Transcript chronic migraine - British Association for the Study of Headache

Chronic Daily Headaches & Medication
Overuse Headache
Diagnosis and Management
4th Biennial Hull-BASH Headache Meeting
Jan 20th 2011
Dr Brendan Davies
North Midlands Regional Headache Clinic
University Hospital of North Staffordshire
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
Chronic daily headache prevalence
USA, Spain, Greece, Italy, China
Population studies - 4%-5%
Women > Men
(Adapted from Castillo et al., 1999 and Guitera et al., 1999)
Recognition of the Problem is the first step !!
Chronic Daily headache - Subtypes
Primary Headache
disorders
Secondary
Headache disorders
Paroxysmal Headache
Long lasting Headache
Attack Duration < 4 hours +/or
Daily or near daily headache
Discrete episodes
Duration > 4 hours per day
Chronic Migraine
Chronic Tensiontype headache
Adapted from Silberstein et al., Neurology (1996) 47: 871-
Hemicrania
Continua
With or without
medication overuse
New Daily
Persistent
headache
The FrHE Study
FrHE=Frequent Headache Epidemiology Study
Scher AI et al. Pain. 2003;106:81-89.
Case control and cohort analyses identified
Independent risk factors for CDH
Not readily modifiable
Migraine
Female Gender
Low education/socioeconomic status
Head injury
Potentially modifiable
Attack frequency
Obesity
Medication overuse
Stressful life events
Snoring (sleep apnea,
sleep disturbance)
The Scope of the Problem
Primary CDH Epidemiology
Pascual, Colas and Castillo. Current Pain & Headache Reports 2001
Prevalence
USA & European studies
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%
* = previous term Transformed in some studies
?
30 < 80%
Consultations for headache with emergency healthcare
practitioners: chronic vs episodic migraine
Varon SF et al. Poster 14th International Headache Congress, 2009, USA.
5.4
Pooled
Episodic migraine
9.0
Chronic migraine
3.5
US
5.8
3.5
Canada
5.5
4.8
Germany
7.7
3.4
UK
14.0
2.3
1.8
France
7.0
Italy
5.5
14.7
Spain
23.2
10.4
10.9
Austrialia
6.2
Taiwan
12.5
0
5%
10%
15%
20%
Proportion of patients consulting an emergency
healthcare professional in the last 3 months
25%
How does Chronic Daily Headache start ?
De novo (Acute?)
headache onset
Headache severity
NDPH
Headache Free before
daily headache
Time
Evolving CDH
Time
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 headache
Pressure/ tight (Non-pulsating)
Mild-moderate
Not worsened by physical activity
<1 of:
Photophobia, phonophobia & mild nausea
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
A daily unremitting headache syndrome
• Initial onset over < 3 days
• Persistent for > 3/12
New Daily Persistent Headache
Primary NDPH
Migrainous type
Featureless (Tension type)
* All may have abrupt onset
Secondary Causes of NDPH
Low CSF Volume Headache*
Raised Intracranial Pressure Headache
CVST*
Chronic Meningitis
Giant Cell Arteritis
Post-Traumatic & Post-Meningitis
Metabolic e.g. Hypercapnia, CO
SAH (Sudden onset)*
Arterial dissection*
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”
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
Recognition of Migraine
The 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
Chronic migraine development
• Infrequent episodic migraine “transforms” into frequent
migraine
• With or without medication overuse
• Analgesics overused by 65%
Background
daily headache
Migraine
attack
& migraine
attack
H/A intensity
10
Overusing
painkillers?
0
Time months/years
Chronic Migraine
The 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
*ICHD-2 =
Previously >15
With or without Analgesic Medication Overuse Headache?
• 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 medication
Odds Ratio
• Factors implicated: High initial headache frequency 20.1
Medication Overuse
19.1
Moderate initial HA frequency
6.2
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
Chronic Migraine Comorbidities
• Mental Health Disorders
Zwart et al., 2003; Buse et al., 2010
– Depression
– Generalised Anxiety Disorder
– Bipolar disorder
• Chronic Musculoskeletal pain
Hagen et al., 2002; Buse et al., 2010
• Restless Legs Syndrome &
Sleep Disoders
Rhode et al., 2007; Chen et al., 2010
Thanks to Dr David Kernick for graphic
Clinical trial data for
preventive pharmacotherapy in “chronic migraine”
Evidence for use in chronic migraine
Anticonvulsants:
Valproate
Topiramate
Gabapentin
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
Double-blind, placebo-controlled trials in CM 10-12
Botox
Antidepressants:
Amitriptyline
Fluoxetine
1.
