Transcript IRM UPDATE-SECTION P

Key Learning Points From:
Women With Migraine:
Effective Strategies for
Positive Outcomes
Copyright © 2006 Thomson Professional Postgraduate Services®. All rights reserved.
Migraine Impact and Prevalence
(American Migraine Study II)
• Currently 28 million people in the United States
older than 12 years with migraine
– 21 million females
– 7 million males
• Migraine prevalence peaks in the group aged
35-45 years
• 1 in 4 households has at least 1 person with
migraine
2
Lipton RB et al. Headache. 2001;41:646-657.
Disability During Migraine Attacks
Percent of Migraineurs
60
Female
Male
53
47
50
40
31
30
20
23
22
18
10
3
2
1
1
0
0
<1
1-2
3-5
≥6
Days of Restricted Activity per Migraine
3
Adapted from Lipton RB et al. Headache. 2001;41:646-657.
Female Preponderance
of Migraine
• The higher prevalence of
migraine in women may be
explained in part by
hormonal factors, including a
sudden decrease in plasma
estradiol occurring at
menstruation.
• A gender difference in
prevalence rates after
menopause suggests that
other factors are also
involved.
Females
30
Prevalence (%)
Males
20
10
0
15-19
20-29
30-39
40-49
50-59
60-69
70-79
>80
Age (years)
4
Breslau N, Rasmussen BK. Neurology. 2001;56:S4-S12.
Chart adapted from Henry P et al. Cephalalgia. 1992;12:229-237.
IHS Classification: ICHD-2
• Primary headache
– symptom based
– tools now available to help measure/monitor
patient disability
• Secondary headache
– etiology based
• Red flags can help separate the diagnoses
IHS=International Headache Society
ICHD=International Classification of Headache Disorders
5
Headache Classification Subcommittee of the International Headache Society. The International
Classification of Headache Disorders, 2nd ed. Cephalalgia. 2004;24(suppl 1):1-160.
Tools for Migraine
Diagnosis/Disability
• Primarily symptom-based
– IHS criteria
• Symptom- and impact-based
– ID Migraine™
• Impact-based/disability
– MIDAS
– HIT-6™
6
Migraine Snapshot
Attacks:
Frequency:
Onset:
Duration:
Location:
Pain:
7
Can occur any time of day (most likely in the morning)
1-10 per month (average 1.5)
Gradual onset, peak, then subsides. Rare “crash
migraine”
4-72 hours (adults)
2-48 hours (children)
Unilateral 60% (always same side 20%)
Bilateral 40%
Moderate to severe
50% pulsating; 50% tight, pressure
Aggravated by movement
Pryse-Phillips WEM et al. Can Med Assoc J. 1997;156:1273-1287.
Russell MB et al. Cephalalgia.1996;16:239-245.
Migraine Triggers
• Diet
• Sleep deprivation
or excess
• Hormonal changes
• Environmental factors
• Exertion/exercise
• Stress and anxiety
• Head trauma
8
Scharff L et al. Headache. 1995;35:397-403.
Differentiating Migraine and
Tension-Type Headaches
9
Migraine
Tension type
• Exacerbated by routine
activity
• Usually moderate to
severe, often unilateral,
aura in a minority of
patients
• Nausea, vomiting,
photophobia, phonophobia
common
• Symptom free between
attacks
• Low impact
• Usually bilateral, mild to
moderate headache
• Photo- or phonophobia
sometimes present
• No nausea or vomiting
Dowson AJ et al. Curr Med Res Opin. 2002;18:414-439.
Acute Migraine Medications
• Specific MOA
– ergotamine/DHE
– triptans
• Nonspecific MOA
–
–
–
–
–
combination analgesics
corticosteroids
neuroleptics/antiemetics
NSAIDs
opioids
MOA=mechanism of action
DHE=dihydroergotamine
10
Snow V et al. Ann Intern Med. 2002;137:840-852.
Comparison of Triptans
Formulation
Usual Oral
Dose (mg)
Most Common AEs
Almotriptan
(Axert®)
Oral tablet
12.5
Nausea, dry mouth, paresthesia
Eletriptan
(Relpax®)
Oral tablet
40
Asthenia, nausea, dizziness,
somnolence
Frovatriptan
(Frova®)
Oral tablet
2.5
Dizziness, fatigue, headache,
paresthesia
Naratriptan
(Amerge®)
Oral tablet
2.5
Nausea, pain/pressure,
paresthesia
Rizatriptan
(Maxalt®)
Oral tablet or
MLT
10
Dizziness, somnolence, nausea,
paresthesia
Sumatriptan
(Imitrex®)
Oral tablet,
SQ, IN
50/100*
Paresthesia, pain/pressure
Zolmitriptan
(Zomig®)
Oral tablet,
ZMT, IN
2.5
Dizziness, paresthesia,
pain/pressure, somnolence
Name
11
*While the PI states that the recommended dosage for this agent
is 50 mg, common use is 100 mg.
