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However, preventive therapy may also be given for less frequent but very disabling symptoms.
It is reasonable to consider a preventive medicine when:
Symptoms are interfering significantly with work, school or social life
Symptoms are occurring at least once a week
Although it is not officially endorsed, the use of a preventive medicine can be helpful to confirm a suspected diagnosis.
Since many migraine disorders are more chronic, treatment with preventive agents often offers the best relief to sufferers, but finding an agent that has tolerable side effects and is effective involves a trial and error process. It is usually most effective and safe to trial one medicine at a time, although some medications work well together in low doses.
These drugs were first used for many other medical purposes, such as prevention of high blood pressure, depression or epilepsy. These medicines act on the transmission of information in our nervous system and, at the low doses needed for preventing migraine, they usually have little or no other effects.
There are no firm rules on how any particular medication should be used. The Food and Drug Administration (FDA) has approved only four of these drugs for prevention of migraine: propanolol, timolol, divalproex sodium (Depakote) and topiramate (Topamax), but that does not mean that there has not been a great deal of research and success with a much larger number of migraine preventive drugs.
A beta blocker or calcium channel antagonist may be more appropriate for a patient with hypertension, while a tricyclic antidepressant may benefit a migraine patient who is depressed or having difficulty sleeping.
These medicines should be started at a low dose to minimize side effects. The dose should be regularly increased in small amounts until an ideal dose is reached.
Many medicines need be taken for 4-12 weeks to know if it works or not. Discuss with your physician the option to discontinue any medication that causes an unpleasant side effect.
Migraine preventative treatments often do not completely prevent all migraine symptoms, but they aim to reduce the frequency and severity of symptoms.
You need to discuss with your health professional issues about pregnancy, weight, sleep disturbances, blood pressure and more.
If a preventive treatment works well, that medication can then be continued for several months (usually 6-12 months). With better symptom control one may want to wean down the dose. When stopping a preventive medicine, there is a risk of the headaches returning. It is unusual for migraine frequency suddenly to bounce back again during weaning down. Migraine illness varies during a lifetime and the use of preventive medication may have to be adjusting for those variations.
This information is NOT intended to endorse drugs or recommend therapy. While these reviews might be helpful, they are not a substitute for the expertise, skill, knowledge and judgment of healthcare practitioners in patient care. Only your doctor can decide which medications are right for you. Never stop, start or change the way you use a prescription medicine without first consulting your doctor.
Calcitonin gene-related peptide, or CGRP, is a neurotransmitter found in both the peripheral and central nervous systems. It has been shown to be released during a migraine attack. It carries pain signals to the brain, particularly of the trigeminal nervous system. It also causes blood vessel to swell increasing the blood in the brain during an attack. CGRP also triggers inflammation throughout the brain.
Blocking the activity of CGRP has been shown to effectively suppress or interrupt migraine symptoms in at least 60% of patients in large clinical studies.
The CGRP blockers equal the efficacy of triptans but without the risks of vasoconstriction or other side effects.
They are a medicine that harnesses a natural function of our immune system. Our bodies manufacture different antibodies to identify and attach to very specific molecules on the surface of foreign bodies or certain cell membranes. Monoclonal means that scientists have been able to create many exact duplicates of the same antibody. Currently, there are four pharmaceutical companies that have manufactured four distinct monoclonal antibodies. Each targets either the neurotransmitter CGRP or the CGRP receptor on the nerve cell that transmits the pain signal to the brain.
Monoclonal antibodies go to work quickly and most people gain some relief within days of taking the medicine. It takes about 30 days for half of the monoclonal antibodies to become inactive.
Monoclonal antibodies are large molecules and they are too big to enter into the brain.
They have all been studied successfully for people with both episodic and chronic migraine. It works for all migraine types, including medication overuse headache. Patients should be 18 years or older.
This new class of medication must be injected either subcutaneously or intravenously. After an initial administration under supervision and in the safety of a medical facility, patients can use the autoinjector at home. The antibodies can be injected subcutaneously in an arm, leg or the abdomen.
The most important features of monoclonal antibodies are that they are not associated with any drug interactions, allergic reactions, carcinogenesis or genetic interference and have minimal side effects.