2.
3.
4.
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
Yurekli VA et al. J Headache Pain 2008;9:37–41.
Bartolini M et al. Clin Neuropharmacol 2005;28:277–279.
Diener HC et al. Cephalalgia 2007;27:814–823.
Silberstein SD et al. Headache 2007;47:170–180.
5.
6.
7.
8.
Spira PJ, Beran RG. Neurology 2003;61:1753–1759.
Krymchantowski AV et al. Headache 2002;45:510–514.
Saper JR et al. Headache 1994;34:497–502.
Saper JR et al. Headache 2002;42:470–482.
9. Bigal M et al., Headache 2008; 48; 1337- 42
10. Diener HC et al., Cephalalgia. 2010 Jul;30(7):804-14
11. Aurora SK et al., Cephalalgia. 2010 Jul;30(7):793-803
12. Dodick DW et al., Headache. 2010 Jun;50(6):921-36
Analgesic Medication Use
1-3 % of the population take
analgesics on a regular basis
7% take analgesics at least 1x/wk
Medication Overuse Headache
IHS 2004 & revised 2005 Classification
Chronic daily headache >15 days/month for >3 months
Regular intake for > 3 months of
Triptan or ergot medication > 10 days / month
Opiate or Combination analgesics > 10 days / month
Simple Analgesics or combinations of above > 15 days month*
And return to Pre-overuse pattern with
cessation of Overuse
* 15 = consensus figure rather than evidence based
Medication Overuse Headache
Clinical Features
Katsarvara et al, Drug Safety, 2001; 24: 921-927.
• Characteristics may vary
– Usually dull, generalised
– Early morning worsening
May differ depending on the drug being overused
Triptans
 Daily migrainous headache
Analgesics  Diffuse featureless headache
Ergots  Diffuse pulsating headache
Chronic Migraine and
Medication Overuse headache (MOH)
• 45-70% sufferers of chronic primary headache experience
> 50% improvement in headache with analgesic withdrawal
Bigal 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”
Does medication overuse matter?
Topiramate in Chronic Migraine
Reduction in headache days
2
placebo
topiramate 100mg/day
0.8
1
0.2
0
n = 27
Medication overuse
32
23
23
-1
-2
-3
-4
(* P < 0.02; ** P < 0.03)
-3.5
*
-3.5
**
Does Medication Overuse always reduce efficacy ?
PREEMPT pooled efficacy of BOTOX®
in medication overuse subgroup* at week 24
Change in frequency from baseline
Headache days/mth†
Moderate/severe
headache days
Migraine days
0
-1
Number of days
Improvement
-2
-3
-4
-5
-6
-7
-8
-9
-5.7
-6.2
-8.2‡
-7.7‡
-6
BOTOX® (n=445)
-8.1‡
Placebo (n=459)
-10
*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.
Silberstein SD et al. IHC 2009. Dodick DW et al., Headache. 2010 Jun;50(6):921-36
Analgesic Overuse Cessation improves
Headache frequency & Drug responsiveness
• 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)
Chronic Migraine & Medication Overuse Headache
“Management controversies?”
What is the most effective strategy for
initial MOH management?
MOH can be effectively managed
initially as an OPD in most cases
85% responders/  2/3 reduction in headache frequency
Rebound Headache &
“Pain killer rebound symptoms”
(Katsarava et al, Neurology, 2002)
Headache intensity worsens
at day 2-4 before
improvement
• 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
• Ergots
• Analgesics
 4 days
(85%)
 7 days
(57%)
 9-10 days + ( 23%)
Prednisolone for Medication Overuse
withdrawal headache?
DB RCT n = 100 (65 with CM)
Pilot DB RC n = 18 only
Prednisolone 60mg taper over 6 days in MOH
Prednisolone 100mg 5 days in MOH
No effect on withdrawal headache in
placebo vs. active treatment group
50%  in moderate-severe rebound headache
in 1st 72 hrs compared with placebo
Dose response?
