For practitioners, physicians and DM Neurology residents.

1. MANAGEMENT OF MIGRAINE
DR GANESHGOUDA MAJIGOUDRA
CONSULTANT NEUROLOGIST
NANJAPPA HOSPITALS DAVANAGERE
9380906082
ganeshgoudam4@gmail.com

2. EPIDEMIOLOGY
The prevalence of migraine is 17.6% in females and 6% in males.
About 1/3rd of the patients are severely disabled or needed bed rest
during the attack

3. DIAGNOSTIC CRITERIA
Migraine without aura
A. At least five attacks fulfilling criteria B-D
B. Headache attacks lasting 4-72 hr (untreated or unsuccessfully treated)
Headache has at least two of the following four characteristics:
1. unilateral location
2. pulsating quality
3. moderate or severe pain intensity
4. aggravation by or causing avoidance of routine physical activity (eg, walking or
climbing stairs)
C. During headache at least one of the following:
1. nausea and/or vomiting
2. photophobia and phonophobia
D. Not better accounted for by another ICHD-3 diagnosis.

4. PATHOPHYSIOLOGY
• pathway
Release of vasoactive
Neuropeptides eg- substance P,
calcitonin gene-related peptide,
and neurokinin A
Project to the rostral brain stem
areas and inturn higher cortical
brain areas

5. CLASSIFICATION OF MIGRAINES
1. Mamindla P, et al. Acta Scientific Pharmaceutical Sci. 2019;3(1): 29-42.

6. TREATMENT OF MIGRAINE
• Treatment can be acute, preventive.
• Acute treatment is initiated during an attack to relieve pain and disability and to
stop progression of the attack.
• Preventive treatment is maintained for months or even years to reduce attack
frequency, severity, and duration.

7. MANAGEMENT OF ACUTE MIGRAINE
Principles of management
1. Education which includes
strategies for identifying and avoiding triggers and
Behavioral management strategies
− Regular sleep, exercise, meals
− Stress management, biofeedback
− Cognitive behavioral therapy Migraine
Triggers
Hormonal
changes
Trauma
Stress and
anxiety
Sleep
deprivatio
n or
excess
Environm
ental
factors

8. Early treatment is associated with good outcomes – has been
proven in randomized controlled trials
EARLY
TREATMENT

9. DRUGS IN ACUTE MIGRAINE
NONSPECIFIC
TREATMENT
NSAIDS
NEUROLEPTICS
SPECIFIC
TREATMENT
TRIPTANS
ERGOTS

10. Non specific drugs- NSAIDS
• NSAIDs with reported efficacy in randomized, placebo-controlled
trials of migraine therapy include

11. NEUROLEPTICS AND ANTIEMETICS
• Hypersensitivity to dopamine in migraineurs is thought to play a role
in premonitory migraine symptoms such as yawning, nausea, and
vomiting

12. CORTICOSTEROIDS
• Used as a single dose of parenteral dexamethasone(10 to 25 mg)
• when added to standard acute migraine therapy, parenteral treatment
with dexamethasone reduces the rate of early headache recurrence
• Adjunctive treatment of acute migraine with oral prednisone was not
beneficial for prevention of recurrent headache in a small trial (110)

13. OPIODS AND BARBITURATES
should not be used for the treatment of migraine, except as a last
resort
Disadvantages
• are not as effective as migraine-specific medications for acute migraine
treatment .
• have a potential for tolerance, dependence, addiction, and overdose
• associated with an increased risk for the development of chronic
migraine and medication overuse headache

14. TRIPTANS
• Mechanism of action – 5HT1B and 1D agonist
1. intracranial vessel vasoconstriction (5-HT1B),
2. peripheral neuronal inhibition (5-HT1D)
3. May also enhance descending inhibitory pain pathways and
influence the function of 5-hydroxytryptamine 1F (5-HT1F)
receptors.
4. Inhibit the release of vasoactive peptides
5. Inhibit transmission in the trigeminal nucleus caudalis thereby
blocking afferent input to second order neurons - mediated by
reducing the levels of calcitonin gene related peptide (CGRP)

