French Guidelines for the Diagnosis and Management of Migraine in

French Guidelines for the Diagnosis and Management of Migraine in Adults and Children

Gilles Gkraud, MD,l Michel Lank-i-Minet, MD,’ Christian Lucas, MD,3 and Dominique Valade, MD,4 on behalf of the French Society for the Study of Migraine Headache (SFEMC)

lDepartment of Neurology, Rangueil Hospital, Toulouse, 2Pain Centel; Pasteur Hospital, Nice, 3Depurtment of Neurology, Sulengro Hospital, Lille, and 4Heuduche Emergency Centel; Lur-iboisi&e Hospital, Paris, France

ABSTRACT

Background: The French Recommendations for Clinical Practice: Diagnosis and Therapy of Migraine are guidelines concerning the overall management of patients with migraine, including diagnostic and therapeutic strategies and assessment of disability

Objective: This article summarizes the guidelines as they apply to adults and children, and proposes future direction for steps toward optimal treatment of migraine in patients in France.

Methods: The recommendations were categorized into 3 levels of proof (A-C) according to the National Agency for Accreditation and Evaluation in Health (ANAES) methodology and were based on a professional consensus reached among members of the Working Group and the Guidelines Review Group of the ANAES.

Results: The International Headache Society diagnostic criteria for migraine should be used in routine clinical practice. Recommended agents for the treatment of migraine in adults include nonsteroidal anti-inflammatory drugs, acetylsalicylic acid (ASA) monotherapy or in combination with metoclopramide, acetaminophen monotherapy, triptans, ergotamine tartrate, and dihydroergotamine mesylate. Patients should use the medication as early as possible after the onset of migraine headache. For migraine prophylaxis in adults, the following can be used: propranolol, metoprolol, oxetorone, or amitriptyline as first-line treatment, and pizotifen, flunarizine, valproate sodium, or topiramate as second-line treatment. Migraine in children can be distinguished from that in adults by shorter duration (2-48 hours in children aged ~15 years), more frequent bilateral localization, frequent predominant gastrointestinal disturbances, and frequent pallor hailing the onset of the attack. The following drugs are recommended in children and adolescents: ibuprofen in children aged >6 months, diclofenac in children weighing >16 kg, naproxen in children aged >6 years or weighing >25 kg, ASA alone or in combination with metoclopramide, acetaminophen alone or in combination with metoclopramide, and ergotamine tartrate in children aged >10 years.

Conclusions: These guidelines are intended to help general practitioners to manage migraine patients according to the rules of evidence-based medicine. (Clin Ther: 2004;26: 1305-13 18) Copyright 0 2004 Excerpta Medica, Inc.

Key words: guidelines, migraine, diagnosis, treatment, adults, children.

Accepted for publicationJuly 22, 2004. Printed in the USA. Reproduction in whole or part IS not permitted. 0149-2918/04/$19.00

Copyright@ 2004 Excerpta MedicaJnc. 1305

CLINICAL THERAPEUTICS ®

I N T R O D U C T I O N The French Recommendations for Clinical Practice: Diagnosis and Therapy of Migraine 1 are guidelines concerning the overall management of patients with migraine, including diagnostic and therapeutic strategies and the assessment of disability caused by migraine. The guidelines were designed for health care professionals involved in the care of patients with migraine (eg, general practitioners, specialists, and pharmacists). This article summarizes the guidelines as they apply to adults and children. The complete text, with full argumentation and references, is available (in French) elsewhere.

These guidelines were developed at the request of the French Society for the Study of Migraine and Headache (Soci t fran aise d' tude des migraines et des c phal es) by the National Agency for Accred- itation and Evaluation in Health (ANAES). The ANAES is an official national agency that uses precise methodology to constitute Working and Review Groups, including specialists, general practitioners, members of the national drug agency, and others. Pharmaceutical companies are not represented in the ANAES, and everyone in the Working and Review Groups must sign a form indicating no conflicts of interest before participating.

Headaches other than migraine are not covered in these guidelines except as part of the differential diagnosis. Other associated topics (ie, conditions associated with migraine [apart from associated psychiatric disorders], predisposing migraine factors, migraine in pregnancy, menstrual migraine, migraine and oral contraception, migraine and smoking, transformed migraine, and rare and complicated forms of migraine headache [International Headache Society (IHS) Codes 1.2.2-1.5, Table 12]) are not discussed in this article.

In addition, a complete comparison of these guidelines with those of other national and international guidelines is beyond the scope of this article, because habits, drugs, and behaviors are different between countries. However, as shown in the reference list, these guidelines were based on evidence-based medicine and used data largely from the international literature.

G R A D I N G OF R E C O M M E N D A T I O N S I N T H E G U I D E L I N E S The recommendations are categorized into 3 levels (A-C), as follows.

Level A recommendations are based on established scientific evidence with the highest level of proof. These include randomized, comparative, controlled trials with high statistical power and without major bias; and/or meta-analyses of randomized, comparative controlled trials; or combinations of well-conducted studies.

