chronic daily headaches & medication overuse headache diagnosis and management dr brendan davies...
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Chronic Daily Headaches & Medication Overuse Headache
Diagnosis and Management
Dr Brendan Davies
North Midlands Regional Headache Clinic
University Hospital of North Staffordshire
4th Biennial Hull-BASH Headache Meeting
Jan 20th 2011
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Frequent Headaches (or Chronic Daily headache)
A headache syndrome (not a diagnosis) characterised by
Headache present on more than 15 days per month for at least 3 months
duration = >180 days per year,
~ 50% of the time!
4-5% of the general population
30-80% of clinic populations
Several possible causes
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Chronic daily headache prevalenceUSA, Spain, Greece, Italy, China
Population studies - 4%-5%
Women > Men
(Adapted from Castillo et al., 1999 and Guitera et al., 1999)
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Recognition of the Problem is the first step !!
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Chronic Daily headache - Subtypes
Primary Headache disorders
Secondary Headache disorders
Paroxysmal Headache
Attack Duration < 4 hours +/or
Discrete episodes
Long lasting Headache
Daily or near daily headache
Duration > 4 hours per day
Chronic MigraineChronic
Tension-type headache
New Daily Persistent headache
Hemicrania Continua
Adapted from Silberstein et al., Neurology (1996) 47: 871-
With or withoutmedication overuse
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The FrHE Study
Case control and cohort analyses identifiedIndependent risk factors for CDH
Not readily modifiable Potentially modifiableMigraine Attack frequencyFemale Gender ObesityLow education/socioeconomic status Medication overuseHead injury Stressful life events
Snoring (sleep apnea, sleep disturbance)
FrHE=Frequent Headache Epidemiology StudyScher AI et al. Pain. 2003;106:81-89.
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The Scope of the Problem Primary CDH Epidemiology
Pascual, Colas and Castillo. Current Pain & Headache Reports 2001
Prevalence Population HA Clinic– New Daily Persistent Headache 0.1% 20%
– Chronic Migraine* 2% 20-60%
– Chronic Tension Type headache 2-3% 10-20%
– Hemicrania Continua ? ?
– With associated Medication Overuse 0.5-1% 30 < 80%
USA & European studies
* = previous term Transformed in some studies
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Consultations for headache with emergency healthcare practitioners: chronic vs episodic migraine
Varon SF et al. Poster 14th International Headache Congress, 2009, USA.
Taiwan
0 5% 10% 15% 20%
Proportion of patients consulting an emergencyhealthcare professional in the last 3 months
25%
6.212.5
Austrialia10.4
10.9
Spain14.7
23.2
7.05.5
France2.3
1.8
UK3.4
14.0
Germany4.8
7.7
Canada3.5
5.5
US3.5
5.8
Pooled5.4
9.0 Episodic migraine
Chronic migraine
Italy
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How does Chronic Daily Headache start ?
Time
Evolving CDH
Time
NDPH
Headache Free before daily headache
De novo (Acute?) headache onset
Hea
dac
he
seve
rity
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New Daily Persistent Headache (NDPH) The IHS (2004) Definition
• A daily headache with onset over < 3 days• Unremitting from onset & persistent > 3 months• No Secondary cause
• 2 of: Bilateral headachePressure/ tight (Non-pulsating)Mild-moderateNot worsened by physical activity
<1 of: Photophobia, phonophobia & mild nausea
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New Daily Persistent Headache“De novo headache” or “CDH with acute onset”
A more useful concept ?
– A “ a headache syndrome” needing investigation to exclude secondary causes that guide specific treatments
– A new headache problem having previously been “Headache free” implies a potentially new pathophysiological process ?
– Highlights the need to consider/exclude a possible 2° headache disorders (NDPH mimics) before diagnosis
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New Daily Persistent Headache
Primary NDPH Secondary Causes of NDPH
Migrainous typeFeatureless (Tension type)
Low CSF Volume Headache* Raised Intracranial Pressure Headache
CVST*Chronic MeningitisGiant Cell Arteritis
Post-Traumatic & Post-MeningitisMetabolic e.g. Hypercapnia, CO
SAH (Sudden onset)*Arterial dissection*
* All may have abrupt onset
A daily unremitting headache syndrome• Initial onset over < 3 days
• Persistent for > 3/12
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NDPH - Clinical Features• “Classically” - Patient remembers the day & date the
headache started & the circumstances
• Prompts investigation for secondary causes?
