Latest management of migraine

1. Management of
Migraine
Dr. Varun Kataria
Consultant Neurologist
Medanta Hospital, Indore

2. What is Migraine?
• One of the most prevalent and disabling medical illnesses
• WHO ranks migraine as the third most prevalent medical
condition and the second most disabling neurological disorder
• lifetime prevalence – 33% in females, 13% in males
• 1 yr prevalence in INDIA 25-27%

4. Common Triggers
Diet
• Hunger
• Alcohol
• Additives
• Caffeine withdrawal
Hormonal changes
• Menstruation
• Menopause
• Pregnancy
Environment
• Visual stimuli
• Odors
• Barometric pressure changes
Other
• Trauma
• Exertion
• Stress/anxiety
• Schedule changes
Source: AHS: Primary Care Migraine Partnership 2004

5. Migraine triggers peculiar to
India
Poor travel
conditions
Too many religion,
Different fasting
practice
Pollution
Henna Application
Joint Family
stress
Work stress
Educational stress
Hot Climate
Mosquito coils

6. Premonitory symptoms
• hours or days before the onset of pain
• M/C- fatigue, impaired concentration, and neck stiffness
• However, other psychological (anxiety, depression, irritability), arousal (drowsiness),
neurological (photophobia), and cranial parasympathetic symptoms (lacrimation), and general
symptoms (eg, yawning, increased urination, nausea, diarrhoea, and food cravings)
• Identification of premonitory symptoms could enable behavioural and
treatment approaches that could mitigate or prevent the headache
phase of migraine

7. Migraine aura
• visual, sensory, language, or disturbances associated with
brainstem dysfunction that usually last between 5 and 60 min
and occur before the headache
• Variable
• M/C – Visual aura

10. Aura
• Paraesthesias are the second most common aura symptom and
usually occur in conjunction with a visual aura. The
paraesthesias usually involve the hand and perioral (cheiro-
oral) region, and the arm, tongue, and lips, and can become
bilateral.

11. Aura v/s TIA
• Bilateral nature of the visual or sensory symptoms
• positive and negative visual phenomena occurring sequentially or
simultaneously
• Development of symptoms over at least 5 min and movement across
the visual field or across different parts of the body, or both
• Sequential appearance of aura symptoms (eg, visual then sensory)
• Stereotyped and often recurrent nature

12. The Headache
• Unilateral (60%), throbbing (50%), and aggravated by physical activity (90%) or
head movement
• Can change sides during or between attacks
• Median time to peak intensity is 1 h and median duration is 24 h (range from 4 to
72 h in adults and 2 to 48 h in children)
• Can involve any part of the head and often involves the posterior cervical and
trapezius regions
• Additional symptoms: sinus pain or pressure (in 40% of patients) and cranial
autonomic features (in 50% of patients)

13. Postdromal phase
• 80% of individuals with migraine
• usually lasts less than 12 h, but can persist for longer than 24 h
• m/c - asthenia, fatigue, somnolence, impaired concentration,
photophobia, irritability, and nausea

14. Principles of treatment
• Manage identifiable triggers
• Treat co-morbid mood and anxiety
• Appropriate use of pain relief meds
• Not more than 2 days a week on reg basis (to prevent MOH)
• Headache diary
• Preventive meds if severe attacks/or inc freq

15. Migraine Management
Acute
treatment
To stop pain
and prevent
progression
Preventive
Treatment
Decrease in
migraine frequency
warranted
Preemptive
treatment
Migraine trigger
time-limited and
predictable
Source: Preventive treatment of migraine: an overview. Cephalalgia. 1997;17(2):67-72.

16. Acute Attack Management

17. Treatment of acute attack (Non specific)

18. Treatment of acute attack (Specific)
To achieve a pain-free state at 2 h, S/C sumatriptan has
the lowest number needed to treat (NNT)
Pain-free rates at 2 h are highest for eletriptan 40 mg and
rizatriptan 10 mg.
Eletriptan 40 mg and frovatriptan 2·5 mg have lowest
recurrence rates
Almotriptan 12·5 mg and naratriptan 2·5 mg have less
side-effects
Rizatriptan, frovatriptan, and zolmitriptan preferred in
patients with sulpha allergy

19. Choosing the Right Triptan!!
Category Usage Triptan
Immediate acting/ultra
fast
Quick onset
Severe pain
Sumatriptan
Fast acting
Moderate onset
Moderate pain
Almotriptan,
Rizatriptan,
Eletriptan
Slow onset/long acting
Slow onset
Long duration menstrual;
prodrome
Frovatriptan,
Naratriptan
Randall Lee Oliver, Choosing the Right Triptan: Discussion of current triptan options in the treatment of migraine.
www.practicalpainmanagement.com/pain/headache/migraine/choosing-right-triptan

