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Headache medications

Ketamine is a medicine that is sometimes given intravenously for anesthesia. It is a controlled drug because it can induce euphoria and is potentially addictive. In a previous post I mentioned several anecdotal reports about the beneifical effect of ketamine for a prolonged migraine aura, hemiplegic migraine and other types of headaches.

A presentation at the recent annual meeting of the American Society of Anesthesiologists described the results of ketamine infusion on severe migraines in patients admitted to the Thomas Jefferson University Hospital in Philadelphia from 2014 to 2016. 48 of the 61 patients (77%) responded to this treatment, meaning that their pain levels improved by at least 2 points on a 1 to 10 scale. On average, the infusion had to be given for 5 days. Side effects included sedation (51%), blurry vision (38%), nausea or vomiting (38%), hallucinations (28%), vivid dreams (13%), and low blood pressure (5%). The authors described the adverse effects as mild in nature and only 1 patient discontinued treatment. However, having hallucinations, drop in blood pressure or vomiting does no sound like mild side effects to me. On the other hand, these were patients whose migraine did not respond to other treatments and they needed to be hospitalized, so these side effects could in fact be acceptable if the treatment ultimately provides relief.

Review of patient records admitted to the same hospital between 2006 and 2014 showed the mean headache pain rating using a 0-10 pain scale dropped from 7 on admission to 4 on discharge. The majority (55 out of 77, or 71%) of patients responded by the same definition of an at least 2-point improvement in headache pain at discharge. Only a quarter of responders maintained this benefit at their follow-up office visit. The mean length of infusion was also 5 days. And again, most patients tolerated ketamine well with “very few serious side effects”.

Anecdotal evidence also exists for the use of ketamine infusions to treat depression. There are some outpatient clinics that offer ketamine infusions for chronic pain and depression and a few of my patients have gone there, but unfortunately with little success.

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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.”

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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.

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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.

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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.

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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.

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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.

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Temporal arteritis occurs in one out of 5,000 people over 50. Women are 3-4 times more likely to be affected. It is not common below the age of 60 and becomes more prevalent with the advancing age. Temporal arteritis is also known as giant cell arteritis because it causes inflammation of arteries with giant cells seen under the microscope.

Headache is often the first symptom and it is typically localized to one temple, but it can involve other parts of the head and occur on both sides. If left undiagnosed and untreated temporal arteritis can cause a stroke and blindness, which can affect both eyes.

Besides headaches, temporal arteritis can cause neck and jaw pain, weakness, muscle aches, and a mild fever. The preliminary diagnosis is made by blood tests (ESR and CRP) and it is confirmed by a biopsy of the temporal artery. Polymyalgia rheumatica is a related rheumatological condition, which can occur alone or with temporal arteritis and it causes severe muscle pains.

Temporal arteritis (and polymyalgia rheumatica) are treated with steroid medications, such as prednisone. Although the initial dose is high, relatively small doses are usually effective for maintenance. Since the condition can last for years and long-term intake of prednisone can cause many potentially serious side effects it is very important to perform a temporal artery biopsy in most cases, rather than rely just on blood tests and clinical diagnosis.

Subcutaneous injection of Actemra (tocilizumab) was just approved by the FDA for the treatment of temporal arteritis. This drug has been available since 2010 for the treatment of rheumatoid and other forms of arthritis. Actemra was injected every two weeks for a year along with prednisone, but more patients were able to get off prednisone if they received Actemra rather than a placebo injection. Unfortunately Actemra also has potentially dangerous side effects, such as serious infections and it requires regular blood tests.

Because headache is one of the main symptoms of giant cell arteritis, the condition is often diagnosed by a neurologist or a primary care doctor. The treatment though is typically handled by a rheumatologist and they are already familiar with tocilizumab.

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Naltrexone, along with naloxone are narcotic (opioid) antidotes, that is they counteract the effect of narcotics and are used to treat overdoses with heroin, fentanyl, Percocet, Vicodin, and other opioid drugs. Surprisingly, low doses of naltrexone (LDN) seem to be effective in treating pain. LDN has been also used to treat symptom in conditions such as depression, fibromyalgia, Crohn’s disease, multiple sclerosis, complex regional pain syndrome (which used to be called reflex sympathetic dystrophy), and autoimmune disorders.

Low dose naltrexone is not a typical pain killer, but may be helping pain by reducing inflammation. Instead of opioid receptors, it works on Toll-like receptor 4 (TLR4) receptors on glial cells. Glial cells surround the nerve cells and play important functions in the brain, beyond just a supporting role that had been assigned to them for many years. Opioid drugs are known to promote inflammation through the brain immune system leading to worsening of pain over time. Recent discoveries have shown that the Toll-like receptors are involved in triggering these inflammatory immune events. These discoveries have led many researchers to look at ways to block TLR4, but so far no such drug has been developed. We do have several existing medications that seem to block TLR4. Besides LDN, amitriptyline (Elavil) and cyclobenzaprine (Flexeril) are two other drugs that block TLR4 and that have been used for years to treat pain.

No large controlled studies of LDN for migraines, pain or any other condition have been conducted to date. Despite the fact that the evidence is only anecdotal and that LDN my work purely through the placebo effect, advantages of LDN are that it is inexpensive and safe. Naltrexone is available in 25 and 50 mg tablets, while the amount used for LDN is between 1.5 to 4.5 mg. This means that it can be obtained only from a compounding pharmacy. Naltrexone is not a controlled substance, but it does require a prescription from the doctor.

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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.

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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.

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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.

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My most commented on blog post (over 150 comments) is on the daily use of triptans. A new report confirms the safety of long-term daily use of sumatriptan injections in cluster patients. Cluster headaches are arguably the most severe type of headaches and the name comes from the fact that they tend to occur in clusters lasting several weeks to several months. However, in some patients headaches become persistent without any remissions and then they are called chronic cluster headaches. The only FDA approved treatment for cluster headaches is injectable sumatriptan (Imitrex). Most patients have one cluster attack in 24 hours, but some have many. A report mentioned in one of my other previous blogs describes a woman (although men are more commonly affected by cluster headaches) who has been injecting sumatriptan daily on average 20 times a day for 15 years.

A recent report by Massimo Leone and Alberto Cecchini is entitled, Long-term use of daily sumatriptan injections in severe drug-resistant chronic cluster headache.

The authors investigated occurrence of serious side effects in patients with chronic cluster headaches who were using sumatriptan injections continuously at least twice daily (the official limit) for at least 2 years. They found fifty three such patients with chronic cluster headaches seen in their clinic between 2003 and 2014. During the 2-year period, all patients were carefully followed with regular visits at their center. Headaches and sumatriptan consumption were recorded in headache diaries. Patients were questioned at each visit about serious side effects and had at least two electrocardiograms. Brain MRI was normal in all patients. None of the patients had a history of stroke, TIA, ischemic heart disease, myocardial infarction, or arrhythmia, or diseases affecting systemic vessels.

In the 2-year study period, no serious side effects were observed and no patients needed to discontinue sumatriptan use. No electrocardiogram abnormalities were found. All patients needed a full dose (6 mg) of sumatriptan injection (prefilled syringes with 4 and 6 mg available). At the end of the study period, 42% noticed some reduction in the efficacy of sumatriptan injections both in terms of time of onset of effect and on pain intensity, but still considered the drug their first choice to treat the attacks.

In the study period, 36 of the 52 patients (69%) used more than 12 mg of sumatriptan in 24 hours (maximum 36 mg in 24 hours) but no increase in number or severity of side effects was observed during the course of the study. Complete loss of efficacy was not reported by any of the patients.

The authors mention that since the launch of sumatriptan injections in 1992 and until 1998, approximately 451 serious cardiac side effects have been reported to occur within 24 hours after administration of sumatriptan injections, tablets or nasal spray, but this is out of more than 236 million migraine attacks and more than 9 million patient exposures between 1992 and 1998. The majority of patients who developed serious cardiac events within 1 to 3 hours of sumatriptan administration had risk factors for coronary artery disease.

The authors concluded that their results showed that long-term daily sumatriptan use in patients free of heart disease did not cause serious side effects and this is in line with observations from previous studies.

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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.

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Zecuity, a skin patch containing a migraine drug sumatriptan was approved by the FDA almost two years ago, but it became available (by prescription) only last month (see my previous post about Zecuity). The product is not available in retail pharmacies, only from a specialty pharmacy. The doctor who prescribes the patch will usually provide information on where to get it. Otherwise, go to zecuity.com, where you can find a section entitled Migraine Support Solutions. At this site you can verify that your insurance covers this product, get it shipped to you, and then get information on how to apply the patch. A discount coupon is also available on the site and it promises that the copay will be as low as $15. That is a good thing, because it looks like (on GoodRx.com) each patch costs $300. Yes, not $30, but $300 a piece, or $1,200 for a box of 4. I don’t think too many people will be buying this patch if their insurance does not cover it.

So, who is the best candidate for Zecuity? Half of migraine sufferers experience nausea and/or vomiting with their attacks. This makes the absorption of oral drugs, such as triptans (Imitrex, Maxalt, Zomig, etc) so slow as to make them ineffective. In such patients we try to bypass the stomach, which until now was possible to do with a nasal spray, suppository, or an injection. Sumatriptan (Imitrex) is available in the US in tablets, nasal spray and self-administered injections. Nasal spray of sumatriptan is not very effective, but injections work better than tablets. Relief from an injection can occur in as quickly as 10 minutes, but injections can cause more side effects, which are mostly unpleasant rather than dangerous. Obviously, most people would rather not get a shot. One form of injectable sumatriptan delivers the medicine through the skin without a needle (Sumavel), but not without pain see this post.

One other triptan, zolmitriptan (Zomig) is available in a nasal spray and it is more effective than sumatriptan nasal spray, but it is not available in a generic form, making it less accessible because of the high cost and restricted insurance coverage.

The perfect patient for Zecuity is someone who experiences nausea and/or vomiting with their migraine attacks and who does not respond to tablets and has side effects from or aversion to injections. Zecuity provides good relief for such patients with the main side effect being skin irritation from the patch. The patch is fairly large, the size of a palm. It uses a miniature battery to generate an electric current, which helps drive the medicine through the skin. Iontopheresis is the name of this process. Iontopheresis has been known for decades, but Zecuity is the first product approved by the FDA to utilize this technology.

