HEADACHE
MANAGEMENT
Elizabeth Treiber, MSN, CRRN, CNP
NEONP Conference
April 24, 2015
Disclaimers
• Opinions contained in this presentation are
the views of the author and do not
necessarily reflect the views of the
Department of Veterans Affairs
• No conflicts of interest
• Off label uses of several medications will
be discussed
(Thanks, Dr. Ronald Riechers, for your
assistance with this presentation)
OBJECTIVES
Describe the difference between
abortive and prophylactic
headache medications.
Apply pharmacodynamics of
headache medications to case
studies.
Key Facts
• Headache disorders are among the most common
disorders of the nervous system.
• It has been estimated that 47% of the adult population
had at least one headache within the last year.
• Accounts for 13 million office/ED visits per year
• Approximately 1 in 30 people have a headache more
days than not, for more than 6 months
Approach to Headaches
• Begins with proper identification of headache type
• Classification is based on history and examination
• Primary
• Secondary
Evaluation of Headaches
• Quality of pain
• Location of pain
• Time of day pain occurs
• Warning symptoms/aura
• Precipitating factors
• Symptoms associated with headaches
• History of chronic or recurring headaches
• Family history of headaches
Clinical Evaluation – Examination
• Vitals signs
• Head and neck palpation
• Neurologic examination
• Signs of elevated ICP
• Focal abnormalities of motor/sensory function
• Cerebellar function
• Reflexes
Red Flag Symptoms
(SNOOP)
• Systemic Symptoms (fever, weight loss)
• Secondary Risk Factors (underlying disease)
• Neurologic Symptoms (confusion, focal exam)
• Onset (sudden, abrupt—first, worst)
• Older Age Onset (>50, giant cell arteritis)
• Pattern Change (first headache or different)
• Previous Headache History (frequency, severity)
(Dodick, 2003)
Types of Headaches
Primary
• Lack an underlying pathologic cause
Secondary
• Have an underlying systemic or local
cause
• Exceedingly rare cause of headache
presentation—high level of patient
anxiety
Primary Headache Disorders
Headache
Type
Characteristics
Associated
Symptoms
Duration
Epidemiology
Migraine
Uni/Bilateral
Throbbing pain
Worsened with
physical activity
Severe intensity
Nausea/Emesis
Photo/phonophobia
4-72 hours
10-15% of
population, 3:1
F:M ratio
TensionType
Bilateral
Pressure or band
like pain
Mild intensity
Typically none
30 min –
several
hours
60-70% of
primary
headaches,
equal M:F ratio
Cluster
Unilateral orbital
or temporal
Short duration
severe pain
Multiple attacks
Lacrimation,
rhinorrhea,
congestion, ptosis,
miosis, conjunctival
injection
15-180 min,
1-8 attacks
per day,
lasting week
to months
<5% of primary
headache
disorders, 6:1
M:F Ratio
Chronic Headache
Medication
Overuse
Headache
(Rebound)
• overuse of analgesic meds>3/week
• >15 headaches/month
Chronic Migraine
• > 8 HA days/month for at least 3
months
• Not MOH or secondary cause
Chronic Tension
Type
• >15/month
• bilateral, non-throbbing, mild, able
to continue activity
Headache
Episodic Headache
Chronic Daily Headache
•Characterize type
•Abortive therapy
•> 15 HA days per month
•Analgesic rebound
•Prophylaxis is key
•Maximum 3 doses/week
Avoid narcotics
& Benzos
Prophylaxis
Abortive
NSAIDs
•GI side effects
Ibuprofen
Naproxen Sodium
Aspirin
Triptans
•Contraindicated in
patients with CAD
Onset of action ~ 4 wks
Combination
Medications
Alternatives
Promethazine
Metoclopramide
•Cognitive side effects Prochloroperazine
•Risk of W/D
Tizanidine
Non-medication
Fioricet
Trigger point injection
Fiorinal
Occipital nerve block
Midrin
Physical therapy
Anti-depressants
•May improve mood
•Improves sleep
AEDS
Nortriptylline