Serious
Risks/Class
Myocardial
infarction,
cerebrovascular
events,
increased
blood
pressure
Source: Package Inserts
Safety of Triptans
• Most AEs are mild and not clinically serious
– occur early after administration and are short lived
– “triptan sensations” (eg, chest pressure)
– CNS side effects (eg, dizziness, fatigue,
somnolence)
• Serious but rare CV and neurologic events
– contraindicated in patients with
• CV disease
• uncontrolled HTN
AEs=adverse events
CNS=central nervous system
CV=cardiovascular
12 HTN=hypertension
Welch KMA. Cephalalgia. 2001;21(suppl 1):25-28.
Dodick DW et al. Cephalalgia. 2004;24:417-424.
Snow V et al. Ann Intern Med. 2002;137:840-849.
Early Intervention With Triptans:
Clinically More Effective
Efficacy and Safety
Percent of Patients
60
Moderate/Severe
Pain Phase†
50
40
Mild Pain Phase*
Mild Pain Phase*
32
30
20
10
0
Moderate/Severe
Pain Phase†
60
Percent of Patients
60
50
40
33
29
30
20
13
14
10
0
Pain-free Response (2-hr)
*Triptan clinical trials
13 †Aggregate data on all approved triptans
Recurrence
Adverse Event
Adapted from Cady RK. Clinical Cornerstone. 1999;
1:21-32. Presented: Rome, Italy; 2000.
Headache Recurrence
• Recurrence = return of episodic headache within
24 hours of initial treatment response
• Prevention of recurrence
– treat early, add NSAID
– use optimal dose
– if HA continues to recur, use a long-acting triptan
14
Tfelt-Hansen P et al. Drugs. 2000;60:1259-1287.
Capobianco DJ et al. Headache. 2001;41:500-502.
Triptans: Long-acting vs
Fast-acting
Usual Oral
Dose (mg)
2 Hour
Response (%)
T 1/2 (hr)
Frovatriptan
2.5
37-46
26
Naratriptan
2.5
—
6
12.5
57-65
3-4
Eletriptan
40
54-65
4
Rizatriptan
10
67-77
2-3
Sumatriptan
50/100*
50-61
2.5
Zolmitriptan
2.5
62-65
3
Triptan
Long-acting
Fast-acting
Almotriptan
*While the PI states that the recommended dosage for this agent
is 50 mg, common use is 100 mg.
15
Source: Package Inserts
Migraine Recurrence For Triptans
Percentage of Patients
60
50
40
30
20
10
0
Almotriptan1
*Frovatriptan 7%-25%
†Rizatriptan 44%-47%
16
Eletriptan2
1Axert®
Frovatriptan 3* Naratriptan 4
Rizatriptan 5† Sumatriptan 6,7 Zolmitriptan 7
[package insert]. 2Relpax® [package insert]. 3Goldstein J et al. 9th Congress of the IHS.
June 22-26, 1999. Barcelona, Spain. 4Klassen A et al. Headache. 1997;37:640-645.
5Teall J et al. Headache. 1998;38:281-287. 6Perry CM et al. Drugs. 1998;55:889-922.
7Schoenen J. Curr Opin Neurol. 1997;10:237-243.
Migraines Can Be Triggered
by Stress and Exercise
Stress
Physical
Exertion
0
20
40
60
80
Percent of Migraine Patients With Triggers
17
Adapted from Scharff et al. Headache. 1995;35:397-403.
Principles of Preventive
Drug Treatment
•
•
•
•
Start with low dose and increase slowly
Need adequate trial (2-3 months)
Avoid drug overuse and interfering drugs
Evaluate therapy
– use migraine calendar/diary
– consider taper (or stop) if HA well controlled
• Take co-existing conditions into account
– determine contraindications (eg, pregnancy) to
minimize potential risks
18
Adapted from the US Headache Consortium Guidelines.
Available at: http://www.aan.com/professionals/practice/pdfs/gl0090.pdf.
Tailor Therapy Appropriately to
Comorbid Conditions
19
Condition
Avoid
Asthma
Depression
Athletic
b-Blockers
Epilepsy
Arrhythmia
Bipolar
Tricyclic antidepressants
(TCAs)
Peptic ulcer disease
NSAIDs
Peripheral vascular disease
Ergots/triptans
Adapted from Silberstein S et al. Headache in Clinical Practice. 2nd ed. 2002:93.
Preventive Medication Groups
• Anticonvulsants
– divalproex
– topiramate
• Antidepressants
– TCAs
– SSRIs
– MAOIs
• b-blockers
• Calcium-channel blockers
• Serotonin antagonists
• Others
–
–
–
–
–
botulinum toxin type A*
coenzyme Q10*
NSAIDs
Petasites hybridus*
riboflavin*
– propranolol
– timolol
MAOI=monoamine oxidase inhibitor
SSRI=selective serotonin reuptake inhibitor
TCA=tricyclic antidepressant
20
*Not approved by FDA for this use.
Silberstein SD. Lancet. 2004;363:381-391.