Disclosure – Teva Pharmaceuticals, manufacturer of Zecuity pays me to give lectures about Zecuity to doctors.

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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).

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Ayurvedic medicine has many healthy aspects. However, a recent story on NPR described the risks involved with the traditional Ayurvedic medicines from India. A very high percentage of Ayurvedic supplements in the category called bhasmas sold in the US contains large amounts of lead and other toxic elements. There is a lot more to Ayurvedic medicine than these supplements, so it is important to separate dangerous parts from things like healthy diet, yoga, and other.

Unfortunately, the US government does not regulate supplements, so there is always a question of safety of these products, especially those made outside the US. The one exception is products made in Germany, where supplements are as strictly regulated as drugs (please note that Petadolex, a butterbur product is made in Germany, but is not allowed for sale there). Many patients ask me about not only Indian but also Chinese herbal medicines, which are often combined with acupuncture and other treatment methods. As a rule, I recommend avoiding products made in China or India, where quality controls are very poor. Instead, you should buy products made by major US manufacturers, although they do not make many traditional Chinese and Indian products. However, you cannot always count on products sold in major US store chains either – recently, herbal products sold at Walgreens, WalMart, Target and GNC were found to have no active ingredients. Thankfully, there were no toxic ingredients in those products.

The largest mass poisoning with a Chinese herbal dietary weight loss product occurred in Europe where 18 patients developed kidney failure and urinary cancer.

In summary, no matter how promising a Chinese or an Indian herbal product may sound, it is not worth the risk.

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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.

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Topiramate (Topamax) is a drug used for the prevention of migraine headaches (and epilepsy) in adults and last year it was also approved for adolescent migraine sufferers. This drug is notorious for causing cognitive side effects, kidney stones,osteoporosis, overheating, and many other side effects. It is contraindicated (just like another migraine drug, Depakote) in pregnancy because of the risk of birth defects.

A new report published in the journal Pediatrics documents an increased risk of eating disorders in adolescents who take Topamax. This report describes 7 female teenagers who developed an eating disorder or whose eating disorder got worse on topiramate.

Considering that we have many other effective preventive drugs for migraine headaches, topiramate should be used only when several other treatments fail.

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Several million Americans suffer from chronic migraines, headaches that occur on at least half of the days and often daily.

A new study suggests one of the way to prevent this disabling disease. In the American Migraine Prevalence and Prevention Study, people with episodic migraines (those occurring on less than half of the day each month) completed the Migraine Treatment Optimization Questionnaire and provided outcome data in 2006 and in 2007. They were asked four questions about the efficacy of their acute migraine therapies and the responses were divided into: very poor, poor, moderate, and maximum treatment efficacy.

Among 5,681 study participants with episodic migraine in 2006, 3.1% progressed to chronic migraine in 2007. Only 1.9% of the group with maximum treatment efficacy developed chronic migraine. Rates of new-onset chronic migraine increased in the moderate treatment efficacy (2.7%), poor treatment efficacy (4.4%), and very poor treatment efficacy (6.8%) groups. The very poor treatment efficacy group had a more than 2-fold increased risk of new-onset chronic migraine compared to the maximum treatment efficacy group.

The authors concluded that inadequate acute treatment efficacy was associated with an increased risk of new-onset chronic migraine over the course of 1 year. They speculated that improving acute treatment outcomes might prevent chronic migraine. However, they also said that reverse causality cannot be excluded, meaning that it is possible that those who would go on to develop chronic migraine had poor response to acute treatment because their headaches were worse and that they would develop chronic migraine regardless of how well their acute treatment worked. However, it makes a lot of sense to assume that effective treatment of individual attacks may prevent headaches from becoming chronic, especially because we know that each migraine attack leaves the brain more excitable for weeks and this makes the next attack more likely.

Effective treatment of acute attacks usually involves the use of triptans, (drugs like sumatriptan, or Imitrex, eletriptan, or Relpax, rizatriptan or Maxalt, and other), although NSAIDs, such as aspirin, iboprofen and other can also help, both alone or in a combination with a triptan. Medications that should not be used are drugs such as Fioricet or Fiorinal (butalbital, caffeine, and acetaminophen / aspirin), codeine, Percocet (oxycodone / acetaminophen), Vicodin (hydrocodone / acetaminophen). These drugs are not only ineffective, but can make it more likely that episodic migraines will turn into chronic. This also applies to other caffeine-containing drugs (Excedrin and other) and even dietary caffeine.

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Epilepsy drugs Depakote and Topamax are two of only four drugs approved by the FDA for the prevention of episodic migraines (the other two are blood pressure medications in the beta blocker family, propranolol and timolol, while Botox is the only drug approved for the preventive treatment of chronic migraines). However, these two drugs are contraindicated in pregnancy. Considering that the majority of migraine sufferers are young women, this is a topic that needs to be revisited regularly, especially when additional data appears.

A new study just published in the journal Neurology followed children in the British National Health Service whose mothers suffered from epilepsy and who were taking Depakote (valproate) or Tegretol (Carbamazepine) or Lamictal (lamotrigine). Only Depakote caused a significant drop in IQ in children whose mother was taking more than 800 mg of Depakote a day. Children whose mother took less than 800 mg (the usual dose for migraines is 500 mg, but sometimes 1,000 mg is needed) did not have a lower IQ, but had impaired verbal abilities and a 6-fold increase in needing educational intervention.

Unfortunately, Tegretol and Lamictal are not effective for the prevention of migraine headaches, while Topamax which is effective, can cause birth defects. Neurontin (gabapentin) is a relatively benign medication, which is safe in pregnancy and it is somewhat effective in the prevention of migraines, including chronic migraines.

Ideally, all drugs should be avoided in pregnancy. We usually advise non-drug approaches, including regular sleep, healthy diet, exercise, biofeedback or meditation, and magnesium supplementation. If this is insufficient, we usually recommend Botox if migraines remain frequent (they often improve in pregnancy). Botox is not approved for use in pregnant women, but considering that it acts locally on nerve endings with very little of it getting into the blood stream, it is most likely safer than any drug that is ingested.

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Cyclic vomiting syndrome (CVS) is usually seen in children. The attacks of vomiting often stop as the child gets older, but then they usually go on to develop migraine headaches. A recent report in Headache describes three adults with CVS. The article also mentions a previous report which described another 17 adults with this syndrome.

CVS typically consists of recurrent stereotypical attacks of incapacitating nausea and vomiting, separated by symptom-free periods. Supporting evidence that helps diagnose this condition include personal or family history of migraine and other symptoms, such as headaches, motion sickness, and sensitivity to light.

Just like in children, CVS in adults is a diagnosis of exclusion, meaning that other causes of vomiting must be considered and ruled out. I mentioned in a previous post that one out of three children with CVS turned out to have another medical problem rather than migraine.

CVS in adults seems to respond well to an injection of sumatriptan (Imitrex). This allows for a quick relief of symptoms and makes this debilitating condition very manageable. Besides Imitrex injections, Zomig (zolmitriptan) nasal spray can sometimes be effective as well.

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Beta blockers (Inderal or propranolol and similar drugs) are used for the preventive treatment of migraine headaches. Over the years, a few patients have told me that they take a beta blocker only when they have an attack of migraine with very good results. A report published in Missouri Medicine describes seven patients whose acute migraine headache went away with eye drops containing a beta blocker. These eye drops are used for the treatment of glaucoma. The authors argue that having medicine go into the eye allows it to get absorbed quickly into the blood stream. This is certainly true, but my first thought was that there is too little medicine in eye drops to produce an effect outside the eye. However, beta blocker eye drops can worsen asthma, lower the blood pressure and slow the heart rate, suggesting that the amount of medicine in eye drops is sufficient to cause effects beyond the eye. Oral beta blockers used daily for the preventive treatment of migraines are also contraindicated in those medical conditions. Considering that eye drops are probably safer than many oral medications used to treat an acute migraine attack and that they most likely work faster, this treatment is worth trying.

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Frequent attacks of migraine are best treated with preventive measures. Several categories of medications have been shown to be effective for the prevention of migraine headaches. These include Botox injections (for chronic migraine), epilepsy drugs (gabapentin, topiramate, divalproex), blood pressure medications (propranolol, atenolol, lisinopril, losartan, and other), as well antidepressants.

Antidepressants, like most other preventive drugs, were discovered to be effective for pain and headaches by accident. We have good scientific proof that you do not need to be depressed to obtain pain and headache relief from these drugs. The effect on pain and on anxiety or depression are independent of each other. However, many patients who have pain and headaches have higher rates of depression and anxiety and these drugs can relieve both conditions.

The oldest category of antidepressants are tricyclic antidepressants. Elavil or amitriptyline was introduced in the US in 1961. Amitriptyline has been extensively tested for a variety of painful conditions, including low back pain, neuropathy pain, migraines, and other. The main side effects of amitriptyline are dry mouth, drowsiness, constipation, and sometimes, weight gain. Other drugs in the family of tricyclic antidepressants often have fewer side effects. Many doctors always begin with nortriptyline or Pamelor, which is a derivative of amitriptyline and may have fewer side effects. Amitriptyline is broken down in the body into nortriptyline, which is less sedating. We also prescribe other tricyclics, desipramine (Norpramine), doxepin (Sinequan), and protriptyline (Vivactil), which also tend to have fewer side effects. When a patient has insomnia and is not prone to gaining wait, amitriptyline may be the better choice since it will also improve sleep.

The starting dose of amitriptyline, nortriptyline, doxepin, and desipramine is 10 or 25 mg taken at night. Then, if this starting dose is ineffective, the dose is gradually increased to 50 mg, then 75, and sometimes higher. Besides being very effective, tricyclics have another advantage – there is a blood test to measure how much of the medicine is absorbed and is circulating in the body. When a patient takes more than 75 – 100 mg without obtaining relief, we do a blood test to see if the blood level is low and we need to increase the dose or if the level is high and the drug is just ineffective. With protriptyline, the least sedating drug, the starting dose is 10 mg and the highest dose is around 30 mg. Treatment of pain and migraines usually requires a much lower dose of a tricyclic than for depression. All of the tricyclics are available in a generic form and are inexpensive.