Level B recommendations are based on scientific evidence provided by studies with an intermediate level of proof, such as randomized, comparative trials with lower statistical power; well-conducted, nonran- domized trials; or cohort studies.

Level C recommendations are based on evidence with a lower level of proof, such as that provided by case-control studies or case series.

Unless specified otherwise, the recommendations proposed were based on a professional consensus reached among members of the Working Group and the Guidelines Review Group of the ANAES. The absence of evidence with a high level of proof does not mean that the recommendations are not pertinent or useful; rather, it should be an incentive for additional studies when possible.

M I G R A I N E IN A D U L T S Prevalence

According to the diagnostic criteria described later, the estimated prevalence of migraine in adults aged 18 to 65 years is 12 to 17 in 100, with a female pre- dominance (female-male ratio, 3:1) .3#

Table I. International Headache Society classification of migraine.*

Code Description

I . I 1.2

1.2.1 1.2.2 1.2.6

1.3 1.5 1.6. I

Migraine wi thout aurar Migraine with aura Typical aura with migraine headache~ Other types of auras§ Rare and complicated forms of migrainell Probable migraine wi thout aura, fulfilling all the diagnostic criteria~ except one

~Adapted with permission. 2 ~SeeTable II 2 for diagnostic criteria of migraine without aura. ¢See Table III 2 for diagnostic criteria of typical aura with migraine headache. §Includes familial and sporadic hemiplegic migraine, basilar-type migraine. IIIncludes retinal migraine, chronic migraine, status migrainous, persi~ent aura, migrainous infarction.

] 3 0 6

G. G@raud et al.

Clinical Diagnosis The recommended diagnostic criteria for migraine

were established in 1988 by the IHS, based on an expert consensus} These criteria are summarized in Tables 112 and 111. 2

Only the diagnoses of migraine without aura (Code 1.1), typical aura with migraine headache (Code 1.2.1), and probable migraine without aura, fulfilling all the diagnostic criteria except one (Code 1.6.1) are covered in this article because the other types of migraine (Codes 1.2.2-1.5) are rarely encountered.

The diagnosis of migraine is based on a clinical triad (professional consensus):

• Recurrent attacks separated by totally pain-free intervals

• Characteristic migraine symptoms • Unremarkable clinical examination The IHS diagnostic criteria for migraine without

aura and for typical aura with migraine headache are presented in Tables 112 and 111, 2 respectively. These criteria are easy to use and enable the clini- cian to ask essential questions in a logical and structured manner. It is recommended to use the

Table II. Diagnostic criteria of migraine without aura.*

A. _>5 Attacks Fulfilling criteria B D B. Migraine attacks lasting 4-72 hours (untreated or unsucces>

fully treated) C. Headache with _>2 of the following characteristics:

Unilateral localization Pulsating quality Moderate or severe pain intensityt Aggravation by or causing avoidance of routine physical activity (eg, walking, climbing stairs)

D. The presence o[_>l of the Following symptoms occurs during the headache:

Nausea and/or vomiting Photosensitivity and phonosensitivity

E. Physical examination between attacks is unremarkable. In case of doubt, organic diseases should be ruled out using appropriate investigations

*Adapted with permission. 2 The term migraine without aura has replaced the former term, common migraine. The presence of criteria A E fulfills the strict diagnostic definition of migraine without aura (International Headache Society [IHS] classification code I. I [Table 12]). If one of the criteria A D is not fulfilled, the diagnosis is probable migraine without aura (IHS code 1.6. I [Table 12]).

tAs measured using a 4qtem painqntensity scale (0 = none, I = mild, 2 = moderate, and 3 = severe).

Table III. Diagnostic criteria of typical aura with migraine headache.*

A. >2 Attacks Fulfilling criteria B D B. Aura consisting of > I of the Following, but not motor weaknesst:

Fully reversible visual symptoms, including positive Features (eg, flickering lights, spots, or lines) and/or negative Features (eg, loss orvision)

Fully reversible sensory symptoms, including positive Features (eg,"pins and needles") and/or negative Features (eg, numbness)

Fully reversible dysphasic speech disturbance C. >2 of the Following:

Homonymous visual symptoms and/or unilateral sensory symptoms

_>1 Aura symptom developing gradually over _>5 minutes and/or different aura symptoms occurring in succession over _>5 minutes

Each symptom lasts 5 60 minutes D. Headache Fulfilling criteria B D for IHS migraine classification

I. I (migraine without auraS) begins during the aura or Follows aura within 60 minutes

E. Physical examination between attacks is unremarkable. In case of doubt, organic diseases should be ruled out using appropriate investigations

IHS = International Headache Society. ~Adapted with permission. 2 The term migraine with aura has replaced the former term, classic or accompanied migraine.

tFor more details, see reference 5. $See Table II 2 for diagnostic criteria of migraine without aura.

