Drugs for Migraine Treatment and Prophylaxis

Question 1

Acetaminophen and NSAIDS

Answer 1

DRUGS FOR ACUTE MILD TO MODERATE ATTACKS

ACETAMINOPHEN & NSAIDs

For mild to moderate attacks not associated with vomiting or severe nausea, acetaminophen and NSAIDs are first choice.

Question 2

Triptans

Answer 2

DRUGS FOR ACUTE MODERATE TO SEVERE ATTACKS

TRIPTANS

Sumatriptan

Triptans are the drug of choice for treatment of moderate-to-severe migraine.

Triptans are selective agonists at 5-HT1D and 5-HT1B receptors. Combination of sumatriptan and naproxen provides better pain relief than either agent taken alone.

Subcutaneous sumatriptan is the fastest-acting and most effective triptan formulation.

ADVERSE EFFECTS

Tingling, flushing, dizziness, drowsiness, fatigue, and a feeling of heaviness, tightness, or pressure in the chest. Angina, myocardial infarction, cardiac arrhythmia, stroke, and death have occurred rarely with triptans.

Triptans are contraindicated in patients with coronary, cerebrovascular or other arterial disease, or uncontrolled hypertension.

Triptans should be used with caution in patients with other risk factors for vascular disease, particularly diabetes.

Question 3

Ergot Alkaloids

Answer 3

DRUGS FOR ACUTE MODERATE TO SEVERE ATTACKS

ERGOT ALKALOIDS

Ergotamine, Dihydroergotamine

Ergotamine acts as an agonist at α-adrenoceptors, 5-HT receptors (particularly 5- HT1B/1D) and dopamine D2 receptors

Based on the mechanism of action of the triptans, the agonist actions of ergot alkaloids at 5-HT1B/1D receptors likely mediate their acute anti-migraine effects.

ADVERSE EFFECTS

Nausea and vomiting are fairly common with ergotamine, but can be prevented by pretreatment with or concurrent use of an antiemetic such as metoclopramide.

Serious adverse effects, such as vascular (including coronary) occlusion and gangrene, are rare and are usually associated with overdosage. Liver disease or fever can accelerate development of severe vasoconstriction.

Dihydroergotamine is a weaker vasoconstrictor than ergotamine and causes fewer adverse effects.

Ergots are contraindicated in patients with arterial disease or uncontrolled hypertension.

Question 4

DRUGS FOR PREVENTION OF MIGRAINE

Answer 4

Patients with frequent or severe disabling migraine headaches should receive prophylactic treatment.

The mechanisms of action of drugs used for migraine prophylaxis are diverse; no single drug has emerged as a clear treatment of choice.

Question 5

B-Blockers

Answer 5

FIRST LINE AGENTS: BETA BLOCKERS

Propranolol Timolol Metoprolol Nadolol Atenolol

For continuous prophylaxis, beta blockers are commonly used. Up to 80% of patients achieve complete or partial response.

Question 6

Valproate

Answer 6

FIRST LINE AGENTS: ANTIEPILEPTICS

Valproate

Valproate is indicated for the treatment of manic episodes associated with bipolar disorder, epileptic seizures, and prophylaxis of migraine headache.

Valproate inhibits voltage gated Na+ channels and T-type Ca2+ channels.

Adverse effects: GI side effects. Thrombocytopenia. Rarely hepatotoxicity. Teratogenic.

Question 7

Topiramate

Answer 7

FIRST LINE AGENTS: ANTIEPILEPTICS

Topiramate

Topiramate is indicated for the treatment of epileptic seizures and prophylaxis of migraine headache.

Topiramate inhibits voltage-gated Na+ channels. Additionally, it is a GABAA receptor agonist and an antagonist at glutamate receptors.

Adverse effects: Somnolence, fatigue, dizziness, cognitive slowing, nervousness, and confusion. Acute myopia, glaucoma. Hyperthermia, renal stones. Teratogenic.

Question 8

Amitriptyline

Answer 8

TRICYCLIC ANTIDEPRESSANTS

Question 9

Nortriptyline

Answer 9

TRICYCLIC ANTIDEPRESSANTS

Question 10

Imipramine

Answer 10

TRICYCLIC ANTIDEPRESSANTS

Question 11

TRICYCLIC ANTIDEPRESSANTS

Answer 11

TRICYCLIC ANTIDEPRESSANTS

Amitriptyline Nortriptyline Imipramine

TCAs can be used in combination with propranolol to increase efficacy and decrease adverse effects. Clomipramine is not effective.

TCAs inhibit norepinephrine and serotonin reuptake.
Adverse effects: Sedation, dry mouth, weight gain.

Question 12

Venlafaxine

Answer 12

SEROTONIN & NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs)

Venlafaxine

Adverse effects: nausea, constipation, insomnia, headaches, sexual dysfunction.

Question 13

Verapamil

Answer 13

CALCIUM CHANNEL BLOCKERS

Verapamil

Calcium channel blockers are used for prevention of migraine, but evidence for their effectiveness is weak. Verapamil is the CCB with most evidence of efficacy.

Question 14

Gabapentin

Answer 14

ANTIEPILEPTICS

Gabapentin

Gabapentin decreases glutamate release; this effect is a consequence of blockade of presynaptic voltage-gated Ca2+ channels.

Adverse effects: sleepiness, dizziness, fatigue

Question 15

Lisinopril and Candesartan

Answer 15

ACEIs & ARBs

Lisinopril and candesartan have reduced migraine frequency by about 30%.

Question 16

Botulinum Toxin

Answer 16

BOTULINUM TOXIN

Pericranial injections of botulinum toxin is marginally effective for prophylaxis of headaches in adult patients with chronic migraine (patients with 15 or more headache days/monts).

Question 17

Naproxen

Answer 17

NSAIDs

NSAIDs such as naproxen and ibuprofen, have been used for short-term prevention of migraine.