• Not usually Unilateral – Think of alternatives– TACs & Hemicrania Continua if ANS symptoms– Temporal Arteritis, Intracranial lesions in elderly etc– Cervicogenic headache?
• 1○ NDPH– “Feature-Full” Migrainous or “FeatureLess” TTH
• “Benign vs. Refractory forms”
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Diagnostic Studies in NDPH if Suspected Low CSF volume/pressure
• Always ask about effect of posture & otological symptoms?
• CT Brain Normal !! “Beware” Bilateral Subdurals?
• CSF Pressure < 60mm H20 ? (but can be normal!)– Normal glucose but may - WCC, Protein, RBC
• Gd-DTPA is investigation
of choice– Diffuse linear Non-nodular
Pachymeningeal enhancement– Tonsillar descent & Brain sagging– Bilateral subdural
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Recognition of MigraineThe IHS criteria 2004 > 90% specificity
5 Headache attacks lasting 4 < 72 hours
• with at least 2 of:– Unilateral– Pulsating– Moderate or severe– Worsened by +/or avoidance
of physical activity
• and at least 1 of– Nausea +/or vomiting Light sensitivity Noise sensitivity
IHCD II Classification 2004 Cephalagia Vol 24; Suppl 1
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Chronic migraine development
• Infrequent episodic migraine “transforms” into frequent migraine
• With or without medication overuse• Analgesics overused by 65%
Time months/years
H/A
in
ten
sit
y
0
10
Migraine attack
Background daily headache
& migraine attack
Overusing painkillers?
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Chronic MigraineThe IHS 2006 Revised Classification
previously Triptan/Ergot responsive?
Headache on > 15 days month
with features of Migraine type headache
On > 8 days / month*
for > 3 months without other cause
of headache
With or without Analgesic Medication Overuse Headache?
*ICHD-2 = Previously >15
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• 1 year longitudinal follow-up study – 450 headache sufferers (Migraine +/- Tension type)
14% developed CDH from an initial intermittent pattern (mean 7 days/month) baseline
• 1/3 were not overusing medicationOdds Ratio
• Factors implicated: High initial headache frequency 20.1Medication Overuse 19.1Moderate initial HA frequency 6.2
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Tips for recognising Chronic Migraine
• History of episodic headache in earlier life?
• Insidious onset of frequent or daily headache
• “Background headache with worsening”
• Worse Headache episodes– Migrainous– Often triggered by recognised by migraine triggers– May be triptan responsive
• Family history of migraine?
• & No “red flag” features
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Chronic Migraine Comorbidities
Thanks to Dr David Kernick for graphic
• Mental Health Disorders Zwart et al., 2003; Buse et al., 2010
– Depression– Generalised Anxiety Disorder– Bipolar disorder
• Chronic Musculoskeletal painHagen et al., 2002; Buse et al., 2010
• Restless Legs Syndrome & Sleep DisodersRhode et al., 2007; Chen et al., 2010
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Clinical trial data forpreventive pharmacotherapy in “chronic migraine”
Evidence for use in chronic migraine
Anticonvulsants:ValproateTopiramateGabapentin
Small double-blind, placebo-controlled trials in CM1,2
Double-blind, placebo-controlled trials in CM3,4
One double-blind, placebo-controlled trial in CDH5
Botox Double-blind, placebo-controlled trials in CM 10-12
Antidepressants: Amitriptyline Fluoxetine
Small open-label trial in TM6
Small double-blind treatment, placebo-controlled trial in CDH7
Alpha-2-adrenergic agonist:Tizandine
Small double-blind treatment, placebo-controlled trial in CDH8
Glutamate NMDA Antagonists:Memantine
Small open-label trial9
Beta-blockers No evidence that they are effective in CM
Serotonergic modulators No evidence that they are effective in CM
Calcium channel blockers No evidence that they are effective in CM
ACE inhibitors and ARBs No evidence that they are effective in CM
1. Yurekli VA et al. J Headache Pain 2008;9:37–41.2. Bartolini M et al. Clin Neuropharmacol 2005;28:277–279. 3. Diener HC et al. Cephalalgia 2007;27:814–823.4. Silberstein SD et al. Headache 2007;47:170–180.
5. Spira PJ, Beran RG. Neurology 2003;61:1753–1759. 6. Krymchantowski AV et al. Headache 2002;45:510–514.7. Saper JR et al. Headache 1994;34:497–502. 8. Saper JR et al. Headache 2002;42:470–482.