The injection is relatively painless but there can be some burning. Constipation is one of the most common complaints. A stool softener may be helpful.
Monoclonal antibodies do cross the placenta and appear in breast milk.
It is not yet clear of what long-term effects of blocking CGRP in a developing fetus or child might be. Therefore, the current recommendation is that if a woman is planning a pregnancy, she stop monoclonal injections for 6 months.
If a woman has a pregnancy while taking this medication, the FDA has a pregnancy registry that will help to collect information about the risk of this medicine.
There are no known drug interactions. Patients who use monoclonal antibodies do not have to stop taking any of their current medications, including migraine interventional and preventive medications or other treatments.
The four different monoclonal antibodies, erenumab, galcanezumab, fremanezumab and eptinezumab are in various stages of FDA approval and availability.
There are some minor differences. Erenumab uses a replicated human antibody while the other three antibodies are partially a mouse antibody but it is not clear that this will make any difference in how our bodies react to these drugs. Erenumab also is the only monoclonal antibody that attaches and blocks the CGRP receptor, or docking station. The other three attach to the CGRP protein itself.
Eptinezumab is the only one that is injected intravenously. A single intravenous dose of eptinezumab is given every 3 months.
When given to prevent chronic migraine, erenumab resulted in an average of a 6.7 days reduction in monthly migraine days compared to where people started from, which would represent 79 fewer migraine days per year
Treatment with either 120 or 240 mg of galcanezumab significantly reduced monthly migraine headache days by 4.7 days compared with placebo (2.8 days). Since not everyone responds to monoclonal antibodies, for one out of three patients, galcanezumab (as well as eptinezumab) reduced monthly migraine days by at least 75%.
The reduction in the average number of headache days per month was 4.3 with fremanezumab quarterly vs. 2.5 with placebo. The percentage of patients with a reduction of at least 50% in the average number of headache days per month was 38% in the fremanezumab-quarterly group, 41% in the fremanezumab-monthly group, and 18% in the placebo group.
Almost 30% of patients receiving a 300 mg dose of the antibody had a 75% reduction in monthly migraine days from their baseline level of 8.6 days per month, compared to 16% of the placebo group.
It is good to know that the calculation of headache day reduction is an average of all study participants. Individual responses vary significantly. Some 10-15% of users have complete resolution of their headaches, while the majority had a 50% or more reduction in headaches but for others there was a mild or no therapeutic response. Nonetheless, these positive results were consistently better than placebo.
Its cost is $575 per month, or $6,900 annually, less than botulinum toxin.
It is available to people with commercial insurance for any type of migraine. Your physician can write a prescription and provide information about different programs that will make the medicine available at your pharmacy with a copay of $0 or $5. Currently, Medicare does not cover erenumab; they are supposed to decide on coverage by November 17, 2018. Medicaid does not cover erenumab; no indication on when they will decide on coverage
This monthly auto-injector costs $575 per month.
There is a program offering people 12 months of this medication free of charge.
This beta-adrenergic blocking drug may suppress the central catecholaminergic system by inhibiting norepinephrine release, reducing neuronal activity and excitability, stabilizing cell membranes and inhibiting nitric oxide production. Altogether the effects make the brain less reactive.
Low blood pressure (dizziness and lightheadedness, cold fingers and feet)
Sexual dysfunction (decreased libido and function)
Worsen asthma (limits use in young adults)
Vivid dreams and nightmares
It is extremely important not to stop the drug abruptly. Lower dose when combined with Rizatriptan (Maxalt). Some evidence suggests that people with migraines who have had a stroke should avoid beta-blockers.
Although not FDA-approved for migraine, several different agents including: Verapamil, Flunarizine (not available in the United States), Nimodipine, Nifedipine, Cyclandelate, and Nicardipine.
Calcium-channel blockers most likely act by suppressing nitric oxide. The drug decreases calcium influx, resulting in decreased activity of neural nitric oxide synthase and lower production of nitric oxide. Calcium-channel blockers can also suppress the neurovascular inflammation by inhibiting the release of vasoactive neuropeptide release and suppressing trigeminal nerve activation.
