profilaxis migraña jnnp pract neurol 2007

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REVIEWPract Neurol 2007; 7: 383–393

Migraine preventionD W Dodick, S D Silberstein

Preventive medications reduce migraine frequency and severity, and improvemigraine-specific quality of life. Recent evidence also suggests that thesesame medications enhance the patient’s response to acute migraine therapies,and may also reduce the likelihood of developing chronic daily headache.However, many patients who should receive or be offered preventivetreatment are not. Most patients can be successfully managed when patientand physician expectations are realistic and aligned, the selection of preventive medications is individualised, and the initiation and titrationstrategy is appropriate and carefully followed. Rational combinations of preventive medications may also be useful. This review provides an evidenceand experience-based approach to the preventive treatment of migraine.

D W DodickProfessor of Neurology,

Department of Neurology, Mayo

Clinic Arizona, Scottsdale, Arizona,

USA

S D SilbersteinProfessor of Neurology,

Department of Neurology, Thomas

Jefferson University, Philadelphia,

Pennsylvania, USA

Correspondence to:

Professor D W Dodick

Department of Neurology,

Mayo Clinic Arizona,

13400 East Shea Boulevard,

Scottsdale, Arizona 85259, USA;[email protected]

3Dodick, Silberstein

www.practical-neurology.com



Migraine is a highly prevalent

neurological disorder that

affects about 13% of the popu-lation in most western indus-

trialised societies. It is one of the leading

causes of health-related disability worldwide,

it is an independent risk factor for both silent

and symptomatic ischaemic stroke and

ischaemic cardiovascular disease, and up to

14% of sufferers progress to a more disabling

chronic form of the disorder (chronic

migraine).1–4 It has a variety of clinical

manifestations including headache, nausea,

vomiting, heightened sensitivity to environ-

mental stimuli such as light, sound and

odours, nasal sinus pressure, neck pain/

discomfort, and transient neurological symp-

toms and signs referred to as the migraine

aura. Aura occurs in up to 30% of migrai-

neurs and may involve the visual, somato-

sensory, language or motor systems. Most

patients with migraine with aura also havemigraine without aura, and the proportion of

attacks associated with aura varies greatly

from a few in a lifetime to most attacks.

The treatment of migraine involves both

acute and preventive drugs, and non-phar-

macological strategies. Preventive treatment

is necessary when the migraine attacks are

unacceptably frequent, prolonged, severe

unresponsive to acute medication, or asso-

ciated with hemiparesis or prolonged aura. It

is therefore designed to reduce the frequency

duration, and/or severity of the attacks. In

addition, preventive treatment often makes

migraine attacks more responsive to acute

migraine therapies, reduces migraine asso-

ciated disability, improves the patient’s ability

to function, and decreases healthcare costs

and use of healthcare resources.

Although there are many therapeutic

agents and other approaches that have been

used for migraine prevention, there is a

robust evidence base for only eight drugs

and two non-pharmacological approaches;those with the best documented efficacy are

some beta-blockers, flunarizine, divalproex

sodium or valproate, topiramate, methyser-

gide and amitriptyline. The decision in clinica

practice as to which of the options is optima

is based on the strength of the evidence for

efficacy, the physician’s clinical experience

the drug’s adverse event profile, the patient’s

preferences, headache subtype (antiepileptic

drugs are generally preferred in migraineurs

with aura), the presence or absence ocoexisting conditions and comorbid disorders

and the potential for childbearing

Specifically, divalproex sodium and valproate

are absolutely contraindicated during preg-

nancy because of the increased risk of neura

tube defects. As unplanned pregnancies are

not uncommon, these drugs are generally not

used in young women of childbearing

potential.

