1. “The Medication Maze”
Norton Headache and Concussion Center
Headache School
April 2013

2. Disclaimer
This talk is not inclusive of all medications
used to treat migraine; this is a simplified
discussion of the common medications used
in treating migraine. There is likely going to
be a medication you are on or have been
treated with not discussed in this lecture,
that does not mean it is not effective or not
used in the treatment of migraine.

3. Treating migraine
• One of the biggest factors that we stress in the treatment of
migraine is thorough evaluation of triggers and lifestyle
modifications
– Diet
– Sleep
– Exercise
– Hydration
– Stress management
• These are all topics that at various times are discussed in
other headache school sessions
• This is a talk about medications, assuming that we are already
looking into and discussing other lifestyle modifications

4. Strategies for treating migraine
• Treating the headache attacks
– Rescue medications / abortive therapy
• Preventing headache
– Prophylactic / preventative therapy
– Goal of preventative therapy is reducing the frequency,
severity, and duration of attacks
– Success is defined as a 50% reduction
– Important to remember that it is management, not a “cure”

5. Rationale for treating migraine
• When to choose a preventative therapy?
– There is no set in stone guideline
– Individualized
• Is the patient willing to take a daily medication knowing
that there is a potential for side effects?
• Is the patient failing rescue medications?
• Is the patient experiencing disability (missed work,
school, or family functions)?

6. Rescue Medications
• Primary goal is to achieve relief of pain,
associated symptoms, and disability within 2
hours of use
• Goal is to use rescue medications 2 or fewer
times per week to prevent developing
medication overuse headache

7. Rescue Medications
• It is important to treat the headache as soon as
possible, as time goes on the medications become
less effective
• Allodynia is defined as pain resulting from
stimulation that would not normally be perceived as
noxious (ie. light touch of the skin)
– To the patient this is perceived as scalp tingling or pain
when lightly touched during a migraine
– To physicians this means that the deep parts of the brain
have been stimulated by the migraine attack and it is often
times more difficult to treat

8. Allodynia
• Once the deeper parts of the brain are activated the
migraine attack becomes much more difficult to treat
– A study using injectable sumatriptan (to be discussed later)
found that in patients without allodynia 93% were free of
pain at 2 hours, but only 15% of patients with allodynia
were pain-free at 2 hours
• The take home message is to treat aggressively and
treat early to improve chances of becoming pain-free
with minimal medication use

9. Rescue Medications

10. Rescue Medications
• In treating migraine unlike treating other conditions
(ie. high blood pressure) we often times suggest
using higher dose medications initially and backing
down the dose if side effects are experiences, rather
than over time escalating doses
– So it is important to understand what potential side effects
can occur with medications and understand that the goal is
being pain-free with TOLERABLE side effects rather than
being with pain and no side effects

11. Rescue Medications
• Need to use caution to avoid medication
overuse headache by using rescue
medications frequently

12. Medication Overuse Headache
• Headache present on ≥15 days/month
• Regular overuse for ≥3 months of one or
more drugs that can be taken for acute
and/or symptomatic treatment of headache
• Headache has developed or markedly
worsened during medication overuse
• Headache resolves or reverts to its previous
pattern within 2 months after discontinuation
of overused medication

13. Medication Overuse Headache
The Cleveland Clinic Manual of Headache Therapy p. 156
Bigal ME, et al. Headache. 2008;48:1157-1168.
Bigal ME, et al. Pain. 2009;142:179-182.

14. Nonspecific Migraine Medications
• Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
• Over 20 forms of NSAIDs available in the US, many
available over-the-counter
• Have anti-inflammatory effects as well as analgesic
(pain relief) effects
• Not processed through the liver
• Kidney metabolism
– Very important for patients with kidney disease, on other
medications that have effects on the kidneys, and in
patients with extreme vomiting (dehydration can lead to
kidney problems)
• Can lead to stomach bleeding with frequent use

15. NSAIDs
• Can be used alone or in combination with
other medications (ie. triptans)
• Are non-sedating
• Have been shown to be effective in treatment
of patients with allodynia
• Because of the availability there is significant
problems with overuse, particularly leading to
medication overuse headache

16. NSAIDs
• Ibuprofen (Advil, Motrin) 400-800mg
• Naproxen (Aleve) 500-550mg
– Available combined with sumatriptan (Treximet)
• Diclofenac (Cambia, Cataflam, Voltaren) 50mg
– Orally disintegrated packets (Cambia) have very rapid
onset of action
• Ketorolac (Toradol)
– Oral form not frequently used
– IV or IM form can be used for prolonged migraine