20. Combination Therapy -
Established
synergy
Overcomes
limitation of
monotherapy
Targets multiple
pathological
process
Enhanced
Efficacy
Improved
Tolerability

21. Sumatriptan + Naproxen
• Sumatriptan
• Selective
vasoconstriction of
blood vessels
Vascular
• Sumatriptan
•Reduction of trigeminal
nerve activation
•Inhibition of vasoactive
neuropeptide release
Neurogenic
• Sumatriptan
•Inhibition of
neurotransmitter release
in brainstem and upper
cervical spinal column
Central
• Naproxen
• Inhibition of PG which
leads to vasoconstriction
of blood vessels
Vascular
• Naproxen
• Reduction of trigeminal
nerve activation
Neurogenic
Synergistic
Effect

22. Treatment of acute attack
• Little evidence - oral or parenteral opioids or butalbital-
containing analgesics for the acute treatment of migraine
• all evidence-based guidelines recommend against their
routine use – adverse effects, the risk of habituation, addiction,
tolerance, withdrawal syndromes, and medication-overuse
headache (MOH)

23. • The greatest risk of progressing from episodic migraine to
chronic migraine is associated with opioids (odds ratio [OR]
1·4) and butalbital-containing medications (OR 1·7) and can
occur with as few as five doses per month
• To prevent MOH - minimising use of simple analgesics < 15
days per month, and triptans, ergots, or combination analgesics
<10 days per month

24. Preventive medications:- Indications
• Attacks are frequent (≥4 attacks per month, or ≥8 headache days per
month)
• Headache interferes with their QOL despite apt. use of acute medications
and lifestyle modification strategies
• If contraindications, treatment resistance, or adverse events preclude the
use of effective acute medications
• Considered, regardless of attack frequency, for patients with the following
rare migraine subtypes:
i. hemiplegic migraine;
ii. migraine with brainstem aura;
iii. frequent, prolonged, or uncomfortable aura symptoms; or
iv. migrainous infarction.

25. Preventive medications

26. • Reduce attack frequency, severity, and duration
and disability
• Improve responsiveness to acute treatment
• Prevent disease progression
Goals of Preventive Therapy
Source: http://tools.aan.com/professionals/practice/pdfs/gl0090.pdf.

27. • Include the patient in the choice of rx
• Set realistic expectations
• Emphasize the importance of minimizing use of
acute treatments
Principles of Migraine
Prevention
Source: http://tools.aan.com/professionals/practice/pdfs/gl0090.pdf.

28. US Headache Consortium
Guidelines
Group 1 Medications
• Medium to high efficacy
• Good strength of evidence
• Mild to moderate side effects
• Propranolol, Divalproex,
Topiramate, Amitriptyline,
Group 2 Medications
• Lower efficacy
• Good strength of evidence
• Mild to moderate side effects
• Atenolol, Metoprolol,
Nadolol, Gabapentin,
Verapamil, Flurbiprofen,
Ketoprofen, Naproxen,
ASA, Fluoxetine,
Nimodipine
Source: Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the
Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000

29. US Headache Consortium
Guidelines
Group 3 Medications
• Good efficacy (based on
expert consensus)
• Lower strength of evidence
• Low to moderate side effects
• Diltiazem, Tiagabine, Tcas,
Paroxetine, Sertraline,
Bupropion, Trazodone,
Venlafaxine
Group 4 Medications
• Medium to high efficacy
• Good strength of evidence
• Side effect concerns
• Methysergide (serotonin
agonist) and MAOIs
Source: Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the
Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000

30. • FDA approved for migraine prevention
• Divalporex Sodium
• Topiramate
• Limited evidence for migraine prevention
• Gabapentin
• Lamotrigine
• Levetiracetam
• Zonisamide
Antiepileptic Drugs (AEDs)

31. • Increases GABA and stabilizes nerve membrane
activation thresholds
• Dose = 500 - 1500 mg daily divided BID or TID
• ER formulation allows for once daily dosing
• Many drug interactions
• Highly protein bound
• Inhibits CYP2C9, 2C19, 2D6
• Must monitor CBC/platelets, LFTs, serum amylase, drug
levels
• Caution when changing formulations due to differences in
bioavailability
Source: Vikelis and Rapoport. CNS Drugs 2010.
Divalproex Sodium

