Most preventive drugs for Migraine are taken orally while all the CGRP drugs are given parenterally either once a month or once every three months.  The problem here is that the preventive medication would be in one’s body for a long period of time and that if a person had side effects from any of the drugs the preventive side effects could last longer than any acute treatment drug side effect, even after stopping the drug.

The CGRP subcutaneous rendered drug side effects could conceivably last a month or longer, while the usual side effect of any oral, nasal, subcutaneous, or intramuscular administration of the drug may last days to weeks before the side effects subside.   

To read my eBook on Migraine Click Here

This is an article by Britt Talley Daniel MD, retired member of the American Academy of Neurology, Migraine textbook author, Podcaster, YouTube video producer, and Blogger.

The possible side effects vary from drug to drug. The following is a discussion of different preventive migraine treatment drugs.

What are the older drugs?

The American Academy of Neurology and the American Headache Society 2012 guidelines for accepted therapy are:  Divalproex sodium, sodium valproate, topiramate, metoprolol, propranolol, and timolol are effective for migraine prevention and should be offered to patients with migraine to reduce migraine attack frequency and severity.  (Level A). Frovatriptan is effective for prevention of menstrual migraine (Level A

Amitriptyline.

Elavil, or now commonly called by the generic name, amitriptyline, came out in 1961 and is one of the oldest drugs used for migraine prevention currently. Although originally intended for treatment of depression by the FDA at doses of 75-150 mg, headache doctors successfully use lower doses such as 10-30 milligrams taken at bedtime to help migraine and insomnia.

A doctor may use it during pregnancy or breastfeeding only if the benefits of taking the medicine outweigh the risks.

Amitriptyline has been linked with a small risk of problems for the unborn baby if you take it in early or late pregnancy.

Common side effects are:  Constipation, dizziness, dry mouth, sleepiness, difficulty urinating, drowsiness, dizziness, blurred vision, palpitations, tachycardia, increased appetite, nausea, vomiting, diaphoresis, weakness, disorientation, confusion, restlessness, insomnia, anxiety, agitation, rash, urticaria, weight gain, libido changes, impotence, gynecomastia, galactorrhea, tremor, hypoglycemia, paresthesiae, photosensitivity.  

Serious side effects are: orthostatic hypotension, syncope, ventricular arrhythmia, QT prolongation, AV block, torsades de pointes, MI, stroke, seizures, extrapyramidal sx, ataxia, tardive dyskinesia, paralytic ileus, angle-closure glaucoma, increased intraocular pressure, agranulocytosis, leukopenia, thrombocytopenia, hallucinations, exacerbation of psychosis, hypomania, worsening of depression, suicidality, SIADH, hepatitis, angioedema, heat stroke, withdrawal sx if abrupt dc.

Read more about it, “Amitriptyline For Migraines,” on my website, www.doctormigraine.com.

Timolol and metoprolol

Timolol and metoprolol are beta blocker medications indicated for treatment of hypertension, cardiovascular event prevention post-MI, angina, and for migraine headache prophylaxis.

Read all about it, “Timolol Eyedrops for Migraine,” on my website, www.doctormigraine.com.

Propranolol

Propranolol is a beta blocker drug indicated for hypertension, atrial fibrillation/flutter, supraventricular arrhythmias, cardiovascular event prevention post-MI, angina, essential tremor,

IHSS Idiopathic Hypertrophic Subaortic Stenosis, and for migraine headache prophylaxis.

Side effects for timolol, metoprolol, and propranolol:

Serious Reactions:  CHF, severe bradycardia, heart block, angina exacerbation if abrupt D/C, MI if abrupt D/C, ventricular arrhythmia if abrupt D/C, Raynaud phenomenon, bronchospasm, hypersensitivity reaction, anaphylaxis, lupus erythematosus, myasthenia gravis exacerbation.

Common Reactions:  bradycardia, fatigue, dizziness, headache, dyspnea, pruritis, nightmares, impotence.

Read my article on “Betablockers For Migraine Prevention,” on my website, www.doctormigraine.com.