Differentiating Migraine and Sinus HA:
HA Is Minor AAO-HNS Sinusitis Criteria
Migraine (primary)
Sinus (secondary)
• Moderate to severe headache,
throbbing, pulsing
• Exacerbated by routine activity
• Frequently unilateral
• Attacks infrequent; symptomfree between attacks
• Attacks last 4-72 hours
• Nausea, photo-/phonophobia
common; vomiting may be
present
• Dull, aching headache,
exacerbated by lying down
• Purulence in nose on exam
• Sense of smell impaired
• Sinusitis evident from CT,
MRI, radiography, or using a
flexible scope
• Headache in sinus areas
coincident with sinusitis
• Face pain/pressure/
congestion
21
Dowson AJ et al. Curr Med Res Opin. 2002;18:414-439.
Lanza DC et al. Otolaryngol Head Neck Surg. 1997;117:S1-S7.
Medication Overuse
Headache (MOH) Management
• Bridging program during withdrawal
–
–
–
–
parenteral dihydroergotamine mesilate
low-dose tizanidine with long-acting NSAIDs
daily doses of a triptan for up to 10 days
short course of steroids, long-acting NSAIDs
• Prophylactic medication
– tricyclic antidepressants, SSRIs, b-blockers, calcium-channel
blockers, antiepileptics, NSAIDs
• Rescue therapy, as needed
– parenteral ketorolac*, antiemetics
SSRI=selective serotonin reuptake inhibitor
*Not FDA approved for this use.
22
Smith TR et al. Drugs. 2004;64:2503-2514.
Menstrually Related Migraine
(MRM) Occurs Days -2 to +3
• Approximately 60% of women who experience
migraine relate the frequency of their attacks to the
menstrual cycle
• Pure menstrual migraine occurs from days -2 to
+3 of menstruation in at least 2 out of 3 menstrual
cycles
• Menstrually related migraine always occurs on
days -2 to +3 in at least 2 out of 3 menstrual
cycles, as well as other times of the cycle
23
Allais G, Benedetto C. Neurol Sci. 2004;25 (suppl 3):S229-S231.
MRM Is More Disabling:
Diary Studies
• 64 women with menstrually related migraine
showed that perimenstrual attacks
– produced longer work-related disability
– were less responsive to acute treatment than
attacks occurring outside of the menses1
• 155 women with migraine history kept diaries for
693 menstrual cycles. Headaches were
– 3.4 times more severe during menstruation2
1Granella
24
F et al. Cephalalgia. 2004;24:707-716.
2MacGregor EA, Hackshaw A. Neurology. 2004;63:351-353.
Risk Factors for Strokes in
Migraineurs With Auras Who Use OCs
• Increased risk of stroke in women migraineurs who
use OCs and1
–
–
–
–
smoke 1 or more packs of cigarettes/d1
have no personal hx but have family hx of migraine
are <45 years of age2
experience focal symptoms ie, aura, especially
prolonged aura1
1ACOG
OC=oral contraceptive
25
(American College of Obstetrics and Gynecology)
Committee on Practice Bulletins-Gynecology. Int J Gynaecol
Obstet. 2001;75:93-106.
2Loder
EW et al. Headache. 2005;45:224-231.
MRM: Treatment Approach
• Begin with standard therapy
• Identify and avoid other triggers
• Use acute, prophylaxis, and nonpharmacologic
treatment as indicated
• Consider targeted prophylaxis
26
Mannix LK et al. Cleve Clin J Med. 2002;69:488-500.
Short-term Prevention Strategies:
1 or more RCTs Support Efficacy
• Perimenstrual estrogen supplementation
• Frovatriptan
– days -2 through +4
– loading dose of 5 mg po twice daily followed by 2.5 mg po
twice daily1
• Naratriptan
– 1 mg po twice daily days -2 through +3
• Naproxen – 550 mg bid2
• Magnesium – 300 or 600 mg daily3,4
None of the above FDA approved
for this use.
RCT=randomized controlled trial
27
1Loder
EW. Neurology. 2004;63:202-203.
VT. Curr Pain Headache Rep. 2004;8:229-237.
3Maizels M et al. Headache. 2004;44:885-890.
4Schuck P et al. Schweiz Med Wochenschr. 1999;129:63-70.
2Martin
Efficacy of Topiramate
Placebo
(n=115; n=114)
Topiramate
50 mg/d
(n=117; n=117)
Topiramate
100 mg/d
(n=125; n=120)
Change From Baseline to
Double-blind Phase
in Average Monthly
Migraine Period Rate (+SE)
0
-1
*
†
-2
TOPMAT-MIGR-001
-3
* *
TOPMAT-MIGR-002
*P<0.001; †P<0.008
28
Adapted from Topamax® [package insert].
Safety of Topiramate
• Common side effects
– paresthesia, fatigue, nausea, appetite loss, dizziness,
weight loss, memory difficulties, diarrhea, concentration
and attention difficulties, and somnolence
• Serious risks
–
–
–
–
29
metabolic acidosis
acute myopia and secondary angle closure glaucoma
oligohidrosis and hyperthermia
cognitive and behavioral changes
Topamax® [package insert].
Conclusions
• Migraine can be treated effectively
–
–
–
–
acute therapies to lessen severity
short-term strategies to prevent MRM
prevention to decrease frequency and disability
timing is critical
• More satisfied patients in your practice!
30