The clinician should be very mindful of any

comorbid and coexistent conditions in

patients with migraine, to maximise the

An illustrative case

A 32-year-old sales executive with a 20-year history of episodic migraine

developed increasingly frequent attacks over 12 months. Her average monthly

frequency was five attacks, each of which lasted for 18 hours, followed by a

‘‘postdromal’’ period of fatigue and lethargy for up to 24 hours. For each

attack, she was using ibuprofen 400 mg when the pain became moderate inseverity, repeating the dose in four hours if needed. She also had insomnia and

mild situational anxiety associated with work-related stress. She had no

comorbid illnesses and took no other medications. Her general physical and

neurological examination was normal except for a body mass index of 28 and

mildly raised systolic blood pressure (144 mmHg). Preventive treatment is

indicated, as is more optimal acute management of her attacks. For the latter, a

higher dose of ibuprofen or naproxen sodium should be used if there is an

adequate period of time during which the pain is mild. However, if this is not

effective, or the patient often awakens with moderate or severe pain,

progresses rapidly from mild to moderate pain, or does not have a mild pain

phase, a triptan should be used as soon as possible as first-line acute therapy.Non-pharmacological management might include biofeedback and relaxation

therapy if available and feasible; this may relieve some of her stress-related

anxiety and contribute to a reduction in attack frequency and/or severity. She

should avoid medications which have a high potential for weight gain if

possible. Topiramate or a beta-blocker would be a reasonable first choice. Each

option should be presented to the patient, the advantages and disadvantages

of each should be discussed, especially the adverse effect profile. She should be

encouraged to assist in the drug selection. A low dose should be started, and

the dose titrated by weekly increments, until she begins to notice a benefit. She

should keep a daily diary that captures headache frequency, severity, associated

symptoms, duration, headache-related disability and acute headache medica-

tions. If dose-limiting adverse effects occur before an effective dose isachieved, coenzyme Q10 100 mg three times daily or petasites (butterbur)

75 mg twice daily could be added, or a small dose of either a beta-blocker (if

topirmate had been started) or topiramate (if a beta-blocker had been started).

Once her headaches are well controlled for 3–6 months, consider slowly

tapering one medication at a time.

384 Practical Neurology

10.1136/jnnp.2007.134023



otential for treatment efficacy and minimise

he potential for adverse effects. Comorbid

lnesses are those that occur more frequently

n association with a specific disorder than

would be expected by chance in the general

opulation. In contrast, coexistent illnesses

ccur together in the same person at a ratehat would be expected by chance. The

omorbid illnesses associated with migraine

hat influence its management include

epression, anxiety disorders, epilepsy and

troke. Coexistent illnesses or disorders that

ccur commonly in the general population

hat will influence the selection of preventive

rugs used for migraine include diabetes

mellitus, hypertension and obesity.6

Pregnancy also influences the choice of

reventive agent.

MECHANISM OF ACTION OFMIGRAINE PREVENTIVE DRUGSDespite the dramatic advances over the past

everal decades in our understanding of the

eurobiology of migraine, there is no animal

model for migraine prevention and only

methysergide was developed specifically for

he preventive treatment of migraine, and

hat was several decades ago. Most drugs

sed for migraine prevention were either

iscovered to be effective by serendipity

beta-blockers) or because of educated

uesses using drugs designed to treat

iseases with an overlapping pathophysiology

epilepsy, depression). Therefore, one should

ot be surprised that the mechanism of

ction of migraine preventive drugs has not

een clearly elucidated. However, recent

nimal studies suggest that several of the

rugs may work through a common mechan-

sm; topiramate, valproate, propranolol, ami-

riptyline and methysergide all have a dose-ependent effect in raising the threshold for

nitiation of cortical spreading depression.7

Cortical spreading depression is currently

widely considered to be the physiological

ubstrate underlying the migraine aura and,

lthough controversial, is also felt by some

uthorities to underlie migraine without aura

s well. Interestingly, this same study7 also

emonstrated that the suppression of cortical

preading depression increased over time,

which provides a scientific rationale for the

linical observation that the efficacy of these

drugs in clinical practice depends on dose-

titration and an adequate duration of treat-

ment.

