Archive
Headache Drugs

Botox is the most effective and the safest preventive treatment for migraine headaches. However, in a very small number of patients, Botox loses its effectiveness over time. This happens for two main reasons – the person develops antibodies as a defense mechanism to block the effect of Botox or headaches change in character and stop responding to Botox.

It is easy to tell these two reasons apart. If Botox fails to stop movement of the forehead muscles and the patient can frown and raise her eyebrows, it is most likely because of antibodies. On a very rare occasion this is due to a defective vial of Botox, so to confirm that antibodies have formed, we give a small test dose amount of Botox into the forehead. If again there is no paralysis, we know that antibodies have developed. This can happen after one or two treatments or after 10, but in my experience over the past 25 years, significantly fewer than 1% of patients develop this problem.

Fortunately, some patients who develop antibodies to Botox, known as type A toxin, may respond to a similar product Myobloc, which is a type B toxin. Myobloc is not approved by the FDA to treat chronic migraine headaches, but it has a similar mechanism of action and has been shown to relieve migraines in several studies. Injections of Myobloc can be a little more painful, it begins to work a little faster than Botox, but the effect may last for a slightly shorter period of time.

An even smaller number of patients have naturally occurring antibodies to Botox, which is most likely due to an exposure to botulinum toxin in food. I’ve encountered 4 or 5 such patients and a couple of them who did go on to try Myobloc, did not respond to it either.

When Botox stops working despite providing good muscle relaxing effect, it could be because the headaches have changed in character, severity or are being caused by a new problem. It could be due a sudden increase in stress level, lack of sleep, hormonal changes, drop in magnesium level due to a gastro-intestinal problem, or another new illness, such as thyroid disease, diabetes, multiple sclerosis, or increased pressure in the brain. Such patients need to be re-evaluated with a neurological examination, blood tests, and usually an MRI scan. One of my patients who was doing well on Botox for several years, did not have any relief from her last regular treatment. Since she had no obvious reasons why her migraines should stop responding to Botox, I ordered an MRI scan. Unfortunately, she turned out to have brain metastases from breast cancer which had not yet been diagnosed.

Read More

Caffeine and opioid (narcotic) drugs, if taken regularly, are proven to worsen headaches. This will not come as a surprise to anyone drinking large amounts of coffee – skipping your morning cup will leave you with a headache. Taking too much Excedrin, Fioricet, or Percocet will also make you want to take these drugs more and more often and with diminishing relief. However, most neurologists and headache specialists believe that triptans (sumatriptan, rizatriptan, et al.) and NSAIDs (naproxen, ibuprofen, et al.) can also cause “medication overuse headaches”. This remains a belief, rather than a scientific fact and it leads to thousands of headache sufferers being unfairly accused of causing or worsening their own headaches. They are being denied a safe and effective treatment that could relieve their suffering and reduce disability. My most popular blog post that so far has elicited 247 comments, is one on the daily use of triptans.

Drs. Ann Scher of Uniformed Services University, Paul Rizzoli and Elizabeth Loder of Brigham and Women’s Hospital have just published an article in a leading neurology journal, Neurology, entitled, Medication overuse headache. An entrenched idea in need of scrutiny. Last year I described a debate on this topic between Dr. Scher and Dr. Richard Lipton of the Montefiore Headache Clinic at the meeting of the American Headache Society. The abstract of this new article can be easily understood by the lay public, so I am including its full text.

“It is a widely accepted idea that medications taken to relieve acute headache pain can paradoxically worsen headache if used too often. This type of secondary headache is referred to as medication overuse headache (MOH); previously used terms include rebound headache and drug-induced headache. In the absence of consensus about the duration of use, amount, and type of medication needed to cause MOH, the default position is conservative. A common recommendation is to limit treatment to no more than 10 or 15 days per month (depending on medication type) to prevent headache frequency progression. Medication withdrawal is often recommended as a first step in treatment of patients with very frequent headaches. Existing evidence, however, does not provide a strong basis for such causal claims about the relationship between medication use and frequent headache. Observational studies linking treatment patterns with headache frequency are by their nature confounded by indication. Medication withdrawal studies have mostly been uncontrolled and often have high dropout rates. Evaluation of this evidence suggests that only a minority of patients required to limit the use of symptomatic medication may benefit from treatment limitation. Similarly, only a minority of patients deemed to be overusing medications may benefit from withdrawal. These findings raise serious questions about the value of withholding or withdrawing symptom-relieving medications from people with frequent headaches solely to prevent or treat MOH. The benefits of doing so are smaller, and the harms larger, than currently recognized. The concept of MOH should be viewed with more skepticism. Until the evidence is better, we should avoid dogmatism about the use of symptomatic medication. Frequent use of symptom-relieving headache medications should be viewed more neutrally, as an indicator of poorly controlled headaches, and not invariably a cause.”

Read More

Sumatriptan (Imitrex), rizatriptan (Maxalt) and the other 5 triptans work on serotonin receptors to stop a migraine attack. Many antidepressants, such as fluoxetine (Prozac), escitalopram (Lexapro), that belong to the SSRI family and venlafaxine (Effexor) and duloxetine (Cymbalta), that belong to the SNRI family of drugs also affect serotonin or its receptors. Because both triptans and antidepressants affect serotonin, it is understandable that there has been concern about the potential for serotonin-related side effects when these drugs are used together.

In 2006 the FDA released a warning, “Potentially Life-Threatening Serotonin Syndrome With Combined Use of SSRIs or SNRIs and Triptan Medications.” Fortunately, this is the case of “fake news”. My colleague in Houston, Dr. Randy Evans under the Freedom of Information Act, requested all the data that the FDA used to issue this warning. He published an article on his findings and concluded that “The data do not support prohibiting the use of triptans with SSRIs or SNRIs.”

A new study presented at the 59th Annual Scientific Meeting of the American Headache Society confirmed Dr. Evans’ conclusion. Dr. Yulia Orlova and her colleagues at the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital in Boston conducted a population-based study using information on more than 6.5 million patients. Over a 14-year period, about 19,000 were prescribed both triptans and SSRI or SNRI antidepressants. Between 4 and 7 patients (0.02% to 0.04%) developed serotonin syndrome.

In most cases serotonin syndrome is mild and consists of shivering, sweating, and diarrhea. Only very rarely it can be life-threatening with high body temperature, agitation, and seizures.

This is an important issue because migraine is 2-3 times more common in those suffering from depression and anxiety, while depression and anxiety are 2-3 times more common in people with migraines. This means that millions of people suffer from both conditions. Most experts agree that combining SSRIs and SNRIs with triptans is very safe.

A similar issue is the prohibition on mixing different triptans within 24 hours. There is not a slightest shred of clinical or scientific evidence for this contraindication. Nevertheless, the FDA-approved label has this warning for every triptan.

Read More

Sumatriptan (Imitrex) injection was introduced 25 years ago, but it remains extremely underutilized. Of course, why would you inject yourself if a pill does the job. Unfortunately, for many migraine sufferers sumatriptan and other triptan tablets do not provide complete or fast enough relief. In many patients tablets do not work well because some wake up with a severe migraine, in some it starts very suddenly, and in others it is accompanied by nausea and vomiting. All these conditions require a quickly acting drug that bypasses the stomach. Zolmitriptan (Zomig) and sumatriptan nasal sprays or sumatriptan nasal powder (Onzetra) sometimes work well and quickly enough, but the gold standard in the abortive treatment of migraines (and cluster headaches) is sumatriptan injection.

