Transcript Practice Parameter: Treatment of Postherpetic Neuralgia

Practice Parameter: Pharmacological
Treatment of migraine headache in
children and adolescents
Report of the Quality Standards Subcommittee of the
American Academy of Neurology and the Practice
Committee of the Child Neurology Society
D. Lewis, MD; S. Ashwal, MD; A. Hershey, MD; D. Hirtz,
MD; M. Yonker, MD; S. Silberstein, MD
Published in Neurology 2004;63:2215-2224
© 2004 American Academy of Neurology
February 25, 2004
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© 2004 American Academy of Neurology
February 25, 2004
Objective of the guideline
• To review evidence on the pharmacological treatments
of migraine headache in children and adolescents.
• Non-pharmacological treatments and biobehavioral
measures are not addressed in the guideline.
© 2004 American Academy of Neurology
February 25, 2004
Methods of evidence review
•
The authors searched databases, including MEDLINE
and CURRENT CONTENTS for relevant articles
published from 1980 through December of 2003.
•
The age qualifier of three years to 18 years was
selected, as this is the age group when most children are
seen for pediatric or neurological evaluation.
© 2004 American Academy of Neurology
February 25, 2004
Methods of evidence review
•
Authors reviewed 166 articles and abstracts, which were
identified for this project. In addition, bibliographies of the
articles cited were checked for additional pertinent
references. Each of the selected articles abstracted and
classified by at least two committee members.
•
Individual committee members reviewed titles and
abstracts for content and relevance. Relevant position
papers from professional organizations were also
reviewed.
© 2004 American Academy of Neurology
February 25, 2004
AAN Strength of evidence
Class I Prospective, randomized, controlled clinical trial with
masked outcome assessment, in a representative
population. Where: primary outcome(s) is/are clearly
defined, exclusion/inclusion criteria are clearly
defined, adequate accounting for dropouts and
crossovers with numbers sufficiently low to have
minimal potential for bias relevant baseline
characteristics are presented and substantially
equivalent among treatment groups or there is
appropriate statistical adjustment for differences.
© 2004 American Academy of Neurology
February 25, 2004
AAN Strength of evidence
Class
II
Prospective matched group cohort study in a
representative population with masked outcome
assessment that meets criteria above OR a RCT in
a representative population that lacks one of above
criteria.
Class
III
All other controlled trials (including well-defined
natural history controls or patients serving as own
controls) in a representative population, where
outcome assessment is independent of patient
treatment.
Evidence from uncontrolled studies, case series,
case reports, or expert opinion.
Class
IV
© 2004 American Academy of Neurology
February 25, 2004
AAN Translation of evidence
to level of recommendation
Level
A
Established as effective, ineffective or harmful for
the given condition in the specified population.
Level
B
Probably effective, ineffective or harmful for the
given condition in the specified population.
Level
C
Possibly effective, ineffective or harmful for the
given condition in the specified population.
Level
U
Data inadequate or conflicting. Given current
knowledge, treatment is unproven.
© 2004 American Academy of Neurology
February 25, 2004
Introduction
• Migraine headaches are common in children; their
frequency increases through adolescence.
• The mean age of onset is 7.2 years for boys and 10.9
years for girls, with prevalence rates reported at:
– 3% for children age 3-7 years
– 4-11% for children age 7-11 years
– 8-23% for children age 11-15 plus years
© 2004 American Academy of Neurology
February 25, 2004
Introduction
• Evaluation includes a thorough medical and family history
and a complete physical examination.
• Diagnosis and assessment of symptoms is complicated by
the inability of children to articulate their complaints.
• Other infectious, allergic, or gastrointestinal disorders of
childhood may mimic symptoms of migraine.
• They difficulty of treating migraine in children is using
medications that have shown efficacy in adults, however,
the appropriate safety and efficacy studies have not been
conducted in children and adolescents.
© 2004 American Academy of Neurology
February 25, 2004
Introduction
2004 International Headache Society classification of
headache disorders; the criteria for pediatric migraine
without aura:
A.Greater than or equal to five attacks fulfilling features B-D
B.Headache attack lasting one to 72 hours
C.Headache has at least two of the following four features:
•
•
•
•
Either bilateral or unilateral (frontal/temporal) location
Pulsating quality
Moderate to severe intensity
Aggravated by routine physical activities
D.At least one of the following accompanies headache:
•
•
Nausea and/or vomiting
Photophobia and phonophobia (may be inferred from
their behavior)
© 2004 American Academy of Neurology
February 25, 2004
Acute Pharmacologic
Treatment
© 2004 American Academy of Neurology
February 25, 2004
Acute Pharmacologic
Treatment
• Recommended general principles for treatment of acute
migraine headache include the following:
– Treat attacks rapidly and consistently without
recurrence
– Restore the patient’s ability to function
– Minimize the use of back-up and rescue medications
– Optimize self-care and reduce subsequent use of
resources
– Be cost-effective for overall management
– Have minimal or no adverse events
© 2004 American Academy of Neurology
February 25, 2004
Clinical questions
•
How safe and tolerable are acute migraine medications
in children and adolescents?
