Evidence Based Guideline of Treatment of Chronic Headache

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Evidence Based Guideline of Treatment of Chronic
Headache

• Asan Medical Center
• Sun U. Kwon

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Limitations

• Headache syndromes Clinically diagnosed
  diseases
• Inhomogeneity
• Level I evidences are insufficient and limited
• Treatment of acute migraine
• Prevention of migraine
• Prevention of tension headache

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Chronic Headache

• Very common
• Migraine
• Tension headache
• Cluster headache
• Other rare headache syndromes
• Diagnosis is based on exclusion ? dilemma
• Secondary headache

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Contents

• Evaluation
• Migraine
• Acute treatment
• Prevention
• Treatment during pregnancy
• Tension headache
• prevention

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Evaluation of Headache

• Using IHS Criteria
• Indications for Neuroimaging
• Focal neurological finding (Gr B)
• Headache starting after exertion or valsalvas
  maneuver
• Acute onset of severe headache
• Headaches awakens patient at night
• Change in well-established headache pattern
• New-onset headache in patient who has HIV or
  cancer (Gr C)

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Treatment of Migraine
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Treatment of Acute Attacks

• Analgesics and NSAIDs
• Ergot Derivatives
• Triptans
• Opiates

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NSAIDs

• First-line or initial choice for all migraine
  attacks
• Followings have evidence for migraine
• 900mg aspirin, 1000mg acetaminophen(?),
  500-1000mg naproxen, 400-800mg ibuprofen
• Combination with antiemetic drugs or drugs for
  improving gastric motility
• Overuse of these drugs should be avoided

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Ergot Derivatives

• Ergotamine and dihydroergotamine (DHE)
• Low cost and long experience
• DHE good evidence for the efficacy
• Erogtamine or café-ergot inconsistent evidence
  with frequent adverse events
• Disadvantages
• Sustained generalized vasoconstrictor
• High risk of overuse and rebound
• Complicated pharmacokinetics

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Triptans

• Choice for moderate to severe migraine attacks
• Advantages over ergotamine
• Selective pharmacology selective 5-HT1b/1d
  agonists
• Established efficacy based on well-designed
  controlled trials
• Well established safety profile
• Moderate side effects
• Disadvantages
• High cost
• Restrictions on their use in the presence of
  cardiovascular diseases

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U.S. Headache Consortium Recommendations

• First-line NSAIDs or acetaminophenaspirincaffe
  ine
• Use migraine specific agents in severe migraine
  or poor responder to NSAIDs
• Triptans, DHE, ergotamine
• Educate patients with migraine about their
  condition and its treatment
• Guard against medication-overuse headache

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AAFP/ACP-ASIM Recommendations

• First-line NSAIDs
• Fail to respond to NSAIDs
• DHE nasal spray
• Triptans
• Educates patients with migraine about their
  condition and its treatment

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Pharmacokinetics of Triptans
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Fast Relief (Controlled Trials)
Pharmacokinetic Characteristics of Triptans
Data derived from multiple studies. MAO denotes
monoamine oxidase, CYP450 cytochrome P450, and
CYP3A4 the 3A4 isoform of cytochrome P450.
Adapted from Goadsby et al. N Engl J Med
2002346(4)257-270.
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Oral Triptans in Acute Migraine
TreatmentMeta-analysis of 53 trials
Michel D. Ferrari et al. Lancet 20013581668-75
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Pain free at 2h
Response at 2h
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Sustained Pain free
Recurrence of headache 2-24h
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For each drug the white bar indicates the
consistency rate for placebo. For Rizatriptan
this could not be calculated d/t different design
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For each drug the white bar indicates the
consistency rate for placebo. For Rizatriptan
this could not be calculated d/t different design
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Any AE placebo substracted
CNS AEs placebo substracted
21
Chest AEs placebo substracted
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Pharmacological Clinical Characteristics in
Comparison with Sumatriptan 100mg
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Choosing A First-Line Triptan (Meta-Analysis)
Adapted from Belsey JB. Journal of Clinical
Research 2001(4)105-125.
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Preventive Treatment

• Indications for migraine prevention
• Beta-blockers
• Calcium-channel blockers
• Antidepressants
• Serotinergics
• NASIDs
• Anticonvulsants
• Botolium Toxin - A

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Indications

• Two or more attacks per months that produce
  disability lasting 3 or more days per months
• Headache attacks are infrequent but produce
  profound disabililty
• Failure, contraindication, or troublesome side
  effects from acute treatments
• Overuse of acute medications
• Very frequent headaches (gt2/week)
• Presence of uncommon migraine conditions
  hemiplegic migraine, migraine with prolonged
  aura, migrainous infarction
• Patients preference

US Evidence Based Guideline for Migraine (2000)
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?- adrenergic Blockers

• Consistent evidences for their efficacy
• Propranolol 120 240mg/d
• Timolol 20-30mg/d
• Propranolol 44 reduction in migraine activity
  (Holroyd KA et al, 1991).
• 60-80 effective (gt50 reduction in attack
  frequency). (Rabkin R. et al 1966)