Sumatriptan injection works within 10-15 minutes and often provides complete relief of the headache and associated symptoms – nausea, sensitivity to light and noise, and other. Because of a sudden surge in the sumatriptan level in the blood, side effects are more common than with tablets. These can include pins-and-needles like sensations, tightness in the neck or chest, or temporary worsening of the headache. These side effects last only 15-20 minutes and do not prevent most patients from using injections.

Sumatriptan injections were originally released only in a 6 mg dose. A few years later, 4 mg dose became available. Last year, a simple-to-use autoinjector with 3 mg of sumatriptan (Zembrace) was approved by the FDA. Studies presented at the recent annual meeting of the American Headache Society in Boston compared the efficacy of 3 mg and 6 mg injections. Surprisingly, they were equally effective and well tolerated. The manufacturer of the 3 mg auto-injector also compared their injection device with two older devices. Findings of this study were not a surprise – Zembrace was easier to use with fewer mistakes and faster preparation and administration. Zembrace requires only two steps – pulling off a cap and pressing the pen-like device against the thigh (and holding it pressed for 10 seconds). Also, of all auto-injectors Zembrace has the thinnest needle.

One potential difficulty is the insurance coverage. Since Zembrace is more expensive, the insurers may offer to pay only for the old type devices with 4 or 6 mg of sumatriptan. The manufacturer does offer discounts and coupons, which you can find online.

The bottom line, if you are not getting good relief of your migraine headaches, ask your doctor about sumatriptan injections. If you have tried injections in the past and did not like the side effects – check if the dose you tried was 6 mg and if yes, you may want to try 3 or 4 mg injections.

Sumatriptan injection is the only FDA-approved treatment for cluster headaches. Cluster headaches are very sudden and brief attacks of excruciating headaches that pills rarely have a chance to control.

Conflict of interest disclosure: last year Zembrace manufacturer paid me to participate in an advisory board meeting.

Read More

Cluster headache is one of the most painful conditions that has lead some patients call it a suicide headache. A new observational study done by researchers at the Eli Lilly company and Stanford University was presented at the recent annual scientific meeting of the American Headache Society.

Considering that cluster headaches are relatively rare, the major strength of this study is its size – 7589 patients. These patients were compared to over 30,000 control subjects without headaches. We’ve always known that cluster headaches are more common in men with previous studies indicating that male to female ratio is between 5:1 and 3:1. However, only 57% of patients in this new report were males. This does not reflect my experience – I see at least five times as many men as women. It is possible that I underdiagnose cluster headaches in women or the study used unreliable data. In fact, the study data was collected from insurance claims, so I suspect that the truth is closer to my experience and to the older published data.

The study did find that thoughts of suicide were 2.5 times more common in patients with cluster headaches compared to controls, while depression, anxiety and sleep disorders were twice as common. Cluster headache patients also were 3 times more likely to have drug dependence. The most commonly prescribed drugs were opiates (narcotics) in 41%, which partially explains high drug dependence rates, steroids, such as prednisone (34%), triptans, such as sumatriptan (32%), antidepressants (31%), NSAIDs (29%), epilepsy drugs (28%), blood pressure drugs, such as verapamil (27%), and benzodiazepines, such as Valium or Xanax (22%).

It is very unfortunate that over a period of one year only 30% of patients were prescribed drugs recommended for cluster headaches. We know that narcotics and benzodiazepine tranquilizers are not very effective and can lead to dependence and addiction. Drugs that are effective include a short course of steroids (prednisone), sumatriptan injections, blood pressure drug verapamil (often at a high dose), some epilepsy drugs and occasionally certain antidepressants. The report did not mention oxygen, which can stop individual attacks in up to 60% of cluster headache sufferers. Nerve blocks and to a lesser extent, Botox injections can also provide lasting relief. It is possible that the data on oxygen, nerve blocks and Botox was not available.

Read More

Unfortunately, opioid hydromorphone (Dilaudid) is still administered to 25% of patients with an acute migraine visiting an ER. Benjamin Friedman and his colleagues at the Montefiore Medical Center in the Bronx compared the efficacy of 1 mg of intravenous hydromorphone with an intravenous nausea medicine, prochlorperazine (Compazine), 10 mg plus diphenhydramine (Benadryl), 25 mg.
They presented their findings last month at the annual meeting of the American Headache Society. The study was blinded, but a safety monitoring committee stopped it early because the results were so lopsided. Prochlorperazine with diphenhydramine was twice as effective (60%) as hydromorphone (31%) in stopping a migraine and in preventing it from coming back within 48 hours.
So, if you end up in an ER for your migraine, refuse hydromorphone (Dilaudid), meperidine (Demerol), or any other opioid (narcotic) medication. Here is my old post with drugs other than prochlorperazine that are also effective.

Read More

Searching on Amazon for books on migraines yields over 2,291 items. Do we need another book? Having just read the latest book on migraines, Understanding Your Migraines, the answer is a definite yes.

The book is written by two colleagues who for many years co-directed the Dartmouth Headache Clinic. Dr. Morris Levin is now the Director of the Headache Center and a Professor of Neurology at UCSF, while Dr. Thomas Ward is Professor of Neurology Emeritus at the Geiser School of Medicine at Dartmouth and the editor of the journal Headache. They are clearly highly qualified to write such a book, but qualifications are not enough – you need to be a good writer as well. And in fact, excellent writing style and case-based discussion are two of the major strengths of the book.

The book consists of 17 chapters, which cover diagnosis and our understanding of the underlying causes of this condition. What the readers will find most useful is the treatment approaches. Drs. Levin and Ward go into great detail about various non-drug options, including nutrition, exercise, meditation, acupressure, herbal products, vitamins and minerals. They also present pros and cons of various medications, nerve blocks and describe in detail the most effective and the safest preventive treatment for chronic migraines, Botox injections.

One chapter is devoted to specifics of migraines in pregnancy and another one to children and adolescents. The book also includes individual chapters on tension-type headaches, cluster and other less common headache types, and postconcussion headaches.

The authors also mention an exciting new treatment option, which we expect to be approved by the end of 2018. Four companies are racing to bring to the market CGRP monoclonal antibodies, which act like vaccines against migraines. A single injection will provide 1 to 3 months of relief with very few side effects. It is likely that this treatment will help about 60% of patients with both episodic and chronic migraines. Cluster headache patients might also benefit from these biologic drugs.

Reading so much information can make it difficult to understand how to actually use it and how to talk to your doctor about all these options. The authors successfully tackle this problem by providing many real-life cases and by including a chapter, How to Communicate with Your Medical Team.

I am sure that this book will help many migraine sufferers find relief. You can buy it on Amazon.

Read More

Beta-blocker propranolol (Inderal) was first approved over 50 years ago for the treatment of hypertension and 10 years later became the first drug to be approved for the prevention of migraine headaches. Beta-blockers that followed, including atenolol, timolol, nebivolol, and other, also work for the prevention of migraines. Beta-blockers are also used to treat benign essential or familial tremor, performance anxiety, and other disorders.

A study recently published in Arthritis Care and Research suggests that beta-blockers also reduce arthritis pain. The researchers evaluated 873 patients who suffered from painful osteoarthritis of the hip and/or knee as well as hypertension and who were taking at least one anti-hypertensive medication. Their analysis took into account age, gender, body mass index (BMI), knee or hip osteoarthritis, history of joint replacement, anxiety and depression. The result of this sophisticated analysis showed that patients who were taking beta-blockers had less pain than patients taking other anti-hypertensive medications. Patients taking beta-blockers were also found to be taking less of opioid (narcotic) and other prescription pain medications.