Amitryptilline
Paroxetine
Fluoxetine
gabapentin
•Mood lability
valproic acid
topirimate
•Neuropathic pain
Beta-blockers
•Non-selective may
have benefit on
autonomic effects of
PTSD
Propranolol
Tension Headache Medications
Abortive
Preventive
• NSAIDS
• TCA
• Muscle Relaxants
• SNRI
• SSRI
• Physical Therapy
Migraine Headache Medications
Abortive
• Triptans
• Antiemetics
• NSAIDS
• Dihydroergotamine
Preventive
• TCAs
• (Amitriptyline, Nortriptyline)
• Topiramate
• Gabapentin
• Betablockers
• (propranolol)
• Promethazine
• Verapamil
• Divalproex
• Botox
• Physical Therapy
Cluster Headache Medications
Abortive
Preventive
• Sumatriptan
• Steroids
• Zolmitriptan
• Verapamil
• Oxygen
• Lithium
Headache - Abortive
• Fundamental principle #1- Limit frequency of abortives
due to analgesic rebound headache
• Ibuprofen, alleve, tylenol all may cause rebound headache (MOH)
• Do not use more than 3 times/week
• Fundamental principle #2- Avoid narcotics due to
dependence risk, rebound headaches, cognitive/mood
effects
Abortive Therapies - Migraine
• OTC preparations
• Excedrin, Goody’s powders, tylenol, advil
• May work for limited population
• High risk of rebound headaches
Abortive Therapies - Migraine
• NSAIDs
• Prescription agents may offer some benefit over OTCs
• Naproxen is usually agent of choice
• Long acting preferred over short acting
Abortive Therapies - Migraine
• Triptans
• Migraine Designer drug
• 5HT1B/1D agonists
• Key is early dosing
• No dependence risk but risk of analgesic
rebound headache exists
• Risk of vasospasm – CONTRAINDICATED IN
PATIENTS WITH CAD/STROKE
Triptans for Migraine
• Sumatriptan (Imitrex)
• Multiple preparations
• Oldest
• Zomig/Maxalt
• ODT preparations
• Frovatriptan
• Long acting agent
Triptans (Sumatriptan, zolmitriptan)
• Pharm Category—Serotonin 5-HT Receptor Agonist
• Use—acute treatment of migraine or cluster HA
• Mechanism of action—causes vasoconstriction in cranial arteries
•
•
•
•
and reduces neurogenic inflammation
Contraindications—ischemic heart disease, cerebrovascular
syndromes, peripheral vascular syndromes, uncontrolled HTN,
hepatic impairment, use within 2 weeks of MAO inhibitor
Caution—Sulfa allergies, seizure history
**Serotonin Syndrome** see next slide
Dosage—Sumatriptan 50mg at onset of severe headache, may
repeat in 1-2 hours if needed—if needs to repeat every HA,
increase to 100mg at onset
Serotonin Syndrome
• American Headache Society published a position paper in
2010 which states:
“the available evidence does not support limiting the
use of triptans with SSRIs or SNRS due to concerns
for serotonin syndrome. Based upon their
pharmacology, the involvement of triptans in
contributing to a serotonin syndrome, either alone or in
combination with other medications, seems implausible.”
http://www.headachejournal.org/SpringboardWebApp/userfiles/h
eadache/file/fda.pdf
Combination Therapies
(old and cheap)
• Fioricet/Fiorinal
• Caffeine + barbiturate + acetaminophen or ASA
(butalbital)
• Dependence risk/High risk of analgesic rebound
• MAJOR RISK OF SEIZURE/DEATH WITH ABRUPT CESSATION
IN DAILY USER
• Midrin (acetaminophen, dichloralphenazone,
isometheptene)
• Treximet (sumatriptan 85 and naproxen 500)
Abortive Therapies - Migraine
• Anti-Nausea agents
• Promethazine, Metoclopramide, Prochloperazine,
Theoretical mechanism based on dopaminergic theory
of migraine
• NO RISK OF ANALGESIC REBOUND
• Caution in chronic use (EPS)
(Extrapyramidal symptoms (EPSs), such as
akathisia, dystonia, psuedoparkinsonism, and
dyskinesia, are drug-induced side effects that can
be problematic for persons who receive
antipsychotic medications (APMs) or other
dopamine-blocking agents.)