Divalproex sodium and Sodium valproate

Divalproex sodium and Sodium valproate are indicated for the treatment of epilepsy, bipolar disorder, and migraine.  Depakote can be a useful single preventive drug if the patient has both migraine and epilepsy, bipolar disorder and epilepsy, or migraine and bipolar disease.

Serious side effects:  hepatotoxicity, pancreatitis, SIADH, hyponatremia, pancytopenia, thrombocytopenia, drug reaction with eosinophilia and systemic sx, hyperammonemia, hypothermia, myelosuppression, aplastic anemia, bleeding, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, hallucinations, psychosis, suicidality, encephalopathy, coma, cerebral pseudoatrophy, parkinsonism, polycystic ovary syndrome.

Common reactions:  headache, nausea, vomiting, asthenia, somnolence, dyspepsia, dizziness, abdominal pain, tremor, alopecia, weight changes, appetite changes, constipation, nervousness, emotional lability, insomnia, peripheral edema, petechiae, ecchymosis, rash, depression, dyspnea, tinnitus, ALT or AST elevated, amnesia, abnormal gait, injection site pain, vision changes, blurred vision, nystagmus, myalgia, photosensitivity.

Possible severe reaction:  severe fetal malformations in pregnant women; should never be given to potentially fertile women.

Read my article, “Depakote-Preventive Treatment For Migraine,” on my website, www.doctormigraine.com.

Topiramate

Topiramate is indicated for treating partial seizures, primary generalized tonic clonic seizures, Lennox-Gastaut syndrome seizures, and for migraine headache prophylaxis.

Serious Reactions

Severe metabolic acidosis, nephrolithiasis, osteomalacia, oligohidrosis, hyperthermia, hypokalemia, hyperammonemia encephalopathy, psychosis, suicidality, leukopenia, anemia, secondary angle-closure glaucoma, acute myopia, maculopathy, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, hemorrhage, pediatric growth suppression, withdrawal seizures if abrupt D/C.

Common Reactions

Cognitive dysfunction, paresthesia, somnolence, hyperammonemia, URI, dizziness, weight loss, fatigue, nervousness, ataxia, anorexia, abdominal pain, taste changes, nausea, visual disturbance, fever, diarrhea, mood disturbance, nystagmus, insomnia, depression, tremor, infection, bleeding, dyspepsia, hypoesthesia, asthenia, anxiety, phosphate decrease.

Read my article, “Topiramate for Migraines” on my website, www.doctormigraine.com.

Frova (Frovatriptan)

Frovatriptan is a long lasting triptan indicated for menstrual migraine prophylaxis used for 6 possible days per cycle.  Frovatriptan’s onset is within 6 hours and its half-life is 26 hours.

Serious reactions are:  coronary vasospasm, myocardial ischemia, MI, ventricular tachycardia, life-threating arrhythmia, hypertension, stroke, cerebral hemorrhage, subarachnoid hemorrhage, intestinal ischemia, peripheral vascular ischemia, hypersensitivity reaction, anaphylaxis, angioedema, serotonin syndrome, headache exacerbation if used more than 10 days/month.

Common reactions are:  dizziness, fatigue, flushing, paresthesia, headache, xerostomia, hot sensation, cold sensation, arthralgia, bone pain, dyspepsia, chest, neck, or jaw pain or discomfort.

Read my article, “How to Treat Migraine Headaches,” on my website, www.doctormigraine.com.

What about the newer drugs?

Nurtec 75 mg ODT.

As of May 2021, Nurtec has been approved by the FDA for both acute and preventive treatment for Migraine, and it is the only drug with both indications.  For prevention it is administered every other day.

Nurtec ODT is the only drug approved for acute and preventive Migraine treatment of adults by the FDA.  The Migraine process releases three neuroinflammatory chemicals—CGRP, Neurokinin A, and Substance P. 

Nurtec ODT 75 mg (rimegepant) blocks the effect of CGRP, which now considered to be one of the most important inflammatory neurochemicals during the Migraine process.  ODT means “orally dissolvable tablet.”  The tablet is put in the mouth and then it dissolves.  Water and a cup or glass are not needed.  Drug effect onset occurs as early as 1 hour after taking Nurtec ODT.

