Do The New CGRP Drugs Work For Migraine?


Migraine is a genetic problem inherited in families. Eighty percent of persons with migraine have a close relative with migraine whether they know it or not.  Migraine has pseudonyms and sometimes the relative doesn't realize they have migraine; they just know they have “sinus headaches, menstrual headaches, one-sided headaches, hungry headaches, or nocturnal headaches.”  Many of these persons never saw a neurologist for headache. They don’t know that they have migrainel

Seventeen percent of the general population has migraine and it is found in women three times more often than men.  Migraine is the fifth most disabling medical problem and 1 out of 10 visits to the ER are for migraine.   The most painful conditions known are childbirth, a kidney stone, and migraine.

Eighty percent of migraines are one-sided and the headache is usually moderate or severe in intensity and may come with nausea, or vomiting, sensitivity to movement, light, or noise.  Migraine starts in the second decade (10-20 years old) and peaks in occurrence in women at age 42 where 25 % of women have migraine.  For men migraine peaks in occurrence at age 38 and 6 % of men have migraine at that age.  For women migraine is their most common, chronic medical problem.

The Migraine Timing Cycle.


migraine timing cycle 300 dpi 1200.jpg

The Migraine Timing Cycle is composed of four steps:

1.The brain stem activates the trigeminal nerve sending pain to the face or back of the head.

2.Within 20-40 minutes the trigeminal and arterial ganglia start to release inflammatory neuropeptides.

3.The neuropeptides-neurokinin A, substance P, and CGRP, cause arterial vasodilatation, and inflammation of the trigeminal nerve, the arteries, and the thalamus.

4.Central sensitization occurs with neuropeptide thalamic inflammation.

The new drugs block the effect of CGRP, and inflammatory protein release during an attack of migraine.  They produce antibodies against the CGRP peptide.  Unlike older preventive drugs for migraine, these new drugs enter right into the migraine process, disrupting inflammatory pathways.

There are 3 of these drugs currently available: Aimovig, Ajovy, and Emgality. They have no drug-drug mal interactions, few side effects, and are veryeffective at stopping migraine attacks. 

Do The New CGRP Drugs Work For Migraine?  Yes, these drugs have had a grand start since they came out in 2018. They have been found to have few side effects and remarkable effectiveness in treating chronic migraine.

Chronic migraine is defined as 15 or more headache days a month, 8 of which have migraine features.  The CGRP drugs reduce migraine by 50 % for half of patients, 75 % for a quarter of patients, and 100 % for 20-30% of patients.

Related questions.

1.Where do these new drugs come from?  Most drugs are found in the dirt, or the field, or the rain forest.  The penicillin mold floated down out of the London sky and settled on an agar plate that Fleming had set on his windowsill and he “found” penicillin, the first powerful antibiotic in the history of medicine.

CGRP drugs are made by DNA polymerization, a lab process of spinning out strands of DNA.  This is a completely novel method of drug production and safe regarding use with other existing drugs.


2.Do these new CGRP antibody-producing drugs react well with other proteins, or with other drugs?  The new CGRP drugs have no drug-to-drug interaction.  This means the new drugs can be safely and reliably used with any known existing drug.  

All currently used drugs have a list of other drugs that possibly cause reactions when used medically. The new CGRP drugs have no such reactions, making them very safe and potentially very usable for patients and prescribing doctors.

Action of CGRP antibody

Action of CGRP antibody

3.What are the side effects of these new drugs?  Three drugs have come out since the summer of 2018.  All of the drugs may have a rare possible serious side effect of a hypersensitive reaction, or anaphylaxis, which is like an allergy to the drug.  Persons who are allergic to rubber or latex may develop the hypersensitive reaction.

The drugs are only approved for adults and are restricted during pregnancy and breast feeding.  

Common side effects are not bad and include:


Muscle cramps

Muscle spasms

Injection site reaction 

Constipation may occur for several months but it improves with time.  Aimovig has the highest rate of constipation-3 %.  The injection site reaction is like the small bruise one gets following getting blood drawn in your arm for lab studies.  No big deal, really.