INDICATIONS FOR AND USE OFPREVENTIVE TREATMENT

Epidemiological studies suggest that thatabout one third of migraineurs need pre-

ventive treatment, but only 3–13% of all

migraineurs currently use preventive therapy

to control their attacks.8 While recent data

suggest that preventive treatment reduces

the risk of progression to chronic migraine,

definitive evidence must await long-term

prospective observational studies.8 It is also

not clear whether preventive medication

reduces the risk of adverse cardiovascular

events such as ischaemic stroke and heartdisease. Therefore, currently, the treatment

goals of preventive medications and non-

pharmacological strategies include the fol-

lowing:

N reduce attack frequency, severity andduration

N improve responsiveness to acute head-ache therapies

N improve function and reduce disability

N reduce overall cost associated with

migraine treatment.As a component of the comprehensive

approach to migraine prevention, all patients

with migraine should be educated about

potential triggers for attacks and guided on

how best to avoid them.

Guidelines that define the indications for

preventive drug treatment have been devel-

oped in the USA and Europe9, 10 (table 1). In

general, patients who experience one or more

migraine attacks per week should be offered

TABLE 1 Indications for preventive drug treatment for migraine

l Recurring migraine that significantly interferes with quality of life and thepatient’s daily routine, despite acute treatment of the attacks

l Frequency of migraine attacks >1/weekl Frequency of acute headache medication use >2 days/weekl Failure of, contraindication to, or troublesome adverse effects from acute

medicationl Presence of uncommon migraine conditions, including hemiplegic

migraine, basilar migraine, migraine with prolonged, disabling or frequentaura, or migrainous cerebral infarction





preventive therapy because recent evidence

suggests that progression to chronic dailyheadache increases significantly at higher

frequencies (fig 1).

PRINCIPLES OF PREVENTIVETHERAPY The success of preventive therapy rests as

much on the strategy employed when

initiating and titrating the medications, and

establishing realistic patient expectations, as

it does on which drug is actually selected. The

following principles, while not evidence-based, reflect practical clinical experience

and can lead to a better outcome:

Minimise adverse effects

N Start the chosen drug at a low dose (forexample, 10 mg amitriptyline daily) andincrease slowly, perhaps every 1–2 weeksby the same dose (for example, 10 mg

amitriptyline week 1, 20 mg week 2–3etc) until therapeutic effects develop.

Setting and reaching target dose

N Set initial target dose (for example30 mg amitriptyline) advising patient tostop earlier if partial efficacy or adverseevents develop. The maximal dose isreached when efficacy is optimal oadverse effects become intolerable.

Efficacy takes time andaccumulates over time

N Give each treatment an adequate trial oat least six weeks at the maximallytolerated dose; remember, the six-weekclock begins only after this dose isachieved. However, based on experienceand randomised trials, the full benefit of adrug may not be realised until six monthshave elapsed from the time of achievingthis dose. A graph illustrating the timecourse and usual response to preventivemigraine therapies may be helpful for thepatient, and improve compliance (fig 2).

Setting expectations for successand adverse effects

N Success is generally defined as a 50%reduction in attack frequency, a signifi-cant decrease in attack duration, or animproved response to acute medicationUnless advised what to expect, patientsunderstandably interpret the term ‘‘pre-vention’’ literally and anything less thancomplete relief of attacks is equated with‘‘failure’’ of the drug.

N The development of adverse effects variesgreatly from patient to patient andcannot be predicted on an individuabasis. The most common adverse effectsand their likely frequency should bediscussed with patients, and rare buserious idiosyncratic adverse effects mustalso be discussed. Most adverse effectsare self-limiting and dose-dependent, andpatients should be encouraged to try totolerate any early adverse effects that

may develop when a new medication isstarted.

Figure 1

Headache frequency at baselinepredicts progression to chronic daily

headache at one year. *The top line

shows the predicted incidence of

intermediate frequent headaches (105–

179 headache days/year) and the

bottom line shows the predicted

incidence of CDH (180+ headache days/

year). Adapted from Scher et al .51

Figure 2

A useful figure to use with patients to

illustrate the cumulative benefit that

occurs over time. This establishes

appropriate expectations, enhances

compliance, and reduces premature

discontinuation.


