Prescrire International Special Edition 2015/Volume 24 N°158
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reduced if a smoker cuts down or
quits, in order to avoid overdose (7).
Valproic acid and ami-
triptyline: second choices.
Valproic acid
, an antiepileptic
drug, has efficacy in preventing
migraine attacks at oral doses of
500 mg to 1500 mg per day (1).
The most frequent adverse effects of
valproic acid
areweight gain and gastro-
intestinal disorders. Other potentially
serious adverse effects include: neu-
ropsychiatric and haematological dis-
orders; pancreatitis; and liver damage
(generally occurring during the first
six months of treatment, and some-
times fatal). Liver enzymes should be
assayed before starting
valproic acid
therapy and then periodically during
the first six months, especially if man-
ifestations of hepatitis occur (anorex-
ia, vomiting, fatigue) (7,10).
Valproic acid
, unlike most other
antiepileptic drugs, is not an enzyme
inducer and carries little risk of phar-
macokinetic interactions, although it
can aggravate the adverse effects of
co-administered drugs that are close
to those of valproic acid (7).
Amitriptyline
, a tricyclic anti-
depressant, has a preventive effect
on migraine attacks at oral doses of
30 mg to 150 mg per day (1). The
main adverse effects of tricyclic anti-
depressants are: disorders due to their
antimuscarinic action; drowsiness;
headache; tremor; convulsions; gastro-
intestinal disorders; weight gain;
postural hypotension; sexual dys-
function; hyponatraemia; and serious
cardiac arrhythmias (7,11).
Tricyclic antidepressants interact
with many other drugs and in partic-
ular, they can aggravate the adverse
effects of other drugs with antimus-
carinic, seizure-inducing or sodium-
lowering effects, as well as drugs
that increase the risk of ventricular
arrhythmias (7).
Catamenial migraine
attacks: same preventive
treatment.
The drug of first
choice for preventing migraine attacks
linked to the menstrual cycle (cata-
menial migraine) is the same as for
other types of migraine (5).
Estradiol,
started shortly before the
expected date of menstruation, does
not have well-documented preventive
efficacy in catamenial migraine (1).
Oestrogen-progestogen
combination
therapy may possibly increase the risk
of stroke in migraine patients, among
other potential adverse effects (3).
Oestrogen-progestogen
combination
therapy usually has no discernible
impact on migraine, although some
women may experience an improve-
ment and others a worsening of symp-
toms. Any changes in migraine head-
ache and accompanying signs should
be carefully monitored during treat-
ment, which should be discontinued if
persistent headache occurs (3).
Regularly reassess the
need for treatment.
The
efficacy and adverse effects of
preventive medication for migraine
attacks should be assessed after 1 to
3 months, for example. To assess the
impact of preventive medicationmore
objectively, it can be helpful if the
patient records the dates on which
migraine attacks occur, along with
their intensity, duration, associated
symptoms, and consequences (in par-
ticular, any medications taken) (1).
When a first preventive treatment
proves unsatisfactory, it should be
replaced rather than combined with
another drug, as this increases the risk
of adverse effects without necessarily
enhancing efficacy (1).
It is good practice to taper preven-
tive treatment after a certain period
(after one year, for example), as the
frequency of migraine attacks fluctu-
ates during life and often diminishes
spontaneously over time (1).
Pregnancy: avoid valproic
acid.
Migraine headaches are
usually less frequent during
pregnancy, especially in the third tri-
mester, thus reducing the need for
preventive treatment (12).
Valproic acid
is teratogenic and can
cause: neural tube defects; urogen-
ital, craniofacial and digital anom-
alies; and serious long-term adverse
effects (autism; altered IQ, language
and behaviour).
Valproic acid
must be
avoided throughout pregnancy and
also by women who may be or may
become pregnant (12-14).
Propranolol
is not teratogenic but,
when taken in late pregnancy, it
can cause neonatal respiratory dis-
tress, bradycardia and hypoglycae-
mia. Gradual
propranolol
withdrawal
during pregnancy is an option to be
discussed with the patient (12).
