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Transcript
Steven Leber, M.D., Ph.D.
TREATMENT OF MIGRAINES
I.
II.
III.
Avoidance of precipitants; regular sleep habits
Sleep
Abortive agents: home use. Most effective if used at onset of symptoms
Drug
Aspirin
Acetaminophen
Ibuprofen
Naproxen
Fioricet (butalbital, caffeine,
and acetaminophen); [Fiorinal
- same but w/ ASA]
Midrin [isometheptene
(sympathomimetic),
dichloralphenazone (mild
sedative), acetaminophen]
Migranal (Nasal
dihyroergotamine)
Sumatriptan
(Imitrex)
Other triptans (e.g.):
Zolmitriptan (Zomig)
Naratriptan (Amerge)
Rizatriptan (Maxalt, Maxalt
MLT—dissolving wafer)
FDA: rizatriptan ≥6 years old;
almotripan ≥12 years old
Usual dose (all p.r.n.)
Adults: 650-1000 mg
Children: 10-15 mg/kg
Adults: 650-1000 mg
Children: 10-15 mg/kg
Up to 400 mg TID-QID; also
available as 50 mg rectal
suppository
5 mg/kg/dose up to BID
Side effects
GI distress, bleeding
Risk of Reye’s syndrome
Overdose may cause hepatotoxicity
GI distress, ulceration, bleeding
Rash, prolonged bleeding time more
common than in adults; GI symtoms and
CNS symptoms (sedation, lightheadedness,
dizziness, headache) similar
1-2 tablets q 4 hrs, up to 6/day
Drowsiness
Dizziness
Dependency
2 tablets at onset of headache, then 1 Transient dizziness
q hr, up to 5 per 12 hr
(less in children)
If does not work in first 1-2 hrs,
probably will not
Adolescents: 1 spray (0.5 mg) into
Variable absorption
each nostril (total dose: 1 mg);
Nausea, vomiting, diarrhea
repeat if needed within 15 minutes
Headache
up to a total of 4 sprays (2 mg);
Vasoconstriction
maximum daily dose: 6 sprays (3
? cerebral vasospasm
mg)/24-hour period; Note: Do not
Risk of ergotism (intense arterial
exceed 8 sprays (4 mg)/week.
vasospasm)
Dependency and withdrawal
Contraindicated in patients with peripheral
vascular disease, severe hypertension, peptic
ulcer disease, ischemic heart disease, and
during pregnancy and nursing
6 mg subcutaneously (adults)
Rebound headache with SQ
Can repeat in 1 hr
Chest tightness, warmth, flushing
25-100 mg p.o. (start with 25; may
Injection-site reaction
give 25-100 mg 2 hours later; if HA Nausea
recurs, can give additional doses q 2 Nasal stuffiness with oral
hrs up to maximum 300 mg per day Nasal spray: throat irritation
Nasal spray.
Otherwise, rare and mild
Contraindicated in hemiplegic and basilar
Maxalt MLT 5 mg
migraine, ischemic heart disease,
uncontrolled hypertension, or within 24
Effective even after headache is well hours of use of ergotamines or 2 week of
established
MAO inhibitors
04/29/17
IV.
Abortive agents: status migrainosus.
Drug
Dihydroergotamine (DHE)
Sumatriptan
(Imitrex)
Other triptans:
Zolmitriptan (Zomig)
Naratriptan (Amerge)
Rizatriptan (Maxalt)
Ketoralac IM
(Toradol)
Chlorpromazine
(Thorazine)
Prochlorperazine
(Compazine)
Steroids
Usual dose
See Pediatric Neurology Clinical
Guidelines.
Precede with metoclopramide (0.2
mg/kg/dose IV up to a maximum of
10 mg/dose) and diphenhydramine
(1 mg/kg/dose IV up to a maximum
of 50 mg/dose). 30 min later, give
DHE 0.015 mg/kg/dose IV up to a
maximum of 1 mg/dose. May repeat
q 8 hrs p.r.n. intractable headaches
up to 5 doses; see protocol.
6 mg subcutaneously (adults)
Can repeat in 1 hr
25 mg p.o.
Nasal spray
Effective even after headache is well
established
Not approved in kids
15-60 mg IM
Side effects
Nausea and vomiting
Low risk of vasoconstriction
0.1 mg/kg q 15 min x3; IV more
effective than IM or PR
7.5-15 gm/dose IV
Orthostatic hypotension
Dystonic reactions
Orthostatic hypotension
Dystonic reactions
Hypertension
Hyperglycemia
Mood changes
Sedation
Respiratory suppression
Abuse
Dependence
Constipation
Behavioral changes, sedation
GI side effects, weight gain
Tremor
Thrombocytopenia, leukopenia
Liver toxicity
e.g., dexamethasone up to 20
mg/day IV in divided doses,
tapering over 2-3 days
Narcotics
IV valproate
10-20 mg/kg
Intranasal lidocaine??