10.1136/jnnp.2007.134023



Selecting and maximising drugchoice

A drug may be selected (for example,divalproex sodium/valproate in a migrai-neur with epilepsy) or avoided (beta-blocker in a migraineur with asthma) onthe basis of the presence of a comorbid orcoexistent illness. Care should be takenhowever not to under-treat a comorbiddisorder by trying to treat two differentconditions with one drug.6 For example, alow-dose tricyclic antidepressant mayeffectively treat migraine but not comor-bid depression. In such a case, optimallytreating both conditions may require twoseparate medications, especially becauseadverse effects are often inevitable anddose-dependent with tricyclic antidepres-sants, and selective serotonin and/or

norepinephrine reuptake inhibitors aregenerally considered first-line agents forthe treatment of depression. Drugs thatare commonly associated with weightgain (for example, divalproex sodium/valproate, amitriptyline) are not the bestfirst choices in an obese patient or onewith a disease that may be exacerbatedby weight gain (for example, diabetesmellitus, hypertension, cardiovasculardisease).

Avoid, if at all possible, preventive drugs

in pregnant or lactating women. Inaddition, because migraine is most pre-valent in women of childbearing age, thepotential for adverse fetal effects shouldbe discussed and drugs used for preven-tion should be stopped if at all possiblewhen women are trying to conceive.Drugs with unequivocal teratogeniceffects (for example, divalproex sodium/valproate) should be avoided in women of childbearing age.

Re-evaluate therapy and, if possible,

taper or discontinue the drug after asustained period of remission (perhaps sixmonths).

Maximise adherence tomedication

A surprising proportion of patients do notcomply with preventive medicationsrecommended and prescribed by theirphysicians. Educating patients abouttitration schedules, expectations for suc-

cess and adverse effects is critical forencouraging adherence. In particular,

with drugs of equivalent eff icacy,patients often select preventive medica-tions based on the adverse effect profilesthey most want to avoid. Therefore,patient preference must be taken intoaccount as patients are more likely to becompliant with a medication they helped

select.

PREVENTIVE MEDICATIONS ANDSTRATEGIES: EVIDENCE ANDEXPERIENCE-BASEDRECOMMENDATIONSA myriad of therapeutic agents and

approaches have been used and tested in

clinical trials for the preventive treatment of

migraine. Recently, an evidence-based prac-

tice parameter has been developed by theQuality Standards Subcommittee of the

American Academy of Neurology.5 This pro-

vides an updated literature review and

recommendations from a previous guideline

published in 2000 and was based on 30

additional, randomised, double-blind, con-

trolled clinical studies that had been pub-

lished from 2000–7. The practice parameter

concluded that there is currently level-I

evidence to support the use of eight drugs

available in the USA (topiramate, divalproex

sodium/sodium valproate, amitriptyline,

metoprolol, propranolol, timolol and extracts

of butterbur (the plants commonly referred to

as butterbur are found in the daisy family

Asteraceae in the genus petasites)), and two

non-pharmacological approaches (relaxation

therapy and biofeedback). Methysergide is

also effective for migraine prevention, but is

limited in practice because of lack of

availability and the associated severe adverse

effects.

The efficacy and safety of several othertherapies and all the drugs that have been

tested were grouped according to the

evidence, with corresponding recommenda-

tions (table 2). However, this guideline did not

include drugs that were not available in the

USA, but are available and used widely in

other countries in North and South America

and Europe (for example, flunarizine, pizoti-

fen). Therefore, based on the evidence,

availability and clinical experience, first-,

second- and third-line medications are listed

in tables 3–5.





BEHAVIOURAL TREATMENTSBehavioural treatments are classified into

three broad categories: relaxation training,

biofeedback therapy, and cognitive-beha-

vioural training (stress-management train-

ing). They have all been shown to be effective

in the preventive management of migraine,

and have been directly compared and inte-

grated with drug treatments. For example,

popranolol and amitriptyline confer additional

clinical benefits when added to therma

biofeedback, relaxation, cognitive-behavioura

therapy or EMG biofeedback.