Promethazine
• Pharm Category—Anti-emetic
• Use—anti-emetic
• Mechanism of action—blocks dopaminergic
receptors in the brain, alpha adrenergic blocker
• Contraindications—hypersensitivity
• Caution—can be sedating, can lower seizure
threshold, can elevate prolactin levels so caution in
breast cancer, may alter cardiac conduction, has
anti-cholinergic effects
• Dosing—12.5mg at for nausea associated with
migraine HA, may take every 6 hours until HA
relieved
Headache - Prophylaxis
• Typical onset of action is 4 weeks on prophylaxis
• Abortive agents should not be used on a daily
basis or for prophylaxis
• Prophylactics:
• Tricyclic Antidepressants (TCAs)
• Anti-epileptics (AEDs)
• Beta Blockers
• Anti-emetics
• Prazosin
TCA’s (Amitriptyline, nortriptyline)
• Pharm Category—tricyclic antidepressant
• Use—antidepressant
• Unlabeled/Investigational—analgesic for certain chronic and
•
•
•
•
neuropathic pain, prophylaxis against migraine headaches
Mechanism of action—increases synaptic concentration of
serotonin and/or norepinephrine in the CNS by inhibition of
their reuptake by the presynaptic membrane
Contraindications—use of MAO inhibitors within past 14
days, acute recovery phase after MI, pregnancy
Precautions—may cause drowsiness, do not abruptly
discontinue
Dosage—Amitriptyline—10mg at bedtime for one week,
then 20mg at bedtime
Headache Prophylaxis
• Amitriptyline or Nortriptyline
• Tricyclic antidepressant
• Helpful if impaired sleep is also an issue
• Useful if also having tension headache
• Check for history of cardiac arrythmias or seizures
• Check for suicide risk—warn about possible risk of
suicide—be sure has suicide prevention number
• Start 10mg at hs for 7 days, then increase to 20mg at hs
Anti-Epileptics: Topiramate (TPM),
valproate (VPA), gabapentin (GBP)
• Pharm Category—Anticonvulsant
• Use—TPM and PVA are FDA approved for prevention of
•
•
•
•
•
episodic migraines, GBP is useful in migraine prevention
based on a few clinical trials
Unlabled/Investigational—neuropathic pain, migraine,
cluster headaches
Mechanism of action—thought to block sodium channels in
neurons, enhancing GABA activity and by blocking
glutamate activity
Contraindications—history of kidney stones for TPM
Precautions—avoid abrupt withdrawal due to increased risk
of seizures, caution in hepatic/renal/pregnancy
Adverse reactions—somnolence, dizziness, nausea
Headache - Prophylaxis
•
Topiramate
•
•
•
•
•
•
Anticonvulsant
Great migraine headache data
Memory impairment/word finding difficulty possible
side effects
Weight loss
Renal stones in 1% of patients on higher doses
Start 25 mg qhs or bid titrate to NMT 100 mg bid
Headache - Prophylaxis
• Valproic Acid
▫ Good headache data
▫ Beneficial for mood lability/aggression
▫ Cons- teratogenicity, poor side effect profile, drug
interactions, hepatotoxicity
▫ ER version preferable, start 500 mg daily titrate to
1500-2000 mg daily, follow labs
Gabapentin
• Pharm Category—anti-convulsant
• Use—adjunct for treatment of seizures
• Unlabeled—chronic pain
• Mechanism of action—exact mechanism unknown
• Contraindications—hypersensitivity
• Caution—renal disease, may cause sedation, avoid
abrupt withdrawal
• Dosage—titrate to 300mg three times daily
Headache - Prophylaxis
• Gabapentin
• Data not as robust as other AEDs
• Benefit for neuropathic pain, anxiety, ?sleep
• Pros- tolerable side effect profile, minimal drug
interactions
• Start 300 mg qhs, titrate up to 600-900 mg tid
Beta Blockers (Propranolol)
• Pharm Category—Beta Blocker
• Use—HTN, tachycardia, arrythmias, migraine headaches
• Mechanism of action—non-selective beta-adrenergic
blocker
• Contraindications—CHF, bradycardia, asthma, COPD,
pregnancy
• Caution—hepatic dysfunction, PVD
• Dosage—Propranolol 10 mg twice daily—if helping,
change to 60mg LA daily
Headache - Prophylaxis
• Propranolol
• Non-selective, lipid soluble Beta blocker
• Pros- Effect on agitation, autonomic symptoms of PTSD
• Cons- Impact exercise tolerance, possible ED
• Caution with use of prazosin and in patients with
asthma
• Do not use in 2nd and 3rd trimesters
• Start 10 mg bid, titrate as tolerated
• Transition to 60mg LA for once daily dosing
Prazosin—More Bang for Your Buck
• Pharm Category—Alpha blocker
• Use—treatment of HTN
• Unlabeled—management of nightmares, headache prophylaxis
• Mechanism of action—inhibits postsynaptic alpha-adranergic
receptors (Alpha Blocker)
• Contraindications—hypersensitivity to quinazolines
• Caution—may cause orthostatic hypotension and syncope
• Dose—1mg at bedtime for one week, then 2mg at bedtime for one
week—titrate to 4 to 6mg—may increase dose to 10-15 mg
http://www.ncbi.nlm.nih.gov/pubmed/12562588
http://www.medscape.com/viewarticle/760070
Botox
• For adults with Chronic Migraine—15 or more
headache days a month, each lasting 4 hours or
more—FDA-approved, preventive treatment.
• Not approved for adults with migraine who have 14 or
fewer headache days a month.