Another category of antidepressants that relieve pain and headaches is serotonin and norepinephrine reuptake inhibitors, or SNRIs. Some of the SNRIs are FDA-approved for various painful conditions, such as neuropathy, shingles, fibromyalgia, and back pains. Most popular SNRIs are Effexor (venlafaxine), which is available in a generic form, Cymbalta (duloxetine), Pristiq (desvenlafaxine), Savella (milnacipran), and Fetzima (levomilnacipran). These drugs have fewer side effects than tricyclics, although they are sometimes difficult to stop because they can cause heightened anxiety and other withdrawal symptoms.

Nardil (phenelzine) is an antidepressant in the family of MAO inhibitors and it has also been used for the preventive treatment of migraine headaches. However, this drug has many potential serious drug-drug and drug–food interactions and most doctors avoid this medicine. Other MAOI drugs are Parnate (tranylcypromine), Emsam patch (selegiline) and other.

SSRIs are the most popular drugs for the treatment of anxiety and depression, but they are ineffective for the treatment of pain, migraines, and other headaches. These drugs include Prozac (fluoxetine), Paxil (paroxetine), Lexapro (escitalopram), Zoloft (sertraline) and other. They are very popular because they have fewer side effects than other antidepressants, although they probably cause higher rates of sexual dysfunction.

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Expiration date on medications does not indicate that the medication is no longer effective or safe after that date. Having had extensive experience with the production and testing of Migralex, I can reassure you that medications remain safe and effective for years after the expiration date. An article just published in the Wall Street Journal’s “Burning Question” column addresses this issue.

The FDA has conducted a study for the Department of Defense testing 122 different drugs. The conclusion of the study was that 88% of the drugs remain effective for an average of 5 and 1/2 years after the expiration date. The main problem with expired drugs is not that they become dangerous to use, but that their efficacy slowly declines. A doctor quoted in the WSJ article says that there have been no reported cases of toxicity from expired medications. But a decline in efficacy could be a problem with life-saving drugs, such as nitroglycerin for heart, EpiPen for allergies, or insulin for diabetes.

It is very important to store the medications in a dry cool place, rather than in a medicine cabinet in the bathroom, which periodically gets hot and humid. Also, do not leave drugs in a car during the summer – the temperature in a locked car left in the sun can rise to 130 degrees and higher.

I usually advise not to use drugs beyond two years of the expiration date even if they were kept in a dry and cool place. Before using an expired drug inspect the tablet to make sure it hasn’t turned colors, smells bad, or became brittle and crumbling. Obviously, if it is an inexpensive generic drug, get a fresh bottle. However, with expensive drugs, such as some triptans (Relpax, Frova, Axert) and injections of Imitrex (sumatriptan) considerable amounts of money can be safely saved. A common scenario is a patient with cluster headaches who has a bout every couple of years and has only expired injections of Imitrex. It usually takes at least a few days to be seen by a doctor and to get a new prescription, while the attacks of cluster headaches can be devastatingly severe. Again, the worst that can happen is that the injection will be less effective, but usually it will still provide some relief.

There is a difference in how long expired drugs remain effective depending on the formulation. For example, tablets are the most stable, while creams and liquid drugs, such as drops, are least likely to last past the expiration date.

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Acetaminophen is what most obstetricians recommend pregnant women take for their headaches. However, it is not very effective for migraine headaches and it is not as safe as we thought (see my recent post). Fioricet is another drug favored by some obstetrician and it is also not very effective and not very safe.

Sumatriptan (Imitrex) was introduced 20 years ago and the manufacturer has maintained a registry of women who took the drug while pregnant. The final results of this registry were just published in the journal Headache. The registry included 626 women who were exposed to sumatriptan during their pregnancies. They also followed women who took two other migraine drugs, naratriptan (Amerge) and a combination of sumatriptan with naproxen (Treximet). However, there were too few women in those groups to make any conclusions about the drugs’ safety.

As far as sumatriptan, the risk of major birth defects was not increased. The authors also reviewed several other large studies which assessed the risk of taking migraine medications during pregnancy. One of the studies were from the Swedish Medical Birth Register, which included 2257 births following first trimester sumatriptan exposure. No risk was found in this study either.

In summary, pregnant women suffering from severe migraines should be prescribed sumatriptan. Most women respond to an oral form (tablet), but those with very severe attacks should be offered an injection.

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The benign nature of white matter lesions (WML) on MRI scans of patients with migraine was noted in a post last year. While they appear to be benign, they are disconcerting nevertheless. It is possible that we haven’t yet discovered the negative effects they may have.

A study by Chinese researchers published in the Journal of Neurology reported on MRI scans in 141 people, including 45 healthy controls without migraines, 38 chronic migraine sufferers who were not overusing acute migraine medications and 58 patients with chronic migraines who were overusing these medications. They found that women, but not men, who were not overusing acute medications had more WML compared with controls and those who were overusing medications. As reported by other researchers, the number of WML increased with age. Interestingly, most patients who overused medications were taking non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen and naproxen. The authors concluded that taking NSAIDs may have a preventive effect on the development of WMLs, possibly because of their anti-inflammatory properties. Previous studies have shown that aspirin does not even cause medication overuse headaches, unlike drugs with caffeine (Excedrin, Fiorinal, Fioricet), opioid analgesics (Vicodin, Percocet, codeine, etc), and to a lesser extent NSAIDs.

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Yesterday, the FDA approved the first preventive (prophylactic) treatment for migraines in adolescents – kids between the ages of 12 and 17. Topamax (topiramate) was first approved by the FDA in 1996 to prevent seizures. It was approved for migraine prevention in adults in 2004.
As the FDA stated in its announcement, “Migraine headaches can impact school performance, social interactions, and family life. Adding dosing and safety information for the adolescent age group to the drug’s prescribing information will help to inform health care professionals and patients in making treatment choices.”
The announcement also stated that “About 12 percent of the U.S. population experiences migraine headaches. Migraine headaches are characterized by episodes of throbbing and pulsating pain in the head, and may occur several times per month. Other common symptoms include increased sensitivity to light, noise, and odors, as well as nausea and vomiting. Many patients experience their first migraine attack before reaching adulthood, and migraine can be just as disabling in teens as it is in adults.

The safety and effectiveness of Topamax in preventing migraine headaches in adolescents ages 12 to 17 was established in a clinical trial that enrolled 103 participants. Those treated with Topamax experienced a decrease in the frequency of migraine of approximately 72 percent compared to 44 percent in participants that took an inactive drug (placebo).

The most common adverse reactions with the approved dose of Topamax (100 milligrams) were paresthesia (a burning or prickling sensation felt in the hands, arms, legs, or feet), upper respiratory infection, anorexia (loss of appetite), and abdominal pain.

Topamax increases the risk of the development of cleft lip and/or cleft palate (oral clefts) in infants born to women who take the drug during pregnancy. The benefits and risks of Topamax should be carefully weighed before using it in women of childbearing age. If the decision is made to use the medication by a woman of childbearing age, effective birth control should be used.”

It is a little surprising that the FDA based its approval on such as small study – 103 patients. I should add that topiramate can also cause cognitive side effects, such as memory and word retrieval problems in a significant percentage of children and adults. Approximately 20% of adults taking topiramate for more than a year or two develop kidney stones. This most likely can also happen in children. As you can tell from this and my previous posts, I am not a big fan of Topamax. In kids particularly we begin with life style and dietary changes, biofeedback, magnesium, CoQ10 and other supplements and even Botox injections, which are very safe, before resorting to prophylactic drugs such as topiramate.
Julie Mauskop
Art credit: JulieMauskop.com

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A severe migraine attack can sometimes land you in an emergency room. With its bright lights, noise, and long waits, it is the last place you want to be in. To add insult to the injury, some doctors will think that you are looking for narcotic drugs and treat you with suspicion, while others will offer ibuprofen tablets. It is hard to think clearly when you are in the throes of a migraine, so you need to be prepared and have a list of treatments you may want to ask for, just in case the ER doctor is not good at treating migraines.

If you are vomiting, first ask for intravenous hydration and insist on having at least 1 gram of magnesium added to the intravenous fluids. Everyone with severe migraines should have sumatriptan (Imitrex) injection at home since it often eliminates the need to go to an ER in the first place. If you haven’t taken a shot at home, ask for one in the ER. The next best drug is a non-narcotic pain medicine, ketorolac (Toradol) and if you are nauseous, metoclopramide (Reglan). Do not let the doctor start your treatment with divalproex sodium (Depakene, drug similar to an oral drug for migraine prophylaxis, Depakote) or opioid (narcotic drugs) such as demerol, morphine, hydromorphone and other.

This post was prompted by an article just published in the journal Neurology by emergency room doctors at the Montefiore Hospital in the Bronx. It was a double-blind trial which compared intravenous infusion of 1,000 mg of sodium valproate with 10 mg metoclopramide, and with 30 mg ketorolac. They looked at relief of headache by 1 hour, measured on a verbal 0 to 10 scale. They also recorded how many patients needed another rescue medication and how many had sustained headache freedom.

Three hundred thirty patients were enrolled in the study. Those on divalproex improved by a mean of 2.8 points, those receiving IV metoclopramide improved by 4.7 points, and those receiving IV ketorolac improved by 3.9 points. 69% of those given valproate required rescue medication, compared with 33% of metoclopramide patients and 52% of those assigned to ketorolac. Sustained headache freedom was achieved in 4% of those randomized to valproate, 11% of metoclopramide patients, and 16% receiving ketorolac. In the metoclopramide arm, 6% of patients reported feeling “very restless”, which can be a very unpleasant side effect of this drug.

The authors concluded that the valproate was less efficacious than either metoclopramide or ketorolac. Metoclopramide was somewhat better than ketorolac but it also had more side effects.

To summarize, ask the doctor to start with hydration and magnesium, then sumatriptan injection, followed by metoclopramide and ketorolac, if needed. If the above treatments do not help, we also give dexamethasone (Decadron, a steroid medication) and DHE-45 (dihydroergotamine). All these medications can be administered in the office and we always tell our patients not to go to an ER and to come into the office if the attack occurs during our office hours.