This type of study shows a correlation between the use of certain medications and pain, however to prove that beta-blockers are indeed effective for the pain of osteoarthritis or any other type of pain, we need prospective blinded studies. Until we have those kind of studies, which often take years to complete, it seems prudent to consider using beta-blockers as first-line drugs for the prevention of migraines in patients who also suffer from arthritis pain.

Read More

Generic drugs should be cheap, but you still may be overpaying for them. I mentioned this problem in a previous post, but it bears repeating – your copay could be higher than an out-of-pocket price for some generic drugs. For example, 9 tablets of generic sumatriptan 100 mg can be purchased from a mail order pharmacy such as HealthWearhouse.com or a local pharmacy you can find on GoodRx.com for about $20. Your copay through your insurance plan could be $25 or much higher. Read more about this in a Bloomberg.com story.

Read More

Beta blockers, such as propranolol (Inderal) and timolol (Blocadren) are the oldest drugs for the prevention of migraine headaches. They’ve been used for this indication for the past 50 years. Calcium channel blockers are not as effective and never received FDA approval, but are also used treat migraine headaches. Verapamil is more effective for the prevention of cluster headaches, but is not approved for this indication either. A third category of blood pressure drugs effective for the prevention of migraines are ACE receptor blockers (ARBs) such as candesartan (Atacand) and olmesartan (Benicar) and ACE inhibitors such as losartan (Cozaar).

Main side effects of these drugs tend to be related to lowering of blood pressure and include fatigue and dizziness. This is a major limitation of blood pressure medications when used in migraine sufferers because they tend to be young women with low blood pressure to begin with. Verapamil is also known to cause constipation.

Beta blockers and to a lesser extent calcium channel blockers, have long been reported to cause depression. A new study just published
in the journal Hypertension explored the association between blood pressure drugs and admission to to the hospital for mood disorders (depression and bipolar). The researchers examined a large hospital database of 525,046 patients with follow-up for 5 years. Patients on ACE inhibitors or ARBs had the lowest risk for mood disorder admissions, and compared with this group, those on beta blockers and calcium channel blockers showed higher risk, whereas those on no blood pressure medications and those on diuretics showed no significant difference. The authors concluded that calcium channel blockers and beta blockers may be associated with increased risk of admission for mood disorders, while ACE inhibitors and ARBs blockers may be associated with a decreased risk of mood disorders.

Migraine sufferers are at 2-3 higher risk of mood disorders even if they are not on blood pressure medications and we often see depression and anxiety in many of our patients. This study makes a strong argument for the use of ACE inhibitors and ARBs ahead of other blood pressure medications. Another advantage of these drugs is that they do not slow down the heart rate, which is the case with beta blockers. Slowing of the heart rate often interferes with the ability to exercise and exercise is probably the most effective preventive treatment for migraine headaches.

I should also mention that epilepsy drugs such as topiramate (Topamax) can also cause depression, even with suicidal thoughts. Besides blood pressure and epilepsy drugs, antidepressants is another category of drugs used for the prevention of migraines, but even these medications can sometimes cause or worsen depression. All drugs have other side effects as well and this is why we always advise starting with sleep hygiene, healthy diet, aerobic exercise, meditation, magnesium, and other supplements.

Read More

About 6% of young children suffer from migraine headaches. After puberty, this number triples to 18% in girls and remains at 6% in boys. Several abortive drugs (drugs taken as needed), such as rizatriptan (Maxalt) and zolmitriptan (Zomig) are approved for migraines in children. Only topiramate (Topamax) is approved for children (over the age of 12) for the prevention of migraines. We do use preventive drugs approved for adults in children as well. These are divalproex sodium (Depakote), propranolol (Inderal), and botulinum toxin (Botox). Many other drugs, such as amitriptyline (Elavil), gabapentin (Neurontin), candesartan (Atacand) are used “off label”, meaning that they are not FDA-approved for migraines in adults or children. One of the reasons that more drugs are not approved specifically for children is the difficulty in conducting research in kids. Their are migraines are usually shorter in duration and often stop occurring for long periods of time without treatment.

A large multi-center 24-week study just published in the New England Journal of Medicine examined the efficacy of topiramate, amitriptyline and placebo in children between the ages of 8 and 17. It was a double-blind study with neither the children and their parents nor the doctors being aware of who was getting which drug or placebo. The study showed no statistically significant difference among the three groups. The main outcome measure was a 50% or higher reduction of headache days. Placebo achieved this result in 61% of children, while this number was 52% for those on amitriptyline and 55% on topiramate. Not surprisingly, side effects were much more common in children taking medications than placebo. Fatigue and dry mouth were the most common side effects from amitriptyline, while topiramate caused mostly tingling and weight loss. Serious side effects occurred in four – three kids on amitriptyline had a serious mood disorder and one on topiramate attempted suicide.

This study did not prove that amitriptyline and topiramate are ineffective since they did help half of the children they were given to, however the placebo worked at least as well. These findings are not surprising since placebo has a powerful effect, which is often more pronounced in children and because children’s migraines often stop on their own. Even in adults, placebo effect has often made clinical trials, particularly in migraines, very difficult. It took a couple of attempts to prove that Botox prevents migraines better than placebo, again not because Botox was ineffective, but because placebo also worked well.

The initial approach to treating migraines in children and adults should always involve looking for modifiable triggers, such as sleep schedule, regular meals with healthy food, elimination of caffeine and sugar, regular exercise, sleep hygiene, meditation or biofeedback, and so on. Our second step is trying supplements such as magnesium (which sometimes is given intravenously because of poor absorption of pills) and CoQ10, which have been proven to be effective both in children and adults. Other, less proven supplements, such as riboflavin, feverfew, and boswellia are also worth trying before starting a daily preventive medication. At the same time, since migraine often causes severe pain, we often prescribe abortive migraine medications, such as sumatriptan or rizatriptan, which are often more effective than ibuprofen and acetaminophen.

It is considered unethical for doctors to prescribe placebo, although we do sometimes prescribe very mild drugs in a small dose (cyproheptadine is one such drug), which is almost the same as prescribing a placebo.

An interesting study of placebo in patients with low back pain was just published in the journal Pain . One group was given the usual treatment and the other received the usual treatment as well as a placebo pill, but they were told that they are being given a placebo. The group that knowingly took placebo had a significant reduction in pain and disability. After three weeks of this trial, the first group was also given a placebo pill and they also had a significant drop in pain and disability. It is possible that the effect is just due to the act of taking a pill, which subconsciously sends a message to the brain that something is being done to fix the problem.

Read More

Medical marijuana was legalized in New York in February of this year. Since then, I’ve prescribed it to over 30 patients and about a third of them have found it to be effective. We are planning an observational study to determine which of the three approved types (inhaled, sublingual, oral) and what ratio of active ingredients (THC/CBD) are preferred by migraine sufferers. Doctors who prescribe medical marijuana do have to take an online training course, but the course does not teach about the optimal use because no one has researched this question. There are also regulatory issues to deal with.

Several sets of guidelines have been published by various medical organizations addressing the proper use of medical marijuana, other than dosing and route of administration. Here are some of the recommendations with my comments:

“The doctor should adhere to current standards of practice and comply with state laws, rules and regulations, which may specify conditions for which a patient may quality.”
Migraine is not one of the conditions listed specifically, but it is often accompanied by neuropathic pain, which is listed.