17. Acetaminophen
• Acetaminophen (Tylenol)
• Most people do not find useful for severe
migraine
• Can be used for mild headache
• Typical dose is 1000mg at onset of headache
• Often times used in combination products (ie.
Fioricet, Midrin, etc)
• Can lead to medication overuse headache
• With heavy usage can lead to liver toxicity,
otherwise no significant side effects

18. Isometheptene
• Midrin
– Contains isometheptene, acetaminophen, and
dichloralphenzone
– Two capsules at onset, followed by one capsule
every hour until relief is achieved (max of 5 per 12
hours)
– Side effects similar to components, dizziness is
common
– Modest effects
– Sparsely available

19. Butalbital
• Combination product
• Butalbital / acetaminophen / caffeine
– Esgic, Fioricet
• Butalbital / aspirin / caffeine
– Fiorinal
• Side effects include incoordination, disinhibition, memory
problems, drowsiness
• If used for extended periods of time and then discontinued
can cause withdrawal seizures
• Significant risk of medication overuse headache
– Studies show when used as few as 5 times per month can lead to MOH

20. Excedrin
• Combination of aspirin, acetaminophen, and
caffeine
• Can be used for mild to moderate migraine
• Due to the multiple products combined there is
significant risk of medication overuse headache
• Available OTC (unregulated by treating physicians
patients can take unlimited amounts)
• In specialty headache clinics this is probably the
most frequently overused medication and causes
more frequent headache

21. Anti-nausea medications
• Can often times alone or in combination be effective
in treating migraine
– Metoclopramide (Reglan)
– Prochlorperazine (Compazine)
– Promethazine (Phenergan) to a lesser extent
• Most common side effects are drowsiness and
dizziness
• More significant side effects include dystonia
(sustained muscle contraction) and akathisia (sense
of restlessness) which can be treated with Benadryl

22. Opiates
• Worth mentioning, but in the hands of
headache specialists are not frequently used
• In migraine, opiates are not well absorbed,
they are associated with increased nausea,
and sedation
• Very quickly can lead to physical dependence
and are quite notorious for causing
medication overuse headache

23. Why opiates are bad

24. Migraine specific medications

25. Triptans
• Introduced in the 1990s
• Often times considered the drug of choice in
treating migraine
• Selective agonists (activators) of serotonin
blocking the release of other inflammatory
chemicals during a migraine attack

26. Triptans
• Available in many different brand names with
varying time of onset and duration of action
• Available in a variety of delivery methods
– Oral tablet
– Oral disintegrating
– Nasal
– Injection
– Patch (in development)

27. Triptans
• Side effects
– Narrow coronary blood vessels by 10-20% (avoid use in
individuals with a history of coronary or cerebro-vascular
disease or uncontrolled risk factors)
– Tighten of the throat, chest, jaw, neck, and limbs
– Numbness of the limbs and around the mouth
– Hot and cold sensations
• Through to be due to esophageal (not heart) related spasm and
muscle contractions
• If warned in advance, most patients can tolerate side effects with
the benefit that they give

28. Triptans
• “Patients vary more than triptans”
• Meaning, just because one did not help or caused
side effects does not mean that another will do the
same
– I give the example of Coke and Pepsi – it’s basically the
same stuff but some people like one and some people like
another, and you won’t know until you’ve tried them
• Or that different routes of administration won’t have
a different effect

29. Triptans

30. Sumatriptan
• Imitrex, Statdose, Sumavel, Alsuma
• First triptan brought to market (1991)
• Available oral, nasal, and subcutaneous injection
• Available as a generic
• Oral dose is 25, 50, 100mg – maximum per 24 hours is 200mg
– Available in combination with naproxen as Treximet
• Subcutaneous (SC) forms (Statdose, Sumavel, Alsuma) are
6mg (max 12mg / 24 hours)
– Have much quicker onset of action (10 minutes) and are great for
patients with significant nausea and vomiting
– Statdose and Alsuma use a needle, Sumavel is needle-less
• Nasal spray is not used all that frequently

31. Quick acting triptans
• Almotriptan (Axert)
– 6.25mg / 12.5mg; max per day is 25mg
• Rizatriptan (Maxalt)
– 5mg / 10mg / 10mg MLT (dissolvable tablet); max per day
is 30mg
• If using propranolol need to use 5mg dose
• Eletriptan (Relpax)
– 20mg / 40mg; max is 80mg per day
• Zolmitriptan (Zomig)
– 2.5 / 5mg; available as nasal spray (5mg); max is 10mg per
day

