Headache and Pain Syndromes

Questions

1. Which of the following statements accurately describes the mechanisms of triptans?

A. 5-HT_1B/1D receptor agonists

B. 5-HT_1B/1D receptor antagonists

C. 5-HT_1F receptor agonists

D. 5-HT_1F receptor antagonists

E. D1 receptor antagonists

View Answer

1. Answer A. (MN-56) Triptans are 5-HT_1B/1D receptor agonists and are used for acute migraine treatment. Ergots, such as dihydroergotamine, are selective 5-HT₁ receptor agonists. Dopamine receptor antagonists, such as metoclopramide and chlorpromazine, can also be used for acute migraine treatment (Table 7.1.1).

TABLE 7.1.1 Acute Treatment of Migraine Attacks^a

Drug	Trade Name	Dosage
NSAIDs
Naproxen^b	Aleve, Anaprox, generic	220-550 mg orally twice a day
Ibuprofen^b	Advil, Motrin, Nuprin, generic	400-800 mg orally q6-8h
Acetylsalicylic acid^b	Aspirin, generic	500-1,000 mg orally twice a day
Tolfenamic acid	Clotam Rapid	200 mg orally; may repeat × 1 after 1-2 h
Diclofenac potassium^b	Cambia, generic	50 mg orally with water
Compound Analgesics
Acetaminophen, aspirin, caffeine^b	Excedrin Migraine	Two tablets or caplets q6h (max 8 per day)
Migraine Specific: Triptans: 5-HT_1B/1D Receptor Agonists
Oral
Naratriptan^b	Amerge, generic	2.5-mg tablet at onset; may repeat once after 4 h
Rizatriptan^b	Maxalt, generic Maxalt-MLT	5- to 10-mg tablet at onset; may repeat after 2 h (max 30 mg/d)
Sumatriptan^b	Imitrex, generic	50- to 100-mg tablet at onset; may repeat after 2 h (max 200 mg/d)
Frovatriptan^b	Frova	2.5-mg tablet at onset; may repeat after 2 h (max 5 mg/d)
Almotriptan^b	Axert	6.25- to 12.5-mg tablet at onset; may repeat after 2 h (max 25 mg/d)
Eletriptan^b	Relpax	20- to 40-mg tablet at onset (max 80 mg/d)
Zolmitriptan^b	Zomig, generic Zomig Rapimelt	2.5- to 5-mg tablet at onset; may repeat after 2 h (max 10 mg/d)
Nasal
Dihydroergotamine^b	Migranal nasal spray	Prior to nasal spray, the pump must be primed four times; one spray (0.5 mg) is administered, followed in 15 min by a second spray.
Sumatriptan^b	Imitrex nasal spray	5- to 20-mg intranasal spray as four sprays of 5 mg or a single 20-mg spray (may repeat once after 2 h, not to exceed a dose of 40 mg/d)
Zolmitriptan^b	Zomig	2.5- to 5-mg intranasal spray as one spray (may repeat once after 2 h, not to exceed a dose of 10 mg/d)
Parenteral
Dihydroergotamine^b	D.H.E. 45	1 mg IV, IM, or SC at onset and q1h (max 3 mg/d, 6 mg/wk)
Sumatriptan^b	Imitrex injection, generic Alsuma Sumavel DosePro	6 mg SC at onset (may repeat once after 1 h for max of two doses in 24 h)
Ditans: 5-HT_1F Receptor Agonists
Lasmiditan	Reyvow	50, 100, or 200 mg taken orally
Gepants: CGRP Receptor Antagonists
Rimegepant	Nurtec	75 mg taken orally
Ubrogepant	Ubrelvy	50 or 100 mg taken orally
Dopamine Receptor Antagonist
Oral
Metoclopramide	Reglan^c, generic^c	5-10 mg/d
Prochlorperazine	Compazine^c, generic^c	1-25 mg/d
Promethazine	Phenergan^c, generic^c	25-50 mg/d
Chlorpromazine	Thorazine^c, generic^c	25-50 mg/d
Parenteral
Metoclopramide^b	Reglan^c, generic	10 mg IV
Prochlorperazine^b	Compazine^c, generic^c	10 mg IV
Chlorpromazine^b	Thorazine^c, generic^c	12.5-25 mg IM or IV (0.1 mg/kg IV at 2 mg/min)
Promethazine	Phenergan^c, generic^c	12.5-25 mg IM or IV (slow)
Neuromodulation
Transcutaneous supraorbital nerve stimulation	Cefaly	Stimulate for 60 min.
sTMS	sTMS mini	Three pulses repeated if no initial response
Noninvasive vagus nerve stimulation	Gammacore	1-2 120-s stimuli to affected side
Remote electrical neuromodulation	Nerivio Migra	45-min stimulation on the upper arm
5-HT, 5-hydroxytryptamine; CGRP, calcitonin gene–related peptide; IM, intramuscular; IV, intravenous; NSAIDs, nonsteroidal anti-inflammatory drugs; SC, subcutaneous; sTMS, single-pulse transcranial magnetic stimulation.
^aAntiemetics (eg, domperidone 10 mg or ondansetron 4 or 8 mg) or prokinetics (eg, metoclopramide 10 mg) are sometimes useful adjuncts.
^bSupported by level 1 evidence.
^cNot all drugs are specifically indicated by the US Food and Drug Administration for migraine. Local regulations and guidelines should be consulted.
Reprinted with permission from Louis ED, Mayer SA, Noble JM, eds. Merritt’s Neurology. 14th ed. Wolters Kluwer; 2022.