“The doctor’s office should not be located at a marijuana dispensary or cultivation center. The doctor should not receive financial compensation from or hold a financial interest in marijuana-related businesses or be affiliated with them in any way.”
This one is easy for us.

“The physician should not use marijuana either medicinally or recreationally while actively engaged in the practice of medicine.”
I’ve never tried it.

“There should be an established doctor-patient relationship before the doctor considers the use of medical marijuana.”
I prescribe it only to our established patients.

“The doctor should do a physical exam and gather health history, including documentation of previous therapies used by the patient and information on any personal or family history of substance abuse, mental illness or psychotic disorders. The diagnosis should justify the consideration of medical marijuana.”
All of our patients undergo a thorough evaluation.

“The doctor should review other treatment options. The known benefits and risks of marijuana should be presented, along with the warning that, unlike with FDA-approved drugs, there is variability and lack of standardization in marijuana preparation.”
We use medical marijuana only after other non-drug and drug treatments fail.

“If the medical marijuana is chosen, a specific treatment plan for a limited period of time should be agreed on, with details documented in the medical record. The doctor should instruct the patient not to drive or operate heavy machinery while using marijuana.”
Yes, I do that.

“The patient should be seen for follow-up visits to monitor for efficacy and side effects of medical marijuana.”
This is a standard practice with any treatment.

“Patients with a history of mental health problems, substance abuse or addiction should be referred for further evaluation as needed.”
I typically avoid prescribing medical marijuana to such patients.

Read More

Nausea is a very common symptom that accompanies migraine attacks. Effective treatment of migraine with a drug like sumatriptan often stops the headache, nausea, and other associated symptoms. However, sometimes pain subsides, while nausea does not, or nausea is much more bothersome than the headache. Nausea can also be a side effect of the most effective injectable migraine drug, dihydroergotamine (DHE-45). We often administer this drug in our office after other injectable drugs (magnesium, sumatriptan, ketorolac, dexamethasone, etc) fail. If nausea is already present, we will always give an intravenous injection of a nausea drug such as ondansetron (Zofran) or metoclopramide (Reglan) before giving DHE. Sometimes these drugs are ineffective in preventing nausea and vomiting induced by DHE and we have to look for other options.

Phenothiazine family of drugs, including prochlorperazine (Compazine), chlorpromazine (Thorazine), and promethazine (Phenergan) are very old and effective anti-nausea drugs. However, they have a potential for a rare but devastating side effect, which consists of persistent involuntary movements of the face (grimacing and lip smacking) and body. The onset of this side effect can be delayed, which is why it is called tardive dyskinesia. It is not unusual for these drugs to cause an immediate severe and very unpleasant restlessness (akathisia), which patients sometimes describe as wanting to crawl out of one’s skin. Metoclopramide (Reglan) can also cause these side effects, but less often.

Ondansetron (Zofran) does not cause any such side effects and should be the preferred drug for nausea of migraine, although it is only approved for nausea caused by chemotherapy or radiation and for post-surgical nausea. Since it has become generic and inexpensive, it can be used for other causes of nausea, including migraines. It is available as an injection or as a tablet.

Aprepitant (Emend) is an anti-nausea drug that has a totally different mechanism of action than the medications described above, so it is possible that it can help when other drugs do not or when other drugs cause side effects.

A study just published in Neurology by Dr. Denise Chou and her colleagues describes the use of oral aprepitant in the treatment of DHE-induced nausea in hospitalized patients.

The authors reviewed hourly diary data and clinical notes of patients admitted to the hospital for the treatment of refractory migraine headaches (status migrainosus) with DHE infusions between 2011 and 2015.

They identified 74 such patients, of whom 24 had daily diaries. In 36 of 57 cases in which aprepitant was given, there was a 50% reduction in the number of other anti-nausea medications given to patients. Of 57 patients, 52 reported that the addition of aprepitant improved nausea. Among 21 of 24 patients with hourly diary data, nausea scores were reduced. In all 12 patients with vomiting aprepitant stopped it. Aprepitant was well tolerated and caused no side effects.

The authors concluded that aprepitant can be effective in the treatment of refractory DHE-induced nausea and vomiting. They also suggested that perhaps this drug could be used for nausea of migraine even when DHE is not given. The only problem, and it is a very big problem, is the cost. This drug is not going to be available in a generic form until 2018. A single capsule of Emend costs $105 with a coupon you can get on GoodRx.com. Without a coupon, it is $145. A single vial for injection costs $345, so we are not going to use this drug for nausea due to migraine or DHE for at least two years, when cheaper generic copies become available.

Read More

CGRP migraine drugs remain on track to get an approval from the FDA within two years. My first post on these drugs appeared in 2007. The first product in this family was tested for the prevention and acute treatment of migraines. It reached the final phase 3 trials and was found to be very effective and safe, but a few patients developed minor liver abnormalities on blood tests. In view of these blood test abnormalities, the manufacturer, Merck decided against completing the trials. A similar medicine, also in a tablet form, is now being developed by Allergan (maker of Botox) and it appears to be free of liver problems.

CGRP (calcitonin gene-related peptide) is a chemical that is released in the brain during a migraine attack. Four companies are targeting the CGRP molecule in a different way. Instead of taking a pill during an attack or daily to prevent migraines, they are developing monoclonal antibodies which bind to the CGRP molecule or its receptor and block its action. These drugs are given by injection. Three of the companies, Amgen, Eli Lily, and Teva are testing intramuscular injection every month, while the fourth one, Alder is testing intravenous administration every three months. Eli Lily is also testing their compound for the treatment of episodic cluster headaches.

To date, there have been several thousand patients exposed to these monoclonal antibodies in clinical trials. What is most surprising to me is their outstanding safety. The side effects have been infrequent and mild. All four companies are conducting large-scale phase 3 trials, which will hopefully confirm their safety. Based on the previous studies, there is little doubt that these studies will show that the drugs are highly effective in preventing migraines. Unfortunately, it will be at least two years before these truly innovative medications become available.

While I am very excited about getting a new and a very different treatment for migraine and cluster headache sufferers, my enthusiasm is tempered by the potential cost of these drugs. Business experts project the cost to be between $12,000 and $18,000 a year. By comparison, the $6,000 yearly cost of Botox injections seems cheap. Only about 100,000 out of several million chronic migraine sufferers have been treated with Botox since it was approved for migraines 6 years ago. This is in large part due to the difficulties in getting approval from the insurance companies. Besides extensive paper work from the doctor, they require that the patient first try and fail two or three preventive drugs. The new CGRP drugs are likely to be the last option in this chain and will require even more paperwork. The result is likely to be a great underutilization of these breakthrough drugs, just as it has been happening with Botox.

I am not suggesting that these drugs should be cheap since literally billions of dollars will have been spent by the time these drugs receive approval. If the companies cannot make a profit, the investment in research will dry up and fewer breakthrough drugs will be developed. This is why most new treatments are developed in the US and not Europe, where drug costs are controlled by the government. Hopefully, in a few years the cost will drop as it has happened with another family of highly effective migraine drugs, the triptans.

Read More

Tremor of the hands is usually a benign condition. It is even called, benign essential tremor or, if it runs in the family, benign familial tremor. Patients with tremor are twice as likely to have migraines, so this is why I am writing about it. Tremor is also a symptom of Parkinson’s disease, but these two types of tremor can be easily differentiated. Parkinsonian tremor is a resting tremor, which means that hands shake at rest, while essential tremor occurs in action, like when trying to drink from a cup.