•
What are the effects on acute headache pain of
medications taken during the attack?
© 2004 American Academy of Neurology
February 25, 2004
Class I Evidence
Author,
Year
Class
Drug: (NSAIDs and nonopiate analgesics )
Efficacy
Hamalainen, I
et al., 1997
(18)
Ibuprofen
Active: 68%
Placebo: 37%
P-value: <.05*
Lewis, et al.,
2002 (19)
Ibuprofen
Active: 76%
Placebo: 53%
P-value: .006
Acetaminophen
Active: 54%
Placebo: 37%
Exact p-values not
provided <.05
I
Hamalainen, I
et al., 1997
(18)
© 2004 American Academy of Neurology
February 25, 2004
Class I Evidence
Author,
Year
Class
Drug: (Triptrans)
Efficacy
Ueberall, 1999
(20)
I
Sumatriptan, Nasal
Active: 85.7%
Placebo: 42.8%
P-value: .03
Winner, et al.,
2000 (21)
I
Sumatriptan, Nasal
Active: 66%
Placebo: 53%
Exact p-values not
provided (~.05)
Ahonen, et al.,
2004 (22)
I
Sumatriptan, Nasal
Active: 64%
Placebo: 39%
P-value: .003
© 2004 American Academy of Neurology
February 25, 2004
Class I Evidence
Author,
Year
Class
Drug: (Triptrans)
Efficacy
Hamalainen,
et
al., 1997(25)
I
Sumatriptan, Oral
Active: 30%
Placebo: 22%
P-value: nonsignificant
Oral Triptans,
Rizatriptan
Active: 66%
Placebo: 56%
P-value: nonsignificant
Winner, et al., I
2002 (26)
© 2004 American Academy of Neurology
February 25, 2004
Conclusions
• For the acute treatment of migraine headaches in
children, both ibuprofen and acetaminophen have been
shown to be safe and effective.
• Sumatriptan is the only 5HT1 agonist that has proven
effective for the treatment of children and adolescents
with migraine with the nasal spray having the most
favorable profile.
• There is only class IV evidence for effectiveness of
subcutaneous sumatriptan. Oral “triptan” agents have
not demonstrated efficacy in class I studies.
© 2004 American Academy of Neurology
February 25, 2004
Recommendations
• Ibuprofen is effective and should be considered for the
acute treatment of migraine in children. (Class I, Level
A)
• Acetaminophen is probably effective and should be
considered for the acute treatment of migraine in
children. (Class I, Level B)
© 2004 American Academy of Neurology
February 25, 2004
Recommendations
• Sumatriptan nasal spray is effective and should be
considered for the acute treatment of migraine in
adolescents. (Class I, Level A)
• There is no supporting data for the use of any oral
“triptan” preparations in children or adolescents. (Class
IV, Level U)
• There is inadequate data to make a judgement on the
efficacy of subcutaneous sumatriptan. (Class IV, Level
U)
© 2004 American Academy of Neurology
February 25, 2004
Preventive Pharmacologic
Treatments
© 2004 American Academy of Neurology
February 25, 2004
Preventive Pharmacologic
Treatments
General principles related to the goals of migraine
preventive therapies are to:
– Reduce attack frequency, severity, and duration
– Improve responsiveness to treatment of acute attacks
– Improve function, reduce disability and improve the
patient’s quality of life
© 2004 American Academy of Neurology
February 25, 2004
Clinical Questions
• What are the effects on the frequency and/or severity of
migraine attacks of medications taken on a daily basis
for prevention of migraine?
• How safe and tolerable are preventive migraine
medications in children and adolescents?
• How do the efficacy and tolerability of preventive
medications for migraine compare to those for placebo?
© 2004 American Academy of Neurology
February 25, 2004
Class I and II Evidence
Author,
Year
Class
Drug (Antidepressants and Efficacy
Calcium Channel blockers)
Gillies, et al., I
1986 (36)
Antidepressant
medications,
Pizotifen
Non-significant
Battostella,
II
et
al., 1993(35)
Antidepressant
medications,
Trazodone
Non-significant
Sorge, et al., I
1988 (42)
Calcium channel blockers,
Flunarizine
p<0.001, 75% had
75-100% reduction
headache frequency
Battistella, et I
al 1990(41)
Calcium channel blockers,
Nimodipine
Non-significant
© 2004 American Academy of Neurology
February 25, 2004
Class II Evidence
Author,
Year
Class Drug (Antihypertensive Efficacy
agents)
Ludvigsson,
1974 (29)
II
Propranolol
81%
Forsythe, et
al., 1984 (30)
II
Propranolol
Non-significant
Olness, et al.,
1987 (31)
II
Propranolol
Non-significant
Sills, et al.,
1982 (32)
II
Clonidine
Non-significant
Sillanpaa,
1977 (33)
II
Clonidine
Active: 32%
Placebo: 34%
P-value: Nonsignificant
© 2004 American Academy of Neurology
February 25, 2004
Conclusions
• Flunarizine was studied in one class I trial and is
probably effective but is unavailable in the US.