Sample size?
Triptan only MOH?
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
Prognosis of MOH treatment
Headache free +/or > 50% reduction in headache frequency
Withdrawal rates at 2 weeks
Short term
• 20-85% @ 2-4 wks
• 60-70% @ 6 months
23%
57%
Medium to long term
• 35-60% @ 1 yr
•  50%
@ 5 yrs
85%
* Multiple observational studies
Medication Overuse Headache
If 6-8 weeks after
acute analgesic medication withdrawal
there is no improvement
The initial diagnosis of
Medication Overuse Headache
is not tenable
Review the Initial Diagnosis !
• 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
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
A pragmatic approach to Long lasting Primary
Chronic Daily headache diagnosis
Bigal ME, Lipton RB. J Headache Pain 2007;8:263–272.
Chronic Daily Headache
Lasting ≥4 hours per day
Continuous strictly unilateral
pain with autonomic features
YES
Hemicrania
continua
YES
New Daily
Persistent
Headache
YES
Chronic Migraine
YES
Chronic TensionType Headache
NO
Clear onset as a daily
syndrome
NO
Migraine or specific acute
medications ≥8 days/month
NO
Featureless holocranial
Headaches with minimal
impairment
Associated
symptoms
define the CDH
syndrome
Need to know more about
best practice in
Headache management
Join BASH !!
&
Go & buy this book !!!
• Chronic Daily Headache is a
symptom & not a diagnosis
Questions?
• Accurate diagnosis
determines both treatment
choice & prognosis
• Medication Overuse is
ubiquitous and must always
be considered...........
• And more importantly properly
addressed !!
BACKUP SLIDES
Chronic Refractory Migraine
What do I do?
& possible “Horizon” therapies?
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%
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
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
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
Comparison of side effects at UHNS with USA
Evidence based treatment of
Chronic migraine
Change From Baseline in Monthly (28-day)
Rate of Migraine/Migrainous Days
Silberstein SD et al. Headache 2007;47:170–180.
Primary Outcome
Migraine/Migrainous Days
Mean baseline ± SD
Topiramate
Placebo
17.1 ± 5.4
17.0 ± 5.0
0
Mean Change
From Baseline
-1
-2
-3
-4
-5
-6
-7
-4.7 ± 6.1
Population
Therapeutic gain
-6.4 ± 5.8
P = 0.010
= 1.7 days
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.
Responder Rates
Silberstein SD et al. Headache 2007;47:170–180.
P = 0.012
70
63
50
Placebo (n = 153)
P = 0.031
60
Patients
(%)
Topiramate (n = 153)
48
52
39
40
P = 0.093
37
29
30
20
10
0
≥30%
≥40%
≥50%
Percent Reduction in Mean Monthly Migraine/Migrainous Days
(NB. - No adjustment for multiplicity)
Botulinum Toxin A in Chronic Migraine
PREEMPT Studies
• 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
Diener HC et al., Cephalalgia. 2010 Jul;30(7):804-14
Aurora SK et al., Cephalalgia. 2010 Jul;30(7):793-803
Dodick DW et al., Headache. 2010 Jun;50(6):921-36
Botulinum Toxin A in Chronic Migraine
PREEMPT 1 & 2 Studies pooled analysis
Mean change from baseline in frequency of headache days
Double-blind phase:
BOTOX® vs. placebo
Open-label phase:
All patients on BOTOX®
Mean change in frequency of headache
days from baseline (days/28-day period)
Study week
0
4
8
0
12
16
20
24
28
32
36
40
44
48
52
56
BOTOX® (n=688)
Placebo (n=696)
-2
-4
At Week 24
BOTOX® treated patients
• Mean 8.4 fewer
headache days/month
• vs. 6.6 with placebo
(p<0.001)1,2
-6
-8
-10
-12
p<0.001
p<0.001
p<0.001
p<0.001
p<0.001
p<0.001
p<0.001
p=0.008
p=0.01
p=0.047
p=0.007
p=0.011
p=0.019
p=0.019
-14
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.
Dodick DW et al., Headache. 2010 Jun;50(6):921-36
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)
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)
• Silberstein & a new concepts in CDH classification - 1994
– “Transformed Migraine” – evolving from an initial episodic pattern
Subjective classification ? Scientific basis ?