15. TRIPTANS
• Onset of Action of Oral triptans - 20 to 60 minutes and, if needed,
the dose may be repeated in 2 to 4 hours.
• Recurrence of headache after initial response occur as many as one-
third of patients
• may be combined with NSAIDs or antiemetic drugs
• Time of Administration
• When given during an aura, triptans do not show consistent efficacy in
aborting or preventing the migraine.
• educate the patient to not take their triptan during the aura phase but
rather early in the pain phase of the attack

16. Triptans
To be avoided in
1. Hemiplegic migraine
2. Basilar migraine
3. Ischemic stroke
4. Ischemic heart disease
5. Prinzmetal's angina
6. Uncontrolled hypertension
7. Pregnancy

17. PREPARATIONS OF TRIPTANS

19. CHOICE OF TRIPTAN
• The 6-mg subcutaneous injection of sumatriptan - the most
efficacious dosage formulation; however, patients often prefer oral
formulations
• The highest likelihood of consistent success was found
with rizatriptan(10 mg), eletriptan(80 mg), and almotriptan(12.5 mg).
• A meta-analysis suggested that eletriptan was the most likely of all the
triptans to produce short-term and sustained benefit .

20. ROLE OF ORAL RIZATRIPTAN IN MANAGEMENT
• Advantages:
• Does not significantly affect the isobaric compliance of the brachial artery.
• No effect on the diameter or vascular resistance of the temporal artery.
• Generally produces only small and transient increases in BP
• Does not affect heart rate in response to sympathetic stimulation
• 20 to 60 mg does not affect serum prolactin concentrations
• Adverse events usually mild and transient
Wellington K, et al. Drugs 2002;62(10):1539-1574.
 MOA: Potently and selectively binds to 5-HT1B/1D subtypes.
 Indication and dosage:
◦ Migraine with or without aura in adults.
◦ Initial dose is 5 or 10mg; additional doses for headache recurrence should be separated by at least 2
hours; no more than 30mg should be taken during a 24-hour period.
 Contraindications: Patients with IHD, any other significant underlying CVD, uncontrolled HTN or hemiplegic or
basilar migraine

21. ORAL RIZATRIPTAN PROVIDES RAPID EFFECTIVE RELIEF
Bell, et al.
• Multicenter, prospective, open-label, cross-over study.
• Adult patient (n=1,489) treated with rizatriptan 10 mg or usual care in cross-over manner
Key outcomes: Rizatriptan led to:
• Lower use of OTC medication
• Fewer prescription rescue medications
• More patients requiring single dose of medication
Bell CF, et al. Clin Ther 2006;28(6):872-880.

22. ORAL RIZATRIPTAN PROVIDES RAPID EFFECTIVE RELIEF
Rizatriptan led to onset of pain relief within 15 minutes
Bell CF, et al. Clin Ther 2006;28(6):872-880.
Rizatriptan 10 mg was associated with better treatment outcomes than a range of acute migraine
medications.
Onset of relief as was early as 15 minutes, and was significantly better for rizatriptan at all time
points.

23. ADVANTAGE OF ORAL RIZATRIPTAN VS. SUMATRIPTAN
Rated themselves as ‘completely satisfied’ or ‘very
satisfied’ with rizatriptan at 2 h
Were symptom-free at 2 h
Pharmacological advantages that rizatriptan
enjoys over sumatriptan (earlier Tmax and higher
oral bioavailability) translate into superior efficacy
for rizatriptan in migraine patients.
Had a 24-h sustained pain-free response with
rizatriptan
More patients treating a moderate/severe headache with rizatriptan:

24. Rizatriptan… to treat
migraines early
The better triptan….
• Pain relief within 15 min
• Lower need for rescue medication
• Sustained pain-free response
• Patient satisfaction

25. THE ROLE OF INTRANASAL ZOLMITRIPTAN IN
MANAGEMENT OF MIGRAINE

26. Zolmitriptan: Effective abortive treatment for migraine attack
• Zolmitriptan, a serotonin 5-HT1B/1D receptor agonist with both central and peripheral
trigeminovascular activity.
• Oral route: Highly effective, well-tolerated, for acute treatment of migraine with/without aura in
adults.
Bird, et al. 2020
• Systematic review, meta-analysis
• Twenty-five studies (20,162 participants)
Zolmitriptan is effective as an abortive treatment for migraine attack
1. Charlesworth BR, et al. CNS Drugs. 2003;7(9):653-667.
2. Bird S, et al. Cochrane Database of Systematic Reviews. 2014. Issue 5:CD008616.