A current strategy in migraine prevention is the suppression of cortical spreading depression. Animal models show that prolonged treatment with Topiramate or Amitriptyline, as well as Beta-blockers, Valproate, or Methysergide, reduced the number of cortical spreading depressions.
For more detailed information on Verapamil’s mechanism of action see drugfx.com.
The most common side effects are related to reducing the pumping mechanism of the heart:
Low blood pressure
Atrioventricular (AV) block
Change in heart rate
Shortness of breath
Increased levels in liver enzymes
Flushing and fluid in the lungs
Avoid Verapamil if they have severe heart abnormalities, low blood pressure, poor heart function, certain heart rhythm problems, certain types of blockages in the heart called second or third degree Atrioventricular (AV) block, rapid heart rate or any allergic reaction to Verapamil.
Anti-seizure drug appear to control migraine symptoms by targeting one or more sites in the brain - altering transmission of neurologic electrical signals through their effects on ion channels, neurotransmitter receptors, and neurotransmitter metabolism. Not all anti-epileptics have equal effectiveness.
Divalproex sodium (Depakote)
Valproic acid (Depakene)/sodium valproate (Epilim)
Tingling in the hands or feet is common but will pass with continued use of Topiramate
Change in taste, particularly with carbonated drinks
Nausea, vomiting, diarrhea, cramps
Fatigue and sleepiness
Topiramate can reduce the efficacy of the contraceptive pill
Interference with mental function (highly dependent upon how quickly the dose is increased and is relatively uncommon among patients started at a low dose and advanced slowly.)
Stop use if slowing your activity or excess fatigue.
Weight loss (Topiramate): Some patients lose weight, as high as 15-20% of their body weight in his practice, and other patients do not lose any weight. Patients tend to come to a new weight and stabilize there. Higher doses generally result in more weight loss.
Valproate and Divalproex can cause serious side effects of inflammation of the pancreas (pancreatitis) and damage to the liver. Monitor liver function and platelets.
Studies show that migraine sufferers have lower brain and blood levels of micronutrients (riboflavin, magnesium and coenzyme Q10) than nonmigraineurs (Hershey, 1999; Hershey, 2007; Mauskop, 1998).
A deficit of these nutrients could play a role in how well nerves can function. The common effect of these micronutrients on mitochondrial dysfunction may explain why they are ineffective for some people who likely do not suffer from this etiology of their migraine disease and only partially reduce symptoms in other people in this complex disease.
Magnesium - Needed in various biological processes that occur with migraine (vasoconstriction, platelet inhibition, secretion of serotonin). Magnesium is also needed as a co-factor for proper functioning of the ATP-synthase, which produces ATP. Furthermore, magnesium is the physiological antagonist at the NMDA-channel which is involved in the regulation of neuronal excitability.
Riboflavin - A precursor for flavin-mononucleotide (FMN) and flavin-adenine-dinucleotide (FAD). Both are essential components of complex I and complex II responsible for electron-transport in the mitochondrial membrane. Like CoQ10, it also works as an antioxidant by mopping up the damaging free radicals.
Memantine - May reduce migraine symptoms by blocking a glutamate receptor in the brain (glutamate N-methyl-D-aspartate receptor antagonist). Like serotonin, glutamate is a chemical that helps to send messages between nerve cells.
Melatonin - Linked to a variety of mechanisms related to the pathophysiology of headaches such as its anti-inflammatory effects, toxic free radical scavenging, reduction of pro-inflammatory cytokine up-regulation, inhibition of nitric oxide synthase activity and dopamine release, GABA and opioid analgesia potentiation, glutamate neurotoxicity protection, neurovascular regulation, and serotonin modulation. Melatonin’s chemical structure is also very similar to indomethacin, a common NSAID. (Peres, 2005)
Coenzyme Q10 - A vitamin-like compound that can be synthesized by the body from phenylalanine and tyrosine. Coenzyme Q10 is needed for all cellular processes requiring energy. Coenzyme Q10 is an electron-carrier, transferring electrons from complex I/complex II to cytochrome C.