Behavioural treatments are options fo

headache sufferers who have one or more

of the following characteristics:

N patient preference for non-drug inter-ventions

N poor tolerance to drug treatments

TABLE 2 Groups of medications used for migraine prevention based on levels of evidence for efficacy according theQuality Standards Subcommittee of the American Academy of Neurology

Group 1 Group 2 Group 3 Group 4 Group 5

Antiepileptic drugsN

Divalproex sodiumN Sodium valproateN TopiramateAntidepressantsN AmitriptylineBeta-blockersN MetoprololN PropranololN TimololSerotonin agonistsN Frovatriptan{Serotonin antagonistsN MethysergideOtherN Petasites (butterbur)

ACE-inhibitorsN

CandasartanN LisinoprilAntiepileptic drugsN GabapentinAntidepressantsN FluoxetineN VenlafaxineAntihistamines/leukotriene antagonistsN CyproheptadineBeta-blockersN AtenololN NadololNon-steroidal anti-inflammatory drugsN AspirinN FenoprofenN FlurbiprofenN IbuprofenN KetoprofenN Mefenamic acid*N NaproxenN Naproxen sodiumSerotonin agonistsN Naratriptan*

N Zolmitriptan*OtherN Coenzyme Q10N MIG-99 (feverfew)N Vitamin B2

Alpha-agonistsN

Clonidine*N GuanfacineAntiepilpetic drugsN CarbamazepineCalcium blockersN DiltiazemN NicardipineN NifedipineN NimodipineN Verapamil

AnticoagulantsN

AcenocoumarolN CoumadinN PicotamideAntiepileptic drugsN TiagabineAntidepressantsN DoxepinN ImipramineN NortriptylineN ProtriptylineN FluvoxamineN ParoxetineN SertralineN MirtazepineN PhenylzineBeta-blockersN AcebutololN BisoprololN PindololSerotonin antagonistsN Methylergonovine(methylergometrine)

Antiepileptic drugsN

ClonazepamN LamotrigineN OxycarbamazepineOthersN AcetazolamideN LanepitantN MontelukastN Omega-3N Vitamin E

*For short-term prophylaxis of menstrually-related migraine.{Perimenstrual prophylaxis.Group 1: medications with proven high efficacy based on at least two Class-I trials (should be used).Group 2: medications probably effective based on one Class-I or at least two Class-II trials (should be considered).Group 3: medications possibly effective based on one Class-II trial or at least two Class-III trials, or conflicting studies (may beconsidered).Group 4: medications cannot be recommended based on inadequate or conflicting data (Class-IV trials or no trials) (we cannotrecommend these drugs one way or the other but some are clearly used frequently—for example, nortriptyline).Group 5: medications probably ineffective (based on one Class-I or at least two Class-II trials (should not be considered).


10.1136/jnnp.2007.134023



medical contraindications to drug treat-ments

insufficient or no response to drugtreatments

pregnancy, planned pregnancy or breastfeeding

history of long-term, frequent, orexcessive use of analgesics or acute

medications that can aggravate headacheproblems

N significant stress or poor stress-copingskills.

There is insufficient or conflicting evidence

to support the use of acupuncture, cervical

manipulation and mobilisation, hypnosis,

transcutaneous electrical nerve stimulation

TABLE 3 First choice medications for the preventive treatment of migraine

DrugRange of effective doses

Common adverseeffects

Rare/uncommonadverse effects Contraindications

Beta-blockers9–15

Propranolol 40–120 mg bd Fatigue,lightheadedness,reversible depression,vivid dreams

Agranulocytosis,Stevens-Johnsonsyndrome,bronchospasm

Severe asthma and diabetes,peripheral vascular disease,heart block, congestive heartfailure

Metoprolol 25–100 mg bdAtenolol 25–100 mg bdNadolol 40–100 mg bdTimolol 20–60 mg bd

Calcium channel blockersFlunarizine10–12 5–10 mg qds Weight gain,

somnolence, drymouth, dizziness,hypotension,depression

Extrapyramidalreactions,parkinsonism

Severe depression,Parkinson’s disease andother extrapyramidaldisorders

Antiepileptic drugsTopiramate16–19 50–200 mg bd Paraesthesia, weight

loss, memorycomplaints

Kidney stones, acutemyopia, secondaryangle closureglaucoma,oligohydrosis andhyperthermia,metabolic acidosis