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Tylenol (acetaminophen, or in Europe it is called paracetamol) is the go-to drug for pain, headaches, and fever during pregnancy. A new study just published in the journal JAMA Pediatrics indicates that this drug may not be as safe as previously thought.

Animal research has long suggested that acetaminophen is a so called hormone disruptor, a substance that changes the normal balance of hormones. It is a well-established fact that an abnormal hormonal exposures in pregnancy may influence fetal brain development.

Danish researchers decided to evaluate whether prenatal exposure to acetaminophen increases the risk for developing attention-deficit/hyperactivity disorder (ADHD) in children. They studied 64,322 live-born children and mothers enrolled in the Danish National Birth Cohort during 1996-2002.

The doctors used parental reports of behavioral problems in children 7 years of age using a specific questionnaire, retrieved diagnoses from the Danish National Hospital Registry or the Danish Psychiatric Central Registry, and identified ADHD prescriptions (mainly Ritalin) for children from the Danish Prescription Registry.

More than half of all mothers reported acetaminophen use while pregnant. Children whose mothers used acetaminophen during pregnancy were at about 1.3 times higher risk for receiving a hospital diagnosis of ADHD, use of ADHD medications, or having ADHD-like behaviors at age 7 years. Stronger associations were observed with use in more than 1 trimester during pregnancy and with higher frequency of intake of acetaminophen.

The researchers concluded that maternal acetaminophen use during pregnancy is associated with a higher risk for ADHD-like behaviors in children.

This presents a difficult problem in treating headaches and pain in pregnant women. Aspirin and other non-steroidal anti-inflammatory drugs such as ibuprofen and naproxen can cause other problems in pregnancy and are particularly dangerous in the third trimester. In women with migraines, acetaminophen tends to be ineffective anyway, so these women should be given migraine-specific drugs, such as triptans (Imitrex or sumatriptan, Maxalt or rizatriptan, and other). They are much more effective than acetaminophen and the woman may need to take much less of these drugs than of acetaminophen. Triptans are also in category C in pregnancy, which means that we do not know how safe they are. Imitrex was introduced more than 20 years ago and we do not that it does not have any major risks for the fetus, but that does not mean that more subtle problems, such as ADHD are also not more common. Another headache drug that should be avoided in pregnancy is Fioricet. It is popular with some obstetricians because it has been on the market for 40 years. However, it contains not only acetaminophen, but also caffeine, which can make headaches worse, as well as a barbiturate drug butalbital, which can also have deleterious effect on the fetal brain.

Fortunately, two out of three women stop having migraines during pregnancy, especially in the second and third trimester. If they continue having headaches, treatment is directed at prevention. Regular aerobic exercise, getting enough sleep, regular meals, good hydration, avoiding caffeine, learning biofeedback, meditation or another form of relaxation, magnesium supplementation, are all safe and can be very effective. Acute treatments that do not involve drugs are often not very practical for a busy person. However, if the headache prevents normal functioning anyway, taking a hot bath with an ice pack on the head at the same time can help some women. Taking a nap, getting a massage, aromatherapy with peppermint and lavender essential oils are good options. For nausea, ginger and Sea Bands are sometimes very effective.

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One of my patients I saw last week developed osteoporosis while taking Topamax (topiramate). Topiramate is known to cause osteoporosis by causing loss of calcium through the kidneys. While osteoporosis is not common, we don’t know if it is really that rare. A side effect that was thought to be rare (less than 1%, according to the manufacturer) when the drug was launched, is kidney stones. Now we know that close to 20% of people taking topiramate for a long time, develop kidney stones. Both kidney stones and osteoporosis occur through similar mechanisms, so it is possible that osteoporosis is also much more common than doctors think.

This patient had no other side effects and topiramate was very effective in controlling her migraines. Since osteoporosis is a very serious and potentially dangerous condition, she will have to stop taking topiramate. However, she does have other options because she has never tried Botox injections and several other drugs for the prevention of migraines.

Another very serious side effect that is not obvious to women taking Topamax, is the potential for serious problems in the fetus. The FDA designates topiramate as belonging to category D: “Pregnancy Category D drugs are those with positive evidence of human fetal risk based on human data, but still may be used in pregnant women in certain situations when its benefits are thought to outweigh potential risks”. Drugs in category B are considered to be safe in pregnancy, while category C means that there is not enough data and category X means it is absolutely contraindicated in pregnancy.

Topamax (topiramate) is one of the more popular drugs for the prevention of migraines (as well as treatment of epilepsy). It works only in half of the patients, while for the other half it doesn’t work or causes unacceptable side effects. The reason for its popularity is that unlike many other medications which can cause weight gain, this one often causes weight loss.

In addition to the side effects that occur over time, there are many that happen quickly and which are usually, but not always, patients easily linked to the drug: 1) cognitive impairment, such as inability to recall a word, slow thinking, or as some patients tell me, feeling stupid, 2) drowsiness, 3) dizziness, 4) fatigue, 5) blurred vision due to an acute glaucoma, and other.

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Generic drugs provide significant savings and 80% of all prescriptions in the US are filled with generic drugs. Many doctors are skeptical when patients complain that the generic is not as good as the brand. But not all generics are created equal, literally. For example, there are about 10 generic manufacturers of Imitrex (sumatriptan). I’ve had patients tell me that certain generics, particularly the ones made by an Indian company Ranbaxy, are much less effective than the brand or generics made by other manufacturers. This problem is widespread and one of my previous posts described a study of the use of generic Topamax (topiramate) in epilepsy patients (this drug is also approved for the prevention of migraines). Patients on a generic were admitted to the hospital more often, had longer hospital stays, and were three times more likely to sustain head injury or a bone fracture.

Yesterday, The New York Times published an expose on the generic manufacturers in India. Ranbaxy was one of the generic drug makers that was reported to have the most problems. Its plants are being repeatedly shut down by the American FDA, who also imposed a $500 million fine. The article cites understaffed regulatory bodies and corruption as the main reasons for poor quality controls. One survey showed that 12% of medications sold in India contained no active ingredients, including life-saving drugs such as antibiotics and cancer drugs. It is not clear what percentage of drugs entering the US is adulterated. At least in India the FDA is allowed to inspect plants and impose fines. In China, the government has refused to let the FDA expand its monitoring. The article has this ominous ending:
“The United States has become so dependent on Chinese imports, however, that the F.D.A. may not be able to do much about the Chinese refusal. The crucial ingredients for nearly all antibiotics, steroids and many other lifesaving drugs are now made exclusively in China.”

So what can you do to protect yourself? By law, the name of the manufacturer must be printed on the medicine bottle you get from the pharmacy. If you find a generic that works well, try to stick to it. If your pharmacy suddenly changes the generic manufacturer and the drug is not as effective or causes side effects, you may want to ask them to get you the generic that worked. The big chains such as Walgreens and CVS may not be able to do it, but most independent pharmacies have more flexibility. You can also try switching from one chain to another since they often stock generics from different companies.

One more tip is from my recent previous post – check GoodRx.com for the lowest prices in your area. Also, it is not unusual for your insurance copay to be higher than the actual cost of medicine. For example, you copay could be $15 or more, while if you buy the same generic drug without insurance, it will cost you $4 or $10. And do not expect the pharmacist to tell you this.

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“Daily triptan use for intractable migraine” is the title of a report by Dr. Egilius Spierings published in the latest issue of the journal Headache. This is a controversial topic, which I addressed in a previous post. Dr. Spierings, who is affiliated with both Tufts Medical Center and Harvard Medical School presents a case of a 50-year-old woman who failed trials of multiple preventive medications. This woman responded well to sumatriptan, 100 mg, which she took daily and occasionally twice a day with excellent relief and no side effects. Dr. Spierings discusses the evidence for Medication Overuse Headaches (MOH), which is common with caffeine-containing drugs, butalbital (a barbiturate), and opioid drugs (narcotics). It is less clear whether triptans cause MOH and he mentions that most patients who end up taking a daily triptan do so only after they failed many preventive (prophylactic) drugs and after they discover that they can have a normal life if they take a triptan daily. This applies not only to sumatriptan, but any other similar drug, such as Amerge (naratriptan), Zomig (zolmitriptan), Maxalt (rizatriptan), Relpax (eletriptan), and other. After 20 years of being on the market, we have no evidence that these drugs have any long-term side effects. In Europe several of these drugs are sold without a prescription. The major obstacle to their daily use has been the cost. However, several of these medications are now available in a generic form and a 100 mg sumatriptan tablet costs as little as $1.50.

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Placebo effect is a curse for medical researchers. Every new treatment has to be shown to be better than placebo and placebo is often very effective. In clinical practice, unlike in research, placebo effect is a good thing, but many doctors fail to maximize its effect. If the doctor emphasizes all of the potential side effects and does not stress positive attributes of a drug, the patient is not likely to respond well. However, if the doctor is enthusiastic about the efficacy of a drug, the results can be dramatically different. Obviously, side effects need to be mentioned as well, but if the drug is really dangerous, it should not be prescribed in the first place.

The importance of placebo effect specifically with migraine drugs was described in a study published in Science Translational Medicine. The findings confirm that patients who receive positive messages about the potential efficacy of their treatment may have better treatment outcomes than patients who receive negative messages.

The study involved 66 migraine sufferers with intermittent attacks. Patients first recorded their baseline pain intensity on a scale from zero (no pain) to ten (maximal pain) for an untreated migraine attack. Then each study participant received a series of six envelopes containing treatment for six subsequent migraine attacks: two of the envelopes were labeled as “placebo”, two as “Maxalt” (rizatriptan, one of the the anti-migraine drugs called triptans) and two as “placebo or Maxalt.” However, for each pair of envelopes with identical labels, one envelope actually contained a placebo pill and the other contained Maxalt.

Patients who had taken Maxalt mislabeled as “placebo” reported roughly 50% less pain relief than those who had taken the Maxalt labeled as “Maxalt.” This suggests that more than half of the drug effect was due to the placebo effect.

The study was conducted by Rami Bursteine, Ted Kaptchuk, and other doctors at Harvard Medical School. Dr. Burstein said that labeling Maxalt as “placebo” likely reduced the effectiveness of Maxalt by giving patients negative expectations about the efficacy of the treatment. Similarly, he says, providing patients with a long list of possible side effects, risks, and adverse events in the context of prescribing a drug in clinical practice could give patients negative expectations, and therefore could potentially reduce drug efficacy, resulting in patients taking more drug.