IHS criteria in routine clinical practice (professional consensus).

Critical analysis of these diagnostic criteria demon- strates an acceptable level of interobserver variability 6 and good specificity, but unsatisfactory sensitivity. 7,s Therefore, Lhe criteria are restrictive and cannot provide the diagnosis in all pauents with migraine. To avoid this problem in roudne practice and thus avoid depriving certain patients of appropriate management, it is recommended to use Code 1.6. ] (probable migraine without aura, fulfilling all diagnostic criteria except one).

Migraine must be distinguished from tension headache, a more diffuse headache that is nonpulsat- ing, not aggravated by exercise, and less intense (mild or moderate pain) than migraine, with no accompa- nying gastrointestinal (GI) symptoms but sometimes with phonosensitivity and/or photosensitivity (IHS criteria of tension headache2). Migraine and tension headache are often associated or intertwined in the same patient. 9

1307


Role of Additional DiagnosticTesting Computed Tomography and Magnetic Resonance Imaging

There is no indication for cerebral computed tomography (CT) or magnetic resonance (MR) imaging (professional consensus) in patients with migraine defined by IHS diagnostic criteria for migraine with or without aura or to differentiate migraine from tension headache. 1° In patients with known migraine, cerebral CT scanning or MR imaging is recommended (professional consensus) in cases of sudden-onset headache (so-called "thunderclap" headache) and recent (past 3 months) headache different from the usual migraine. In cases of acute, severe, intense headache that develops in <1 minute and lasts >1 hour, emergency noncontrast cerebral CT scanning or MR imaging is recommended. M

Electroencephalography Electroencephalography (EEG) is not indicated in

patients with migraine as defined by the IHS diagnostic criteria ~2 (professional consensus). EEG is not recommended to rule out secondary headaches; CT scanning and MR imaging are indicated for this (professional consensus).

Sinus and Cervical Spine Radiography, Ophthalmic and Orthoptic Examination, and Abdominal Sonography

There is no indication for radiography of the sinus- es or the cervical spine, ophthalmic examination, orthoptic examination, or abdominal sonography for the diagnosis of migraine (professional consensus).

Assessment of Disability to Optimize Management Migraine has a serious impact on patients' lives

because of the frequency of the attacks (>2 attacks/ month in 42%-50% of patients); their duration (>24 hours in 39% of patients); their intensity (severe or very severe in 48%-74% of patients); the presence of associated GI symptoms; and the disruption of activities of daily living (ADLs), including those in occupational, social, and family life. 3,<~3

To achieve optimal management of migraine, it is recommended (professional consensus) to advise patients to keep a diary Patients should note the date, duration, intensity, and triggering factors of the attack, as well as any medications used to treat it.

This diary can be used by the physician to better determine the severity of the migraine, to take into account the impact of the disease on ADLs, and to assist in the choice of treatment and type of follow-up measures required.

Anxiety and/or depressive disorders concurrent with migraine further aggravate disability. 1~-16 Careful history taking is recommended to look for signs of depression or anxiety, and to focus therapy not only on the pain but also on any associated depression and anxiety.

Several scales have been developed to measure the quality of life and productivity of migraineurs. 17-~9 Two scales--the Short-Form Headache Impact Test 2° and the Migraine Disability and Assessment (MIDAS)X~--have been translated into French but have not been assessed in migraine management in France. Among the migraine population, it would be important to identify those patients who require reg- ular medical care. Further research should be per- formed in this area.

Pharmacologic Treatment Migraine is a largely underdiagnosed condition. In

French studies, 3,~ 30% to 45% of migraineurs have never consulted a physician for migraine, and are unaware that they have migraine and that appropriate treatment is available. This situation leads to widespread self-medication for attacks; -50% of migraineurs use over-the-counter drugs to treat their attacks.

Study of the treatment patterns of migraineurs has revealed overconsumption of nonspecific analgesics, with several doses being taken during the same attack and with half of patients having no significant migraine relief 2 hours after dosing. = It also reveals underuse of migraine-specific treatments by patients who would benefit from them, such as those with severe attacks, those whose migraine is disabling, and/or those who do not attain relief with nonspecific drugs.

Acute Treatment Acute treatments for migraine attacks can be classi-

fied into 2 categories: nonspecific agents (analgesics and nonsteroidal anti-inflammatory drugs [NSAIDs]) and migraine-specific agents (ergot derivatives and triptans), which, by their effect on serotonin (5-HT~B/~ >)

1308

G. G@raud et al.

receptors, inhibit neurogenic inflammation and vasodilatation considered to be the cause of migraine headache. 23

Nonspecific Agents Recommended nonspecific agents include NSAIDs

(naproxen sodium, 2<25 ibuprofen, 2<2r ketoprofen, 28 or diclofenac potassium > [level A]); acetylsalicylic acid (ASA) monotherapy 3° (level A) or in combination with metoclopramide 31,32 (level A); and acetaminophen monotherapy 33 (level C). Combining metoclopramide hydrochloride with ASA improves the risk for GI symptoms but does not potentiate the analgesic effect of ASA (professional consensus). No clinical evidence shows that combining caffeine with acetaminophen or ASA potentiates the effect of these drugs. Adjunctive use of caffeine cannot be recommended because it may induce drug abuse or dependence/addiction (professional consensus).

