Published Articles for Botox

Published Articles for Botox® use in Headache

Updated 12-29-02

Note: All studies referenced in this summary involved the use of BOTOX® (Botulinum Toxin Type A) Purified Neurotoxin Complex (Allergan Inc.).

1. Migraine: Annotated literature review

Reference:	Silberstein S, et al. Headache, 40 2000:445-450
	Title	Botulinum Toxin Type A as a Migraine Preventive Treatment
	Question Addressed	“To Assess the safety and efficacy of botulinum toxin type A (Botox; Allergan, Inc) in the prevention of migraine.”
	Type of study	A: Double blind, vehicle controlled study N=123
	Outcomes of Study	Frequency and severity of migraine, migraine associated symptoms, days of acute migraine medication use
	Patient Characteristics	Migraine with or without aura
	Test/ Intervention	BTX-A 25U, 75U or placebo
	Results	(25 U dose) improvement up to 3 mos. Ż migraines Ż HA severity Ż days with acute migraine meds. Ż migraine associated vomiting No serious adverse events (75 U dose) non-statistical decrease in migraine increased treatment related adverse events
	Conclusions	“Pericranial injection of botulinum toxin type A, 25 U, was found to be a safe treatment that significantly reduced migraine frequency, migraine severity, acute medication usage, and associated vomiting.”

Reference:	Binder WJ, et al. Otolaryngology Head Neck Surg, 123 2000:669-676
	Title	Botulinum toxin type A (BOTOX) for treatment of migraine headaches: An open-label study
	Question Addressed	“The objective of this clinical experience was to evaluate the correlation between pericranial botulinum toxin type A (Botox, Allergan Corp, Irvine, CA) administration and alleviation of migraine headache symptoms.”
	Type of study	B: Nonrandomized open-label N=106
	Outcomes of Study	Headache frequency and severity
	Patient Characteristics	Migraine, possible migraine, non-migraine
	Test/ Intervention	BTX-A 5U-110U
	Results	Improvement up to 4.1 mos. Complete elimination of HA Ż HA severity & duration
	Conclusions	“BOTOX was found to be a safe and effective therapy for both acute and prophylactic treatment of migraine headaches. Further research is needed to explore and develop the complete potential for the neuroinhibitory effects of botulinum toxin.”

Reference:	Blumenfeld, AM Headache Q,, 12 2001:241-244
	Title	Impact of botulinum toxin type A treatment on medication costs and usage in difficult-to- treat chronic headache: case studies
	Question Addressed	“To assess the benefits of BTX-A in the treatment of difficult-to-treat chronic headache by evaluating its impact on acute medication usage.”
	Type of study	B: Retrospective Case Series Review N=5
	Outcomes of Study	Change in annual cost of headache-related medication usage
	Patient Characteristics	Migraine unresponsive to conventional therapy Four of the five patients also had features of tension-type, transformed, chronic daily, and/or rebound headache (ie. Combination headache)
	Test/ Intervention	BTX-A 40U-100U “Follow the pain”, multiple sites
	Results	improvement up to 2 mos. Ż migraine frequency Ż migraine severity Ż medication costs savings on medications No adverse events
	Conclusions	“BTX-A-induced decreases in the frequency and/or severity of chronic headaches led to decreased headache medication costs. A reduction in ED and office visits may provide further savings.”

Reference:	Klapper & Klapper Headache Q 10 1999:141-143
	Title	Use of Botulinum Toxin in Chronic Daily Headaches Associated With Migraine
	Question Addressed	“To evaluate the effect of Botulinum Toxin Type A (BTX-A) in chronic daily headache with migraine features.”
	Type of study	B: Open label, prospective N=5
	Outcomes of Study	Frequency of headache, medication usage
	Patient Characteristics	Tension type headache and migraine headache
	Test/ Intervention	BTX-A 75U Multiple + fixed site, fixed dose
	Results	improvement Ż migraine frequency/month Ż severity Ż medications No adverse events
	Conclusions	“Four of five patients experienced marked relief of both tension-type and migraine headaches.”