Strikingly, the study also revealed that placebo treatment mislabeled as Maxalt was just as effective in reducing pain as Maxalt mislabeled as placebo. “No one’s ever seen that before in human history, in my knowledge,” Kaptchuk says, referring to the comparison. “It raises the possibility that the placebo effect can be harnessed directly.”

The improvement in symptoms that occurred in patients who knowingly took the placebo pill may have occurred because people often become conditioned to associate taking a pill with feeling better, although no one can explain why or how the placebo treatment works.

It is considered unethical for doctors to prescribe placebo, but they may want to consider first trying drugs that may not be the most effective, but are significantly safer than the stronger ones. One such example in my own practice pertains to the use of epilepsy drugs. Depakote (divalproex) and Topamax (topiramate) are approved by the FDA for the prevention of migraines, while Neurontin (gabapentin) is not. In fact, Neurontin is less effective, but it has significantly fewer side effects. Also, Neurontin is not dangerous if the patient were to get pregnant, while the other two drugs are.

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Branded triptan medications are extremely expensive with one pill of Relpax or Frova costing $30 – $40. Fortunately, Imitrex, Maxalt, Amerge, and Zomig tablets are available in a generic form. However, even the generic version of Amerge is $3 to $4 a pill, although generic Imitrex and Maxalt can be found for $2. Unfortunately, some patients respond only to Relpax, Frova or Zomig nasal spray, which insurance companies tend not to pay for. Other people need medications that are not available in the US, such as domperidone, an excellent drug for nausea or flunarizine, a calcium channel blocker for the preventive treatment of migraine (not such an excellent drug because of its side effects).

Some patients who need a branded product or one not available in the US buy drugs from online Canadian pharmacies. But how do you know if the pharmacy is legitimate? Some sites that claim being a Canadian pharmacy in fact are not Canadian and the drugs they sell are fakes. One way to find a legitimate Canadian pharmacy is to check if it is certified by the Canadian International Pharmacy Association. You can also check if the pharmacy is certified by the PharmacyChecker.com and is listed on their free website.

When buying locally, you can find a pharmacy with the cheapest price for a specific drug by going to GoodRx.com. But do not assume that if a pharmacy offers the lowest price on one drug, its prices on other drugs will also be the lowest.


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The approval of the lower dose Sumavel device is a good opportunity to again remind migraine sufferers about the benefits of injectable sumatriptan. Many doctors do not even mention to their patients that sumatriptan is available in an injection that is easy to self-administer. Obviously, if a tablet of sumatriptan (Imitrex) or another triptan works quickly and prevents the headache from becoming disabling, there is no need for an injection. However, when the tablet does not work fast or well enough or if nausea makes it difficult to swallow tablets, injection can be a life saver. Injections of sumatriptan are available in a variety of devices. One of them is Sumavel, an injection without a needle. This device propels the medicine through the skin as a very thin jet of fluid. It is perfect for those with needle phobia. It also has the advantage of not having to worry about the proper disposal of needles. Having a choice of a 4 mg or a 6 mg dose allows patients with frequent cluster headaches to take 3 4 mg doses in 24 hours (maximum recommended dose is 12 mg). The 4 mg dose is also useful for people who get side effects from 6 mg, since 4 mg may be sufficiently effective without causing side effects.

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Dihydroergotamine (DHE-45) is considered to be the most effective injectable migraine drug. In addition to injections, it is been available in a nasal spray form (Migranal), but the nasal spray is much less effective than the injection. Early next year we expect to have an inhaled version of dihydroergotamine, Levadex. Clinical trials indicate that it could work as fast and as well as the injection and may have fewer side effects. Dihydroergotamine constricts blood vessels and just like triptans (Imitrex or sumatriptan and other) is contraindicated in people with cardiovascular disease, such coronary artery disease, heart attacks, and strokes. The perception has always been that dihydroergotamine, because it is a less pure drug than triptans, is a stronger vasoconstricter than triptans. However, a recent study by Dutch researchers suggests that this may not be the case.

This study compared the contractile effects of sumatriptan and DHE in human coronary arteries. The study looked at both large (proximal) and small (distal) coronary arteries. The arteries (removed from the body) were exposed to sumatriptan (Imitrex) and DHE. In larger (proximal) coronary artery segments sumatriptan was a stronger constricter than DHE but the difference was not significantly different. In contrast, in smaller (distal) coronary arteries, the contractile responses to sumatriptan were significantly larger than those to DHE. At clinically relevant concentrations contractions to both sumatriptan and DHE in proximal as well as distal coronary arteries were below 6%. The researchers concluded that coronary artery contractions to DHE in distal coronary artery are smaller than those to sumatriptan, although in the clinical situation both drugs are likely to induce only a slight contraction. So, both drugs are relatively safe and dihydroergotamine may be safer than sumatriptan, although both should not be given to migraine sufferers who also have cardiovascular disease or multiple risk factors, such as hyprtension, diabetes, high cholesterol, smoking, and other.

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Topamax (topiramate) has been reported to cause inability to sweat which can lead to hyperthermia or overheating. At first, this condition was reported as a rare complication, but a study of 173 children showed that 22 of them or more than 10% developed this side effect. The ability to sweat returns when the drug is stopped. Sweating allows the body to coll off and loss of this mechanism can be dangerous in hot weather or during vigorous exercise. Those who take Topamax should speak to their doctor if they notice reduced sweating.

Topiramate is an effective drug which the FDA approved for the prevention of migraine headaches as well as epilepsy and mood disorders. However, in large clinical trials only half of the patients put on this drug for the treatment of migraines stayed on it. The other half either did not obtain relief of their migraines or developed side effects. One of the most common side effects is impairment of cognitive functions – people can’t remember names, can’t come up with the right words, or as some have told me they feel stupid. Other people become very tired from Topamax because they develop metabolic acidosis – their bodies become too acidic. Long-term side effect of kidney stones was also thought to be rare when the drug was introduced, but subsequent studies showed that up to 20% of patients develop kidney stones.

The full extent of side effects of any new drug does not become apparent until years after its introduction. This does not mean that we can afford to wait for years before trying new drugs since some of the patients who come to our center with migraine headaches do not respond to the available treatments. What we can do is monitor these patients very closely and stop the drug as soon as possible.

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Botox injections is the only FDA-approved treatment for chronic migraine headaches. This is a very effective (works in 70% of chronic migraine patients) and very safe treatment. The only major drawback is its cost. However, there is a great variation in the cost from doctor to doctor and hospital to hospital. This post was prompted by an email I received from a former patient. Here are some excerpts from our exchange (with her permission):

“You’ve been my doctor now for many years, and I was just in your office over the summer for Botox treatment, but I live now in Charlottesville, VA and UVA’s hospital down here charges around $6000 for the same procedure that your office can do for $2250. With my insurance, I’m still responsible for 20% of the bill, and I can’t afford to have the procedure done here in Charlottesville.

They tell me it’s because they’re paying for facilities and staff, but even the drug is more than twice as much…THAT doesn’t make sense at all! This treatment has changed my life quite dramatically for the better. I’m so much healthier, more productive, creative, and all around a better citizen and human being as a result of not having constant headaches.”

Part of my response to her: “I am not surprised about the $6,000 price tag – I recently gave a lecture at Harvard and they also charge $6,000 and so do Mayo and Cleveland Clinics. They all also charge $2,000 for IV magnesium, while we charge $250.”

Our out-of-pocket fee for Botox injections is often only $1,700 and sometimes less, depending on the amount of Botox injected. However, the majority of our patients are covered by insurance and they have to pay only their usual copay. Almost all insurance plans now pay for Botox injections for chronic migraines, although they often require trials of prophylactic medications before they approve Botox.


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Cleveland Clinic doctors established that migraine patients who are educated about sumatriptan (Imitrex) and other triptans tend to do better. It is not a surprising discovery, but it highlights the importance of patient education. The study involved 207 patients at the Cleveland CLinic, Mayo Clinic, Brigham and Women’s Hospital. Here are some important facts that migraine sufferers need to know.

One such fact, taking medicine early, seems obvious, but many patients often wait to take a triptan for a variety of reasons. They often think that it may not be a migraine, but rather a tension headache that will not require a triptan. Others are reluctant to take medication because it might be dangerous, although the most common reason is that patients often don’t get enough medicine from their insurer. These are expensive drugs, even in a generic form. However, it is more expensive to lose a day of work and if the medicine is taken early one tablet may be sufficient, but if taken late, the patient may need 2 or 3 tablets to abort an attack.

Another fact is that you do not need to take an aspirin (or Migralex) or ibuprofen before resorting to a triptan if the headache is very severe. Many people often keep trying an over-the-counter drug first, even if they always end up taking a triptan. It is OK to combine aspirin or ibuprofen with a triptan if a triptan alone is insufficient.

Migraine sufferers should also know that triptans are contraindicated in people with coronary artery disease. If you had a heart attack, suffer from angina or have multiple risk factors (hypertension, diabetes, high cholesterol, smoking, etc).


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At the New York Headache Center we always try to avoid using medications and use alternative (i.e. non-drug) therapies first. We often succeed, but unfortunately, many of our patients do end up taking some drugs. However, when choosing among many medications, we start with the ones that are least likely to harm. Depakote (sodium valproate) is an effective drug for the treatment of epilepsy, mood disorders, and migraines. While we do prescribe Depakote to our patients, it has never been our first, second, or third choice because we already know that it can cause liver problems and fetal malformations. A recent study published in Neurology adds another reason to avoid this medication.

Patients with intractable epilepsy who were taking Depakote were compared with those who were taking other epilepsy medications and with healthy controls. MRI scans showed that those taking Depakote had thinning of the parietal lobes of the brain, had lower total brain volume, and lower white matter volume. This was a small study, but it was conducted because of previous reports of brain atrophy. Fortunately, those previous reports showed that brain atrophy was reversible when the medication was stopped. If you are taking sodium valproate for migraine headaches or a mood disorder, do not stop taking it without consulting your doctor since stopping it suddenly can worsen your condition and in epilepsy patients, cause seizures. But do discuss alternative options with your doctor, although some people may not be able to stop it if no other drugs provides relief of their symptoms.