2. A 25-year-old woman presents for evaluation of headaches. She endorses repeated attacks of unilateral throbbing pain aggravated by movement, improved by sleeping, and associated with sensitivity to light and sound. The attacks occur 1 to 2 times a week. Which of the following medication strategies would be most likely to reduce her pain and improve her quality of life?

A. Start acute treatment for migraine headaches with sumatriptan

B. Start acute treatment for migraine headaches with sumatriptan in addition to daily nortriptyline as a preventive treatment

C. Start acute treatment for migraine headaches with sumatriptan in addition to daily verapamil as a preventive treatment

D. Start daily nortriptyline for preventive treatment

E. Start daily verapamil for preventive treatment

View Answer

2. Answer B. (MN-56) The patient meets clinical criteria for migraine headache given the presence of unilateral throbbing pain, aggravated by movement, and associated photophobia and phonophobia (Table 7.2.1). Acute therapy with triptans, nonsteroidal anti-inflammatory drugs, calcitonin gene–related peptide (CGRP) receptor antagonists, or dopamine antagonists should be started in all patients who have migraine headaches. Given the patient is having more than four headaches per month, she should also be started on a preventive medication such as nortriptyline. Preventive medications for migraine include beta-blockers, such as propranolol; anticonvulsants, such as valproate or topiramate; antidepressants, such as nortriptyline; or CGRP pathway antagonists.

TABLE 7.2.1 Simplified Diagnostic Criteria for Migraine

Repeated Attacks of Headache Lasting 4-72 h in Patients with a Normal Physical Examination, No Other Reasonable Cause for the Headache, and
At Least Two of the Following Features	Plus at Least One of the Following Features
Unilateral pain	Nausea/vomiting
Throbbing pain	Photophobia and phonophobia
Aggravation by movement
Moderate or severe intensity
Adapted with permission from Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders. 3rd ed. Cephalalgia. 2018;38(1):1-211. Copyright © 2018 International Headache Society.

3. A 35-year-old man presents with recurrent unilateral headaches concentrated over his left forehead with associated ipsilateral lacrimation and conjunctival injection. The patient endorses around 100 headaches per day that occur at different times of day with no pattern and last around 30 seconds. Although headaches wax and wane in intensity they do not completely resolve per patient. He is trialed on indomethacin, which fails to alleviate his symptoms. Based on the patient’s constellation of symptoms, MRI of the brain should be performed to evaluate for which of the following?

A. Cavernous sinus lesion

B. Cerebellopontine angle tumor

C. Compression of the left trigeminal nerve by vascular loops of the anterior inferior cerebellar artery

D. Compression of the left trigeminal nerve by vascular loops of the superior cerebellar artery

E. Pituitary mass

View Answer

3. Answer E. (MN-56) The patient has a trigeminal autonomic cephalalgia (TAC) as evidenced by the presence of unilateral neuralgiform headache with autonomic symptoms. The presence of autonomic symptoms, ie, lacrimation, conjunctival injection, rhinorrhea, and lack of a refractory period, is what differentiates TACs from trigeminal neuralgia, which can also present as a stabbing headache within distribution of the trigeminal nerve. The patient above suffers from short-lasting unilateral neuralgiform headache with cranial autonomic symptoms (SUNA). Patients with SUNA classically suffer multiple daily headaches (3-200) that have very short duration (<2 minutes), as opposed to cluster headaches or paroxysmal hemicrania, where headaches typically last at least several minutes (Table 7.3.1). Of note, the poor response to indomethacin and the fact that headaches do not occur in a regular pattern also help differentiate it from paroxysmal hemicranias and cluster headache, respectively; in cluster headaches, at least one headache must occur around the same time of day every day. Moreover, the lack of a refractory period is classic for SUNA. In patients with TAC, MRI brain should be performed to exclude a pituitary lesion, as these can be associated with this type of headache. Compression of the left trigeminal nerve by vascular loops of either the anterior inferior or superior cerebellar artery would be appropriate if the patient suffered from trigeminal neuralgia. Lesions in the cerebellopontine angle or cavernous sinus would not be expected to cause the patient’s symptoms.

