Topiramate in the prevention and treatment of migraine: efficacy, safety and patient preference

Figures & data

Table 1 Substances used for migraine treatment recommended by EFNS Guideline on the treatment of migraine¹⁶

LR	Substance	Dose (if not given in mg)	Side effects	Contraindications
Acute migraine treatment
A	ASA	1000 (oral) 1000 (iv)	gastrointestinal side effects, abdominal pain, clotting abnormality, risk of bleeding	gastric ulcer, bleeding diathesis, pregnancy (months 7–9)
A	Ibuprofen	200–800	side effects as for ASA, edema	like ASA (less bleeding tendency), renal failure, pulmonary embolism
A	Naproxen	500–1000	like ibuprofen	like ibuprofen
A	Acetaminophen/paracetamol	1000 (oral or suppository)	liver damage	liver and kidney failure
A	Diclofenac	50–100	like ibuprofen	like ibuprofen
A	ASA plus paracetamol plus caffeine	250 (oral) 200–250 50	see ASA and paracetamol	see ASA and paracetamol
B	Metamizol	1000 (oral) 1000 (iv)	allergic reaction, changes in blood count, risk of agranulocytosis in iv use risk of hypotension	hematopoietic system disease
B	Phenazon	1000 (oral)	see paracetamol	unknown
B	Tolfenamic acid	200 (oral)	side effects as for ASA	unknown
A	Sumatriptan	25, 50, 100 (oral) 25 (suppository) 10, 20 (nasal spray) 6 (subcutaneous)	angina, nausea, distal paresthesia, fatigue sensation of cold in subcutaneous use – local skin reaction at injection site	arterial hypertension (untreated), coronary heart disease, peripheral artery occlusive disease, cerebrovascular disease, multiple vascular risk factors, Raynaud’s disease, pregnancy, lactation, age under 18 (except sumatriptan nasal spray), severe liver or kidney failure, age above 65, simultaneous treatment with ergotamine, within 2 weeks after break off from treatment with a MAO inhibitor
A	Zolmitriptan	2.5, 5 (oral) 2.5, 5 (nasal spray)	see sumatriptan	see sumatriptan
A	Naratriptan	2.5 (oral)	see sumatriptan (probably milder/fewer side effects)	see sumatriptan
A	Rizatriptan	10 (oral) 5 mg (when additionally on propranolol)	see sumatriptan	see sumatriptan
A	Almotriptan	12.5 (oral)	see sumatriptan (probably milder/fewer side effects)	see sumatriptan
A	Eletriptan	20, 40 (oral) 80 allowed if 40 not effective	see sumatriptan	see sumatriptan
A	Frovatriptan	2.5 (oral)	see sumatriptan (probably milder/fewer side effects)	see sumatriptan
Prophylactic migraine treatment
A	Metoprolol	50–200	oft: fatigue, arterial hypotension occ.: sleep disturbances, dizziness	a: AV block, bradycardia, asthma and sick sinus syndrome
A	Propranolol	40–240	s: hypoglycemia, bronchospasm, bradycardia, gastrointestinal side effects, impotence	r: diabetes mellitus, depression, diabetes mellitus, orthostatic disregulation
A	Flunarizine	5–10	oft: fatigue, weight gain occ: gastrointestinal side effects, depression s: hyperkinesia, tremor, parkinsonism	a: focal dystonia and depression, pregnancy and lactation r: familiar parkinsonism
A	Valproic acid	500–1800	oft: fatigue dizziness, tremor occ: exanthema, hair loss, weight gain s: elevation of liver enzymes/disturbance in liver function	a: liver failure, pregnancy, alcoholism, polycystic ovaries
A	Topiramate	25–100	oft: fatigue, cognitive disturbance, weight loss, paresthesia occ: change in taste, psychosis s: glaucoma	a: renal insufficiency, nephrolithiasis, glaucoma
B	Amitriptyline	50–150	oft: dry mouth, fatigue, dizziness, sweating occ: constipation, impotence, incontinence, restlessness	a: glaucoma, prostatic adenoma and hyperplasia r: heart insufficiency
B	Venlafaxine	2 × 75–150	oft: fatigue, loss of concentration s: impotence, arterial hypertension	a: severe hypotension
B	Naproxen	2 × 250–500	gastrointestinal side effects	a: gastric ulcer, bleedings r: asthma bronchiale
B	Petasites	2 × 75	occ: burping, gastrointestinal side effects s: liver disturbances	a: pregnancy and lactation
B	Bisoprolol	5–10	see metoprolol and propranolol
C	Gabapentin (1200–1600 mg), Magnesium (24 mmol), Tanacetum parthenium (3 × 6.25 mg), Riboflavin (400 mg), Coenzyme Q10 (300 mg), Candesartan (16 mg), Lisinopril (20 mg), Methysergide (4–12 mg)

Notes: Evidence class A indicates the presence of multiple randomized controlled clinical trial; evidence class B indicates one randomized trial exists or multiple uncontrolled trials were performed; evidence class C refers to common expert opinion or single case reports.