Reference:	Wheeler AH Headache 38 1998 468-471
	Title	Botulinum Toxin A, Adjunctive Therapy for Refractory Headaches Associated With Pericranial Muscle Tension
	Question Addressed	Evaluate the myalgia ,severity and frequency of migraine type headaches
	Type of study	D: Case Reports N=4
	Outcomes of Study	Pain (VAS), tenderness and spasm
	Patient Characteristics	Intractable daily headache and craniofacial pain who failed conventional therapy
	Test/ Intervention	BTX-A 20U-100U “Follow the pain”; multiple sites
	Results	improvement Ż severity Ż frequency No adverse events
	Conclusions	“This alleviated myalgia and reduced the severity and frequency of migraine-type headaches with a concomitant reduction in subsequent medical and physical therapy interventions. Judicious use of botulinum toxin A into defined areas of pericranial muscle tension may be useful for reducing primary myalgia and secondary headache.”

Reference:	Poungvarin N J Med Assoc Thai 84 2002:1199-1203
	Title	The First World Report of Botulinum A Toxin Injection for Status Migrainosus
	Question Addressed	Efficacy of Botox in status migrainosus
	Type of study	D: Case report N=1
	Outcomes of Study	Headache relief
	Patient Characteristics	Status migrainosus
	Test/ Intervention	BTX-A 25U Single site, single dose,
	Results	improvement up to 2 mos. Complete HA elimination
	Conclusions	“Dramatic response was observed within 1 hour of injection and status migrainosus was aborted within 10 hours. He was headache-free and had no further attack of migraine for another 2 months.”

Migraine: Published, Peer Reviewed Abstracts

Reference:	Relja M. Europ J Neurol, 4(2)1997:S71-S73
	Title	Treatment of Tension-Type Headache by Injection of Botulinum Toxin Type A: Double Blind Placebo-Controlled Study
	Question Addressed	“To evaluate the safety and efficacy of botulinum toxin A (BTX-A) injections in the treatment of patients with chronic tension-type headache (TTH).”
	Type of study	A (Published Abstract): Double blind, placebo controlled N=16
	Outcomes of Study	Total tenderness score, severity and duration of headache
	Patient Characteristics	Tension-type headache
	Test/ Intervention	BTX-A 35U-80U “Follow the pain”; multiple site injection protocol.
	Results	improvement up to 2 mos. Ż HA severity Ż HA duration No adverse events
	Conclusions	“The study concluded that injections of BTX A are an effective and safe prophylactic treatment for patients with TTH.”

Reference:	Barrientos N., Chana P Headache 2002 May;42(5):452 ABS S106
	Title	Efficacy and safety of botulinum toxin type A (BOTOX) in the prophylactic treatment of migraine
	Question Addressed	“To measure the safety and efficacy of botulinum toxin type A (BTX-A: Botox®, Allergan, Inc.) in the prophylaxis of migraine.”
	Type of study	A (Published Abstract): Randomized, double blind, placebo controlled N=30
	Outcomes of Study	Frequency and duration of migraine attack, acute analgesic use
	Patient Characteristics	Migraine
	Test/ Intervention	BTX-A 50U Single/multiple sites, “follow the pain” approach; multiple treatments
	Results	improvement up to 3 mos. Ż frequency of migraine attacks Ż migraine duration Ż acute use of medications (NSAIDS & triptans) Ż migraine with nausea Adverse event: frontal asymmetry lasting 30 d/n=1
	Conclusions	“BTX-A is an effective treatment for the prevention of migraine in this patient group, as demonstrated by reduced frequency and duration of attacks, and the reduction of acute analgesic use after treatment. These findings warrant further study in other patient populations.”