Hypersensitivity

Divalproex sodium orsodium valproate20–22

500–1500 mg bd Nausea, weight gain,tremor, alopecia,somnolence,dizziness, vomiting,drug interactions

Pancreatitis,hyperammonaemiaand encephalopathy,multi-organhypersensitivityreaction

Hepatic disease, pancreatitis,pregnancy, urea cycledisorders, thrombocytopenia

Triptans*23–25

Frovatriptan 2.5 mg bd Dizziness, fatigue Angina, myocardialinfarction

Ischaemic heart disease,stroke, uncontrolledhypertension, peripheralvascular disease, hemiplegicand basilar migraine

Naratriptan 2.5 mg bd or tds Paraesthesia, neck/throat tightness

Zolmitriptan 2.5 mg bd Paraesthesia, neck/throat tightness,dizziness, somnolence,chest heaviness,asthenia

Non-steroidal anti-inflammatory drugs*26–29

Naproxen sodium 550 mg bd Nausea, dyspepsia,abdominal pain

Severe allergic reaction Active peptic ulcer disease,gastrointestinal bleedingMefenamic acid 250–500 mg bd

bd, twice daily; tds, three times daily; qds, four times daily.*For prevention of menstrual migraine.





(TENS), occlusal adjustment, and hyperbaric

oxygen for migraine prevention.

COMBINATION THERAPY There is little evidence to support the use of

multiple (>2) preventive treatment drugs for

migraine prevention. Despite this, combina-

tion therapy is a useful and frequently

employed strategy in clinical practice, espe-

cially in patients who seem to easily develop

adverse effects, or for those who are not

optimally controlled on one drug.

Combination therapy is also often used in

migraineurs who have ‘‘transformed’’ or

developed chronic migraine—a more recalci-

trant form of migraine where patients

experience more than 15 days of headache

each month and more than eight migraine

attacks each month. For example, an anti-

epileptic drug can be combined with a beta-

blocker or tricyclic antidepressant. In thisfashion, the individual drugs can be kept at

low dosage, minimising adverse effects, but

taking advantage of a potentially synergistic

effect between two medications with different

mechanism(s) of action. One can also combine

a conventional preventive medication with one

or more of the treatments that may fall into the

‘‘alternative or complementary’’ medicine

group, such as riboflavin, coenzyme Q10,

butterbur, and/or magnesium. There are pla-

cebo-controlled studies which support the use

of each of these alternative therapies, they are

invariably very well tolerated, and there may be

a synergistic or enhanced placebo response

with their combined use.

MENSTRUAL-RELATEDMIGRAINEPreventive therapy may eliminate all head-

aches except those associated with menses

An alternative strategy is short-term prophy-

laxis just during a defined period of increased

vulnerability. As menstrual-related migraine

typically occurs at the same time each month

or in association with symptoms that herald

its occurrence, the timed use of medications

is appropriate. Women who are already using

preventive medication and continue to have

menstrual-related migraine can increase the

medication dose before their menses. Women

who do not use preventive medicine or have

migraine mainly with their menses can just be

treated perimenstrually with short-term pro-phylaxis. Of course, regular periods and a

predictable relation between the attacks and

the periods are essential for this strategy to

succeed. Drugs that have been used perimen-

strually for short-term prophylaxis include

non-steroidal anti-inflammatory drugs, ergo-

tamine, dihydroergotamine, methysergide

methergine, triptans and magnesium (table 6)

ACKNOWLEDGEMENTSThis article was reviewed by Roger Cull

Edinburgh, UK.

TABLE 4 Second choice medications for migraine preventive treatment (either less efficacy and/or more adverseeffects)

DrugRange of effec-tive doses

Common adverseeffects


Amitriptyline19, 30–32

Nortriptyline25–100 mg qds25-100 mg qds

Weight gain,constipation, asthenia,dizziness, somnolence,fatigue, blurred vision,dry mouth, druginteractions

Cardiacarrhythmia,syncope,orthostatichypotension,pancytopenia

Acute recovery phase followingmyocardial infarction, cisaprideuse, monoamine oxidase inhibitoruse, hypersensitivity to tricyclicantidepressants

Petasites (butterbur)33 75 mg bd Nausea, bloating, flatus,vomiting, diarrhoea,dyspepsia, lowerabdominal pain

Dysgeusia,insomnia

Hypersensitivity, pregnancy andlactation

bd, twice daily; qds, four times daily.