27. Rapid action of zolmitriptan nasal spray
• Zolmitriptan appears in plasma as early as 5 minutes after nasal spray administration
• Early plasma concentrations are higher after administration of nasal spray than after oral administration
Gawel, et al., 2005
• REALIZE study: international, multicenter, 2-phase study of zolmitriptan nasal spray 5mg in the acute
treatment of migraine
• Zolmitriptan (n=448), placebo (n=439)
Total symptom relief a higher for zolmitriptan as early as 10 minutes post-dose
Gawel M, et al. Headache. 2005;45(1);7-16.

28. Zolmitriptan nasal spray relieves pain and associated symptoms producing higher total symptom relief
than placebo, starting as early as 10 minutes post-dose.
Headache response significantly higher with
zolmitriptan starting at 10 min post-dose
Pain-free rate significantly higher with zolmitriptan
starting at 10 min post-dose
•Among patients with severe headache, the proportion who were able to perform normal activities was
significantly higher with zolmitriptan starting 30 min post-dose
Gawel M, et al. Headache. 2005;45(1);7-16.

29. Rapid action of zolmitriptan nasal spray: Return to normal activities
Dodick, et al, 2005
• Randomized, double-blind, parallel-group study
• Zolmitriptan nasal spray (5.0,mg), or placebo
Key outcome: Starting 15 minutes post-dose, Zolmitriptan nasal spray led to a higher proportion of patient:
• Returning to normal activities
• With resolution of non-headache symptoms
Dodick D, et al. CNS Drugs. 2005;19(2):125-136.

30. Zolmitriptan
Excellent 21.4%;
Good 32.7%
Placebo
Poor 58.1%
Fair 16.9%
Patient
Global
Impression
Zolmitriptan: Desirable efficacy outcome, good tolerability, patient satisfaction, fast onset of action
Key outcome: Starting 15 minutes post-dose, Zolmitriptan nasal spray led to a higher proportion of patients:
With resolution of photophobia and phonophobia
Dodick D, et al. CNS Drugs. 2005;19(2):125-136.

31. Head to relief in minutes
with… Intranasal zolmitriptan
• Acts within 10 minutes
• Resolution of headache and non-headache symptoms
• Return to normal activity
• Patient satisfaction

32. DIHYDROERGOTAMINE (DHE)
• Mechanism of Action
1. an alpha-adrenergic blocker that is a weaker arterial vasoconstrictor and more potent
venoconstrictor than ergotamine tartrate.
2. Inhibition of second-order neurons in the trigeminocervical complex
3. It is also a potent 5-HT 1b/1d receptor agonist.
• Has fewer side effects than ergotamine
• it does not cause the development of physical dependence or rebound headaches
• Available preparations - nasal spray (1 puff [0.5 mg] in each nostril, repeat in 15 minutes,
2-mg maximum daily dose).
• Injected DHE (0.5 mg to 1 mg, repeat in 1 hour, 3-mg maximum daily dose) - can be
selfadministered at home
• Contraindications
1. Pregnancy
2. Uncontrolled HTN
3. h/o CVA

33. PROPYLAXIS OF MIGRAINE

34. PROPYLAXIS

35. CLASSES OF TREATMENTS USED FOR PREVENTIVE TREATMENT OF MIGRAINE

36. Herbal and Nutritional Supplements for Prevention of Migraine

37. RECENT ADVANCES IN MANAGEMENT

38. TRANSCRANIAL MAGNETIC STIMULATION
• Analysis was based upon 164 patients who treated at least one attack of
migraine during the aura phase.
• Pain freedom at two hours post-treatment was significantly greater with
the TMS device compared with sham stimulation (39 versus 22
percent, absolute risk reduction 17 percent, 95% CI 3-31 percent)
• Significance for a sustained pain-free response was maintained at both
24 and 48 hours. There were no serious adverse events

39. TRANSCRANIAL MAGNETIC STIMULATION
• Second-line intervention - for those who have episodic migraine with
aura that does not respond to first-line therapy or who are unable to
take these agents because of contraindications or intolerance.
• TMS should not be used to treat migraine for patients who have
epilepsy, since there is theoretical concern that TMS could trigger
seizures