• Receive injections into multiple facial muscles every 3
months
http://www.ncbi.nlm.nih.gov/pubmed/20487038
http://onlinelibrary.wiley.com/doi/10.1111/j.1526-4610.2010.01678.x/full
Drug Interactions
Headache Drug
PTSD Drug
Interaction
Tricyclic
Antidepressants
SSRIs
Inc TCA levels
2) Serotonin
syndrome
Triptans
SSRIs
Serotonin
Syndrome*
Prazosin
Additive lowering
of BP, orthostasis
Benzodiazepine
Additive increase
in sedation
Propranolol
Tricyclic
Antidepressants
1)
Deciding which medication to use
(Liz’s Pearls)
• Be sure not MOH headache (Rebound headache)
• Hx kidney stones—NOT topiramate
• Hx cardiac issues—NOT amitriptyline
• Hx suicidal ideation—NOT amitriptyline
• Bradycardic—NOT propranolol
• Neuropathic pain—gabapentin or topiramate
• Frequent migraines—topiramate
• Sleep issues—amitriptyline
• Weight issues—topiramate
• Try PRAZOSIN!
Education
• Education is the single most important step
in helping patients manage their
headaches.
• Hand-outs from American Headache Society
• Medication Overuse Headaches
• Triggers
• Non-pharmacologic Management
Headache Journal
• Date
• Time
• Intensity
• Preceding Symptoms
• Triggers
• Medication
• Relief
http://www.achenet.org/assets/1/7/Monthly_Headache_Diary.pdf
http://www.headaches.org/pdf/Headache_Diary.pdf
Triggers
• Stress
• Bright lights
• Lack of sleep
• Foods—nitrites, nitrates, aged cheese, MSG, raw
onions, chocolate, caffeine (see National
Headache Foundation Low Tyramine Headache
Diet)
https://www.headaches.org/pdf/Diet.pdf
Interdisciplinary Team Approach
• Behavioral Psychologist
• Headache medication education
• Triggers
• Headache diary
• Sleep hygiene
• Relaxation techniques
• Biofeedback
• SootheAway Machine
• Physical Therapy
• Neck exercises/stretches
• Dry needling
• Trigger Point Injections
Case Study # 1 – Cody
• 22 y/o male c/o headaches 3-4 days/week
• Hx brief LOC in high school baseball game
and brief LOC after IED explosion in
Afghanistan 2011
• What do you want to know?
• Gets HA 3-4 days/week—some mild, some severe
• HAs occur randomly throughout the day
• Takes tylenol 2-3 times/week—helps mild HA but
•
•
•
•
•
just dulls pain for severe HA
Pain—throbbing, center of forehead
Feels like he “hears his heartbeat” in his head
Phonophobia with severe HA, no photophobia
Gets nauseated with severe HA
Severe HA lasts a couple of hours, stops activities,
lays in dark room with cold cloth on head
• What else do you want to know?
• PM Hx:
• PTSD (sleeps 3-4 hours/night)
• Hematuria twice in past—work-up was negative—
intermittent right flank pain continues and is sometimes quite
severe
• Meds:
• Sertraline 50mg daily
• Trazodone 100mg at hs prn sleep
• Tylenol prn headache
• Soc Hx:
• ETOH—2-3 beers/night
• ½ PPD
• Caffeine—one cup coffee in am, energy daily prior to
working out
• Physical Exam:
• BP 134/78, P 100
• Neurologic exam is normal
• What type of headache?
• What meds would be appropriate or not
appropriate?
• What instructions should be given to patient?
• Type of headache
• Episodic Migraine
• Appropriate Meds
• Abortive:
• Triptan for migraine—caution about frequency of use
• Promethazine—nausea and helps with HA pain
• Preventive:
• TCA (interaction with SSRI)
• Topiramate (hematuria, flank pain)
• Propranolol (patient is tachycardic, good for tension HA)
• Prazosin (helps with sleep)
• Instructions
• Caution about MOH headache
• Decrease caffeine intake
• Non-pharm mgmt—thermal, trigger foods, HA diary
Case Study # 2 – David
• 28 y/o male, gets daily headaches
• Hx concussion without LOC in 10/2005 after IED
explosion, concussion with LOC 11/2005 after
IED explosion
• What do you want to know?