10.1136/jnnp.2007.134023



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TABLE 5 Third choice medications for migraine preventive treatment (either less efficacy and/or more adverse effects)

DrugRange of effectivedoses Common adverse effects


Aspirin14, 34 325 mg qds Nausea, dyspepsia, bruising Hypersensitivity

reactions

Active peptic ulcer disease,

hypersensitivity reaction,gastrointestinal bleeding

Gabapentin35, 36 300–1600 mg tds Peripheral oedema,dizziness, somnolence,ataxia

Magnesium37–39 400–600 mg qds DiarrhoeaCandesartan40 4–16 mg qds Hypotension, exacerbation

congestive heart failureTransaminaseelevation, mildhyperkalaemia

Pregnancy, lactation

Lisinopril41 10–20 mg qds Dizziness, headache,cough, fatigue, musclecramps, diarrhoea

Angioedema Hereditary or idiopathicangioedema, anuria, orhypersensitivity to othersulfonamide-derived drugs

Botulinum toxintype A42

25–250 units Muscle weakness, neckpain, ptosis, flu-likesymptoms, headache

Keratitis, cornealulceration

Myasthenia gravis and otherdisorders of neuromusculartransmission.

Venlafaxine43, 44 75–225 qds Somnolence, insomnia,dizziness, headache,sweating, nausea, drymouth, nervousness,anxiety, abnormalejaculation, impotence,decreased libido

Concomitant use of monoamine oxidase inhibitors,caution in lactating mothers

Riboflavin45 400 mg qds Yellow-orangediscoloration to urine

Coenzyme Q1046

150–300 mg tds Diarrhoea, nausea,heartburn, appetitesuppression, interactionwith warfarin

Headache, dizziness,irritability, agitation,mild increase in liverenzymes, skin rash,pruritus, exanthema

Concomitant therapy withhypoglycaemic agents, diabetesmellitus. Statins may inhibitnatural synthesis of coenzymeQ10, hypersensitivity tocoenzyme Q10

Fluoxetine47–49 10–80 mg qds Asthenia, nausea,diarrhoea, insomnia,anorexia, impotence,tremor, anxiety/nervousness

Serotonin syndrome Concomitant use of monoamine oxidase inhibitors,thioridazine, pimozide

tds, three times daily; qds, four times daily.





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TABLE 6 Preventive treatment of menstrual migraine

Perimenstrual use of standard preventive drugsPerimenstrual use of non-standard preventive drugsl Non-steroidal anti-inflammatory drugsl Ergotamine and its derivativesl Triptans (eg, naratriptan, frovatriptan, zolmitriptan)l MagnesiumHormonal therapyl Oestrogens (with or without androgens or progestagen)l Combined oral contraceptivel Synthetic androgens (Danazol)l Anti-oestrogen (Tamoxifen)l Medical oophorectomy (GnRH analogues)Dopamine agonists (Bromocriptine)

PRACTICE POINTS

l Preventive treatment reduces migraine frequency and may preventprogression to chronic migraine.

l Initiate preventive medication in patients having one or more migrainesper week, or using acute headache medication >2 days/week.

l Individualise drug selection by using a preventive that may treat acomorbid or coexistent illness/disorders and by avoiding a drug which willexacerbate another underlying condition.

l Select preventive drug based on evidence; use first-line therapies whenpossible.

l

Establish expectations for a realistic response (in general, 50% of patientshave at least a 50% reduction in migraine frequency), cumulative benefitover time, and the need for patience during the dose titration phase.

l When there is a partial but suboptimal response, or dose-limiting adverseeffects, combining two preventive drugs with different mechanisms of action may be useful.

l The decision to taper and discontinue a preventive medication is for thepatient. However, once excellent control has been established for a periodof at least six months, then an attempt to taper the medication isreasonable, especially as the natural history of the disorder is to remit overtime.


10.1136/jnnp.2007.134023



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