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?- adrenergic Blockers

• Propranolol is more efficacious in patients with
  migraine alone amiltriptyline was superior for
  patients with mixed migraine and tension-type
  headache (Mathew NT. 1981)
• Atenolol, metoprolol, nadolol limited
  evidence
• Acebutolol, alprenolol, oxprenolol, pindolol
  ineffective

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Calcium Channel Blockers

• Evidence for nifedipine, nimodinpine, verapamil
  is poor but suggesting modest effect.
• Flunarizine (5-10mg/d) proven efficacy and
  commonly used
• Adverse effects sedation, weight gain,
  depression, extrapyramidal symptoms

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Antidepressants

• Amitriptyline effective in many trials
• Effective dose 30 -150mg/d
• Frequent adverse effects
• No evidence for nortriptyline, doxepine etc
• Limited evidence of a modest effect for
  fluoxetine (10 -40mg/d)
• No evidence from controlled trials for other
  SSRIs, SNRIs (venlafaxine)

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Sertonergics

• DHE consistent positive findings in 4
  placebo-controlled trials
• Ergotamine or combination drugs evidence is
  insufficient with numerous S/E
• Methysergide semisynthetic ergot
• Strong evidence
• Serious S/E retroperitoneal and retropleural
  fibrosis
• Lisuride, pizotifen effective

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NSAIDs

• Naproxen modest effect from 5 of 7
  placebo-controlled trials
• Other NSAIDs have similar trends

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Anticonvulsants

• Valproic acid
• Good evidence for efficacy
• Adverse events are common
• Topiramate
• Strong evidence 75-150mg
• S/E weight loss, tingling
• Carbamazepine, Vigabatrin ineffective

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Topiramate and Migraine

• Retrospective chart analysis showed topiramate
  had potential effect in reducing frequency and
  severity of migraine

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Design Overview
DOUBLE-BLIND PHASE
BASELINE PHASE
BLINDED EXTENSION PHASE
TITRATION
MAINTENANCE
WASH-OUT
PROSPECTIVE BASELINE
200 MG/DAY TPM
100 MG/DAY TPM
160 MG/DAY Propanolol
PLACEBO
UP TO 14 DAYS
28 DAYS
8 WEEKS
18 WEEKS
gt 6 MONTHS
VISIT 2 Randomization
VISIT 4
VISIT 8
Quarterly Visits
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Botulium Toxin A
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Botolium Toxin A

• For the prophylactic treatment,
• One study both positive negative evidence of
  level IB
• One study significant positive evidence of
  level II
• Three other study positive but level III
• Therefore, botolium toxin A has significant
  evidence for migraine prophylaxis

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Treatment During Pregnancy

• Consider risk (teratogenic effect) versus
  benefits
• Clinical trials for pregnancy is very rare
• Medication is rarely recommended during pregnancy
• Acute Pain killer paracetamol
• Aspirin (avoid during puerpural period)
• Preventive Propranolol

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Recommendation

• Drugs have Proven efficacy
• Propranolol 80-240mg/d
• Timolol 20-30mg/d
• Divalproex sodium 500 1500mg/d
• Sodium valproate 800 1500mg/d
• Amitriptyline 30 150mg/d
• Topiramate 75 100mg/d

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Management of Tension Headache
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EBM of Tension Headache

• Treatment with antidepressants
• TCAs (amitriptyline, nortriptyline)
• SSRIs (fluoxetine, sertraline, etc)
• Treatment with acupuncture
• Treatment with botolium toxin-A

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TCAs in Tension Headache
Amitriptyline has a statistically significant and
clinically relevant effect in The prophylactic
treatment. However, it does not eliminate the
headache And numerous adverse effect.
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TCAs Stress Management
Randomized Controlled Trial with chronic tension
headache
JAMA 20012852208-2215
TCAs stress management each produced larger
reductions in Headache activity, analgesic
medication HA related disability Combined
therapy was more likely to produce clinically
significant Reductions in HA index scores
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TCAs in Tension Headache

• Clinically effective in prevention
• Numerous and common adverse effects in
  therapeutic dose (10-75mg/d)
• Efficacy of SSRI?
• Bendtsen L. Jensen R. Olesen J. A non-selective
  (amitriptyline), but not a selective
  (citalopram), serotonin reuptake inhibitor is
  effective in the prophylactic treatment of
  chronic tension-type headache.
  JNNP. 199661285-90, 1996 Sep.

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Recent Trials

• Fluoxetine effective in chronic and episodic
  tension type headache, although fluoxetine
  effective is less sustained.
• Oguzhanoglu A et al
• Use of amitriptyline and fluoxetine in
  prophylaxis of migraine and tension-type
  headaches. Cephalalgia. 199919531-2, 1999 Jun
• Venlafaxine has potential in tension headache
  prophylaxis.
• Adelman LC et al
• Venlafaxine extended release (XR) for the
  prophylaxis of migraine and tension-type
  headache A retrospective study in a clinical
  setting. Headache. 200040(7)572-80

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Acupuncture

• Several trials including placebo controlled
  randomized trial failed in its efficacy for
  episodic and chronic tension type headache
• Acupuncture for ETTH multicenter randomized
  controlled trial
• AR White et al
• Cephalalgia 200020632-637
• Acupuncture is ineffective in the prevention of
  ETTH

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Botox Tension Headache
Botox has no evidence for prevention of tension
type headache