32. Slow acting triptans
• Naratriptan (Amerge)
– 1, 2.5mg; max is 5mg per day
– Available as generic
• Frovatriptan (Frova)
– 2.5mg; max is 7.5mg per day
• These are useful for menstrual migraine (as a week-
long preventative)
• Also used in combination with another drug (ie.
naproxen or Cambia)

33. Ergots
• Ergotamine tartrate available since 1925
• Dihydroergotamine (DHE) more refined
version available since 1945
– These were the only available migraine specific
medications until triptans introduced in 1990s
• Effect many chemicals in the nervous system
which explains why they are so effective, but
also explains the side effects

34. Ergots / DHE
• Nausea is the major side effect
– May actually increase nausea of migraine rather than improve it
• Again contraindicated in patients with vascular disease,
coronary artery disease, etc.
• Available IV (hospital use)
• Intramuscular – can be administer at home
• Intranasal (Migranal) – very easy to use at home
– Inhaled in each nostril and then repeated in 15 minutes
– Much less effective than IV / IM
• Orally inhaled DHE (Levadex) coming to market soon
– Inhaled orally at home with blood levels as high as IV, but with less
nausea
• Should be a great drug when commercially available (maybe later this
year)

35. Preventative Medications

36. Preventative Medications
• There are no “migraine specific” medications
used in the prevention of migraine
• Use medications from other classes
– Blood pressure medications
– Antiseizure medications
– Antidepressants
– Serotonin antagonists
– Vitamin supplements
– Botox

37. Preventative Medications
• Important to identify patients that are using
frequent rescue medications and may be on
the way to developing medication overuse
headache
• Patients who have disabling headache that is
not easily treated with rescue medications
• Ideally treat multiple conditions with a single
medicatio
– ie. high blood pressure and migraine

38. Antidepressants
• Tricyclic antidepressants
– Amitriptyline (Elavil)
– Nortriptyline (Pamelor)
– Protriptyline (Vivactil)
• Side effects
– Elavil and Pamelor are sedating and taken at night (useful
for patients with sleep trouble)
– Vivactil is stimulating, but needs to be taken 3x per day
– Cause dry mouth, constipation, weight gain
– At high doses can cause heart related issues that may
require an EKG to be checked

39. SSRI / SNRI
• SSRI
– Fluoxetine (Prozac)
– Paroxetine (Paxil)
– Fluvoxamine (Luvox)
• SNRI
– Venlafaxine (Effexor)
– Duloxetine (Cymbalta)
– Desvenlafaxine (Pristiq)
• SNRIs tend to be more effective for migraine than
SSRIs
– Venlafaxine (Effexor) has the best evidence for use in
prevention of migraine

40. SSRI / SNRI
• Side effects
– Weight gain
– Sexual dysfunction
– Sedation
– Nervousness

41. Antiseizure Medications
• Recently have become most frequently used
medications for prevention of migraine
– Topiramate (Topamax)
– Valproate (Depakote)
– Gabapentin (Neurontin)
– Zonisamide (Zonegran)

42. Topiramate (Topamax)
• One of the most frequently used medications in the
prevention of migraine
• Has several advantages, but also does have some
side effects to be aware of
• Effective in nearly 50% of patients that use it
• Rather than weight gain, often times causes weight
loss
• Optimal dose is 50mg twice per day
– If side effects occur, sometimes may use nighttime only
dosing

43. Topiramate (Topamax)
• Side effects
– Up to 13% of patients experience cognitive dysfunction of trouble with
processing information and trouble finding words
– Numbness / tingling of fingers, toes, face
• Actually a predictor of which patients will benefit from topiramate use
• Potassium supplementation can help
– Risk of kidney stones
– Glaucoma
– Reduced sweating (important in athletes / overheating)
• Recently identified birth defects
– Oral cleft (palate, lip) 11 times higher than general population
– Rated as Category D for pregnancy
• Reduced oral contraceptive effectiveness
– At doses greater than 200mg / day

44. Valproate (Depakote)
• Quite effective, but less commonly used due to side
effect potential
• Optimal dose is 500 – 1,500mg per day
• Side effects
– Weight gain
– Hair loss
– Pancreatitis
– Liver problems
• Significant effects with women of child-bearing
potential
– Neural tube defects (ie. spina bifida)