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Acute treatment of episodic and chronic migraine headaches in the US leaves a lot to be desired. Results of the American Migraine Prevalence and Prevention Study lead by Dr. Richard Lipton indicates that the acute treatment of migraine headaches in patients with chronic migraines is significantly worse than in patients with episodic migraines. Chronic migraines are defined as those occurring on 15 or more days each month, while patients who have 14 or fewer migraines a month are classified as having episodic migraines.

The researchers developed a specific questionnaire to assess acute treatment of migraine headaches. The questionnaire evaluated the effect of treatment on people’s functioning, how rapid was the relief, relief consistency, recurrence risk, and tolerability or side effects. They examined responses from 8612 persons who met criteria for migraine (chronic migraine = 539; episodic migraine = 8073). The treatment scores were significantly lower for persons with chronic migraine vs episodic migraine. The conclusion was that the questionnaire was a robust tool for measuring treatment optimization and that acute treatment was suboptimal for both episodic and chronic migraines, particularly for chronic migraines, suggesting that there are opportunities for improving care.


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Candesartan (Atacand) is a relatively new blood pressure medication in the family of ACE receptor blockers (ARBs), which is also effective in the preventive treatment of migraine headaches. Another ARB, Benicar, or olmesartan has also been shown to be effective in preventing migraine headaches. Propranolol (Inderal), a beta blocker, is one of the oldest preventive drugs for migraines and many doctors often use it first. A recent study by Norwegian doctors compared candesartan with propranolol and placebo. They conducted a triple-blind, double crossover study, with 72 adult patients with episodic or chronic migraine, recruited in an outpatient clinic and through advertisements. Participants underwent three 12-weeks’ treatment periods on either candesartan (Atacand) 16 mg, propranolol slow release (Inderal LA) 160 mg, or placebo. The primary outcome measure was days with migraine headache in a 4 week period. They also looked at days with headache, hours with headache, proportion of responders (50% reduction of migraine days from baseline), and side effects.

Their analysis showed that candesartan and propranolol were equally effective and both were superior to placebo. Both drugs had more side effects than placebo, but side effects were different. The researchers concluded that candesartan should be included in the arsenal of drugs recommended for migraine prevention. The advantage of ARBs, such as Atacand and Benicar, is that unlike beta blockers they do not slow down the heart rate, which can be a problem during exercise. During exercise heart rate increases to deliver more blood to the muscles and lungs, but propranolol prevents this increase in the heart rate, which makes people feel tired, short of breath and not able to exercise as hard as they’d like. This is a significant problem since I recommend regular aerobic exercise as the first and the most important preventive treatment for migraine (and tension-type) headaches.
Julie Mauskop
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A non-steroidal anti-inflammatory (NSAID) drug naproxen (Aleve) alone seems to be more effective than naproxen combined with sumatriptan (Treximet), according to a study by Dr. Roger Cady and his colleagues from Missouri, which was presented at the International Headache Congress in Boston.
This was a small study involving 39 patients who suffered with moderate to severe attacks of migraine. The researchers looked at possible effect of acute medications on frequency of headaches. As migraine frequency increases, so too can the risk of medication overuse, which leads to more headaches. On the other hand, frequent administration of acute medications may act both as an acute and prophylactic treatment. The patients in the study were 18 to 65 years of age, with frequent episodic migraine with or without aura, in Stage 2 migraine (3 to 8 headache days per month) or Stage 3 migraine (9 to 14 headache days per month). Patients were asked to treat their migraines with sumatriptan/naproxen (Group A) or naproxen alone (Group B) for 3 months. Patients in Group B had a statistically significant reduction in migraine headache days at month 3 compared to baseline. Group A also had a reduction of migraine headache days but this decrease did not reach statistical significance over baseline. In addition, subjects in Group B had a statistically significant reduction of migraine attacks at all three months of the study compared to baseline. A greater than 50% reduction in the number of migraine days at month 3 occurred in 43% (6/14) of subjects in Group B compared to 17% (3/18) of subjects in Group A. Sumatriptan/naproxen was statistically superior to naproxen at 2 hours in reducing the migraine headache severity. The amount of acute medication used decreased from baseline to months 1-3 for both groups. Both treatments were well tolerated. The authors concluded that naproxen provides headache relief at 2 hours and reduces frequency of headache days and migraine attacks. Despite both groups using similar quantities of naproxen, this was not seen in sumatriptan/naproxen group, but sumatriptan/naproxen is more effective as acute treatment at 2 hours in reducing headache severity but does not significantly reduce attack frequency or the number of headache days.
If confirmed by larger studies, this is a very surprising discovery because there is little evidence indicating that triptans, like sumatriptan in this study, cause increased frequency of migraines due to medication overuse. In fact, this study did not show that sumatriptan did that, but only that naproxen alone was better at preventing migraine headaches. We also know from Dr. Richard Lipton’s large studies that aspirin has a preventive effect and naproxen and other NSAIDs do not, although they do not worsen headaches either. The large and multi-decade Framingham study showed that 81 mg of aspirin taken daily also has small but statistically significant beneficial effect in preventing migraine headaches. As far as acute treatment of migraines, in a review by an independent organization, Cochrane Reviews, the extra strength dose of aspirin (1,000 mg) was shown to be as effective as 100 mg of sumatriptan.

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Zomig (zolmitriptan) is the fourth triptan (out of seven) to become available in a generic form. This spells big relief for migraine sufferers who rely on this drug. Only tablets and orally disintegrating tablets (ZMT) will become available, not the nasal spray. Nasal spray offers faster relief and for some patients it is as fast as sumatriptan injection (Imitrex, Sumavel, Alsuma). It may take another 6 months for the price to drop significantly from the current $30 to $45 a pill because at this point only four companies are coming out with a generic version. There are about 10 manufacturers making generic Imitrex. Generic sumatriptan (Imitrex) is now available for $3 a pill, while the other two generics, Maxalt (rizatriptan) and Amerge (naratriptan) are still more expensive.

One caveat with the generics is that the quality sometimes is not as good as that of the brand. Of approximately 10 generic sumatriptan versions, my patients have found that 2 are very ineffective. One of these two manufacturers which is based in India (Ranbaxy), recently paid $500 million fine to the FDA for improper manufacturing, storing and testing of drugs. Many generic manufacturers are based in India and most of them produce good quality products. One of them is Dr. Reddy’s Laboratories. Of the four generic manufacturers of Zomig two are based in India (Glenmark and Zydus), one in Taiwan (Impax) and one is based in the US (Mylan) but also has many manufacturing plants in India. An Israeli company Teva, the largest manufacturer of generics in the world is known for their high quality products and it also has plants in many countries, including India.

Once you find a product that works, stick with that generic manufacturer even if you have to switch pharmacy chains since the entire chain usually carries the same generic. The law requires that the name of the manufacturer is printed on the medicine bottle your receive from the pharmacy, so it is easy to find out who the manufacturer is.

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Pregnant women are admonished not to take any medications while pregnant. Fortunately, two out of three women stop having migraines during pregnancy, especially during the second and third trimester. Unfortunately, one third of women continue having migraines and in some they get worse. Tylenol (acetaminophen), which is deemed to be the safest pain medicine in pregnancy is also the weakest pain killer and does nothing to relieve the agony of a migraine attack. Many obstetricians say that they are also “comfortable” giving drugs containing butalbital (a barbiturate) and caffeine along with acetaminophen (Fioricet) because these drugs have been around for many years. However, barbiturates are really not good for the developing brain while regular intake of caffeine can cause worsening of migraine headaches. Narcotic (opioid) analgesics are not exactly healthy either. Not taking any medications is also harmful to the mother and the fetus because severe pain causes serious distress to both and vomiting, which often accompanies migraines, can cause dehydration. Not treating migraine attacks may also lead to chronic migraines with pain present continuously. So, what is a pregnant woman to do?
At the recent annual meeting of the American Congress of Obstetricians and Gynecologists several doctors expressed their preference for the use of triptans in pregnant women. Sumatriptan (Imitrex) was first introduced 20 years ago and a registry of women who took sumatriptan during pregnancy suggests that this is a safe drug. Pregnancy registry for rizatriptan (Maxalt), which is the second triptan to come to the market 15 years ago, also suggests that it is a safe drug. Of course, it cannot be said that these drugs are proven to be safe for pregnant women because some yet undetected risk may still be present. However, compared to the alternatives and considering that triptans are much more effective, it is logical to recommend their use in pregnancy.
Besides treating an acute attack with triptans we always recommend preventive measures, such as magnesium supplementation (400 mg, on top of what is in a prenatal vitamin, which is usually only 100 mg), biofeedback, regular sleep, and exercise.
Preventive drugs that can cause major problems in the fetus and are contraindicated in pregnancy include divalproex (Depakote) and topiramate (Topamax). On the other hand, Botox is probably a safe preventive treatment in pregnant women suffering from chronic migraine headaches.


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Abuse of prescription narcotic (opioid) drugs is growing at an alarming rate and they are responsible for tens of thousands of deaths due to overdose every year. While all such drugs can cause addiction, there appears to be a difference among these drugs. A study recently published in The Journal of Pain suggests that a new opioid pain killer, tapentadol (Nucynta) is less likely to cause addiction than oxycodone (Percocet, Percodan, Endocet). The study was conducted by the manufacturer of Nucynta, a subsidiary of Johnson & Johnson. The researchers looked at the risk of shopping behavior (going to more than one doctor to obtain prescriptions) in over 150,000 patients. People who were prescribed oxycodone were four times more likely to be doctor shoppers than those who were prescribed tapentadol. Also, 28% of those prescribed oxycodone were asking only for oxycodone, while only 0.6% of those prescribed tapentadole were asking for tapentadol. This means that of those prescribed tapentadol less than one percent were asking only for tapentadole and the rest asked for other narcotics. Tapentadol has another advantage in that it causes less nausea and constipation than other opioid drugs.