• The evidence is insufficient to determine efficacy for the
antihistamine cyproheptadine, the antidepressant
amitriptyline, and the anticonvulsant agents valproic
acid, topiramate, and levetiracetam for prevention of
pediatric migraine.
• There is conflicting class II evidence regarding
propranolol and trazodone. Clonidine, pizotifen,
nimodipine and timolol were not shown to be more
effective than placebo.
© 2004 American Academy of Neurology
February 25, 2004
Recommendations
• Flunarizine is probably effective for preventive therapy
and can be considered for this purpose but it is not
available in the United States. (Class I, Level B)
• There is insufficient evidence to make any
recommendations concerning the use of: (Class IV,
Level U)
–
–
–
–
–
Cyproheptadine
Amitriptyline
Divalproex sodium
Topiramate
Levetiracetam.
© 2004 American Academy of Neurology
February 25, 2004
Recommendations
• Recommendations cannot be made concerning
propranalol or trazodone for preventive therapy as the
evidence is conflicting. (Class II, level U)
• Pizotifen and nimodipine (Class I, Level B) and
clonidine and timolol (Class II, Level B) did not show
efficacy and are not recommended.
© 2004 American Academy of Neurology
February 25, 2004
Future Research
© 2004 American Academy of Neurology
February 25, 2004
Standardized criteria:
•
For the diagnosis of migraine headaches in children
and adolescents are needed to facilitate proper
diagnosis and to provide a case definition that could be
used as part of therapeutic clinical trials.
•
Of the responses to treatment of migraine in children
and adolescents need to be established that are
related to the frequency, duration, severity, and
disability of headaches.
© 2004 American Academy of Neurology
February 25, 2004
•
The safety and efficacy of currently available
medications used to treat migraine headaches in
adults need to be established in children and
adolescents, particularly the dose and age range in
which these medications are deemed safe and
effective to use. Failure of an agent for acute or
preventive therapy to demonstrate efficacy to a
statistically significant degree does not imply that these
medications have no role in the pediatric population
and their use must be based upon good clinical
judgment.
© 2004 American Academy of Neurology
February 25, 2004
•
It is essential that multi-centered, placebo-controlled
clinical trials be conducted to assess the safety,
tolerability, and efficacy of medications used for the
acute and preventive treatment of pediatric and
adolescent migraine.
•
Efforts must be made to develop novel and innovative
study designs which will address the critical issue of
high placebo response rates encountered in clinical
trials in children and adolescents which has proven to
be the major impediment to demonstration of efficacy.
© 2004 American Academy of Neurology
February 25, 2004
•
There are no epidemiological studies of the incidence
or prevalence of status migraine [defined by the
International Headache Society as a prolonged attack
(≥ 72 hours) of unremitting headache] in children or
adolescents. These epidemiological studies are
needed, as well as treatment studies directed at this
clinical entity.
•
It will be important to understand the variations in
effects of treatments by age and gender.
© 2004 American Academy of Neurology
February 25, 2004
Participants
AAN Quality Standards
Subcommittee Members
Gary Franklin, MD, MPH (CoChair); Gary Gronseth, MD
(Co-Chair); Charles E. Argoff,
MD; Steven A. Ashwal, MD (exofficio); Christopher Bever, Jr.,
MD; Jody Corey-Bloom, MD,
PhD; John D. England, MD;
Jacqueline French, MD (exofficio); Gary H. Friday, MD;
Michael J. Glantz, MD;
Deborah Hirtz, MD; Donald J.
Iverson, MD; David J.
Thurman, MD; Samuel Wiebe,
MD; William J. Weiner, MD,
and Catherine Zahn, MD (exofficio).
© 2004 American Academy of Neurology
CNS Practice Committee
Members
Carmela Tardo, MD (Chair);
Bruce Cohen, MD (Vice-Chair);
Elias Chalhub, MD; Roy
Elterman, MD; Murray Engel,
MD; Bhuwan P. Garg, MD; Brian
Grabert, MD; Annette Grefe, MD;
Michael Goldstein, MD; David
Griesemer, MD; Betty Koo, MD;
Edward Kovnar, MD; Leslie Anne
Morrison, MD; Colette Parker
MD; Ben Renfroe, MD; Anthony
Riela, MD; Michael Shevell, MD;
Shlomo Shinnar, MD; Herald
Silverboard, MD; Russell Snyder,
MD; Dean Timmons, MD; Greg
Yim, MD; and Mary Anne
Whelan, MD.
February 25, 2004
To view the entire guideline and additional AAN
guidelines visit:
AAN.com/Guidelines
Published in Neurology 2004;63:2215-2224
© 2004 American Academy of Neurology
February 25, 2004