Feverfew - A study of 17 migraine patients, those on feverfew had half as many headaches. (Johnson, 1985) In a second study of 72 patients those who took feverfew had a 24% reduction in the mean number and severity of attacks although the duration of the individual attacks was unaltered. (Murphy, 1988)
Butterbur (Petasites hybridus) 50 or 75 mg - This herbal remedy has been used for migraine and other uses for centuries. More recently, two studies (Diener, 2004; Lipton, 2002) demonstrated efficiency and safety of butterbur in adults. Another study (Lipton, 2004) showed that patients who used 75 mg butterbur twice daily for 4 months enjoyed 58% migraine attack reduction versus 28% in placebo group.
Risk of side effect increases with higher doses. If any of these symptoms were to occur, a lower dose may still be well tolerated and effective.
Diarrhea (remember Milk of Magnesium)
Risk of side effect increases with higher doses. If any of these symptoms were to occur, a lower dose may still be well tolerated and effective.
Diarrhea (remember Milk of Magnesium)
Minimal because the absorption of oral riboflavin is limited. At high doses it will produce:
A harmless yellow discoloration of urine
Excess melatonin can cause
Short-term feelings of depression
Hypothermia (reduced body temperature)
Stimulate overproduction of the hormone prolactin, which can cause hormonal problems and even kidney and liver issues in men
Nausea and/or vomiting
Heartburn and stomach pain
Loss of appetite
Itching or rash
Increased heart rate
Mouth sores when chewing fresh feverfew leaves
The butterbur plant also contains liver-toxic pyrrolizidine alkaloids and potential cancer causing chemicals, which are removed by a special patented treatment and only marketed under the name Petadolex®. No part of the Petasites plant should be ingested other than the commercial products. The United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA) announced in 2012 that Butterbur products are linked with liver toxicity and should be removed from the market.
Studies have reported safety and good tolerability of commercially available butterbur products that are free of potentially carcinogenic pyrrolizidine alkaloid constituents, when used short-term, orally and in recommended doses.
Four major types of antidepressants are available:
Tricyclic antidepressants (TCAs)
Selective serotonin re-uptake inhibitors (SSRIs)
Monoamine oxidase inhibitors (MAOIs)
Serotonin norepinephrine re-uptake inhibitors (SNRIs)
All have been used for prevention of migraine, although they occasionally cause headaches to worsen. They are useful in patients with co-existing depression, anxiety, tension-type headache or primary stabbing headache. The most commonly used antidepressants are TCAs and SSRIs.
Amitriptyline inhibits the uptake of both norepinephrine and serotonin (5-HT), allowing them to be more effective. Amitriptyline may inhibit the formation of sodium channels within neurons, enhance GABA’s suppression of migraines, potentiate endogenous opioids, and inhibit the transmission of pain signals in the midbrain (the descending monoamine system). Serotonin receptors are found throughout the vestibular and cochlear cells of the inner ear, as well as the trigeminal system.
Possible side effects
Weight gain (affects 20% of users and those who have weight gain, add only 7 pounds on average)
Dry mouth or eyes
Sleepiness (People who sleep poorly often benefit from these medicines)
These medicines are also antidepressants, but they can act as pain relievers. Not usually as effective as amitriptyline or nortriptyline. There is very limited evidence to support the use of SNRIs in migraine.
Antidepressants take 3-10 days to be effective. Taper off this medication after 6 months.
Slight increase in BP slightly
Problems with vision
Worse head pain
Drowsiness, dizziness, feeling nervous
Changes in appetite or weight
Mild nausea, constipation
Decreased sex drive, impotence, or difficulty having an orgasm
The Sphenopalatine Ganglion (SPG) is a group of nerve cells located just beneath the mucosa high in the nasal cavity, above the deep tail of the middle turbinate. It carries pain and pressure signals from the nose, sinuses and face. It also is linked to the autonomic nervous system that produces a runny, stuffy nose.
One of the most common blocking techniques involves applying or injecting an anesthetic (a numbing medicine) in the SPG. Lidocaine and the longer lasting Marcaine (bupivacaine) are the two commonly used anesthetics. The use of Marcaine by topical administration is outside the FDA approved routes of administration at this time. There are different techniques for delivering the anesthetics.