Nurtec ODT is safe for Migraineurs with cardiovascular risk factors.  Nurtec ODT is compatible with most drugs, including:  CGRP preventive medication for Migraine, oral contraceptives, some antidepressants, preventive medication for Migraine, and triptans for Migraine.

What are the possible side effects of taking Nurtec ODT?

Serious adverse reactions.  Nurtec ODT may cause a serious hypersensitivity reaction with trouble breathing, rash, swelling of the face, mouth, tongue, or throat.

Common mild side effect is nausea, present in 2.%.

Read my article, “Nurtec for Migraines,” on my website, www.doctormigraine.com.

Aimovig

Aimovig (erenumab) is a new CGRP blocking preventive drug for Migraine.  CGRP is a neurochemical which is released during in the migraine process and blocking it significantly improves migraine attacks.

Aimovig has few side effects, can be taken safely with all other drugs, and is given by a subcutaneous injection every month. 

Serious side effects are hypersensitivity reaction, anaphylaxis, severe constipation, and hypertension.

Common side effects are injection site reaction, constipation, and muscle cramps or spasms. 

Serious side effects are rare and the common side effects are not bad.  Constipation may occur in 3% but it improves with time.  The injection site reaction is like the small bruise one gets following getting blood drawn in your arm for lab studies.

Read my article “Vascular Safety of Aimovig (erenumab) For Migraine Prevention” on my website, www.doctormigraine.com.

Ajovy

Ajovy (fremanezumab) is CGRP blocking preventive drug for Migraine.  It is given subcutaneously in adults monthly.  Ajovy has mild side effects.

Serious side effects-may occur, but none reported.

Common reactions are:  injection site reaction, hypersensitivity reaction, rash, pruritis, and urticaria.

Read my article, “Ajovy for Migraines,” on my website, www.doctormigraine.com.

Emgality

Emgality (galcanezumab) is a Calcitonin Gene-Related Peptide (CGRP) for preventing migraine.

Serious side effects are hypersensitivity reaction.

Common side effects are injection site reaction and muscle cramps or spasms.

Select Safety Information.  Emgality may cause allergic reactions, such as itching, rash, hives, and trouble breathing. Allergic reactions can happen days after using Emgality.

Read my article, “Emgality for Migraine and Cluster Headaches,” on my website, www.doctormigraine.com.

Vyepti

Vyepti (Eptinezumab) has been approved for both episodic and chronic migraine.  It is a monoclonal antibody inhibitor of (CGRP) and is given by IV infusion monthly.

Serious reactions-hypersensitivity reaction.

Common reactions are:  nasopharyngitis, angioedema, urticaria, facial flushing, and rash.

Read my article, '“Vyepti For Migraines,” on my website, www.doctormigraine.com.

Botox

Botox (onabotulinumtoxinA) OnabotulinumtoxinA, or as it is colloquially known in the world, Botox, is a famous dermatology, beauty assisting, facial line erasing drug which also works for chronic migraine headache and has an indication from the FDA for migraine prevention for patients with chronic migraine (15 headache days a month, 8 of which have migraine features).  Botox does not work for episodic migraine (14 or less headache days a month) or for Tension type headache.

Botox is a neurotoxic protein produced by the bacterium Clostridium botulinum.  It prevents the release of the neurotransmitter acetylcholine at the neuromuscular junction.  This can result in paralysis of striated muscle found in the eye muscles, diaphragm, arms, and legs. 

Serious reactions-hypersensitivity reaction, anaphylaxis, toxin effect spread, dysphagia, respiratory failure, autonomic dysreflexia, urinary retention, retrobulbar hemorrhage, corneal ulcer, myasthenia gravis exacerbation, facial paralysis, seizures.

Common reactions-ptosis, UTI, ocular vertical deviation, neck and extremity pain, superficial punctate keratitis, ocular dryness, headache, fatigue, asthenia, muscle weakness, sweating, fever, infection, hematuria, dysuria, nausea, pruritus, arthralgia, myalgia, back pain, appetite decrease.

Read my article, “Does Botox work for Chronic Migraine?” on my website, www.doctormigraine.com.

Summary

The new CGRP drugs for Migraine prevention and acute therapy are better tolerated than older drugs.

To read my big book on Migraine Click Here.

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All the best.

Britt Talley Daniel MD