Abuse potential is also reduced by making the pill temper resistant. About two years ago Oxycontin, which is one of the most popular (and most abused) long-acting narcotic pain killers was reformulated to make it difficult to crush. Because Oxycontin is a long-acting drug and does not give a quick high, addicts usually crush the tablet and inject or snort it. The new formulation prevents it from being crushed and in the past two years the abuse (and the sales) of Oxycontin has dropped. The FDA recently denied permission to sell generic versions of Oxycontin because they did not have such temper-resistant properties.

Unlike with other types of pain, opioid drugs seem to be less effective in the treatment of migraine and other headaches. Headache patients often report little relief from these drugs, as well as side effects, such as nausea and sedation. Opioid analgesics, such as codeine, hydrocodone (Vicodin), oxycodone (Percocet), and other can actually make headache worse in some patients by causing rebound, or medication overuse headaches. However, there are exceptions to this rule and a very small number of our patients respond only to opioid drugs and a few are doing well with daily long-acting narcotics. To make sure these drugs are not being abused we carefully select and closely monitor such patients.

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Preventive drugs for migraine headaches help less than half of the patients they are given to. There is no significant difference in effectiveness in these drugs. They reduce frequency of attacks by 50 percent, according to a review published in the recent issue of the Journal of General Internal Medicine.

Dr. Shamliyan from the University of Minnesota in Minneapolis and her colleagues conducted a literature review to identify high quality clinical trials of preventive drugs versus placebo.

Based on 215 published trials, the researchers found that all FDA-approved drugs, including topiramate (Topamax), divalproex (Depakote), timolol (Blocadren), propranolol (Inderal) and off-label medicines metoprolol (Toprol), atenolol (Tenormin), nadolol (Corgard), captopril (Capoten) and lisinopril (Zestril); and candesartan (Atacand) were effective in reducing monthly migraine frequency by 50 percent or more in 20% to 40% of patients. Topiramate, other off-label antiepileptics, and antidepressants had higher levels of side effects and were more likely to be stopped by patients because of side effects. While there were no significant differences in benefits between approved drugs, candesartan and other blood pressure drugs were the most effective and had fewest side effects for the prevention of episodic migraines.

The authors also noted that there was no evidence for long-term effects of drug treatments (that is trials lasting more than three months).

This review confirms my bias in favor of Botox injections over drugs. Botox helps not only 70% of chronic migraine patients, but in my anecdotal (but involving thousands of patients) experience it is equally effective for the prevention of frequent episodic migraines.


Photo credit: JulieMauskop.com

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The release of a generic substitute of the branded drug Imitrex (sumatriptan) has dramatically reduced the cost and improved the access to this uniquely effective migraine drug. The generic sumatriptan was released four years ago and now the price of one tablet is down to about $3 from over $20. The cost of two other generic triptans, Amerge (naratriptan) and Maxalt (rizatriptan) has remained very high, but it is expected to drop as more companies begin making generic copies. However, generics are not always the exact copies of the original branded drug that we expect them to be. In my previous post in 2009 I mentioned a study that showed that the generic Topamax (topiramate) does not work as well as the brand for some patients. I have also seen this with sumatriptan – my patients tell me that some generics do not work very well or at all. Out of about 10 generics of sumatriptan, I would guess that two are of poor quality. Once you find a generic that works for you, try to stick with the same generic manufacturer. The name of the manufacturer is printed on the bottle the pharmacy gives you. If one pharmacy does not have your generic, try another one. Here is a part of an email I just received from a patient (she gave me permission to share it with you):
“Just wanted to share with you that my pharmacy filled my maxalt melt prescription with yet another generic brand yesterday, which I found very unpleasant.
Previously the generic refills I’d gotten were from a company called PAR. The PAR pills resembled the original MAXALT melts in style of packaging (foil packets in plastic case) in taste and most important in melt-ability (never timed it but it always seemed to dissolve within 5 to 10 seconds–basically immediate dissolve)
But yesterday’s refill was from Mylan. These melts came in a regular prescription bottle of pills. I called the pharmacy after they were delivered thinking they accidentally gave me non-melts. They checked and told me, no, these were melts, just from a different company. They explained that this company (Mylan) packages them like any other pill (in bottles).
When I took the pill last night it felt like what i imagine it would feel like if you took a chewable vitamin and then waited for it to disintegrate in your mouth. It took minutes to “melt”, instead of seconds, and a grainy feeling remained even after that. it also made my upper palate sore, and tasted bad.
Today I called my pharmacist to double check that this was a melt and they checked again and it is. Luckily they were good enough to switch the rest of the prescription to the PAR generic brand. They also told me they would no longer carry the ones from Mylan. (They did say the Mylan generic is cheaper, though, so not sure how this will work out in the future.)”

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Cambia (diclofenac) is a prescription anti-inflammatory drug (NSAID) which is approved by the FDA for the treatment of migraine headaches. It is sold as a licorice-tasting powder that has to be dissolved in water before being ingested. This drug belongs to the same family as Advil or Motrin (ibuprofen), Aleve (naproxen), and prescription drugs, such as Relafen (nabumetone), Celebrex (celecoxib), and other. One of the drugs in this category, Viox (rofecoxib) was taken off the market because it increased the risk of heart attacks and strokes. A recent study published in an online medical journal, PLOS Medicine and translated into lay language in an NPR article indicates that diclofenac is as dangerous as Vioxx in causing heart attacks and strokes. The study also indicates that diclofenac unfortunately is one of the most popular NSAIDs in the world. It is probably safe to take Cambia a few times a month to treat migraine headaches, however, it should be avoided by people with other risk factors for heart disease and strokes. These risk factors include migraine with aura, high blood pressure, high cholesterol, diabetes, smoking, oral contraceptives, family history of heart disease, and other. Aspirin (in Migralex and other products), on the other hand, is the only NSAID that has been shown to prevent strokes, heart attacks, and several forms of cancer.
Cambia
Photo credit: CambiaRx.com

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Daily and prolonged intake of high doses of triptan medications (sumatriptan, or Imitrex, rizatriptan, or Maxalt, eletriptan, or Relpax and 4 others) has been shown to be safe in at least three clinical reports. I also have a few patients who have good control of their headaches and no side effects after many years of taking high doses of triptans daily. (I am not suggesting that it is healthy to take any medicine daily for years, but some people have no other choice because without this treatment they are disabled). A report just published in The Journal of Clinical Pharmacy and Therapeutics describes a patient who also was taking high doses of triptans daily (zolmitriptan or Zomig and frovatriptan or Frova tablets and sumatriptan injections), but who developed severe depression on two occasions when the triptans were stopped suddenly. The first bout of depression was very difficult to treat despite trials of several antidepressant drugs (amitriptyline, or Elavil, mirtazapine, or Remeron, and duloxetine, or Cymbalta, with addition of quetiapine, or Seroquel). All these antidepressants work through the serotonin system. His second bout of depression responded very well to bupropion (Wellbutrin), an antidepressant that works on norepinephrine and dopamine, rather than serotonin. This report suggests that while it may be safe to take triptans daily for a long time, they can affect the serotonin mechanisms in the brain and that they should never be stopped suddenly. Another important lesson is that if depression does develop after stopping daily triptans, the preferred drug may be bupropion.

Photo credit: JulieMauskop.com

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Migraine headaches that occur at around the time of menstrual period tend to be more severe and more difficult to treat. Analysis of studies that involved 187 women with menstrual migraines who treated at least one of their attacks with frovatriptan (Frova) and one with another triptan showed that frovatriptan was more effective. While all triptans were equally effective in providing pain relief at 2 and 4 hours, rate of headache recurrence was significantly lower for frovatriptan. After 24 hours, 11% of women who took frovatriptan had a recurrence of their headache, but with other triptans 24% had their migraine come back. After 48 hours, the numbers were 15% for frovatriptan and 26% for other triptans. One caveat is that all of these studies were funded by the maker of frovatriptan.

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I see many patients who tell me that “I’ve tried every migraine drug” and seek me out to explore non-drug approaches, such as herbs, supplements, Botox, acupuncture and other. I always try to avoid using medications (and have written books on non-drug approaches), but some patients do best with a combination of medications and non-drug approaches. So, when someone tells me that they’ve tried “every drug”, I tell them that I’ve never seen such a person because there are so many drugs that we use to treat headaches. For example, they might’ve tried a blood pressure medication, but we have many different anti-hypertensive drugs and they work in different ways. One type of blood pressure medication may work when another does not. Also, if one drug caused side effects, another in the same or different category may not.
Here is a brief description of blood pressure medications that are used for the prophylactic treatment of headaches. The first medication approved by the FDA for the prevention of migraine headaches was propranolol (inderal) (methysergide or Sansert was approved earlier, but it is no longer available in the US). Propranolol was originally developed for the treatment of hypertension and then accidentally was found to help migraine headaches as well. A second beta blocker, timolol (Blocadren) was also tested, was found to work well and it also received FDA approval. Other beta blockers, such as atenolol (Tenormin), labetalol (Normodyne), and nebivolol (Bystolic) were also shown to be effective. Nebivolol tends to have fewer side effect, but it is not yet available in a generic form, so it can be relatively expensive. Propranolol is available in a slow release form (Inderal LA) which can be taken once a day, while regular propranolol goes in and out of the body quickly and needs to be taken two or three times a day. Atenolol and nebivolol produce effect that lasts all day, so they can be taken once a day. Atenolol is very inexpensive and I always remind patients to ask the pharmacist about the price without insurance because the insurance co-pay can be higher than the out-of-pocket cost of the drug. Most pharmacists will not volunteer this information.
Because beta blockers worked for migraines other blood pressure medications were also tested. Calcium channel blockers, such as verapamil (Calan), amlodipine (Norvasc), diltiazem (Cardizem), and other do not seem to be as effective as beta blockers. High doses of verapamil are very effective for the prevention of cluster headaches.
Another category of blood pressure medications, ACE (angiotensin converting enzyme) inhibitors, such as lisinopril (Zestril, Prinivil), enalapril (Vasotec) and other do help probably as well as beta blockers. These medications sometimes cause cough or other side effects and can be substituted by similar drugs in the category of ACE receptor blockers (ARBs). ARBs do not cause cough and may have fewer other side effects. Drugs in this group that were studied for the prevention of migraine headaches include olmesartan (Benicar), losartan (Cozaar), and candesartan (Atacand).