Even though it is benign, essential tremor can be incapacitating and socially embarrassing. Fortunately, in most people it responds to treatment. We usually start with propranolol (Inderal), a drug that belongs to the beta-blocker family, which is used for the treatment of high blood pressure and migraines. If propranolol or another beta-blocker is ineffective or causes side effects (due to low blood pressure or slow pulse), tremor can be treated with epilepsy drugs such as primidone (Mysoline), gabapentin (Neurontin), zonisamide (Zonegran), or an alpha-2 agonist such as clonidine (Catapres), which is a different type of blood pressure medicine.

In rare cases, tremor affects not hands but the voice. I recently treated such a patient. He tried some medications, but when they did not help, he was given Botox injections into the vocal cords. This reduced the tremulousness of his voice, but only partially. Botox can also help with hand tremor, but because there are so many small muscles involved, the results are not very good. Taking careful history revealed that this patient tried only 10 mg of propranolol and when it did not help, he stopped it. I decided to give it another try and built up the dose to 30 mg, which provided complete relief without any side effects. For migraines, we usually go up to 60 to 120 mg of propranolol, but some patients need and tolerate even higher doses.

Read More

Medication overuse headache (MOH), which is sometimes called rebound headache, is included in the International Classification of Headache Disorders. However, this is one of several headache types whose existence is still debated. After years of indocrination, most neurologists and headache specialists strongly believe that every drug taken for acute treatment of headaches can cause MOH. However, we have good evidence only for caffeine and for opioid (narcotic) pain medications. It is far from proven in case of triptans (sumatriptan or Imitrex, and other) or NSAIDs (ibuprofen or Advil, naproxen or Aleve, and other).

Last week, I attended the annual scientific meeting of the American Headache Society (AHS) and was happy to see that despite an almost universal acceptance of the diagnosis of MOH, the organizers set up a debate on the existence of MOH. The debaters included two top experts in the field, Drs. Richard Lipton of Montefiore Headache Clinic in the Bronx and Ann Scher of the Uniformed Services University in Bethesda. Dr. Lipton and Scher have collaborated on many research projects and have published many important articles on headaches together, so the debate was friendly and based on facts.

Dr. Scher quoted the American Council on Headache Education, an affiliate of the AHS:

“It is important to know that intake of medications for acute treatment should be limited to less than twice a week. Some methods which can prevent the onset of medication overuse headache include following instructions on how to take medications, avoid use of opioid medications and butalbital combination medications and limit use of simple analgesics to less than 15 days a month and triptans less than 10 days a month”.

And then she posed a question: How many are being harmed vs helped by this advice?

While Dr. Lipton quoted scientific articles supporting the existence of MOH, Dr. Scher’s conclusions reflected my clinical experience that MOH is not a proven entity as it relates to triptans and NSAIDs. I see it only in those who overuse caffeine or caffeine-containing drugs (Excedrin, Fioricet, etc) or narcotic pain killers (Percocet or oxycodone, Vicodin or hydrocodone, and other).

Dr. Scher concluded that, “Since the existence of MOH has not been proven (and may be non-provable for practical purposes), one is obligated to remain agnostic about this entity. And the corollary is that there is no evidence that undertreating will prevent headache frequency progression and may harm more people than help”.

In fact, the same headache experts who limit abortive therapies to twice a week, recommend aggressive abortive therapy for migraines because undertreatment of episodic migraine can lead to its transformation into chronic migraine.

She also indicated that “Quality of evidence for medication withdrawal alone as treatment for MOH is poor” and “Medication withdrawal alone is not clearly better than doing nothing and may be worse”. Meaning that in addition to withdrawal of the acute medication, patients should be given prophylactic treatment.

Studies indicate that after one year, 60% and after two years, 70% of those with chronic migraines (15 or more headache days in a month) revert to episodic ones (less than 15 headache days a month) regardless of treatment. In 15% headaches decrease to less than one a week. This is because fortunately, migraines often improve with time on their own.

We have evidence that Botox injections and some preventive medications can make discontinuation of acute medications easier. We always try to stop Fioricet (butalbital, acetaminophen, and caffeine), Fiorinal (butalbital, aspirin, and caffeine), Excedrin (caffeine, acetaminophen, aspirin) with the help of regular aerobic exercise, biofeedback or meditation, magnesium and other supplements, Botox injections, and sometimes preventive medications.

However, we do have several dozen patients whose headaches are controlled by the daily intake of triptans. These patients have tried given prophylactic medications, Botox injections and other treatments, but find that only triptans provide good relief and eliminate migraine-related disability. The most commented on post on this blog (with 175 comments to date) is one on the daily use of triptans.

Read More

Hemiplegic and basilar migraine are rare types of migraine. Hemiplegic migraine is accompanied by a paralysis of one side of the body. Basilar migraine derives its name from the basilar artery, which supplies blood to the brainstem. Symptoms of brainstem dysfunction (double vision, unsteady gait, vertigo, difficulty speaking) made doctors think that ischemia or lack of blood flow in that artery caused these symptoms. We now know that this is not the case and basilar migraine may be just another form of migraine with aura.

The FDA ruled that sumatriptan (Imitrex), other triptans, and ergotamines (DHE-45, Cafergot) are contraindicated in patients with basilar and hemiplegic migraine because of the unsubstantiated fear that these drugs may cause constriction of blood vessels that might be already constricted resulting in a stroke. There is little evidence that symptoms of hemiplegic and basilar migraine are caused by the constriction of blood vessels. It is most likely due to the dysfunction of the brain cells. In addition, constriction of blood vessels by the triptans is very mild.

A study just published in the journal Headache examined 67 patients with basilar and 13 with hemiplegic migraines who were treated with triptans and dihydroergotamine (DHE-45). None of these patients suffered a stroke or a heart attack.

This is not the first report of the safe use of triptans in the treatment of basilar and hemiplegic migraines. Although the total number of patients reported is small, it appears that triptans and ergots are probably safe in these types of migraines. Some doctors are afraid to prescribe triptans to such patients out of fear of litigation. There is a good chance that the next edition of the classification of headache disorders will no longer include basilar migraine because it is recognized as being just a form of migraine with aura. Ergots and triptans are not contraindicated in migraine with aura.

Read More

Sumatriptan (Imitrex) and similar drugs (so called triptans) are “designer” drugs that were specifically developed for the treatment of migraine headaches. They are very effective, but do not help all migraine sufferers. Anti-inflammatory pain killers, such as aspirin and ibuprofen work well for some people and sometimes these drugs are combined with triptans to achieve better relief.

Many migraineurs experience nausea and sometimes vomiting as part of their migraine, which prevents or delays the absorption of medicine, making it ineffective or less effective. To address this problem, two of the triptans, sumatriptan and zolmitriptan (Zomig) are available in a nasal spray form. Sumatriptan can be also self-administered as an injection and recently a skin patch of sumatriptan (Zecuity) became available. An anti-inflammatory pain medicine, ketorolac is also available as a nasal spray, as does a narcotic pain killer, Stadol (butorphanol). While Stadol is addictive and has other serious side effects, intranasal ketorolac (Sprix) is a very good pain medication. Sprix works much better than the ketorolac tablet, but not as well as an injection of ketorolac (Toradol).

Intranasal ketorolac was compared with intranasal sumatriptan in a study that was recently published in the journal Headache. The study showed that ketorolac and sumatriptan nasal sprays were equally effective and both were better than placebo spray. Both drugs caused nasal irritation and unpleasant taste in some patients, but these were not severe.