Opiate analgesics (eg, codeine sulfate, propoxy- phene hydrochloride, tramadol hydrochloride, mor- phine sulfate) should not be used alone or in combination for migraine because of the risk for abuse or dependence/addiction (professional consensus). 2~

Migraine-Specific Agents Triptans 23 (level A) are effective for migraine

headache, associated GI symptoms, and phono-/ photosensitivity. Ergotamine tartrate 3. (level B) and dihydroergotamine mesylate nasal spray 35 (level A) or injection 36 (level B) are recommended.

Only the compounds listed in Table IV are licensed in France (Autorisation de mise sur le march [AMM]) for the indication of the acute treatment of migraine.

activities? If the patient says yes to all 4 of these questions, his

or her treatment regimen should not be changed. If the patient says n o to at least 1 of these 4 ques-

tions, the physician should prescribe an NSAID and a triptan together. The patient should be instructed to start with the NSAID and use the triptan only if relief is not obtained 2 hours after receiving the NSAID. If the NSAID is ineffective or poorly tolerated, a triptan should be prescribed as the first-line drug.

There are various medicaP r and economic 38 argu- ments for using triptans as the first-line treatment in patients with severe attacks and/or patients who are greatly disabled by migraine. However, due to the lack of validated scales in French for routine clinical practice, no professional consensus exists there.

Patients Previously Treated with Migraine-Specific Agents If a patient treats with ergotamine tartrate, his or

her treatment regimen should not be changed if he or she has effective migraine relief (no pain or mild pain) 2 hours after receiving ergotamine, has no contraindications to its use, and is not requiring increas- ingly higher doses 3. (professional consensus).

Each triptan has efficacy and tolerability profiles different from the others, but these differences are minimal 23 (level A). A patient who does not respond to 1 triptan may respond to another. > A patient who does not respond to a particular triptan during an initial migraine attack may respond to it in subsequent attacks (level A). Before concluding that a particular triptan is ineffective in a patient, it should be tried for _>3 attacks, unless it is poorly tolerated (professional consensus).

Therapeutic Strategy Patients Previously Treated with Nonspecific Agents

During a patient's initial consultation, it is recommended to ask the patient about his or her usual migraine medication practices and the relief obtained with it (professional consensus), using the following questions:

• Do you have significant relief <2 hours after taking the medication?

• Is the medication well tolerated? • Do you take only 1 dose? • Two hours after taking the medication, can you

resume normal occupational, social, and family

Method of Use Irrespective of the type of treatment, the patient

should take the medication as early as possible after the onset of migraine headache. Delaying administra- tion of an oral triptan after the onset of a migraine headache might reduce the likelihood of complete relief, increase the risk for headache recurrence and adverse effects, and prolong suffering *°#1 (level A). If an ergot derivative or triptan is being used, the patient should wait until a headache develops before treating an attack preceded by aura (professional consensus).

For all patients with migraine, the total number of doses taken per month should be counted, using

1309

r-

Z Z C

Tabl

e IV

. D

rugs

lic

ense

d in

Fra

nce

(Aut

oris

atio

n de

mis

e su

r le

mar

ch~

[AM

M])

for

the

ind

icat

ion

of t

he a

cute

tre

atm

ent

of m

igra

ine.

Age

s Tr

eatm

ent T

ype/

A

ppro

ved

Act

ive

Subs

tanc

e fo

r; y

Dos

e A

dver

se E

ffect

s C

ontra

indi

catio

ns

%

Sym

ptom

atic

tre

atm

ents

for

mig

rain

e he

adac

he a

nd a

ssoc

iate

d G

I dis

turb

ance

s C

arba

spiri

n ca

lciu

m +

met

oclo

pram

ide

HC

I >1

0

Lysi

ne a

cety

lsal

icyl

ate

+ m

etoc

lopr

amid

e >

I 0

M ig

rain

e-sp

ecifi

c tre

atm

ents

E

rgot

der

ivat

ives

Erg

otam

ine

taFL

rate

>

I 0

Dih

ydro

ergo

tam

ine

mes

ylat

e >1

6 an

d <6

5

900

mg,

giv

en a

t atta

ck o

nset

900

mg,

giv

en a

t atta

ck o

nset

Adu

lts: 2

mg/

d, m

ax 6

mg/

d an

d 10

mg/

wk

Chi

ldre

n >

I 0 y

ears

: hal

f dos

e

Intra

nasa

l sol

utio

n: I

spra

y in

eac

h no

stril

at a

ttack

ons

et; i

njec

tabl

e so

lutio

n: I

am

pule

, may

be

repe

ated

on

ce 3

0-60

min

lat

er- (

max

2 m

g/d

and

8 m

g/w

k)