In early pregnancy,
amitritptyline
is
an option when
propranolol
cannot be
used. When taken in late pregnancy,
however,
amitritptyline
can cause seda-
tion, antimuscarinic effects and with-
drawal symptoms in the newborn (12).
©Prescrire
Literature search and methodology
This review is based on articles published
in our French edition
la revue Prescrire
up
to issue 368 (June 2014) and on our guide to
drug interactions. Other references include
Martindale The Complete Drug Reference
(
) and UpToDate
(
, up to 7 May 2014. This
review was prepared using the standard
Prescrire
methodology, which includes verif-
ication of the choice of documents and their
analysis, and multiple quality controls.
1-
Prescrire Editorial Staff “Pharmacological pre-
vention of migraine: to be considered case by case”
Prescrire Int
2006;
15
(85): 184-188.
2-
Prescrire Editorial Staff “Treatment of migraine
attacks”
Prescrire Int
1995;
4
(20): 188-190.
3-
PrescrireRédaction“Accidentscardiovasculairesde
la contraception hormonale orale. Rares, ils survien-
nent essentiellement chez des femmes à risque”
Rev
Prescrire
1998;
18
(182): 205-217.
4-
Cutrer FM et al. “Pathophysiology, clinical mani-
festations,anddiagnosisofmigraineinadults”UpTo-
Date 2014.
5-
CalhounAH et al. “Estrogen-associatedmigraine”
UpToDate 2014.
6-
Prescrire Rédaction “Maux de tête”
Rev Prescrire
2008;
28
(301): 840-841.
7-
Prescrire Rédaction “2-1-5. Patients sous bêtablo-
quant”, “12-1. Patients épileptiques”, “12-2.
Patients migraineux”, “19-3-4. Patients sous antidé-
presseur imipraminique”, “19-5-1. Patients encore
tabagiques”, “Fiche B4. Hyponatrémies médica-
menteuses en bref”, “Fiche E6a. Hépatites aiguës
médicamenteusesenbref”,“FicheP2.Lesinducteurs
enzymatiques en bref”
Rev Prescrire
2013;
33
(362
suppl. interactions médicamenteuses).
8-
Prescrire Editorial Staff “Headache and acupunc-
ture”
Prescrire Int
2006;
15
(85): 195.
9-
“Propranolol hydrochloride” Martindale, The
Pharmaceutical Press 2014.
10-
Prescrire Rédaction “Le
valproate de sodium
(Dépakine°), le foie et l’enfant”
Rev Prescrire
1981;
1
(7): 26.
11-
Prescrire Editorial Staff “Drug-induced weight
gain”
Prescrire Int
2012;
21
(123): 11-14.
12-
PrescrireEditorialStaff“Migraineandpregnancy.
Choice of treatment”
Prescrire Int
2014;
23
(153):
243-245.
13-
Prescrire Editorial Staff “Valproic acid: long-term
effectsonchildrenexposedinutero”
PrescrireInt
2009;
18
(104): 253-257.
14-
Prescrire Editorial Staff “Valproic acid in utero:
autism”
Prescrire Int
2014;
23
(147): 72.
15-
Prescrire Editorial Staff “Topiramate: migraine
prevention: best avoided”
Prescrire Int
2006;
15
(84):
132-133.
16-
Prescrire Editorial Staff “Botulinum toxin type A
for migraine. First, do no harm”
Prescrire Int
2011;
20
(122): 287-290.
17-
PrescrireRédaction“Dérivésdel’ergotdeseigle:
quelques retraits du marché français, tardifs mais
bienvenus”
Rev Prescrire
2014;
34
(364): 100.
Treatments to avoid
Some medicines have an unfavour-
able harm-benefit balance in the pre-
vention of migraine: methysergide and
dihydro-ergotamine, ergot derivatives;
flunarizine, a “hidden” neuroleptic; topi-
ramate, an antiepileptic agent; long-term
non-steroidal anti-inflammatory drugs;
botulinum toxin A; pizotifen, an antimus-
carinic antihistamine (1,7,15-17).
Prescrire Int • February 2015