Abbreviations: ASA, acetylsalicylic acid; AV, atrioventricular; oft, often; occ, occasionally; s, seldom; a, absolute; r, relative; LR, level of recommendation; MOA, monoamine oxidase inhibitor.

Table 2 Topiramate common interactions

Interacting drug	Form of interaction
Phenytoin	Decrease of plasma concentration of topiramate
	Increase plasma level of phenytoin
Carbamazepine	Decrease of plasma concentration of topiramate
Digoxin	Decrease in digoxin plasma level (seen after a single shot of topiramate [found in a single trial])
Estrogens	Decrease in effectiveness of oral contraception (seen in 200 mg, 400 mg and 800 mg daily doses of topiramate)
Hydrochlorothiazide	Increase of topiramate plasma levels; higher decrease in plasma potassium levels as usual
Lithium	Change of lithium plasma concentration
Metformin	Reduction of topiramate oral plasma clearance; increase of metformin plasma level
Pioglitazone	Decrease in plasma levels of pioglitazone and its active metabolites
Glibenclamide	Reduction of glibenclamide plasma levels, reduction of the systemic bioavailability of some glibenclamides active metabolites
Valproic acid	Hyperammonemia with or without encephalopathy, in most cases with reduction of signs and symptoms after discontinuation of one of both drugs
Carbonic anhydrase inhibitors	Increase of effect on carbonic anhydrase inhibition

Table 3 Withdrawal rates in the three MIGR trials

	MIGR-001 Silberstein et al^Citation35				MIGR-002 Brandes et al^Citation36				MIGR-003 Diener et al^Citation19
Group (TPM dose in mg)	50	100	200	PLC	50	100	200	PLC	100	200	PROP	PLC
No of patients randomized	125	128	117	117	120	122	121	120	141	144	144	146
n withdrawal after randomization (withdrawal in % of patients randomized)	57 (45.6)	45 (35.2)	72 (61.5)	48 (66.7)	61 (50.8)	59 (48.4)	51 (42.1)	57 (47.5)	47 (33.4)	79 (54.9)	42 (29.2)	47 (32.2)
Withdrew due to AEs (% of overall withdrawal)	21 (36.8)	24 (53.3)	38 (52.8)	11 (22.9)	20 (32.8)	32 (54.2)	25 (49.0)	14 (24.6)	37 (78.7)	63 (79.7)	29 (69.0)	15 (31.9)
Withdrew due to lack of efficacy (% of overall withdrawal)	10 (17.5)	6 (13.3)	8 (11.1)	21 (43.7)	15 (24.6)	11 (18.6)	12 (22.5)	21 (36.8)	1 (2.1)	2 (2.5)	3 (7.1)	13 (27.7)
Withdrew due to subjects choice (% of overall)	10 (17.5)	6 (13.3)	8 (11.1)	3 (6.3)	8 (13.1)	6 (10.2)	5 (9.8)	7 (12.3)	5 (10.6)	8 (10.1)	3 (7.1)	7 (14.9)
No patients in intent to treat cohorts	117	125	112	115	117	120	117	114	139	143	143	143
No withdrawal after intent to treat	49	42	67	46	58	57	47	51	45	78	41	44

Abbreviations: AE, adverse events; TMP, topiramate; PLC, placebo; PROP, propranolol.

Members of the task forceEversSAfraJFreseAEFNS guideline on the drug treatment of migraine – report of an EFNS task forceEur J Neurol200613656057216796580

 PubMed Web of Science ®Google Scholar

SilbersteinSDNetoWSchmittJJacobsDGroupMIGRSTopiramate in migraine prevention: results of a large controlled trialArch Neurol200461449049515096395

 PubMedGoogle Scholar

BrandesJLSaperJRDiamondMTopiramate for migraine prevention: a randomized controlled trialJAMA2004291896597314982912

 PubMed Web of Science ®Google Scholar

DienerHTfelt-HansenPDahlöfCTopiramate in migraine prophylaxis–results from a placebo-controlled trial with propranolol as an active controlJ Neurol2004251894395015316798

 PubMed Web of Science ®Google Scholar