Rel

ated

to m

etoc

lopr

amid

e:

neur

opsy

chia

tric

diso

rder

s, ta

r-di

ve

dysk

ines

ia, e

xtra

pyra

mid

al s

ympt

oms,

en

docr

ine

diso

rder

s

Rel

ated

to s

alic

ylat

e: G

I dis

turb

ance

s,

hem

orrh

agic

syn

drom

e,

hype

rsen

sitiv

ity r

eact

ions

, R

eye'

s syn

drom

e

Erg

otis

m, n

ause

a, vo

miti

ng

Intra

nasa

l sol

utio

n: tr

ansi

ent

loca

l re

actio

ns, n

asal

obs

truct

ion,

rh

inor

rhea

. In

ject

able

sol

utio

n: e

rgot

ism

, pr

ecor

dial

pai

n

Rel

ated

to m

etoc

lopr

amid

e:

pheo

chro

moc

ytom

a, G

I bl

eedi

ng,

sten

osis

or

perfo

ratio

n of

the

GI t

ract

, hi

stor

y of

dru

g-in

duce

d ta

r-di

ve

dysk

ines

ia

Rel

ated

to s

alic

ylat

e: ac

tive

gast

rodu

oden

al u

lcer

, hyp

erse

nZiv

~ to

sal

icyl

ates

, risk

for-

hem

ords

age

Hyp

erse

nsiti

vity

to e

rgot

der

ivat

ives

, pe

riphe

ral v

ascu

lar d

isea

se, c

oron

ary

arte

ry d

isea

se, s

hock

, hyp

erte

nsio

n,

seve

re in

fect

ion,

sev

ere

liver

- failu

re

(con

tinue

d)

Tabl

e IV

. (C

ontin

ued)

Age

s T

reat

men

t Typ

e/

App

rove

d A

ctiv

e Su

bsta

nce

for,

y D

ose

Adv

erse

Effe

cts

Con

trai

ndic

atio

ns

SSR

As

8 65

Alm

otrip

tan

mal

ate

Elet

ripta

n Fr

ovat

ripta

n su

ccin

ate

Nar

atrip

tan

HC

I R

izat

ripta

n be

nzoa

te

Sum

atrip

tan

succ

inat

e

Zolm

itrip

tan

Tabl

et:

12.5

mg/

d, m

ax 2

5 m

g/d

Tabl

et: 4

0 m

g/d,

max

80

mg/

d Ta

blet

: 2.5

mg/

d, m

ax 5

mg/

d Ta

blet

: 2.5

mg/

d, m

ax 5

mg/

d Ta

blet

, lyo

phili

sate

: 10

20

mg/

atta

ck

Tabl

et: 5

0 10

0 m

g/d,

max

300

mg/

d;

subc

utan

eous

inj

ectio

n: 6

mg/

atta

ck,

may

be

repe

ated

onc

e; s

uppo

sito

ry:

25 m

g, m

ax 5

0 m

g/d;

nas

al s

pray

: 10

20

mg/

atta

ck

Tabl

et: 2

.5 m

g/d

max

10

mg/

d;

nasa

l spr

ay: 5

mg/

0.1

mL

Vasc

ular

- flu

shin

g; v

eFLi

go; a

sthe

nia;

so

mno

lenc

e; n

ause

a; vo

miti

ng; c

oron

ary

spas

m (

< I%

of

atta

cks)

; m

oder

ate

or- s

ever

e hy

peFL

ensi

on;

pare

sthe

sia;

se

nsat

ions

of w

eakn

ess,

ting

ling,

hea

t, pr

essu

re, o

r- tig

htne

ss

Hyp

erse

nsiti

vity

to S

SRAs

; his

tory

of

myo

card

ial

infa

rctio

n or

isc

hem

ic

hear

t di

seas

e, c

oron

ary

vaso

spas

m

(Prin

zmet

al's

ang

ina)

, or-

perip

hera

l va

scul

ar- d

isea

se, s

troke

, or

- tra

nsie

nt

isch

emic

atta

ck; s

ever

e liv

er- f

ailu

re;

mod

erat

e or

- sev

ere

hype

FLen

sion

or

unc

ontr

olle

d m

ild h

yper

tens

ion;

co

mbi

natio

n w

ith m

onoa

min

e ox

idas

e in

hibi

tor-

GI =

ga~

roin

te~i

nal;

HC

I = h

ydro

chlo

ride;

max

= m

axim

um; S

SRAs

= se

lecL

ive se

roto

nin

rece

ptor

ago

nist

s.


a diary, to identify excessive use of medication (>10 d/mo for >3 months). Excessive use occurs fre- quently in patients with migraine and can lead to the development of chronic daily headache related to medication overuse 21 (professional consensus). This is true of all the migraine medications.