4.How are the drugs administered?  All of the drugs are given by subcutaneous injection with a small gauge needle either in the top of the thigh or 2 inches adjacent to the belly button in the abdomen, once a month.  Ajovy has an option of being given three times the monthly amount as 675 mg once every 3 months.  Emgality requires 2 120 mg subcutaneous injections the first month to start the treatment, but after that it’s given once a month like the other drugs.  The injections are similar to those given by Type 2 diabetics four times a day, every day.

Some patients are hesitant to consider the drugs because of the needle injection mode of delivery, but they get through it considering the great benefits of these drugs.  When I ask patients on their return to visit how the shots are going, they usually look at me and say, “It’s not as bad as I imagined.”

Aimovig subcutaneous injection in thigh.

Aimovig subcutaneous injection in thigh.


5.What are the clinical results of using the new CGRP drugs? The results of the three drugs are similar and they all seem to work well, and about the same.  Fifty percent of patients have fifty percent reduction of migraine attacks.  Twenty-five percent of patients have 75 % reduction of migraine attacks and another 20-30 percent of patients are super responders with 100 % reduction of migraine. It seems the drugs work better as time goes on, better at 4 months than at 1 month.

6.Are doctors required to check blood parameters for patients taking CGRP antibodies?  No medical monitoring or blood work is required for the new drugs.

7.How do the new CGRP drugs compare with older preventive drugs?  The older drugs used by neurologists for migraine prevention are:  Inderal (propranolol), Atenolol, topiramate, dialprovex, and amitriptyline and nortriptyline.  Inderal could drop the blood pressure and pulse and cause a “tired syndrome.”  Topiramate may cause start up symptoms of finger/lip tingling, a “Coke tastes flat” problem, and cognitive/word finding issues so that patients called the drug, “Dopamax.”  Amitriptyline, at low dose of 10-20 mg taken at night, could give a dry mouth, constipation, or weight gain.

These drugs have always had a lot of side effects and only reduced migraine 30-40, sometimes 50 % of the time.  Patients would start out strong and then by 3-4 months they would stop taking the drugs. Some of them using amitriptyline for sleep and migraine prevention would hang on to amitriptyline to treat insomnia.

All of these drugs had to be taken daily. In drug trials for the CGRP drugs 89 % of patients stayed on the subcutaneous, once a month treatment, while 40 % of patients taking one of the older drugs would be off treatment by 4 months. 

8.Are CGRP drugs safe for persons with hypertension, coronary artery disease, heart attack, stroke, or TIA problems?  Yes, the new CGRP drugs are safe for the listed problems.  Triptans, the best drugs for acute therapy for migraine are contraindicated for these problems, but CGRP antibodies are safe. 

9.How long does it take the body to metabolize these CGRP drugs?  The half-life of Aimovig is 28 days, Emgality-28 days, and Ajovy-31 days.                                                 

10.What is the expense/insurance coverage of these drugs?  I tell patients that I struggle and work hard to learn neurology and headache, but I don’t do insurance, which is a very complicated, multifaceted process.  

Aimovig was the first CGRP drug released and available in Dallas in July 2018.  They had a much more restricted group of insurances they accepted first, but then the other drugs quickly came out, Ajovy and then Emgality, and the insurance coverage situation improved.  There’s nothing like a free market and competition to prod insurance companies to change.

Aimovig in the U.S. costs $6,900 annually. Persons with insurance are being covered, while the non-insured and Medicare patients are not being covered. It usually takes 20 years for the patent on a brand name drug to expire and the drug to become generic.

11.What about use of the new CGRP antibody drugs for pregnancy or lactation?  There is no current indication for the use of CGRP antibody drugs during pregnancy or while breastfeeding.  The FDA statement regarding CGRP antibody drugs is: 

Pregnancy-caution is advised during pregnancy.  No human data is available, no known risk of fetal harm based on animal data at 20 times recommended human dose.

Lactation–caution is advised for breast-feeding.  No human data available to assess risk of infant harm or effects on milk production.

Good luck with this.

Britt Talley Daniel MD