• HAs occur daily—50% are mild (3/10) with
pain located in forehead—50% are severe
with pain behind right eye
• HAs last 4-6 hours--takes tylenol and it helps
except for the really bad headaches
• Phonophobia and photophobia
• Occasionally nauseated
• Must go lay down in quiet, dark room
• Has not tried cold cloth
• PM Hx:
• Intermittent chest pain for last 6 weeks—ECG wnl, to see GI
next week
• Constant low back and hip pain—occasional
numbness/tingling in left leg—waken at night due to back
pain
• Meds:
• Vitamin D
• Nexium
• Tylenol several times/day for HA and back pain
• Social History:
• No etoh, no tobacco, one soda/day with lunch
• PE:
• BP 124/86 P 74
• Neuro exam wnl except for back pain with heel walk
• What type of headache?
• What meds would be appropriate or not
appropriate?
• What instructions should be given to patient?
• Type of headache:
• Medication overuse headache (rebound)
• Episodic migraine
• Medications:
• Abortive:
• Triptans (caution on overuse)
• Prophylactic:
• Propranolol (pulse 74)
• Topiramate (no hx kidney stones)
• Amitriptyline (recent chest pain)
• Gabapentin (helps with back pain & sleep)
• Prazosin (not having PTSD sxs)
• STOP DAILY TYLENOL USE
Case Study #3 – Nancy
• 42 y/o female
• Mild headaches 3-4 times/week
• Severe headache once/month
• Mild headaches start in her neck and
progress upward into head
• Usually occur in the afternoon and evening
• No N/V or photophobia/phonophobia
• Able to continue with her activities
• Severe HA occurs approx once/month
around the time of her menses—
photophobia—must lay in dark room with
cold cloth on head
• PM Hx:
• Was in MVA 5 years ago—cervical strain
• Meds:
• Vitamin D
• MVI
• Synthroid 50mcg
• Social History
• Glass of wine with dinner
• No tobacco
• 5-6 cups of coffee/day
• 3 school age children, elderly parents, works full time,
recently returned to school
• PE
• BP 130/74, P 76
• Neuro exam wnl
• What type(s) of headache?
• What meds would be appropriate or not
appropriate?
• What instructions should be given to patient?
• What type of headache?
• Tension or cervicogenic
• Menstrual migraine
• What meds would be appropriate or not appropriate?
• Tension
• Tizanidine (muscle relaxant) (abortive)
• NSAIDS (abortive)
• (caution rebound HA)
• Amitriptyline (prophylactic if frequency increases)
• Menstrual Migraine
• Naproxen 500mg BID starting 3-5 days prior to menses
• Triptan
• What instructions should be given to patient?
• Decrease caffeine intake
Case Study #4 -- Aaron
• 36 y/o Army veteran with history of
mild TBI/concussion--involved in fire
fight in Iraq in 2004--received blow to
head possibly from Humvee door-could not see or hear for several
minutes--felt dazed--unable to carry
out his duties for several minutes.
• Veteran gets migrainous type headaches approximately
2-3 times/month—pain left side of head—photophobic—
phonophobic—blurred vision—must go lay down in dark
room.
• Veteran describes the worst headache of his life occurring
approximately one month ago--3 days prior to this
headache veteran had significant difficulty operating a
machine at work that he was normally proficient in
operating--his headache has waxed and waned in
intensity since then but has not ever completely resolved.
His dizziness with position change has increased during
this time.
• Neuro exam is wnl except for MOCA exam which
is 25/30 (normal is 26/30).
• Meds: fluoxetine 60mg daily
• Veteran is currently taking alleve or motrin on a
daily basis for this headache.
• Veteran is otherwise functioning quite well--he is
maintaining full time employment, engaged with
his family, and in general good spirits.
What do you do now?
• What type of headache?
• Concerns?
• Ideas for treatment?
• What instructions should be given to patient?
Plan:
• MRA/MRI of head ordered to be done asap
• (worst headache red flag, neuro symptoms of forgetfulness)
• Stop daily use of any pain medications, including alleve and
motrin--these may cause rebound headaches
• Start promethazine 12.5mg prn for current daily headache-may take with alleve, but again, do not use alleve more than
2-3 times/week or rebound headaches may occur
• Start sumatriptan 50mg at onset of severe headache--do not
take more than twice/week or rebound headaches may occur.
• Follow up with neurology after MRA/MRI has been completed.
Follow Up
• MRI/MRA wnl
• Continue sumatriptan and promethazine—both
are working well
• Abbreviated Neuro-Psyche eval wnl
• Consult Behavioral Medicine for education and
SootheAway machine
• Encourage continued f/u with mental health
Case Study # 5 -- Brandon
• 22 y/o OIF/OEF National Guardsman--sustained
a mild TBI/concussion while deployed to
Afghanistan in 2013--exposed to multiple
explosions while doing route clearance--on one
occasion he felt dazed/dizzy/confused
immediately afterward and "out of it" the rest of
the day--no LOC--after several other explosions
he felt dazed for very short period of time.