Migraine Prophylaxis Nonpharmacologic Prophylactic Treatments

Relaxation, biofeedback, and cognitive and behavioral therapies for stress management have been

shown to be effective in the prophylactic treatment of migraine ~2 (level B) and can be considered in some patients, depending on their psychological profile. Data ~3-~5 in the literature are insufficient to draw conclusions about the efficacy of acupuncture, homeop- ath> and cervical manipulation for the prevention of migraine.

Pharmacologic Prophylaxis Drugs prescribed for prophylactic treatment of

migraine are listed in Table V. ~6#r The following drugs

TableV. Drugs* used in France for the prophylaxis of migraine in adults. 46,47

Active Substance Daily Dosage Adverse Effects Contraindications

Propranolol HCI 40 240 mg

Hetoprolol succinate

Timolol maleatet

Atenololt

Nadolol

Oxetorone fumarate

Amitriptyline HCI

Pizotifen maleate

Valproate sodiumt

Hethysergide maleate

Flunarizine HCI

Gabapentint

Indoramin

I 0(~200 mg

I 0 ~ 0 mg

100 mg

80~40 mg

60 180 mg (I 3 tablets)

1030 mg in the evening

Progressive dosage to 3 tablets/d (0.5 1.5 mg)

50(~ 1000 mg

2 6 mg (I 3 tablets); discontinuation required for I m o q 6 m o

10 mg (I tablet in the evening); <6 mo consecutively

1200 2400 mg

50 mg

Topiramate 50 200 mg

Common: asthenia, poor exercise tolerance; rare (<1% of attacks): insomnia, nightmares, impotence, depression, hypoglycemia

Common: somnolence; rare (< I% of attacks): diarrhea requiring discontinuation

Dry mouth, somnolence, weight gain

Common: sedation, weight gain; rare (< 1% of attacks): digestive disorders, vertigo, muscle pain, asthenia

Nausea, weight gain, somnolence, tremor, alopecia, abnormal liver function test results

Common: nausea, vertigo, insomnia; rare (< I% of attacks): retroperitoneal fibrosis

Common: somnolence, weight gain; rare (<1% of attacks): depression, extrapyramidal syndrome

Nausea, vomiting, convulsion, somnolence, ataxia, vertigo

Somnolence, nasal congestion, dry mouth, ejaculation disorders

Vertigo, ataxia, somnolence, dysarthria, paresthesia, irritabili~ asthenia, weight loss

Asthma, heart failure, atrioventricular block, bradycardia (note: possible aggravation of migraine with aura)

Glaucoma, prostatic adenoma

Glaucoma, urethroprostatic disorders

Liver disease

Hypertension, coronary insuf- ficiency, arteriopathy, gastric u Icer, liver and/or kidney failure

Depression, extrapyramidal syndrome

Hypersensitivity to gabapentin

Hypersensitivity to one of the active compounds; Parkinson's disease; severe heart, liver, and/or kidney failure

Hypersensitivity to one of the active compounds and/or to sulfamides

HCI = hydrochloride. *All of these drugs are given in tablet form. tThis drug has not been approved for the prophylaxis of migraine.

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have been approved for this indication in France~6#7: flunarizine hydrochloride, methysergide maleate, metoprolol succinate, oxetorone fumarate, pizotifen, and propranolol hydrochloride (all level A); and dihydroergotamine and indoramin hydrochloride (both level B). Amitriptyline hydrochloride is approved for the indication of refractory pain (level A).

The following drugs are approved for indications other than prophylactic treatment of migraine but are also effective for this indication: atenolol, divalproate, valproate sodium, gabapentin, nadolol, naproxen sodium, timolol maleate, and topiramate (all level A)28

There is no evidence that ASA, fluoxetine hydrochloride, cyclandelate, or dihydroergocryptine is effective in prophylaxis of migraine.

Therapeutic Strategy (Professional Consensus) When to Use Pharmacologic Prophylaxis

It is recommended to start prophylactic treatment in 2 situations: (1) as a function not only of the frequency and the intensity of the attacks but also of the ADL disability caused by them; and (2) when a patient has taken 6 to 8 doses of acute migraine medication per month for _>3 consecutive months, even if the medication is effective, to avoid medication overuse (this applies to migraine-specific and/or nonspecific agents).

The introduction of preventive treatment should be combined with patient education. The patient should be advised that preventive treatment does not elimi- nate migraine attacks but does limit their frequency and intensity. Keeping an attack diary is helpful for assessing the efficacy of the prophylactic treatment.