9. Bigal M et al., Headache 2008; 48; 1337- 4210. Diener HC et al., Cephalalgia. 2010 Jul;30(7):804-1411. Aurora SK et al., Cephalalgia. 2010 Jul;30(7):793-80312. Dodick DW et al., Headache. 2010 Jun;50(6):921-36
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Analgesic Medication Use
1-3 % of the population take analgesics on a regular basis
7% take analgesics at least 1x/wk
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Medication Overuse Headache IHS 2004 & revised 2005 Classification
Chronic daily headache >15 days/month for >3 months
Regular intake for > 3 months of
And return to Pre-overuse pattern with cessation of Overuse
* 15 = consensus figure rather than evidence based
Triptan or ergot medication > 10 days / month
Opiate or Combination analgesics > 10 days / month
Simple Analgesics or combinations of above > 15 days month*
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Medication Overuse Headache Clinical Features
• Characteristics may vary – Usually dull, generalised – Early morning worsening
Katsarvara et al, Drug Safety, 2001; 24: 921-927.
May differ depending on the drug being overused
Triptans Daily migrainous headache
Analgesics Diffuse featureless headache
Ergots Diffuse pulsating headache
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Chronic Migraine and Medication Overuse headache (MOH)
• 45-70% sufferers of chronic primary headache experience
> 50% improvement in headache with analgesic withdrawalBigal et al., Cephalagia (2004) 24; 483-; Zeeberg et al, Neurology (2006) 66; 1894-
“In the absence of data it is generally accepted that patients are refractory to prophylactic medication while overusing analgesic medications and that they become responsive after analgesic medication withdrawal”
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Does medication overuse matter?Topiramate in Chronic Migraine
(* P < 0.02; ** P < 0.03)
*
Red
uctio
n in
hea
dach
e da
ys
0.2
0.8
-3.5 -3.5-4
-3
-2
-1
0
1
2 placebo topiramate 100mg/day
n = 27 32 23 23
**
Medication overuse
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Does Medication Overuse always reduce efficacy ?
PREEMPT pooled efficacy of BOTOX® in medication overuse subgroup* at week 24
*Of the total pooled PREEMPT population, 64.8% and 66.1% of BOTOX® and placebo groups, respectively, overused acute headache pain medication (simple analgesics, ergotamine/DHE, triptans, opioids, combination of analgesics or any combination of the preceding classes).
†Headache days are reported as headache days per 28 days; change in frequency of headache days was the primary endpoint of the pooled analysis. ‡p<0.001.
Nu
mb
er o
f d
ays
-10
-9
-8
-7
-6
-5
-4
-3
-2
-1
0
Migraine daysModerate/severeheadache days
-6
-8.1‡
-5.7
-7.7‡
-6.2
-8.2‡
BOTOX® (n=445)
Placebo (n=459)
Imp
rove
men
t
Headache days/mth†
Change in frequency from baseline
Silberstein SD et al. IHC 2009. Dodick DW et al., Headache. 2010 Jun;50(6):921-36
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• Tertiary referral centre study – n=175– Refractory CDH population with MOH
• 55% with migraine
– Previously refractory to 1-5 migraine preventatives
– 30 - 40% of individuals became responsive to Migraine preventatives post MOH treatment
• (8 month mean follow-up)
Analgesic Overuse Cessation improves Headache frequency & Drug responsiveness
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Chronic Migraine & Medication Overuse Headache“Management controversies?”
What is the most effective strategy for initial MOH management?
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MOH can be effectively managed initially as an OPD in most cases
85% responders/ 2/3 reduction in headache frequency
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Rebound Headache & “Pain killer rebound symptoms”
(Katsarava et al, Neurology, 2002)
• Headache gets worse before better • in at least 70%
• Withdrawal symptoms– Nausea, vomiting– Autonomic activation
– Sleep disturbance & agitation
• Mean Duration & severity determined by overused drug class
• Triptans 4 days (85%)• Ergots 7 days
(57%)• Analgesics 9-10 days +
( 23%)
Headache intensity worsens at day 2-4 before improvement
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Pilot DB RC n = 18 only
Prednisolone 100mg 5 days in MOH
50% in moderate-severe rebound headache in 1st 72 hrs compared with placebo
DB RCT n = 100 (65 with CM)
Prednisolone 60mg taper over 6 days in MOH
No effect on withdrawal headache in placebo vs. active treatment group
Dose response?