The main problem with intranasal ketorolac is its cost. On GoodRx.com the price of 5 vials of Sprix (with a coupon) is about $1,000. Each vial is good for one day of use; it contains 8 sprays (15 mg each) and the usual dose is one spray into each nostril, repeated every 6 hours as needed. However, there is a way around the cost of this medication. Ten 30 mg vials of generic ketorolac for injections cost $15. You just need to buy a nasal spray bottle, empty the contents of the vial into it and use it as needed.

Read More

Sumatriptan is now available in a nasal powder form. We already have sumatriptan in a tablet, injection, nasal spray, and a skin patch. I mentioned this product over 5 years ago and finally it was just approved by the FDA. This does not mean it will be available right away as it often takes many months for the company to ramp up production. In some cases, such as with inhaled migraine drug Semprana (formerly called Levadex), it takes years before the manufacturer achieves FDA quality standards of production.

OptiNose is the company that developed Xsail Breath Powered Delivery Device which is used to deliver sumatriptan nasal powder. OptiNose licensed the product to Avanir Pharmaceuticals and they named it Onzetra. Onzetra is a fast-acting dry powder that is delivered into the nasal cavity. The patient exhales into the device, which seals the nasal cavity, and this carries the medication from the device directly into one side of the nose.

Nasal powder should be much more effective and more consistently effective than the nasal spray. The problem with the nasal spray is that the liquid tends to leak out of the nose or into the mouth, while the powder sticks to the nasal mucosa and all of it gets absorbed. And while the nasal spray contains 20 mg of sumatriptan and Onzetra only 11 mg, Onzetra should be more effective. Similarly, only 6 mg of injected sumatriptan is much more effective than 100 mg of sumatriptan in a tablet. But do we need another form of sumatriptan? Actually this may be a very good product for people who have a sudden onset of a severe migraine or those who vomit with their attacks. The injection works well for these patients, but many would rather avoid the pain of a shot. Zecuity, a new transdermal form of sumatriptan would seem to be a good choice, except for the fact that it works much slower than Onzentra.

The approval of Onzetra Xsal was based on the data from Phase 2 and 3 clinical trials, safety data from over 300 patients, and the historical data from various other formulations of sumatriptan, which have been on the market for over 20 years. One of the studies showed a significantly greater proportion of Onzetra Xsail patients reported headache relief at 30 minutes (42% vs. 27%) and at every time point up to 2 hours post-dose vs. placebo patients (68% vs. 45%).

Onzetra Xsail will be supplied as a disposable nosepiece containing a capsule and a reusable device. Each capsule contains 11 mg of sumatriptan and each kit contains 8 doses.

onzetratm-xsailtm-photo-1-5-HR

Read More

Magnesium deficiency is a regular topic on this blog. Up to half of migraine sufferers are deficient in magnesium, but magnesium levels are rarely checked by doctors. Even when magnesium level is checked, it is usually the serum level, which is totally unreliable. The more accurate test is RBC magnesium or red blood cell magnesium because 98% of body’s magnesium resides inside cells or in bones. At the New York Headache Center we often don’t bother checking even the RBC magnesium level, especially if other signs of magnesium deficiency besides migraines are present. These include coldness of hands and feet or just always feeling cold, leg muscle cramps, palpitations, anxiety, brain fog, and in women, premenstrual syndrome or PMS (bloating, breast tenderness, irritability). For these patients we recommend daily magnesium supplementation and sometimes monthly magnesium infusions.

About 20 to 30 million women suffer from moderate or severe PMS, and a recent study published in the American Journal of Epidemiology indicates that having PMS increases the risk for hypertension (high blood pressure) later in life.

This study was done at the University of Massachusetts, Amherst and it involved 1,260 women who suffered from moderate or severe PMS as well as more than 2,400 women with mild or no PMS. Women with moderate or severe PMS were 40 percent more likely to develop high blood pressure than those with mild or no PMS symptoms. The researchers adjusted the risk for other risk for hypertension, such as being overweight, smoking, drinking, inactivity, use of birth control pills, postmenopausal hormone use, and family history of high blood pressure.

The association between moderate or severe PMS and high blood pressure was most pronounced among women younger than 40, who were three times more likely to develop hypertension.

Interestingly, the risk of high blood pressure was not increased in women with moderate or severe PMS who were taking thiamine (vitamin B1) and riboflavin (vitamin B2). Other researchers found that women who consumed high levels of those vitamins were 25 to 35 percent less likely to develop PMS.

Unfortunately, the researchers did not look at magnesium levels or magnesium consumption in these women. A strong association exists between magnesium deficiency and high blood pressure. There is also an association between an increased magnesium (and potassium) intake and reduced risk of strokes. Supplementation with magnesium during pregnancy decreases the risk of hypertension during pregnancy. There is also a strong association between magnesium and depression.

There are literally hundreds of scientific articles on beneficial effects of magnesium, but unfortunately magnesium remains ignored by mainstream physicians. However, consumers are ahead of most doctors and many do take magnesium supplements. This is helped by many print and online articles and many books. Some of these books include Magnificent Magnesium, Magnesium Miracle, Magnesium – The Miraculous Mineral of Calm, and my two books – The Headache Alternative: A Neurologist’s Guide to Drug-Free Relief and What Your Doctor May Not Tell You About Migraines.

Migralex is a product I patented and developed for the treatment of headaches. It contains an extra-strength dose of aspirin and magnesium. Magnesium in Migralex acts as a buffering agent and reduces the risk of stomach irritation by aspirin. Migralex is available at CVS stores, Amazon.com, and Migralex.com.

Read More

Richard Wenzel PharmD of the Diamond Headache Clinic in the latest issue of the leading medical journal, Headache writes about the shocking fact that this country’s pharmaceutical industry cannot reliably supply medications for patients. He also talks about a connected, also undeniable development: “generic drugs currently push the boundaries of affordability”.

Drug shortages involve easily replaceable drugs, but also many life-saving cancer medications. Headache sufferers have not been spared, especially those with severe illness requiring injectable products; droperidol has been unavailable since 2013, various haloperidol and magnesium products are currently on backorder, and the availability of ketorolac, diphenhydramine, and valproic acid has recently been sporadic.

Dr. Wenzel writes that as of July, 2015, the American Society of Health Systems Pharmacists (ASHP) cited 265 active drug shortages. There’s also a “drugs no longer available” list of 57 medications unlikely to ever be commercially manufactured again, including ergotamine.

In the past two years, injections of dihydroergotamine, an irreplaceable migraine drug developed in 1940s, had been unavailable for two periods of lasting several months. The cost of this generic drug skyrocketed from 10 to up to $130 for a single dose.

Scarcities of raw materials, disruptions to manufacturing plants (eg, hurricane damage), insufficient FDA staff to provide prompt approval for production facilities, industry consolidation, and decisions to stop producing a marginally profitable or unprofitable product have all been cited as shortage reasons.

According to the Healthcare Supply Chain Association the costs of 10 drugs widely prescribed among the general public have jumped up to 8000% in as little as one year (2013–2014). For example, a single tablet of an antibiotic doxycycline went from $0.04 to over $3.60 and the new cost of Isuprel, a heart medication went from $180 to $2700 for a single ampule.