Drugs to Use in Prophylaxis No compound has been shown to be more effica-

cious in migraine prophylaxis compared with the others (level A). Thus, the choice of drug depends on the risk-benefit ratio, including adverse effects, contraindications, drug-drug interactions, and any comorbidities the patient may have. "+9 Taking into account the risk-benefit ratio, the following drugs can be used: propranolol, metoprolol, oxetorone, or amitriptyline as first-line treatment; pizotifen, flunarizine, valproate sodium, gabapentin, or topiramate as second-line treatment. Methysergide is effective for third-line prophylaxis, but its use is associated with a risk for retroperitoneal fibrosis; thus, it should be

reserved for patients with severe migraine resistant to other treatments. ~6 Dihydroergotamine (10-20 mg) is widely used for first-line prophylaxis in France and is well tolerated. ~6 However, its efficacy remains to be confirmed.

Starting Treatment Prophylaxis should begin with a single drug, at a

low dose. The dose should be increased progressive- ly until the optimal dose is achieved, with adverse effects taken into account.

Evaluation of E~cacy The efficacy of migraine prophylaxis should be

assessed after >3 months of treatment. Treatment is considered to be effective if the frequency of migraine attacks is reduced by >50%. It is also important to take into account the reduction in the consumption of acute-treatment medications and the intensity and duration of the attacks as measured using the diary.

Alternative Prophylaxis If prophylactic treatment is unsuccessful, and the

patient has not experienced any adverse effects, the dose can be increased. Or, a different prophylactic drug can be used. After each prophylactic monotherapy has been tried, 2 drugs may be combined, each at a low dose to reduce the risk for adverse effects with either drug.

Discontinuation If successful, prophylactic treatment should be

continued for 6 months to 1 year. The dose should then be decreased slowly (over 3-6 months) prior to discontinuation. The same treatment can be restarted if the frequency of the attacks increases again.

MIGRAINE IN CHILDREN Prevalence

The prevalence of migraine in children (aged 5 to 15 years) is estimated to be between 3% and 10% in France. 5o

Clinical Diagnosis Migraine in children can be distinguished from that

in adults by shorter duration (2-48 hours in children aged <15 years2), more frequent bilateral localization, frequent predominant GI disturbances, and frequent

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pallor hailing the onset of the attack. 5° As in adults, it is recommended to use IHS Code

1.6.1 (probable migraine without aura, fulfilling all the diagnostic criteria but one) to avoid depriving some children of appropriate management. The lack of sensitivity of the IHS diagnostic criteria for migraine without aura is more pronounced in children than in adults. 51,52

Role of Additional DiagnosticTesting The role of additional diagnostic testing is the same

for children as in adults, except that indications for neuroimaging should be expanded because of the difficul- ty in establishing the cause of headache in children. 53

Assessment of Disability to Optimize Management

As in adults, no quality-of-life scale has been validated in French. Instead, it is recommended to keep a diary of the attacks to help the child and his or her family identify precipitating factors, evaluate treatment efficacy, and enable the physician to assess the characteristics of migraine (attack frequency, intensity, and associated GI symptoms) and its impact on daily life (eg, missed school days).

Pharmacologic Treatment Acute Treatment Nonspecific/Migraine-Specific Agents

The following drugs are recommended for children and adolescents in acute first-line treatment of migraine (professional consensus): ibuprofen in children aged >6 months, 5~ diclofenac in children weighing >16 kg, naproxen in children aged >6 years or weighing >25 kg, ASA alone or in combination with metoclopramide, acetaminophen alone or in combination with metoclopramide, and ergotamine tartrate in children aged >10 years. Sumatriptan succinate nasal spray (10-20 mg) is effective 55,56 (level A) for the treatment of moderate to severe migraine attacks in adolescents aged 12 to 17 years.

Data 57 in the literature are insufficient to draw conclusions about the efficacy of oral or injectable sumatriptan in children and adolescents, and sumatriptan nasal spray in children aged 5 to 12 years.

Therapeutic Strategy It is recommended (professional consensus) to

instruct patients and their families to use/administer acute medications as early as possible after the onset of migraine headache. The rectal route should be used in cases of nausea or vomiting. The intranasal route should be used in children aged >12 years and in children weighing >35 kg. If acetaminophen, ASA, and other NSAID treatments are unsuccessful, sumatriptan nasal spray should be the next line of treatment. If aura develops preceding a migraine attack, the child should wait for the development of headache before treating with triptans or ergot derivatives.

Migraine Prophylaxis Nonpharmacologic Prophylaxis

Relaxation, biofeedback, and cognitive and behavioral therapies for stress management are recommended for migraine prophylaxis in children, as in adults 58 (level B). These treatments have been shown to be more effective than beta-blockers 59 (level B).

Pharmacologic Prophylaxis Physicians should prescribe drugs as prophylactic

treatment only after failure of nonpharmacologic treatments (professional consensus). There is a lack of established scientific evidence about the efficacy of prophylactic treatments in children, but the following drugs can be recommended if nonpharmacologic treatments are unsuccessful or if migraine attacks are particularly frequent or severe, with a significant handicap in ADLs (professional consensus): flunarizine 5 mg/d in children aged >10 years, dihydroergotamine 5 to 10 mg/d, pizotifen 1 mg/d in children aged >12 years, propranolol 2 to 4 mg/kg.d, metoprolol 25 to 30 mg/d, oxetorone 15 to 30 mg/d, and amitriptyline 3 to 10 mg/d. These compounds should be used at low doses to reduce the occurrence of adverse effects, particularly sedation.