Sample size?
Triptan only MOH?
Prednisolone for Medication Overuse
withdrawal headache?
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The “Stop - Start Strategy”in MOH
• OPD Based MOH withdrawal
• Abrupt GP supervised Analgesic withdrawal for 4 weeks when on established prophylaxis– Worse before better !!!– Written Support protocol & patient education
– Prednisolone Rescue option ?– Early follow-up – better outcome ?
• Start early new Migraine Drug Prophylaxis – When? What?
• Failed OPD withdrawal or no change in Headache – Review comorbidities again & Consider Inpatient strategy
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Prognosis of MOH treatment Headache free +/or > 50% reduction in headache frequency
Short term• 20-85% @ 2-4 wks• 60-70% @ 6 months
Medium to long term• 35-60% @ 1 yr 50% @ 5 yrs
* Multiple observational studies
Withdrawal rates at 2 weeks
85%
57%
23%
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Medication Overuse Headache
If 6-8 weeks afteracute analgesic medication withdrawal
there is no improvementThe initial diagnosis of
Medication Overuse Headache is not tenable
Review the Initial Diagnosis !
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• 1st described 1984 –Sjaastad & Speirings
• Rare !!• 93+ cases in world
literature to 2001…..
• Female > males 2-3:1• Onset 4th & 5th decade• No obvious triggers
– c.f. Migraine
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Hemicrania Continua“Women with constant Hemicrania tearing & nasal congestion”
• (Daily) mild-moderate Strictly side-locked unilateral pain• Mild-moderate background intensity with exacerbations
• Exacerbations associated with– Ipsilateral autonomic symptoms in up to ¾ patients
– Minimal or Absent autonomic symptoms in up to 1/3
– Photophobia, phonophobia & nausea in ~1/2
• Absolute headache response to Indometacin treatment– Mean oral dosage <150mg / day (ensure tried up to 225mg)
+/- “ blinded Indotest”Rare cause but very treatable cause of CDH/NDPH
Consider Indometacin trial in all with new onset side locked especially refractory hemicrania
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A pragmatic approach to Long lasting Primary Chronic Daily headache diagnosis
Bigal ME, Lipton RB. J Headache Pain 2007;8:263–272.
Hemicrania continua
New Daily Persistent Headache
Chronic Migraine
Chronic Tension-Type Headache
Featureless holocranial Headaches with minimal
impairment
Continuous strictly unilateral pain with autonomic features
Clear onset as a daily syndrome
NO
Migraine or specific acute medications ≥8 days/month
Chronic Daily HeadacheLasting ≥4 hours per day
Associated symptoms
define the CDH syndrome
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Need to know more about best practice in
Headache management
Join BASH !!
&
Go & buy this book !!!
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Questions?
• Chronic Daily Headache is a symptom & not a diagnosis
• Accurate diagnosis determines both treatment choice & prognosis
• Medication Overuse is ubiquitous and must always be considered...........
• And more importantly properly addressed !!
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BACKUP SLIDES
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Chronic Refractory Migraine
What do I do?
& possible “Horizon” therapies?
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Short term Chronic migraine prevention by greater occipital nerve blockade
Occipital nerve blockade (ONB) – 2% Lidocaine (2 ml) +/- 80 mg depo-medrone– Response rate: 50% for up to 1 month
Afridi et al. Pain 2006
Ashkenazi et al. JNNP 2007
– AEs• local discomfort• alopecia (1-2%)
Shields et al., Neurology 2004
Open label outcome data Tobin & Flitman Headache 2009
• 108 ONB patients• No benefit in 20%
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In-Patient Management of Chronic Migraine +/- MOH
• When?– Failure of outpatient approach & significant impairment– Medication type +/or comorbidities
• How?– Inpatient Supportive care
• Hydration/drugs to combat withdrawal symptoms• iv Dihydroergotamine, i.v lidocaine• Steroids, Neuroleptics, Anti-emetics & Anxiolytics?