Application of numbing medicine on cotton swabs in the nose
Application of numbing medicine via catheters (thin plastic tubes) into the nose. Three devices have been FDA approved for performing SPG blocks: Sphenocath®, Allevio®, and Tx360®. They are claimed to be more effective than cotton swabs but do not require any needles.
Injection the SPG through an area in the cheek or mouth. Some specialists use an x-ray machine to correctly place the injection.
Repeated use of an anesthetic nasal spray. Example, a compounding pharmacy can mix a 2% lidocaine spray.
A burning sensation or numbness in the nose or in and around the eyes
Numbness in the throat (This can be a strange change in sensation that makes it feel as if you are gagging but it will return to normal in 1-2 hours). Avoid eating and drinking until your throat feels normal again since you do not want food or drink to mistakenly go into your lungs and cause an infection.
Drop in blood pressure
Allergic reaction to Marcaine and other local anesthetic agents
Repeated anesthetic application to the nasal mucosa may hurt that tissue. It is not yet clear how to many SPG blocks is too much
Botulinum toxin type A is a neurotoxin that causes a temporary cessation of nerve activity. It lasts 2-4 months. FDA-approved for prevention of chronic migraine only.
The appropriate use for botulinum toxin type A is a person with chronic migraine headache symptoms (more than 15 headache days per month of which at least 8 are migrainous, for more than 3 months) and there has been adequate management of medication overuse.
It is recommended that a chronic migraineur try at least three migraine preventative medicines at effective dosages for 6 weeks or more.
Discomfort at injection site: 12%
Temple hollowing: 23%
Neck weakness: 27%
Eyelid droop: 10%
Erythema and/or bleeding at injection site
Infection at an injection site
Rare hypersensitivity reactions include anaphylaxis, urticaria, soft-tissue edema, and dyspnea
Rare reports of adverse events involving the cardiovascular system
Chiropractic, physical therapy and massage are all modalities that have been shown to have similar effectiveness in controlling the intensity of pain for migraineurs (Chaihi, 2011). Studies have shown that they might be comparable to the effectiveness of some preventive medications, but often the studies are not of the most rigorous quality. They may be most effective when combined with other therapies.
Examples of external manipulations are:
Cefaly is a headband designed to deliver electrical impulses to nerves that transmit migraine pain and thereby theoretically suppress this trigger mechanism. In 2014 the device became the first transcutaneous electrical nerve stimulation (TENS) system to win FDA approval for migraine prevention.
The device consists of a battery-operated electrical pulse generator and a self-adhesive electrode. The patient applies the electrode to the middle of the forehead and lowers a headband containing the electrical pulse generator over the forehead to engage a pin located on the electrode. Pressing a button on the band generates a pulsed electric current that stimulates the upper branches of the trigeminal nerve.
Peripheral nerve stimulation (PNS) of the occipital nerves is a potentially promising therapy for chronic migraine patients. The concept is to implant a neurostimulator near the occipital nerves, near the back of the neck.
Recently Plastic surgeons have advertised nerve decompression surgery as an innovative new treatment of migraine headaches.
The Surgical Migraine Procedure is the removal of the corrugator muscles (small muscles associated with the eyebrows). They are responsible for the frown lines above the nose. The theory is that with the removal of the muscles, there is a reduction of migraine-generating electrical signals to the brain along the trigeminal nerve. Muscles in the temples, inside the nose, and back of the neck can also be removed for the same reason.
This procedure may not be effective for all migraine sufferers and each patient should undergo a botulinum toxin (Botox) test. Only those who have a 50% reduction of headaches with Botox should try migraine trigger point decompression.
The relationship between migraine and the symptoms of acute, recurring and chronic sinusitis has not yet been fully worked out, but there is a significant body of information to argue that our sensory nervous system can either enhance or closely simulate the symptoms of a sinus infection.
While it might seem to be an odd decision to operate on patients complaining of facial pressure and other sinus symptoms, but also meet the diagnostic criteria of chronic migraine disease, a study of 229 patients with medically refractory chronic rhinosinusitis were evaluated at 6,12 and 18 months after sinus surgery with quality-of-life questionnaires. All patients with and without migraine had a statistically similar QOL improvement.