TABLE 7.3.1 Clinical Features of the Trigeminal Autonomic Cephalalgias

	Cluster Headache	Paroxysmal Hemicrania	SUNCT/SUNA
Gender pain	M > F	F = M	F ~ M
Type	Stabbing, boring	Throbbing, boring, stabbing	Burning, stabbing, sharp
Severity	Excruciating	Excruciating	Severe to excruciating
Site	Orbit, temple	Orbit, temple	Periorbital
Attack frequency	1/alternate day to 8/d	1-20/d (>5/d for more than half the time)	3-200/d
Duration of attack	15-180 min	2-30 min	5-240 s
Autonomic features	Yes	Yes	Yes (prominent conjunctival injection and lacrimation)^a
Migrainous features^b	Yes	Yes	Yes
Alcohol trigger	Yes	No	No
Cutaneous triggers	No	No	Yes
Indomethacin effect	—	Yes^c	—
Abortive treatment	Sumatriptan injection or nasal spray Zolmitriptan nasal spray Oxygen Noninvasive vagus nerve stimulation	No effective treatment	Lidocaine (IV)
Preventive treatment	Verapamil Lithium Galcanezumab	Indomethacin	Lamotrigine Topiramate Gabapentin
F, female; IV, intravenous; M, male; SUNA, short-lasting unilateral neuralgiform headache attacks with cranial autonomic features; SUNCT, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing.
^aIf conjunctival injection and tearing not present, consider SUNA.
^bNausea, photophobia, or phonophobia; photophobia and phonophobia are typically unilateral on the side of the pain and seen in patients with a personal or family history of migraine.
^cIndicates complete response to indomethacin.
Reprinted with permission from Louis ED, Mayer SA, Noble JM, eds. Merritt’s Neurology. 14th ed. Wolters Kluwer; 2022.

4. A 35-year-old man presents to clinic for follow-up of chronic migraines. His prior neuroimaging is unremarkable. He is well known to your practice and has been trialed on multiple preventive migraine medications for these headaches, including propranolol, amitriptyline, and riboflavin, without any success as he still has three to four headaches a week. Which of the following would be the most appropriate next step?

A. Repeat MRI first given persistent headache despite medical therapy

B. Trial an anticonvulsant, such as topiramate, as this class of medications has not been used before

C. Trial erenumab

D. Trial onabotulinum toxin (Botox) injections

E. Choice C or D

View Answer

4. Answer E. (MN-56) The patient in question has a history of chronic migraines that have failed to improve with three different oral medications. Additional neuroimaging is not needed given that neither headache semiology nor examination has changed. At this point onabotulinum toxin type A injections, or alternatively monoclonal antibody therapy with calcitonin gene–related peptide (CGRP) receptor antagonists such as erenumab, would be best to treat his treatment-refractory chronic migraines (Table 7.4.1).