The medical community has been trying to address the problem of shortages and high costs through various organizations and the congress, but to no avail. Actually, the government is to blame in some cases. Besides the FDA staff shortages, low payments by the government (and insurers) that do not cover the cost of production is another common reason. When all pharmaceutical companies stop manufacturing a non-profitable or money-losing drug, one company jumps back in and because it is the only one making this medicine, they can charge exorbitant amounts for a generic drug.

Read More

Propranolol was first introduced as a blood pressure drug 50 years ago and about 40 years ago it was discovered to be effective for the prevention of migraines. This is quite a remarkable drug because it is also used for rapid heart beat, heart attacks, tremor, and performance anxiety. Public speakers, musicians, and others take a small dose before performances and the drug reduces the physical stress responses such as sweating, tremulousness, weakness, and other. Blinded studies showed that musicians perform better when given a beta blocker compared to musicians who are given a placebo pill.

Since the introduction of propranolol, another two dozen beta blockers have been developed. The newer, so called selective beta blockers (they attach to only one type of stress receptor) tend to have fewer side effects than propranolol and other non-selective beta blockers. Selective beta blockers can be given to patients with well-controlled asthma, while non-selective ones can cause an asthma attack.

Recent studies have shown that chronic stress promotes the growth and spread of cancers. Researchers at MD Anderson Cancer Center decided to review the records of 1,425 patients who were treated for ovarian cancer at four hospitals between 2000 and 2010. Of these, 268 had been treated with a beta blocker while receiving chemotherapy for their ovarian cancer. The average survival of those who were on a beta blocker was 48 months compared to 42 months for those who were not. A more dramatic difference was found between those who were taking a non-selective beta blocker (propranolol in almost all cases): they lived 95 months – twice as long as women not on a beta blocker.

Considering these findings, if I decide to prescribe a beta blocker, I may start prescribing propranolol as the first-line drug for the prevention of migraines. And only if the patient has side effects, will I switch them to a selective beta blocker, such as atenolol or nebivolol (Bystolic). Common side effects of beta blockers are fatigue and dizziness from a drop in blood pressure and difficulty exercising because the heart rate cannot increase high enough to provide for the increase in demand for oxygen. Because regular aerobic exercise is my first recommendation for the prevention of migraines, I tend to reserve beta blockers for patients whose blood pressure is high or at the high end of normal range, whose pulse is fast, and for those who fail other preventive drugs and Botox (however, most insurers approve Botox for chronic migraines only if the patient fails 2 or 3 preventive drugs, including a beta blocker).

Read More

The Food and Drug Administration (FDA) has just released a new strengthened warning about NSAIDs. Prescription and over-the-counter NSAIDs (ibuprofen, naproxen, nabumetone, diclofenac, and other) are widely used for the treatment of pain including different types of headaches. They are fairly safe, especially in young healthy people who take NSAIDs for an occasional headache. However, the risk of strokes and heart attacks and heart failure is higher in older people, especially those with risk factors such as smoking, diabetes, hypertension, high cholesterol, and other. These risks are present with all NSAIDs, except for aspirin, which in fact can sometimes lower these risks. So, when in doubt, take aspirin, which is the main ingredient of my product, Migralex. Migralex is fast acting and is less likely to upset your stomach because of the buffering effect of magnesium. You can buy Migralex on Migralex.com, Amazon.com, and CVS stores.

Here is the full text of FDA’s announcement:

Safety Announcement
The U.S. Food and Drug Administration (FDA) is strengthening an existing label warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) increase the chance of a heart attack or stroke. Based on our comprehensive review of new safety information, we are requiring updates to the drug labels of all prescription NSAIDs. As is the case with current prescription NSAID labels, the Drug Facts labels of over-the-counter (OTC) non-aspirin NSAIDs already contain information on heart attack and stroke risk. We will also request updates to the OTC non-aspirin NSAID Drug Facts labels.
Patients taking NSAIDs should seek medical attention immediately if they experience symptoms such as chest pain, shortness of breath or trouble breathing, weakness in one part or side of their body, or slurred speech.

NSAIDs are widely used to treat pain and fever from many different long- and short-term medical conditions such as arthritis, menstrual cramps, headaches, colds, and the flu. NSAIDs are available by prescription and OTC. Examples of NSAIDs include ibuprofen, naproxen, diclofenac, and celecoxib (see Table 1 for a list of NSAIDs).

The risk of heart attack and stroke with NSAIDs, either of which can lead to death, was first described in 2005 in the Boxed Warning and Warnings and Precautions sections of the prescription drug labels. Since then, we have reviewed a variety of new safety information on prescription and OTC NSAIDs, including observational studies,1 a large combined analysis of clinical trials,2 and other scientific publications.1 These studies were also discussed at a joint meeting of the Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee held on February 10-11, 2014.

Based on our review and the advisory committees’ recommendations, the prescription NSAID labels will be revised to reflect the following information:

The risk of heart attack or stroke can occur as early as the first weeks of using an NSAID. The risk may increase with longer use of the NSAID.
The risk appears greater at higher doses.
It was previously thought that all NSAIDs may have a similar risk. Newer information makes it less clear that the risk for heart attack or stroke is similar for all NSAIDs; however, this newer information is not sufficient for us to determine that the risk of any particular NSAID is definitely higher or lower than that of any other particular NSAID.
NSAIDs can increase the risk of heart attack or stroke in patients with or without heart disease or risk factors for heart disease. A large number of studies support this finding, with varying estimates of how much the risk is increased, depending on the drugs and the doses studied.
In general, patients with heart disease or risk factors for it have a greater likelihood of heart attack or stroke following NSAID use than patients without these risk factors because they have a higher risk at baseline.
Patients treated with NSAIDs following a first heart attack were more likely to die in the first year after the heart attack compared to patients who were not treated with NSAIDs after their first heart attack.
There is an increased risk of heart failure with NSAID use.
We will request similar updates to the existing heart attack and stroke risk information in the Drug Facts labels of OTC non-aspirin NSAIDs.
In addition, the format and language contained throughout the labels of prescription NSAIDs will be updated to reflect the newest information available about the NSAID class.

Patients and health care professionals should remain alert for heart-related side effects the entire time that NSAIDs are being taken.

Read More

Hopefully, your doctor has given you many treatment options, so that you can manage even the most severe attacks at home (including Compazine or Phenergan anti-nausea suppositories for when you are very nauseated or vomit and Imitrex or sumatriptan injection pen for severe pain). However, many people end up in an ER, where they are usually given an injection or intravenous medications. Unfortunately, there is no standard protocol for the best way to treat an acute migraine that does not respond to oral medications. Ideally, the first step should be an infusion of magnesium, which can provide fast relief for up to 50% of patients. Some ER doctors give an injection of sumatriptan or a non-narcotic pain killer ketorolac (Toradol). Others will give a nausea drug which can also help pain such as metoclopramide (Reglan) or prochlorperazine (Compazine). An allergy medicine, diphenhydramine (Benadryl) is also a popular choice.

A study by Dr. Benjamin Friedman and his colleagues at the Albert Einstein COllege of Medicine in the Bronx compared the efficacy of intravenous Reglan combined with Benadryl and Reglan without Benadryl. This was a double-blind study, meaning that neither the doctor giving the medicine nor the patient knew what was being given. They recruited 208 patients, which is a high enough number to produce reliable results. And the results showed that Reglan without Benadryl provided as much relief as with Benadryl.

Benadryl is not a dangerous drug, but can make you drowsy, so if you can, ask the doctor not to give it to you. It is not easy to tell a doctor what to do, especially during a severe migraine attack. But if doctor is agreeable, ask for intravenous magnesium followed by either sumatriptan or ketorolac injection as well as metoclopramide for nausea.