2
Rebound headache
Chest tightness, warmth, flushing
Injection-site reaction
Nausea
Nasal: throat irritation
Otherwise, rare and mild
GI symptoms, headache, rash
V. Prophylactic agents
Drug
Aspirin
Usual dose
Adults: 650-1000 mg
Children: 10-15 mg/kg
Adults: 400 mg q 4-6 hrs
5 mg/kg (275-375 mg)/dose given
BID
Adults: start at 80 mg/day ÷ BID,
advance slowly to effective dose
(usually 160-240 mg/day ÷ TID)
Children: start at 1 mg/kg/day ÷
TID, advance to 2-4 mg/kg/day ÷
TID
Side effects
GI distress, bleeding
Risk of Reye’s syndrome
Ibuprofen
GI ulceration, bleeding
Naproxen
GI ulceration, bleeding, rash, sedation,
dizziness
Propanolol
Bradycardia, fatigue
Orthostatic hypotension
(some other ß-blockers,
Bronchospasm
generally those without partial
Mood changes, vivid dreams, insomnia
agonist activity, effective as
Use with extreme caution in patients with
well)
cardiac failure, diabetes (masks
hypoglycemia), asthma
Metoprolol (selective ß1
2-6 mg/kg/day ÷ BID
Similar to propanolol, but with less frequent
bronchospasm
antagonist)
Atenolol (selective ß1
1-2 mg/kg/day; single dose
Similar to propanolol, but with less frequent
bronchospasm
antagonist)
Cyproheptadine
2-4 mg/day ÷ BID
Sedation
Advance slowly as tolerated up to 8- Weight gain and increased appetite
16 mg/day if needed
Dry mouth
Methysergide
Start at 2 mg/day and gradually
Retroperitoneal fibrosis with long-term use
(USE WITH EXTREME
increase to 6 mg/day ÷ TID
Nausea and vomiting
CAUTION)
After 4-5 months, taper over 2-3
Insomnia
wks and stop for 1 month
Dizziness
Vasospasm
Amitriptyline
25 mg qHS, increasing weekly by
Sedation
25 mg/day;
Dry mouth, urinary retension, constipation
final dose generally 50-150 mg/day Postural hypotension
Confusional episodes
May take up to a month to work
Protriptyline
15-40 mg/day ÷TID-QID
Similar to amitriptyline, but less sedating
Nortriptyline
25 mg qHS, increasing weekly by
Similar to amitriptyline, but less sedating
(Pamelor)
25 mg/day to up to 75 mg qHS (but
some suggestion that 10 mg
advancing to 30 mg qHS may work
as well); levels should be monitored
for doses between 100 and 150
mg/day
Verapamil
80 mg/dose ÷ TID-QID
Constipation
May take up to 1-2 months to work
Valproate
Gradually increase to 15-60
Behavioral changes, sedation
mg/kd/day (??)
GI side effects, weight gain
Tremor
Thrombocytopenia, leukopenia
Liver toxicity
Other anticonvulsants (phenobarbital, phenytoin) have also been used.
VI. Behavioral treatment
Biofeedback (temporal artery; thermal)
Relaxation therapy
Self-hypnosis
3
Triptans
Generic name
Brand
name
Sizes
Adult
starting
dose;
repeat
time;
max per
24 hours
12.5 mg/
2 hr/
25 mg
Cost
per
dose
(2005)
Comments
Almotriptan
Axert
6.25, 12.5
mg tabs
$22-23
20, 40 mg
tabs
40 mg
2 hr/
80 mg
$22-24
Frova
2.5 mg tab
$24
Naratriptan
Amerge
1, 2.5 mg
tabs
2.5 mg
2 hr
7.5 mg
2.5 mg/
4 hr/
5 mg
Rizatriptan
Maxalt
5, 10 mg
tabs
10 mg/
2 hr/
30 mg
$22-23
FDA approved for
≥12 years old.
Similar to oral
sumatriptan in efficacy
but may have fewer
side effects.
Higher dose (80 mg)
may be as efficacious
as rizatriptan but high
rate of side effects.
Lowest NNT in one
study
Slow onset, long halftime. Few side
effects.
Slow onset, long halftime. Few side effects.
Lower recurrence
risk. Useful
prophylactically for
menstrual migraine
FDA approved for ≥6
years old. Greatest
early efficacy of oral
triptans, but rebound
more likely. Reduce
dose if using
propanolol.
Eletriptan
Relpax
Frovatriptan
Rizatriptan
dissolvable
tab
Sumatriptan
tablet
Maxalt
MLT
5, 10 mg
$23
Imitrex
Sumatriptan
nasal spray
Imitrex
25, 50,
100 mg
tabs
5, 20 mg
10 mg/
2 hr/
30 mg
50 mg/
2 hr/
200 mg
20 mg/
2 hr/
40 mg
4
$25-26
$21-25
Gold standard
$32-33
Rapid onset but 2-hr
efficacy similar to oral
zolmitriptan
Sumatriptan
Injectable
Imitrex
6 mg
Zolmitriptan
Zomig
2.5, 5 mg
tabs
Zolmitriptan
dissolvable
tabs
Zolmitriptan
nasal spray
Zomig
2.5, 5 mg
Zomig
5 mg
6 mg/
1 hr/
12 mg
2.5 mg/
2 hrs/
10 mg
2.5 mg/
2 hrs/
10 mg
5 mg
2 hrs
10 mg
$79
Most rapid onset and
greatest efficacy but
most side effects
$22-24
$22-25
$32
Ranking:
Speed:
Sumatriptan SQ > sumatriptan nasal spray = rizatriptan tab/wafer > zolmitriptan> sumatriptan
oral = almotriptan > naratriptan
Early efficacy (1 and 2 hr)
Sumatriptan SQ > rizatriptan tablet/wafer > sumatriptan nasal spray = zolmitriptan >
sumatriptan oral = almotriptan > naratriptan
Tolerability
Naratriptan = almotriptan > sumatriptan oral = zolmitriptan = rizatriptan > sumatriptan nasal
spray > sumatriptan SQ
Recurrence
Naratriptan = almotriptan < zolmitriptan = rizatriptan = sumatriptan SQ, oral, nasal spray
Formulations
Sumatriptan > rizatriptan = zolmitriptan > naratriptan = almotriptan
5