• Clonidine or lofexidine if opiates
• Identify & Treat Comorbidity
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In-Patient Management of Medication Overuse Headache
• When?– Failure of outpatient approach– Medication type +/or comorbidities
• How?– Supportive care
• Hydration/drugs to combat withdrawal symptoms– Clonidine if opiates – Anti-emetics & Neuroleptics
• Iv Anti-nocioceptive drugs– i.v. Aspirin & iv Dihydroergotamine– i.v. AEDs
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Intravenous Inpatient Therapies for Chronic Migraine at UHNS
iv Dihydroergotamine (DHE)• Central 5HT receptor agonist
– 5HT 1A, 1B, 1D & 5HT2A & 2C Receptors
– CGRP & Sub-P release blocked
– α-Adrenergic antagonist
– D1 &D2 receptor agonism
• USA since 1986
• Indications:– Status Migrainosis
– Chronic Migraine +/- MOH
– Refractory Chronic Cluster Headache
• USA -Open label data
• Data on iv DHE inpatients at UHNS• 42 patients audited 2007-8• Age 31-73 yrs• 5 day iv therapy course• Most had failed on >3 preventatives
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Comparison of side effects at UHNS with USA
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Evidence based treatment of Chronic migraine
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Change From Baseline in Monthly (28-day) Rate of Migraine/Migrainous Days
Primary OutcomeMigraine/Migrainous Days
-7
-6
-5
-4
-3
-2
-1
0
Mean Change From Baseline
Mean baseline ± SD
-6.4 ± 5.8
-4.7 ± 6.1
P = 0.010
17.1 ± 5.4
Topiramate
17.0 ± 5.0
Placebo
N=153 for topiramate and placebo groups.P-value based on ANCOVA model including treatment and center as main effect, and baseline monthly migraine/migrainous or migraine days as covariates.
Population Therapeutic gain
= 1.7 days
Silberstein SD et al. Headache 2007;47:170–180.
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Responder Rates
2937
63
5248
39
0
10
20
30
40
50
60
70
Topiramate (n = 153) Placebo (n = 153)
Patients (%)
≥30% ≥40% ≥50%
Percent Reduction in Mean Monthly Migraine/Migrainous Days(NB. - No adjustment for multiplicity)
P = 0.012
P = 0.093
P = 0.031
Silberstein SD et al. Headache 2007;47:170–180.
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• 2 Trials: PREEMPT1 and PREEMPT 2• Phase 3, parallel-group, placebo-controlled studies of Botulinum toxin
A 155-195U in Chronic Migraine
1384 patients randomised (Botulinum toxin A 688, Placebo 696)31 injections per treatment session
Botulinum Toxin A in Chronic MigrainePREEMPT Studies
Diener HC et al., Cephalalgia. 2010 Jul;30(7):804-14Aurora SK et al., Cephalalgia. 2010 Jul;30(7):793-803Dodick DW et al., Headache. 2010 Jun;50(6):921-36
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p<0.001
Botulinum Toxin A in Chronic MigrainePREEMPT 1 & 2 Studies pooled analysis
Mean change from baseline in frequency of headache days
Mean ± standard error. The double-blind phase included 688 subjects in the BOTOX® group and 696 in the placebo group.
Headache days at baseline: 19.9 BOTOX® group vs. 19.8 placebo group, p=0.498.
At Week 24
BOTOX® treated patients• Mean 8.4 fewer
headache days/month• vs. 6.6 with placebo
(p<0.001)1,2
Mea
n c
han
ge
in f
req
uen
cy o
f h
ead
ach
e d
ays
fro
m b
asel
ine
(day
s/28
-day
per
iod
) 52484440363228241612840
Study week
020 56
-2
-4
-6
-8
-10
-12
-14
BOTOX® (n=688)
Placebo (n=696)
p=0.019
p=0.047p=0.007
p=0.01p=0.008
p<0.001p<0.001
p<0.001p<0.001
p<0.001
Double-blind phase:BOTOX® vs. placebo
Open-label phase:All patients on BOTOX®
p<0.001
p=0.019 p=0.011
Dodick DW et al., Headache. 2010 Jun;50(6):921-36
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Why Chronic Migraine and not Chronic tension type headache?
• Several cohort studies identified CDH with neurobiological features of Migraine – (not tension type !)Messinger et al., (1991), Pfaffenrath et al., (1993), Sanin et al (1994), Sandrini et al.,(1993)
• Silberstein & a new concepts in CDH classification - 1994– “Transformed Migraine” – evolving from an initial episodic pattern
Subjective classification ? Scientific basis ?
Natural history studies – supportive (Mathew et al., 1982, Sandrini et al, 1993)
“Positive “family history of Migraine in ¾ of patients
Response to Conventional anti-migraine preventatives (Lipton et al, 2000)
Biochemistry of Throbbing “Tension type” CDH & ↑CGRP (Ashina et al, 2000)