PROPOSITIONS FOR FUTURE ACTION To optimize the treatment of migraine in patients in France, the MIDAS 21 must be validated in studies of migraine. The MIDAS also must be tested as an evaluation tool for deciding when to initiate--and to test the effect of long-term treatment. Patients requiring regu- lar medical care should be identified. Migraine recommendations should be adapted for individual patients.

Regarding prophylaxis, the efficacy of migraine prophylaxis with dihydroergotamine must be evalu-

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ated using the methodology defined by the IHS. For children, valid and reliable diagnostic criteria

must be developed. Also, the efficacy of acute treatment and prophylactic treatment should be evaluated in this patient population.

Finally, due to rapid evolution of migraine treatments, the recommendations established by the Work- ing Group should be revised in 5 years.

A C K N O W L E D G M E N T S These guidelines were drawn up at the request of the French Society for the Study of Migraine Head- ache (Soci t fran aise d' tude des migraines et des c phal es) by the ANAES.

Members of the Working Group included: Chairman: Gilles G raud (Toulouse); Project Managers: Marie-Christine Mignon (ANAES, Paris) and Nathalie Preaubert (ANAES, Paris); Members: Gilles Baudesson (Saint-Ouen-Iiaum ne), Jacques Birge (Boulay), Fr d rique Brudon (Villeurbanne), Mayer Cikurel (Le Cheznay), Catherine Denis (Saint Denis), Elsa Diarte (Saint-Denis), Nathalie Dumarcet (Saint-Denis), Mohammed E1 Amrani (Paris), Louis- Pierre Jenoudet (Bron), Michel Lanteri-Minet (Nice), Christian Lucas (Lille), Jean-Fran ois Maurin (Arm es), Philippe Michel (Bordeaux), Naji Mimassi (Brest), Jean-Claude Mselati (Orsay), Philippe Nicot (Panazol), Clara Pelissier (Paris), Patrick Pochet (Clermont-Ferrand), Fran oise Radat (Bordeaux), Jacques Robert (Melun), and Dominique Valade (Paris).

Members of the Guidelines Review Group included: Daniel Annequin (Paris), Sylvie Aulanier (Le Havre), Alain Autret (Tours), Laurent Barl (Lons- Le-Saunier), Patrick Bastien (ANAES), G rard Mer (ANAES), Henri Becker (Cannes), Claude Belmas (Perpignan), Fran ois Boureau (Paris), Philippe Bourrier (Le Mans), Jean-Claude Bourrin (Draguig- nan), Nathalie Brion (Versailles), H 1 ne Chapoulart (Bordeaux), Christelle Creac'h (Saint-Etienne), Anne Donnet (Marseille), Virgine Dousset (Bordeaux), Alain Eschalier (Clermont-Ferrand), Nelly Fabre (Toulouse), Jean Feullet (Sorbiers), Fran ois Fr t (Chaulnes), Jean-Yves Gauvrit (Lille), Bernard Gay (Rions), Philippe Giffard (V nisieux), Patrick Ginies (Montpellier), Pierre Giraud (Annecy), Evelyne Guegan-Massardier (Rouen), Michel Hamon (Paris), Philippe Holfliger (Nice), Michel Huguet (Vii-

leurbanne), Olivier Joyeux (Valence), Catherine Jung (Strasbourg), Lucette Lacomblez (Paris), Jacques Lagarde (I2Isle-Jourdain), Pierre Landrieu (LeKremlin- Bic tre), Claire Lejeune (Paris), Pierrette Lhez (Bordeaux), Claudie Locquet (Paris), Jacques Maillecourt (Dreux), Alain Masclet (Thiers), H 1 ne Massiou (Paris), Jean Maupetit (Libourne), Jean- Fran ois Meder (Paris), Samuel Merran (Paris), G rard Mick (Voiron), Philippe Pariser (Paris), Jean Parrot (Paris), Andr Pradalier (Colombes), Robert Pujol (Saint-B at), Daniel Reizine (Paris), Catherine Rummens (Bayonne), Jean-Michel S nard (Toulouse), Carole Sereni (Paris), Alain Serrie (Paris), Christine Tommasi-Davenas (V nisieux), Christophe Tzourio (Paris), Martine Veyri-Courtade (Toulouse), and Francis Vuillemet (Colmar).

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Address correspondence to: Gilles G raud, MD, Department of Neurology, H pital de Rangueil, TSA 50032, Toulouse 31059, France. E-mail: [email protected]

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Documents

French Guidelines for the Diagnosis and Management of Migraine in