• Daily headaches--occasionally last all day long—
continues with activities—5/10 pain
• Bad headache occurs every 3-4 days—must go in
dark/quiet room—9/10 pain
• Nauseated
• Neck also hurts
• Photophobic/phonophobic
• Cold water on face helps
• Takes tylenol or ibuprofen on almost daily basis
• Pain sometimes starts in neck and works its way up
• Difficulty with sleep initiation--wakes at slightest noise--
nightmares almost every night--irritable--hyperalert--does
not like to go into crowds.
• Neuro exam is wnl except for fine tremor in bil
UE--right more than left--numb area in lateral
aspect of right calf--and MOCA score of 18/30
(normal is 26 and above).
• Only prescribed medication is etodolac 400mg
every 6 hours as needed for pain
• VS are wnl
• No history of kidney stones or heart disease
What do you do?
• What type of headache?
• Instructions to patient?
• Treatment ideas?
Plan
• Stop daily use of any analgesic including tylenol, ibuprofen,
etodalac as these may be causing rebound headaches--use no
more than 3 times/week.
• Start prazosin for nightmares/restless sleep/headache
prophylaxis. Take 1mg at bedtime for one week, then 2mg at
bedtime for one week, then 3 mg at bedtime for one week, then
4mg at bedtime. Be careful when getting out of bed because
you might feel dizzy.
• Start sumatriptan 50mg at onset of migrainous type
headaches. May repeat in two hours if not effective. Do not
take more than twice/week or rebound headaches may occur.
• Consult Behavioral Medicine, Neuro-psyche testing, physical
therapy
Follow Up One Month Later
• Veteran is currently sleeping better--he is not as
wakeful and nightmares are slightly less frequent-he is now sleeping 6-7 hours/night instead of 4
hours/night.
• Mental health prescribed sertraline 50mg daily.
• Headaches are better with use of sumatriptan,
however veteran is taking the sumatriptan approx
3 times/week.
• Now What?
Add Prophylactic Medication
• Which one?
• Any other medication adjustments?
• What instructions should be given to patient?
Next step
• Start topiramate for headache prophylaxis. Take 25mg at
bedtime for one week, then take 50mg at bedtime.
• Increase sumatriptan to 100mg at onset of severe headache--
may repeat in 2 hours if needed. Do not take more that
twice/week or rebound headaches may occur.
• In 2 weeks, after topiramate dose has been titrated to 50mg,
then increase the prazosin to 5mg at bedtime for one week,
then 6mg at bedtime in an effort to continue to improve sleep
and decrease nightmares. Wait two weeks to initiate increase
in prazosin so increase in prazosin does not occur at the same
time as initiation of topiramate.
• Continue f/u with mental health providers.
Case Study #6 – D.R.
• 43 y/o male injured during football game
while training with National Guard in
Virginia in 2011—had C2-C7 posterior
cervical laminectomy—is currently able to
ambulate without a device—good control of
bowel/bladder—has ongoing neck and
upper back pain, headaches.
Case Study #6 (continued)
• Headaches—pain shoots up from neck or chin area--
occurs without warning several times/day--electrical and
squeezing pain--occurs on both right and left side--eyes
occasionally tear during these episodes--these shooting
HAs have been increasing in frequency--also gets
throbbing headache 3-4 times/week--photophobic--last 30
minutes to 60 minutes--must occasionally go into dark
room and rest. Has seen PT for dry needling--is doing
neck stretches and HEP on daily basis. Currently has
throbbing headache. Neck and shoulder pain--takes
oxycodone for neck and shoulder pain approx once/week-takes ibuprofen twice/day--occasionally skips the middle
of the day dose of gabapentin unless needed--Pulse 82100.
• What type of headache?
• What instructions to patient?
• What meds would be appropriate?
Plan
• Instructed veteran to try to decrease ibuprofen to
not more than 3 times/week--concern that
ibuprofen may be causing rebound headaches-possible consideration of naproxen instead of
ibuprofen for longer effect with less doses.
• Take gabapentin 900mg every 8 hours as
ordered—this will help with pain management
and also headache prophylaxis.
• Start propanolol 10mg twice daily for headache
prophylaxis.
Follow Up
• Good results with propranolol 10mg twice
daily—changed to propranolol SA 60mg
once daily
• Better pain control with use of gabapentin
every 8 hours (Can also help with
headache prophylaxis)
RESOURCES
Prazosin—Results of One Study
• Ruff et al.