32. • Dose titration in clinical trials:
• Initial dose = 25 mg daily
• Titrate by 25 mg every week
• Monitoring
• Electrolytes (bicarbonate, potassium)
• Weight
• Hydration status and s/sx of kidney stones, metabolic
acidosis, & glaucoma
• Drug Interactions
• Reduces digoxin and estradiol levels
• Phenytoin and carbamazepine  AUC of topiramate
Source: Vikelis and Rapoport. CNS Drugs 2010.
Topiramate

33. • FDA approved for migraine prevention
• Propranolol: 60-240 mg PO once daily for LA or divided
BID or TID for IR
• Timolol: 10-30 mg PO daily in 2 divided doses
• Limited evidence for migraine prevention
• Nadolol: 20-240 mg PO once daily
• Atenolol: 50-150 mg PO daily or divided BID
• Metoprolol: 100-200 mg daily or divided BID for IR
formulation
Beta Blockers
Source: The prevention of migraine: a critical review with special emphasis on beta-adrenoceptor blockers. Br J Clin Pharmacol 2001

34. Beta Blockers
Advantages
• Thoroughly studied and
widely used
• Propranolol and Timolol are
FDA approved
• Good choice for patients
with HTN, tremor and
anxiety
Disadvantages
• Side effects = fatigue,
dizziness, depression,
exercise intolerance, may
worsen aura
• Precaution in patients with
severe asthma, depression,
bradycardia, Raynaud's,
overt CHF
Source: The prevention of migraine: a critical review with special emphasis on beta-adrenoceptor blockers. Br J Clin Pharmacol 2001

35. Therapeutic limitations
Hypotension Betablockers, Lisinopril, Candasartan, Flunarizine
Asthma Betablockers
Epilepsy Tricyclics
Obesity Tricyclics, VPA, Flunarizine
Depression, PVD Betablockers, Flunarizine
Women with child bearing potential VPA
Glaucoma, renal stones Topiramate

36. Combination of treatments where monotherapy has failed.
Combination of more than one drug
Synergistic effects through the action on different
pathophysiologic mechanisms
Better outcome with the use of lower dosages.
Pascual et al. Bending the rule of monotherapy for migraine prevention? Headache 2005; 45: 748-50
Step Care
Approach

37. Nonmedical treatment

38. Nonmedical
treatments
• avoidance of reproducible and
predictable trigger factors
• behavioural treatments, including
biofeedback-assisted relaxation
training and cognitive behavioural
therapy, have been shown to have
an efficacy similar to preventive
drugs
• aerobic exercise

39. Diet

40. Risk of developing chronic migraine
Several modifiable risk factors:
• high baseline attack frequency (one per week),
• overuse of acute medications,
• caffeine consumption,
• snoring,
• obesity, and
• inadequate acute treatment of migraine attacks
• Female sex, allodynia, head injury, low socioeconomic status,
depression, anxiety, and comorbid pain disorders are also risk
factors for chronic migraine

41. Chronic migraine
Chronic migraine is defined by the
presence of headache on more
than 15 days per month, and that
at least 8 days meet diagnostic
criteria for migraine with or without
aura
Onabotulinum toxinA and
topiramate have been shown to be
effective for individuals with
chronic migraine, even when
acute medications are overused

42. Emerging treatments
lasmiditan, a 5-HT1F agonist (No activity - 5-HT1B)
• more selective
• removing any vasoconstricting effect
• effective for the acute treatment of migrain
CGRP function-blocking gepants and Mabs
Neuromodulation

43. CGRP receptor antagonist
• Gepants are Probably Effective in Preventing Migraine but
Uncertain in CH
• Atogepant
• Rimegepant

44. Other possible t/t
• mGluR5 – glurants
• Pituitary adenylate cyclase activating peptide (PACAP):
PAC-1 blocker
• Nitric oxide synthase based approaches
• Orexin 1 & 2: rexants

45. CGRP
MABs
• CGRP MAbs have Similar Efficacies in
Preventing Migraine in Episodic Migraine
Subjects (v/s Topiramate)
• CGRP MAbs have Similar Efficacies in
Preventing Migraine in Chronic Migraine
Subjects (v/s Botox, PREEMPT)
• CGRP MAbs are Effective in Migraine Subjects
who Failed Preventives
• CGRP MAbs are Effective for Preventing
Episodic Cluster Headache (galcanezumab)

46. Neuromodulati
on

48. • Migraine is ranked 6th in world for YLD
• Correct diagnosis is important
• Acute treatment should be only SOS
• Prophylactic therapy is best option for migraine
patients
• Drugs should be individualized and selected
which suits the patient
• Long acting propranolol seems to be a promising
breakthrough for improving compliance and
ensuring better control of migraine
Conclusion