Refractory Headache Challenges and Strategies. David W. Dodick, M.D. Department of Neurology Mayo Clinic Phoenix Arizona USA

Transcription

1 Refractory Headache Challenges and Strategies David W. Dodick, M.D. Department of Neurology Mayo Clinic Phoenix Arizona USA

2 Headache Masters School, Tokyo 2013

3 Definition of refractory/intractability depends on: Who you are: primary care physician, neurologist, headache specialist Where you are: availability of people (other disciplines), resources (health system), therapeutic options What your/patient expectations are: cure, improved function, quality of life Headache 2010;50:

4 SATISFACTION = REALITY EXPECTATIONS

5 1. We missed something a. Wrong diagnosis b. Exacerbating factor c. Inadequate treatment 2. Patients is refractory

6 WHY HEADACHE MAY BE REFRACTORY SECONDARY DIAGNOSIS IS MISSED

7 Reason 1: Many patients with Secondary Headache Will Have History of Primary Headache Disorder Lifetime migraine prevalence 43% and 18% Lifetime TTH 78% ( > )

8 Reason 2: Many Patients with Secondary Headache will have Migraine or Tension-type Phenotype Often forgotten Frequency and duration 5 attacks lasting 4-72 hours Pain criteria: 2 of the following 4 Unilateral Pulsating Moderate or severe intensity Aggravation by routine physical activity Associated symptoms: 1 of the following Nausea and/or vomiting Photophobia and phonophobia Not attributable to another disorder Lack specificity

9 77% of patients with headache secondary to brain tumor meet ICHD criteria for tensiontype headache (Forsythe and Posner Neurology 1992) New-onset chronic tension-type headache is a diagnosis of exclusion

10 Reason 3: Warning symptoms not elicited SNOOP4 Red Flags Systemic symptoms (fever, weight loss) or Secondary risk factors (HIV, cancer) Neurologic symptoms (or signs) Onset: abrupt, peak <1 min Older: >50 (GCA; glaucoma, cardiac cephalgia ) Previous headache history (new or change in pattern/progression) Postural (worse in upright/supine position) Precipitated by Valsalva (exertion) Pulsatile tinnitus (diplopia, transient visual obscurations) Dodick DW. Seminars in Neurology 2010;30(1):74-81

11 Reason 4: Relying on CT to rule out secondary causes of headache

12 Reason 4: Wrong Imaging Test! Secondary causes of headache missed on CT Head o Pressure CSF Leak (SIH) Intracranial hypertension o Infections Meningoencephalitis Cerebritis and brain abscess o Neoplastic disease Parenchymal and extra axial neoplasms (especially posterior fossa) Meningeal carcinomatosis Metastatic brain tumors Pituitary lesions PIN the secondary diagnosis SIH=spontaneous intracranial hypotension

13 Reason 5: Wrong Imaging Test Vascular imaging not performed

14 WHY HEADACHE MAY BE REFRACTORY PRIMARY DIAGNOSIS IS MISSED

15 Diagnosis of Migraine (EM/CM) in US Practices Of 775 patients meeting EM criteria Only 45% see an HCP Only 39% diagnosed by an HCP Only 26% receive treatment Of 1254 patients meeting CM criteria Only 41% see an HCP Only 11% diagnosed by an HCP Only 4.5% receive treatment Only 10% of HCP consult a neurologist and 4% consult a specialist Lipton RB, et al. Headache 2013;51: Dodick DW, Headache 2016;56:

16 Diagnosis of primary headache disorder Know the criteria for migraine, tension-type, and cluster headache Use a systematic approach to history taking Location (if unilateral, is it side-locked) Cranial autonomic features Diurnal variation (nocturnal, awakening) Frequency and duration of individual episodes Monthly Frequency of headache days Remitting or unremitting pain

17 Why is Migraine Frequently Mistaken For Tension-Type Headache (TTH)? Guilt by location: Neck pain (75%) and bilateral headache (40%) Guilt by association: Stress (as trigger) comorbid anxiety/depression TTH overrides probable migraine (ICHD needs refinement; TTH should have no associated symptoms)

18 Why is Migraine Frequently Mistaken for Sinus Headache? Pain often located over sinuses Migraine often triggered by weather changes Tearing/nasal congestion common (up to 50%) Resolution attributed to sinus medication

19 1. We missed something a. Wrong diagnosis b. Exacerbating factor c. Inadequate treatment 2. Patients is refractory

20 Exacerbating factors Medications (e.g. dipyridamole, SSRI) Acute medication overuse Estrogen (COC, HRT, menopause) Dietary or lifestyle factors Occupational or environmental Comorbid illness/condition (psychiatric, obesity, obstructive sleep apnea)

21 1. We missed something a. Wrong diagnosis b. Exacerbating factor c. Inadequate treatment 2. Patients is refractory

22 WHY HEADACHE MAY BE REFRACTORY PHARMACOTHERAPY IS INADEQUATE 2013 MFMER slide-22

23 Acute Treatment Fails Recurrence, partial or inconsistent response Early Rx (while pain is mild) Increase dose Combination Rx (triptan+nsaid) Switch drug or route of administration Overuse Establish use limits Consider prevention Becker WB. Continuum 2015;21:

24 WHY HEADACHE MAY BE REFRACTORY COMPLIANCE 2013 MFMER slide-24

25 Amitriptyline N=1,164 Nortriptyline N=653 Citalopram N=1,150 Sertraline N=622 Fluoxetine N=421 Paroxetine N=190 Venlafaxine N=277 Propranolol N=699 Metoprolol N=395 Nadolol N=110 Atenolol N=195 Topiramate N=2,604 Gabapentin N=860 Divalproex N=292 Total N=9,632 Proportion of Patients Persistent 86% discontinue at 12 months 40% 35% 30% 25% 20% 15% 10% 19% 21% 10% 10% 31% 17% 29% 14% 33% 17% 23% 10% 36% 19% 24% 13% Persistent At 6 Months Persistent at 12 Months 32% 29% 28% 26% 24% 21% 20% 18% 16% 16% 14% 12% 11% 8% 5% 0% Antidepressants Beta Blockers Anticonvulsants All Classes Hepp Z, et al. Cephalalgia 2015;35:

26 Improving compliance Start very low, go very slow (e.g. topiramate 15mg q2 wks) Combination therapy One drug for two diseases not always optimal (e.g. tricyclic in patient with migraine and depression) Minimize dose/side effects; maximize efficacy with different MOA Beware the claim of tachyphylaxis Always have side effect discussion Always set expectations for efficacy Dodick DW, Silberstein SD. Practical Neurology 2007;46:1-13

27 Preventive medication side effects Expect them Many attenuate/resolve over time Some may be attenuated (selenium for divalproex induced hair loss ( ug) potassium for topiramate induced paresthesias (20-40mEq/day)

28 Headache Days/28 Days (Mean Change From Baseline) Headache Days/28 Days Efficacy is cumulative and takes time Onset of effect Maximal effect Week: Week 24 Primary Endpoint -6 p< p<0.001 p<0.001 p< p<0.001 p<0.001 p<0.001 p=0.008 p=0.01 p=0.007 p=0.047 p=0.019 p=0.011 p=0.019

29 Effective prevention may be reduction in severity and not frequency January ~ February 2012 ~ March Sun Mon Tue Wed Thu Fri Sat Severe Moderate Mild

30 Effective prevention may be reduction in severity and not frequency January ~ February 2012 ~ March Sun Mon Tue Wed Thu Fri Sat Severe Moderate Mild

31 WHY HEADACHE MAY BE REFRACTORY PHARMACOLOGIC RANGE OF OPTIONS NOT EXPLORED 2013 MFMER slide-31

32 Migraine Preventive Medications (Guidelines and Beyond) Others: Memantine Lisinopril Candesartan Amiloride Duloxetine Zonisamide Simvastatin + vitamin D Verapamil Flunarizine Silberstein et al., Neurology 2012 Holland et al., Neurology 2012 Silberstein SD. Continuum 2015;21:

33 Onabotulinumtoxin A* 155 Units-31 injection sites * For chronic migraine Blumenfeld A. et al. Headache 2010;50: )

34 Injection Therapy Blumenfeld A, et al. Headache 2013;53: )

35 Injection Therapy: Trigger Point Injections Robbins M., et al. Headache 2014;54:

36 NON-INVASIVE NEUROMODULATION THERAPIES Supraorbital nerve stimulation Vagal nerve stimulation Single pulse TMS

37 Refractory Headache: Infusion Center and Inpatient Treatment Protocols Repetitive IV infusions for 3-5 days Dihydroergotamine mg plus antiemetic Divalproex sodium 6.4 mg / kg Methylprednisolone mg or Dexamethasone 4-8mg Q12h Magnesium sulfate 1gram q 24h Ketorolac 30mg Q12-24h Diphenhydramine 50mg Lorazepam 0.5mg

38 WHY HEADACHE MAY BE REFRACTORY NON-PHARMACOLOGIC RANGE OF OPTIONS NOT EXPLORED 2013 MFMER slide-38

39 Complementary and Alternative Medicine 200mg bid Level B 300 mg Level B mg Level B 300mg daily Level C 3-25mg Silberstein et al., Neurology 2012 Holland et al., Neurology 2012

40 Psychology CBT/Biofeedback Neurology Psychiatry PMR Acupuncture Dietician Multidisciplinary integrated headache care Sleep physiology Exercise physiology Headache nurse specialist Integrative medicine specialist (meditation, yoga, message) Women s Health Specialist

41 WHY HEADACHE MAY BE REFRACTORY HEADACHE/PATIENT IS TRULY REFRACTORY 2013 MFMER slide-41

42 Primary Goal: Restore function when pain cannot be eliminated Requires willingness to withdraw from opioids or other analgesics Develop treatment goals that include an active lifestyle Behavioral strategies of goal setting, paced activity, improved physical conditioning, decreased pain avoidance, stress management Bruce B., et al. Curr Pain Head Reports 2009;13:67-72

43 Typical patient Significant functional decline, extremely debilitated, unable to be employed or function in home setting Medication overuse, demoralization, depression, anxiety High medical utilizers: failed medication trials, surgery, injections, implantable technology, extensive and varied physical therapy programs, psychiatric and psychological care Bruce B., et al. Curr Pain Head Reports 2009;13:67-72

44 Occupational therapists Social Work Psychiatry Psychology Physical therapists Dietician Chronic Pain Rehabilitation 3-week outpatient day or inpatient treatment program Vocational rehabilitational Chemical dependency counselors Nursing Chaplains Pharmacists Bruce B., et al. Curr Pain Head Reports 2009;13:67-72

45 Pain severity (p<0.001) Depression (p<0.001) Physical functioning (p<0.001) General activity level (p<0.001) House, work, social activities (p<0.001) Interference of pain in life (p<0.001) N=195 Mean duration = 10.8 years 44% MOH 52% major depression 3-week intensive hospital-based outpatient treatment program Pain catastrophizing (p<0.001) Bruce B., et al. Curr Pain Head Reports 2009;13:67-72

46 1. We missed something a. Wrong diagnosis b. Exacerbating factor c. Inadequate treatment 2. Patients is truly refractory In my practice >80% Assuming appropriate expectations <20%

47 ありがとうございました