randomized clinical and
manometric study. Am J Surg. 2005;189(4):429-434.
334. Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-
neurogenic) in adults: AUA/SUFU guideline. J Urol. 2012;188(6 Suppl):2455-2463.
335. Carruthers J, Fagien S, Matarasso SL, Botox Consensus G. Consensus recommendations on the use of
botulinum toxin type a in facial aesthetics. Plast Reconstr Surg. 2004;114(6 Suppl):1S-22S.

Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org