Reference:	Eross & Dodick Neurology 2002 Apr;58(Suppl 3):A497 ABS S64.005
	Title	The effects of botulinum toxin type A on disability in episodic and chronic migraine
	Question Addressed	“The objective of this study is to determine the effects of botulinum toxin type A (BTX-A) on disability in patients suffering from episodic or chronic migraine.”
	Type of study	B (Published Abstract): Prospective, open-label, feasibility study N=54
	Outcomes of Study	Migraine Disability Assessment Scale (MIDAS), headache days, average pain (VAS)
	Patient Characteristics	Migraine headache
	Test/ Intervention	BTX-A 25U-75U Multiple site, multiple injections
	Results	improvement up to 3 mos. Ż Migraine Disability Assessment Scale (MIDAS) Ż frequency
	Conclusions	“Conclusions will be available and presented at the 44th Annual AHS Scientific Meeting.”

Reference:	Mathew NT et al. Headache 2002 May;42(5):454 ABS S107
	Title	“Disease modification” in chronic migraine with botulinum toxin type A: long-term experience
	Question Addressed	“To report our experience over 2 years of using Botox in carefully selected patients with refractory chronic migraine, who benefited from the treatment and underwent repeat treatments.”
	Type of study	B (Published Abstract): Retrospective, open label N=112
	Outcomes of Study	Migraine Disability Assessment Scale (MIDAS), acute medication use
	Patient Characteristics	Chronic migraine

Silberstein S, et al. Headache, 40 2000:445-450

Title

Botulinum Toxin Type A as a Migraine Preventive Treatment

Question Addressed

“To Assess the safety and efficacy of botulinum toxin type A (Botox; Allergan, Inc) in the prevention of migraine.”

Patient Characteristics

Migraine with or without aura

Title

Botulinum toxin type A (BOTOX) for treatment of migraine headaches: An open-label study

Question Addressed

“The objective of this clinical experience was to evaluate the correlation between pericranial botulinum toxin type A (Botox, Allergan Corp, Irvine, CA) administration and alleviation of migraine headache symptoms.”

Patient Characteristics

Migraine, possible migraine, non-migraine

Title

Question Addressed

Patient Characteristics

Title

Use of Botulinum Toxin in Chronic Daily Headaches Associated With Migraine

Question Addressed

“To evaluate the effect of Botulinum Toxin Type A (BTX-A) in chronic daily headache with migraine features.”

Patient Characteristics

Tension type headache and migraine headache

Headache 38 1998 468-471

Title

Botulinum Toxin A, Adjunctive Therapy for Refractory Headaches Associated With Pericranial Muscle Tension

Question Addressed

Evaluate the myalgia ,severity and frequency of migraine type headaches

Patient Characteristics

J Med Assoc Thai 84 2002:1199-1203

Title

The First World Report of Botulinum A Toxin Injection for Status Migrainosus

Question Addressed

Efficacy of Botox in status migrainosus

Patient Characteristics

Europ J Neurol, 4(2)1997:S71-S73

Title

Treatment of Tension-Type Headache by Injection of Botulinum Toxin Type A: Double Blind Placebo-Controlled Study

Question Addressed

“To evaluate the safety and efficacy of botulinum toxin A (BTX-A) injections in the treatment of patients with chronic tension-type headache (TTH).”

Patient Characteristics

Barrientos N., Chana P Headache 2002 May;42(5):452 ABS S106

Title

Efficacy and safety of botulinum toxin type A (BOTOX) in the prophylactic treatment of migraine

Question Addressed

“To measure the safety and efficacy of botulinum toxin type A (BTX-A: Botox®, Allergan, Inc.) in the prophylaxis of migraine.”

Patient Characteristics

Eross & Dodick Neurology 2002 Apr;58(Suppl 3):A497 ABS S64.005

Title

The effects of botulinum toxin type A on disability in episodic and chronic migraine

Question Addressed

“The objective of this study is to determine the effects of botulinum toxin type A (BTX-A) on disability in patients suffering from episodic or chronic migraine.”

Patient Characteristics

Mathew NT et al. Headache 2002 May;42(5):454 ABS S107

Title

“Disease modification” in chronic migraine with botulinum toxin type A: long-term experience

Question Addressed

“To report our experience over 2 years of using Botox in carefully selected patients with refractory chronic migraine, who benefited from the treatment and underwent repeat treatments.”

Patient Characteristics