45. Gabapentin (Neurontin)
• Less commonly used
• Optimal dosing is 900 – 2,400mg
– Needs to be dosed 3x per day
• Side effects
– Drowsiness
– Dizziness
• No drug interactions, no effect on kidneys or
liver
• Sometimes used as a rescue medication

46. Zonisamide (Zonegran)
• Similar to topiramate
• Sometimes effective in patients that respond
to topiramate but experience side effects
• Side effect profile similar
• Optimal dosing not exactly known, but most
suggest around 200mg at night

47. Blood Pressure Medications
• Beta blockers
• Calcium channel blockers
• Other blood pressure medications
– Not frequently used
• Useful in patients with co-existent high blood
pressure

48. Beta Blockers
• Propranolol
• Timolol
• Atenolol
• Metoprolol
• Nadolol
– Lower blood pressure and heart rate
• Can lead to light-headedness
– Can reduce aerobic capacity
– Worsen asthma
– Avoid in diabetics
– Can worsen depression

49. Calcium Channel Blockers
• Verapamil
• Diltiazem
– Generally well tolerated
– Often times more useful in patients with migraine
with aura
– Side effects include light-headedness,
constipation, and swelling of legs

50. Serotonin antagonists
• Rarely used outside of headache specialty
clinics
• Methylergonovine (Methergine)
– Similar to methysergide (Sansert) which is no
longer readily available
– Usually used 3-4x per day
– Triptans should not be given concominantly

51. Vitamin Supplements
• Not as well studied as prescription medications (product of
financing of studies)
• Magnesium
– 400+mg / day
– Diarrhea can occur
• Riboflavin (B2)
– 25 – 400mg / day
– Will discolor urine
• Coenzyme Q10
– 100mg 3x / day
– Costly (sometimes)
• Butterbur and Feverfew also felt to be effective

52. Botox
• OnabotulinumtoxinA
• Famous for being used for “wrinkles”
• Found to be effective in patients with chronic
migraine
– Greater than 15 days of headache per month for
greater than 3 months
• In clinical trials patients using opiates and
butalbital were excluded as they tend to do
worse

53. Botox
• 155 units injected into 31 sites given every 3
months
• Minimal side effects
– Injection site pain is largest
• Up to 9 days less per month of headache
• FDA approved

54. PREEMPT Protocol Fixed-dose, Fixed Injection Sites; one size fits all
• In the US, Botox is available in 2 vial • This comes out to 4 (1 ml) syringes,
strengths with 100 or 200 Units all 30 gauge ½ inch needles
•Normal Saline is the diluent • Each injection is 0.1 cc
• For the 100 unit vial, 2 cc Normal •There are 5 units onabot/0.1 ml
Saline; For the 200 unit vial, 4 cc NS
Blumenfeld A et al. Headache 2010;50:1406-1418 .

55. PREEMPT pooled analysis: mean change from baseline
in frequency of headache days (primary)
Double-blind
phase: patients on
Open-label phase: all • Patients treated with
patients on onabot
onabot or pbo onabot averaged of 8.2
fewer HA days/month
at Wk 24 vs placebo,
6.2 HA d/mo; p<0.001)
days from baseline (days/28-day period)
••Onabot (n=688)
Mean change in frequency of headache
Onabot (n=688)
••Pbo (n=696)
Pbo (n=696) • Patients receiving
placebo first, that is 3
cycles, never catch up
to those who received
5 cycles, suggesting
cumulative benefit
Headache days at baseline: 19.9 onabot vs 19.8 placebo, p=0.498.
Dodick DW et al. Headache 2010;50:921–936.

56. Conclusions
• Rescue medications
– Use migraine specific medications as much as
possible
– Treat as early as possible in the attack
– Add NSAIDs to triptans if necessary
– Avoid opiates and butalbital as much as possible
– Limit rescue medications to 10x per month if
possible

57. Conclusions
• Preventative treatment
– When migraine is frequent or disabling
pharmacologic prevention should be used to avoid
medication overuse
– Individualize treatment with other medical
conditions
– Give medications 2-3 months to see if they are
effective
– Set realistic expectations (not a cure)

58. Questions?
Discussion
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59. Norton Headache and Concussion Center
Headache School
• How Diet Affects • Headache related to injury
Headaches August 8 • 6 to 7:30 p.m.
May 16 • 6 to 7:30 p.m.
• What is a migraine aura?
• Women and Headaches September 12 • 6 to 7:30 p.m.
June 13 • 6 to 7:30 p.m.
• Alternative headache
• Biofeedback and stress treatments
management October 17 • 6 to 7:30 p.m.
July 11 • 6 to 7:30 p.m.