40. CALCITONIN GENE-RELATED PEPTIDE
Monoclonal antibodies
MONO CLONAL ANTIBODIES
• Subcutaneous monoclonal antibodies (ie,
erenumab, fremanezumab, and
galcanezumab) targeting calcitonin gene-
related peptide (CGRP) or its receptor
have contributed substantially to
prevention of migraine and in reducing
disability in people with episodic and
chronic migraine.
• The regulatory approval of intravenous
eptinezumab has further expanded the
choices for migraine prevention.
ORAL CGRP PEPTIDES
• Trials performed in the past 5 years
have shown the efficacy of oral
rimegepant and atogepant, small
oral CGRP receptor antagonists (ie,
gepants), in preventing episodic
migraine but no evidence was
available for the efficacy of gepants
in preventing attacks in individuals
with chronic migraine.

41. ORAL AGENT - ATOGEPANT
The PROGRESS trial provided compelling evidence that atogepant
(60 mg once a day or 30 mg twice a day) reduced the mean monthly
number of migraine days over a 12-week treatment period for
participants with chronic migraine
This trial addressed an unmet need, and results support oral
atogepant as a viable alternative to subcutaneous and intravenous
treatments.
The availability of various compounds with different dosing
schedules, half-lives, and methods of administration allows for
tailored treatment plans to meet individual preferences and needs.
For some people with migraine, longer-acting medications with less
frequent administration (eg, subcutaneous monoclonal antibodies
targeting the CGRP pathway) might be more suitable, whereas for
others, oral medications that are cleared from the body rapidly
might be preferred
Lancet Neurol. 2024 Jan;23(1):17-19

42. EARLY USE OF UBROGEPANT TO ABORT MIGRAINE
HEADACHE (NOVEMBER 2023)
• Ubrongepant improved the proportion of patients who remained free
of moderate to severe headache at 24 hours compared with placebo
• Acute migraine treatments, including calcitonin gene-related peptide
(CGRP) antagonists, are typically given at headache onset,

43. NASAL SPRAY - ZAVEGEPANT
In 2023, a pivotal phase 3 randomized controlled trial introduced a novel addition to
this class: zavegepant, which is administered intranasally.
Zavegepant nasal spray was superior to placebo for the coprimary endpoints of
pain freedom and freedom from the most bothersome symptom at 2 h, without
any safety concern or clinically significant tolerability issues.
Zavegepant has onset of pain relief within 15 min and sustained effects lasting
up to 48 h.
This drug can offer an alternative for individuals with
 Migraine and severe nausea or vomiting,
 Rapid escalation of pain,
 Early pain recurrence,
 Inadequate response to triptans, or
 Tolerability issues with oral medications
Lancet Neurol. 2024 Jan;23(1):17-19

44. SPECIAL SITUATIONS
• CHILDREN - studies have suggested that NSAIDs and triptans are effective,
with fast-acting treatments offering some therapeutic benefit (nasal sprays).
• Nonpharmacological therapies also offer benefit in some patients including
sleep,biofeedback, stress management, and physical therapy.
• In cases in which patients experience significant adverse effects, options
include switching to naratriptan or to a different class of agents altogether.
• ELDERLY use acetaminophen, COX-2 inhibitors, opioids, and
neuroleptics. Try to avoid ergots, DHE, triptans, and NSAIDs.
• PREGNANCY use acetaminophen, opioids, corticosteroids, and
neuroleptics.
• Avoid ergots, DHE, and triptans. Limit aspirin and NSAIDs during the third
trimester

45. TAKE HOME MESSAGE
• Make a specific diagnosis
• Assess migraine severity and its impact
• Educate patient about the migraine triggers and emphasise behavioural
therapies
• Determine the patient’s preferences and needs and comorbid condition
• Emphasise early therapy during prodrome, aura and early pain phase in case
of triptans
• Nonoral formulations in patients with nausea and vomiting
• Limit the use to 2-3/week to avoid medication overuse headache
• Fluid replacement in patients presenting to ED should not be forgotten

46. THANK YOU
DR GANESHGOUDA MAJIGOUDRA
CONSULTANT NEUROLOGIST
NANJAPPA HOSPITALS DAVANAGERE
9380906082
ganeshgoudam4@gmail.com