• Nonrandomized, controlled trial of 80 OIF vets
• Headaches, cognitive function, daytime sleepiness
Ruff RL et al. JRRD 2009;46:1071-84
For the Entire Study Group, Prazosin
Improved Performance
Table 1: Impact of Intervention consisting of sleep hygiene counseling &
prazosin on daytime sleepiness (ESS), cognitive function (MOCA) & headaches
Performance of
veterans at
baseline and after
intervention
(N=74)
ESS
Scores
(0-24)
MOCA
Score
(0-30)
Headache
Pain
Intensity
(0-10)
Headache
Frequency
(#/month)
Baseline
16.1 + 0.28
24.5 + 0.49
7.28 + 0.27
12.4 + 0.94
After Sleep
Hygiene &
Prazosin
7.28 + 0.34
(p<0.001)
28.6 + 0.59
(p<0.001)
4.08 + 0.19
(p<0.001)
4.77 + 0.34
(p<0.001)
The Benefits of Prazosin Lasted
Table 3: Comparison of the veterans who were or were not taking prazosin 6
months after completion of the study period.
Performance
of veterans 6
months after
the study
period
ESS Scores
(0-24)
MOCA Score
(0-30)
Headache
Pain Intensity
(0-10)
Headache
Frequency
(#/month)
Taking
Prazosin (64)
3.97+ 0.18
29.0 + 0.13
2.39 + 0.12
1.88 + 0.14
Not Taking
Prazosin (10)
10.5 + 0.58
24.8 + 0.51
5.80 + 0.29
7.00 + 0.54
(p<0.001)*
(p<0.001)*
(p<0.001)*
(p<0.001)*
4.85+ 0.31
28.4 + 0.21
2.85 + 0.17
2.57 + 0.25
All subjects
(74)
* comparison of veterans taking vs. not taking prazosin
Indications for Neuro-Imaging
Evans RW. CONTINUUM: Lifelong Learning in Neurology
2006;12:213-234
Secondary Headache – Etiology
• CNS causes
• Non-CNS Causes
• Mass Lesion
• Vasculitis/GCA
• Aneurysm
• Infection
• Venous sinus thrombosis
• Glaucoma
• Arterial dissection
• Cervicogenic headache
• Chronic menigitis
• Malignant HTN
• CSF hypotension
• Drugs (illicit and
prescribed)
Secondary Headache
Posttraumatic Headache
• Start within 7 days of trauma, milder, neck trauma
Vascular Headache
• Ischemia, vasculitis, hemorrhage, giant cell
arteritis
Remember Red Flags
• Neuroimage: new neuro signs, new sudden onset
severe HA, HIV + with new HA, > 50 y/o with new type
HA
VA Pharmacy Newsletter June 2013
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Risk of Serotonin Syndrome with Triptans and SSRIs/SNRIs
Prepared by Roland Rovito, PharmD – Inpatient Pharmacist
The concurrent prescribing of 5-hydroxytryptamine receptor agonists (“triptans”) and either selective serotonin reuptake
inhibitors (SSRIs) or serotonin/norepinephrine reuptake inhibitors (SNRIs) is a controversial clinical topic due to concerns
regarding serotonin syndrome (SS), an adverse drug reaction that results from increased synaptic serotonin levels. Clinical
features include mental status changes, dysautonomia, and neuromuscular dysfunction; severity can range from mild to lifethreatening. Cases usually occur within 24 hours of serotonergic medication changes and are thought to be underreported due
to their sudden onset, transient nature, and low level of harm perceived by patients.
Based upon case reports, the Food and Drug Administration issued an alert regarding potential “life-threatening” SS in patients
on both a triptan and SSRI or SNRI in 2006. The quality of the reports used has been debated, as many cases fail to meet
diagnostic criteria for SS; however, it must be noted that these criteria have not been validated for use in post-marketing safety
reports. The mechanism for SS secondary to triptan use has also been debated, as animal models implicate 5-HT2A and
possibly 5-HT1A receptors in SS; at common doses, triptans have high affinity for 5-HT1B, 5-HT1D, and 5-HT1F receptors, low
affinity for 5-HT1A receptors, and no activity at 5-HT2A receptors. While chronic high-dose triptan use has shown increased
serotonin synthesis in animal models, acute triptan use has contrarily shown autoreceptor activation and decreased serotonin
synthesis and release, possibly preventing SS.
Given the high comorbidity of migraine with certain psychiatric disorders, it is not surprising that 20-25% of patients treated with
triptans also take an SSRI or SNRI. The concurrent use of these medications may be needed for effective treatment, and
avoiding co-prescription due to potential SS may lead to unnecessary morbidity and decreased quality of life. Therefore, while
the number of patients experiencing SS due to concurrent triptan and SSRI or SNRI use remains unknown and further study
into this adverse drug reaction is needed, it is difficult to use current evidence to rationalize the avoidance of this combination.