Read More

For years researchers have tried to find ways to block various chemicals (neurotransmitters) released during a migraine attack, including serotonin, CGRP, nitric oxide, substance P, glutamate, and other. Triptans (such as IMitrex or sumatriptan), the first “designer” drugs for migraine, which were developed over 20 years ago, bind to a very specific subtype of serotonin receptor and are very effective in stopping a migraine attack.

A very promising new type of migraine medications is being developed by at least four different companies – Alder, Amgen, Eli Lily, and Teva. These drugs are monoclonal antibodies against the CGRP molecule or the CGRP receptor. CGRP (calcitonin gene-related peptide) is widely distributed in the body and is involved in regulating blood vessel opening and in the function of the nervous system. All four companies developing these drugs recently presented the results of their phase II clinical trials and the data looks very promising. The antibody tightly binds to its target (CGRP molecule or receptor) with the effect lasting a month, or in case of the Alder drug, up to 6 months. The Alder drug is given every six months intravenously, while the other three, are given every month by an injection into the muscle.

All four drugs appear to be very effective in preventing migraine attacks when compared to a placebo injection. And fortunately, at least so far, they all look very safe. However, in phase II trials only a couple of hundred patients are treated and we need to await the results of the larger and more definitive phase III trials to confirm the safety and efficacy of this new group of medications. This means that the earliest we will see these drugs approved by the FDA is in about 3 years.

It is possible that these drugs will be effective not only for the prevention of migraines, but also for stopping an acute migraine attack.

Read More

Zolmitriptan is one of seven triptans available in the US and it comes in tablets (Zomig), orally disintegrating tablets, that is tablets that melt in your mouth (Zomig ZMT), and nasal spray (Zomig NS). The nasal spray was just approved for children 12 and older. It is available in 2.5 mg and 5 mg strength and the 2.5 mg is the starting dose, but kids are allowed to take 5 mg dose up to twice a day.

My previous post mentioned the approval of Treximet, a combination of sumatriptan (Imitrex) and naproxen (Aleve) in adolescents. However, Zomig is the only triptan in a nasal spray form (the second triptan available in a nasal spray is sumatriptan or Imitrex) approved in the US for children. The advantages of this form of drug delivery is that it tends to have faster onset of action and it can be taken when severe nausea or vomiting precludes the use of oral medications. Sumatriptan nasal spray is approved in kids in Europe, so there is no reason not to use it as well, however Zomig spray seems to be better than Imitrex spray. The amount of fluid in a single dose of Zomig is less than that in Imitrex and the spray droplets are of smaller size, leading to better retention of fluid in nasal passages and better absorption. Also, many patients complain of a very unpleasant taste with Imitrex spray, although this can be avoided by sucking on a hard candy while spraying. This will carry the saliva out of the mouth down the throat and the drug will not reach the mouth. When using nasal sprays it is important not to sniff them up your nose because this will carry the medicine into the throat rather than having it stay in the nose where it gets absorbed faster.

Since we are on the topic of nasal sprays, I should mention three other nasal sprays that can be used to treat headaches. Migranal nasal spray contains dihydroergotamine, which is one of the strongest injectable migraine medications. However it is a lot less effective in a nasal spray form. Sprix is a nasal spray of ketorolac (Toradol), a nonsteroidal anti-inflammatory drug, which is also much stronger when injected. It is also available in a tablet, but the tablet is not any stronger than aspirin or ibuprofen. The third nasal spray is Stadol NS and it contains butorphanol, a strong narcotic pain killer. It should be avoided because it is very addictive.

Read More

Narcotics are not only ineffective for the treatment of headaches, but they can also make headaches worse and transform an episodic migraine into chronic. A study mentioned in a previous post showed that more than half of migraine sufferers who went to an ER were given a narcotic.

A new study recently published in the journal of the International Headache Society, Cephalalgia showed that if patients presenting with a headache to an ER are treated with an injection of opiates (narcotics) they will stay in the hospital longer than if no narcotics are given. This treatment also leads to an increased risk of return visits to the emergency department within seven days.

The study was conducted by two neurologists, Dr. McCarthy at Puget Sound VA Healthcare System in Seattle and Dr. Cowan at Stanford University in California. They examined charts of 574 people and discovered that 23% received a narcotic when they were seen at an emergency department. Only 53% were given an injection of a drug recommended by a published consensus of headache experts. These include sumatriptan (Imitrex, the only injectable triptan), prochlorperazine (Compazine), metoclopramide (Reglan), chlorpromazine (Thorazine), ketorolac (Toradol), aspirin, acetaminophen, and dihydroergotamine. The remaining 24% were given an injection of another non-narcotic drug.

Patients who were given opiates were 4 times more likely to have a long stay, compared with patients given first-line recommended medications. 69 participants had at least one readmission for headache, of whom 20 returned to the emergency department within seven days. Interestingly, patients who had a CAT or an MRI scan of the brain had a significantly higher rate of early return visits, compared with those who did not have neuroimaging. Approximately 8% of people given opiates had early return visits, compared with 3% of patients given first-line recommended drugs.

Dr. McCarthy was quoted saying that “Opiates have shown less headache pain reduction, higher rates of headache recurrence, and increased sedation, compared with first-line recommended specific headache medications”. He added that regardless of whether the acute headache was diagnosed as a migraine or a tension-type headache, it is likely to respond to most non-narcotic injectable treatments.

An editorial accompanying this article concluded that “The most important intervention emergency physicians can deliver for their headache patients is to connect them with outpatient physicians savvy about headache management, who will then provide these headache patients with appropriate acute therapeutics, initiate preventive therapy, and counsel their patients against receiving opioids in the emergency department”.

Read More

Placebo effect is a well-documented phenomenon, which is particularly pronounced when treating migraine headaches. Intravenous (IV) infusion of saline water is a placebo commonly used in studies where placebo is compared to a medication also given IV.

It is baffling why a group of Canadian physicians decided to test the effect of (IV) fluids on migraines in children and adolescents seen in an emergency room (the study was just published in Headache). They compared a group of children who were told that they will get only IV fluids with another group who was told that they might also get a medication with the IV fluids. The second group actually watched a nurse add something to the bag of IV fluid, but the children were not told that it was just more of the saline water. The researchers thought that the expectation of getting a medicine will help relieve their migraine headache. In fact neither group, the one who received IV fluids without expecting any medicine and the group who thought that they may be getting medicine had much relief. Strangely, the doctors concluded that additional studies using larger volumes of IV fluids are warranted. As if there is a chance that giving more fluids will stop a severe migraine. Sadly, intravenous fluids are often used in emergency rooms as a treatment for migraines in adults and children and we did not need this study to show that it is an ineffective approach. Doing more such studies seems unethical. Imagine a parent getting up in the middle of the night, taking a sick child to an emergency room where the child receives only intravenous fluids and is sent home with the child still in pain.

Emergency rooms, even in the medical mecca of New York City, are notorious for using ineffective treatments for migraine headaches. If not intravenous fluids, patients often get narcotic (opioid) pain killers, tranquilizers, or antihistamines, such as Benadryl. Some patients are just given a tablet of ibuprofen and are sent home after waiting for hours to be seen and treated. Here is a previous post on what to ask for if you end up in an emergency room with a severe migraine. Obviously, some doctors will not comply with your request, but it is worth asking.

Read More