TABLE 7.4.1 Preventive Treatments in Migraine^a

Drug	Dose	Selected Side Effects
β-Blockers		Fatigue, postural symptoms, bradycardia, depression, nightmares
Propranolol^b	40-120 mg twice a day	Caution in patients with asthma
Metoprolol^b	25-100 mg twice a day	—
Timolol^b	5-10 mg twice a day	—
Atenolol	25-100 mg every day	—
Nadolol	40-240 mg divided twice or 3 times a day	—
Anticonvulsants
Topiramate^b	25-200 mg/d	Paresthesias, cognitive impairment, weight loss, nausea, fatigue, glaucoma, and metabolic acidosis; caution with nephrolithiasis
Valproate^b	400-600 mg twice a day	Drowsiness, weight gain, hair loss, tremor, hematologic or liver abnormalities, fetal abnormalities
Gabapentin	900-3,600 mg every day	Dizziness, sedation, weight gain
Antidepressants
Amitriptyline	10-100 mg at night	Drowsiness, dry mouth, constipation, blurred vision, postural hypotension, weight gain
Nortriptyline	10-100 mg at night	*Note:* Some patients may only need a total dose of 10 mg, although generally, 1-1.5 mg/kg body weight is required.
Doxepin	10-75 mg at night	Sedation, dry mouth, weight gain
Venlafaxine^b	75-150 mg every day	Nausea, insomnia, dizziness, fatigue, nervousness
Serotonergic Drugs
Pizotifen^c	0.5-2 mg every day	Weight gain, drowsiness
CGRP Pathway Monoclonal Antibodies
Eptinezumab (Vyepti)	100 or 300 mg IV quarterly	—
Erenumab (Aimovig)	70 or 140 mg SC monthly	—
Fremanezumab (Ajovy)	225 mg SC monthly or 675 mg SC quarterly	—
Galcanezumab (Emgality)	240 mg SC loading dose then 120 mg SC monthly	—
Neuromodulation
sTMS	sTMS mini	2-8 pulses 2-3 times daily
Transcutaneous supraorbital nerve stimulation	Cefaly	Stimulate 20 min daily
Other Classes
Flunarizine^c (calcium channel blocker)	5-15 mg every day	Drowsiness, weight gain, depression, parkinsonism
Candesartan (ARB inhibitor)	16 mg every day	Dizziness, hypotension
Onabotulinum toxin type A^b (Botox)	155 units divided in 31 sites (PREEMPT protocol)	Loss of brow furrow, ptosis, pain at injection sites, neck stiffness
Complementary Agents
Petasites (butterbur)^b	75 mg twice a day	Stomach upset
Riboflavin (vitamin B₂)	400 mg every day	Urine discoloration
Magnesium	500-600 mg every day	Increased bowel motility
Feverfew (MIG-99)	6.25 mg 3 times a day	Stomach upset, nausea
ARB, angiotensin II receptor blocker; CGRP, calcitonin gene–related peptide; IV, intravenous; PREEMPT, Phase III Research Evaluating Migraine Prophylaxis Therapy protocol; sTMS, single-stimulation.
^aCommonly used preventives are listed with typical doses and common side effects. Not all listed medicines are approved by the US Food and Drug Administration; local regulations and guidelines should be consulted.
^bSupported by level 1 evidence.
^cNot available in the United States.
Reprinted with permission from Louis ED, Mayer SA, Noble JM, eds. Merritt’s Neurology. 14th ed. Wolters Kluwer; 2022.

5. What blood vessel most commonly causes vascular compression of the trigeminal nerve associated with trigeminal neuralgia?

A. Anterior inferior cerebellar artery

B. Basilar artery

C. Posterior cerebral artery

D. Posterior inferior cerebellar artery

E. Superior cerebellar artery

View Answer

5. Answer E. (MN-57) Other blood vessels in the posterior fossa can also cause compression of trigeminal neuralgia, but the superior cerebellar artery is most commonly identified at the time of surgical intervention.

6. Which of the following drugs has best evidence of efficacy for the treatment of trigeminal neuralgia?

A. Carbamazepine

B. Gabapentin

C. Lamotrigine

D. Oxcarbazepine

E. Topiramate

View Answer

6. Answer A. (MN-57) Other medications listed are also used for trigeminal neuralgia, but carbamazepine remains the best choice based on evidence-based medicine criteria. Oxcarbazepine is mechanistically similar to carbamazepine, is easier to titrate, and requires less monitoring than carbamazepine, although it has been less studied in treatment of trigeminal neuralgia.

7. A 75-year-old man has recently developed trigeminal neuralgia on the right side of his face. He was started on carbamazepine 100 mg twice a day, after complete blood testing. His dose was gradually increased to 200 mg twice a day with a therapeutic blood level and 80% improvement of his pain. He is having side effects at this dose, including upset stomach, and his white blood cell count is down to 1.4. Which of the following interventions would be most reasonable?

A. Continue carbamazepine 200 mg twice a day and add gabapentin

B. Continue carbamazepine 200 mg twice a day, and add phenytoin 100 mg at night

C. Discontinue carbamazepine and start lamotrigine

D. Discontinue carbamazepine and start oxcarbazepine

E. Increase carbamazepine to 300 mg twice a day

View Answer

7. Answer D. (MN-57) Discontinuing carbamazepine and starting oxcarbazepine is most likely to help in this case. The patient had clinical improvement with carbamazepine, although is having side effects with this medication, and he has new leukopenia. Patients on carbamazepine should have complete blood count, liver function tests, sodium level, and carbamazepine level periodically checked. Given his clinical improvement with carbamazepine, it is most reasonable to transition him to oxcarbazepine. Oxcarbazepine requires monitoring mainly for hyponatremia. Carbamazepine and phenytoin have multiple drug interactions and are likely to increase the risk of falls in this age group. Lamotrigine is an option; however, this medication requires slow up-titration, and thus the patient may not see a therapeutic benefit for several weeks (Table 7.7.1).

Only gold members can continue reading. Log In or Register to continue