For select patients, the benefits of clinically-appropriate concurrent therapy likely outweigh the risk of SS, and as such, these
medications may cautiously be used together. Patients should be educated on SS and it would be advised for providers to
document that the risks versus benefits were evaluated and discussed with the patient.
References:
Evans RW, Tepper SJ, Shapiro RE, Sun-Edelstein C, Tietjien GE. The FDA alert on serotonin syndrome with use of triptans
combined with selective serotonin reuptake inhibitors or selective serotonin-norepinephrine reuptake inhibitors: American
Headache Society Position Paper. Headache. 2010;50(6):1089-1099.
Fine A, Bastings E. Triptans and serotonin syndrome [letter]. Headache. 2012;52(7):1184-1185.
Sclar DA, Robison LM, Castillo LV, et al. Concomitant use of triptan, and SSRI or SNRI after the US Food and Drug
Administration alert on serotonin syndrome. Headache. 2012;52(2):198-203.
Tepper SJ, Shapiro RE, Sun-Edelstein C, Evans RW, Tietjen GE. Triptans and serotonin syndrome – a response [letter].
Headache. 2012;52(7):1185-1188.
Wenzel RG, Tepper S, Korab WE, Freitag F. Serotonin syndrome risks when combining SSRI/SNRI drugs and triptans: Is the
FDA’s alert warranted? Ann Pharmacother. 2008;42(11):1692-1696.
Triptans for Migraine
Loder E. NEJM 2010;363:63-70.
Prophylaxis - Evidence
Loj J, Solomon GD. Clev Clin J Med 2006;73:793-816
References/Resources
• Evans, R. W., Tepper, S. J., Shapiro, R. E., Sun-Edelstein, C.,
Tietjen, G. E. (2010). The FDA alert on serotonin syndrome
with use of triptans combined with selective serotonin reuptake
inhibitors or selective serotonin-norepinephrine reuptake
inhibitors: American Headache Society position paper.
Headache 2010; 50: 1089-1099.
• http://www.americanheadachesociety.org/professional_resourc
es/headache_fact_sheets/ (Chronic daily headache,
Concussion and post-traumatic headache, Generalized anxiety,
PTSD & migraine, How to choose a preventive medication for
migraine, Triptan therapy for acute migraine, Migraine overuse
headache)
• http://www.americanheadachesociety.org/professional_resourc
es/headache_journal_toolboxes/ (Headache after sportsrelated concussion, Post-traumatic headache in veterans,
Triptans SSRIs/SNRIs and serotonin syndrome)
References/Resources (Continued)
• Lipton, R. B., Serrano, D., Nicholson, R. A., Buse, D. C.,
Runken, M. C., & Reed, M. L. (2013). Impact of NSAID
and triptan use on developing chronic migraine: Results
from the American migraine prevalence and prevention
(AMPP) study. Headache 2013; 53: 1548-1563.
• Loder, E., Weizenbaum, E., Frishberg, B., & Silberstein,
S. (2013). Choosing wisely in headache management:
The American Headache Society’s list of five things
physicians and Patients should question. Headache,
2013; 53:1651-1659.
• Marshall, R. S., & Mayer, S. A. (2007). On call neurology.
Philadelphia, PA: Saunders Elsevier.
• Ruff, R. L., Riechers, R. G., & Ruff, S. S. (2010)
Relationship between mild traumatic brain injury
sustained in combat and post-traumatic stress disorder.
F1000 Med Rep.2010: 2:64. Retrieved from
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990449/
References/Resources (Continued)
• Ruff, R.L, Ruff, S.S., Wang, X. (2009) Improving sleep:
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•
Initial headache treatment in OIF/OEF veterans with
blast induced mild traumatic brain injury. JRRD
2009;46:1071-84
Tepper, S. J., & Tepper, D. E. (Eds.). (2012). The
Cleveland Clinic manual of headache therapy. New York,
NY: Springer.
Turkowski, B. B., Lance, B. R., Bonfiglio, M. F. (2005).
Drug information handbook for advanced practice
nursing. Hudson, OH: Lexicomp.
Westover, M. B., Choi, E., Awad, K. M., Greer, D. M.
(Eds.). (2010) Pocket neurology. Philadelphia, PA:
Lippincott Williams & Williams.
Whyte, C. A., Tepper, S. J. (2010). Pearls & Oy-sters:
Trigeminal autonomic cephalalgias. Neurology, 2010:74:
e40-e42.
• Headache Disorders, WHO Fact Sheet N277, October 2012