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Steroid injections are routinely used at our Center for the treatment of cluster headaches and occipital neuralgia. I just received a call from a concerned patient with cluster headaches who recently received an occipital nerve block with methylprednisolone acetate (Depo-Medrol), the same drug that caused fungal meningitis in almost 200 patients, of whom 14 died. His cluster headaches stopped after the injection and he had no symptoms of meningitis, but understandably he was still concerned. All of the patients who contracted meningitis were given epidural injections which are given for low back or neck pain with medicine deposited near the meninges or soft covering that envelopes the spinal cord. All of them received a tainted product manufactured by a compounding pharmacy, which was not licensed to mass produce such medications. Their product was significantly cheaper than the same medicine produced by the largest pharmaceutical company in the world, Pfizer. We have never used any other products except for the one made by Pfizer. I an addition to methylprednisolone (Depo-Medrol) some doctors use a different steroid, triamcinolone, which is manufactured by Brystol Myers Squibb under the name Kenalog. Whenever you receive a steroid injection for back pain, joint inflammation, cluster headaches, or any other indication, ask the doctor if the steroid you are going to receive was manufactured by a major pharmaceutical company. In case of epidural steroid injections, you should also question if these injections are really necessary because they have never been proven to be effective in the first place and even pure untainted products have been associated with spinal cord damage and other serious side effects.
Epidural steroid injection:
epidural steroid injectionOccipital nerve block

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Steroid medications can be very effective for migraine headaches that fail to respond to other medications. Steroids, such as prednisone, dexamethasone, methylprednisolone have many potential serious side effects if taken for a long time. We know about these long-term side effects from patients with asthma, arthritis, lupus and other conditions who have take steroids daily for months and even years. However, these medications are relatively safe if taken for only a few days. If a severe headache does not respond to Migralex, sumatriptan, (Imitrex), or other medications, I prescribe a two-day course of dexamethasone. The usual dose is 8 mg daily for two days. Other doctors prescribe a six-day course of methylprednisolone (Medrol Dosepak). However, if a headache completely resolves after two days, it seems unnecessary to continue this medication for the full six days. In the office, we also give intravenous dexamethasone which provides faster relief than tablets. Another indication for steroids is for cluster headaches. A ten-day course of prednisone (starting with 100 mg and reducing by 10 mg every day) can sometimes stop the entire cluster period. Unfortunately, for some cluster headache sufferers headaches return as soon as the dose of prednisone is lowered. If no other preventive medication, such as verapamil, lithium, topiramate (Topamax) or divalproex (Depakote) work, some patients with severe attacks are willing to accept the risk of long-term side effects of steroids. Some of these side effects are weight gain, diabetes, stomach ulcers, glaucoma, high blood pressure, and osteoporosis.

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Injections of sumatriptan (Imitrex) are very underutilized. Many doctors fail to offer this option to their migraine and cluster headache sufferers because they are not aware of this option or more often because they are not aware how debilitating migraines can be or because they consider it to be dangerous. Patients who wake up with a severe headache (migraines commonly occur in the morning) and have to go to work or take care of their children often become disabled for the day because oral medications are not effective. Another group of patients who benefit from injections are those with nausea and vomiting. But you do not have to have a severe attack or have vomiting to take an injection. I have occasional migraines, usually triggered by wine or lack of sleep and if I take an oral medication it will usually help, but it may take an hour or even two before it works. So, if I have a headache late in the evening, I take an injection which stops my migraine within 10 minutes and I can fall asleep right away instead of waiting for an hour before the tablet takes effect. Sumatriptan injection is the only drug approved for the treatment of cluster headaches and it is a true life saver for cluster sufferers.
It is very easy to give yourself an injection of sumatriptan. There are three different devices on the market. The oldest one is a little more cumbersome to use, which can be a factor when you are in the midst of a severe attack, but it costs the least and is more likely to be covered by the insurance. Another injector, Sumavel does not have a needle – the device shoots the medicine into the skin through a tiny hole. This device is easier to use but some people complain that it is more painful despite it being needleless. The third device, Alsuma is identical to the one used in the Epi-Pen and it is also very easy to use. Sumatriptan is also available in vials. Some people prefer to use vials for several reasons. First, they are cheaper, second, they may be less painful to inject since you can use a syringe with a smaller needle than the ones in autoinjectors and third, some people get excellent results and fewer side effects with a smaller dose and the vial allows them to use 2 or 3 mg. Being able to use 2 or 3 mg at a time is particularly useful for cluster headache patients who have one or two headaches a day for extended periods of time and don’t get enough injections from their insurer.
If you suffer from severe migraine or cluster headaches ask your doctor about injections of sumatriptan. The main contraindication is heart disease or multiple risk factors for heart disease, but otherwise it is a very safe medicine. In Europe tablets of sumatriptan are sold without doctor’s prescription.

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Migraine patients can sometimes benefit from an Alzheimer’s drug, Namenda (memantine). All drugs for the preventive treatment of migraines, including Botox, had been first approved for a completely different indication. Beta blockers and other high blood pressure drugs, epilepsy drugs, and antidepressants are the most commonly used medications for migraine. It is surprising that such a wide variety of medications with very different mechanisms of action would all provide relief for migraines. We have only a basic understanding of how these drugs might work because they were discovered to help migraines by accident. Namenda is a very old medicine that has been available in Europe for over 30 years. It was used for a variety of neurological conditions, but in the US it was introduced and approved only for Alzheimer’s disease in 2003. It works by blocking an NMDA receptor, which is found in brain cells and which is responsible for letting calcium into the cells. Excessive inflow of calcium leads to many negative effects, including propagation of pain messages along the nervous system. Magnesium is a natural NMDA receptor blocker and we often add Namenda to magnesium for stronger effect. Namenda is not a very strong medication, meaning that it probably works for less than half of the patients, but it also causes fewer side effects than many other drugs. It is well tolerated even by the elderly Alzheimer patients, although like any other drug it can cause side effects, including nausea, drowsiness, and dizziness. Another problem with the drug is that some insurance companies do not pay for it because it is not approved for the prevention of migraines.

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Chronic and episodic paroxysmal hemicrania and hemicrania continua are rare types of headaches that have one common feature – they respond very well to indomethacin (Indocin). The diagnosis is actually based not only on clinical features but also on the response to indomethacin. Indomethacin belongs to the category of NSAIDs (non-steroidal anti-inflammatory drugs) such as aspirin, ibuprofen, naproxen, and other. Indomethacin is somewhat unique in the way it works and it is often stronger, however it also causes more gastrointestinal side effects than other NSAIDs. Symptoms of paroxysmal hemicrania are similar to those of cluster headaches: the pain is very severe, very brief (lasting a few minutes) and occurs anywhere from a few times to a few hundred times a day. The pain is always one-sided, localized to the eye and it is often accompanied by tearing, nasal congestion, and redness of the eye. Hemicrania continua is very different in that it is present constantly and it is not very severe, but it also involves only one side of the head. Hemicrania continua is often mistaken for chronic migraine or chronic tension-type headache, which leads to ineffective treatments. The dose of indomethacin varies from 25 to 75 mg, taken three times a day. Some patients with these headache types do not tolerate indomethacin, which can cause heartburn, stomach ulcers, bleeding ulcers and other side effects. In those patients we try epilepsy drugs, other NSAIDs (which may or may not be better tolerated), as well as Botox injections and sometimes these treatment do help, if not as well as indomethacin, at least enough to improve patients’ quality of life.

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We should not complain about our health care system. People in such advanced European countries as Netherlands have it much worse. I just saw a 27-year-old Dutch woman with chronic migraines who has been coming to see me for Botox injections every three months for the past 3 years. Three years ago she was told by her neurologist to quit law school because even if she was able to graduate, her migraines will prevent her from being able to hold a job. She is graduating from law school this June. Her doctors also told her not to take sumatriptan (called Imigran in Europe and Imitrex in the US) more than once or twice a week and take only aspirin on other days. This approach made her unable to function on the five days when she did not take sumatriptan, but even with sumatriptan her headaches were still disabling. Botox injections produced a significant improvement in the severity of her attacks, although not in the frequency. However, now sumatriptan provides complete relief and she can function normally. She tried to find a way to get Botox injections in Holland and offered to pay the doctor. He was not able to do it because medicine is socialized in Holland and he could not accept payment for procedures not covered by the health service. She turned to the government and offered to reimburse the health service for Botox, but they also refused. She is fortunate in that she is able to afford to come to New York every three months and buy as much sumatriptan as she needs to function normally.
Things are not much better in the UK and other European countries. The UK approved the use of Botox for chronic migraine before it was approved in the US. However, their national health service also refuses to pay for it. My Italian colleagues have told me that as a society they’ve decided that Botox was too expensive to be used for the treatment of migraines, despite the evidence that it works. I should note that just like many other drugs, Botox is significantly cheaper in Europe than in the US.

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Muscle relaxants can be surprisingly effective for the prophylactic treatment of migraine headaches. It is surprising because migraine is a brain disorder and not a disorder of muscles. However, studies have shown that during a migraine attack muscles are in fact very contracted and that is probably why people find some relief by rubbing their temples and the back of the head. We also thought that Botox works by relaxing these tight muscles, but it turned out that it also works on nerve endings. Muscle relaxants also do more than just relax muscles – they actually work on brain mechanisms of migraines. Not all muscle relaxants help migraines and the most evidence exists for tizanindine (Zanaflex). A double-blind study was done by Dr. Alvin Lake and his colleagues and it showed very good efficacy and few side effects. The target dose was 8 mg three times a day, but the average dose was 18 mg a day. The main side effect of this drug is sedation, but otherwise it is fairly benign. Baclofen (Lioresal) is another muscle relaxant that has been subjected to a double-blind study and was found to be effective for the prevention of migraine headaches. The drug was also given three times a day with a total dose ranging from 15 to 40 mg a day. The main side effect of baclofen is also sedation. Other muscle relaxants, such as metaxalone (Skelaxin), cyclobenzaprine (Flexeril), clonazepam (Klonopin), and other have helped some patients, but there are no scientific studies to prove their efficacy in migraine.

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How much sumatriptan (or another triptan) is too much is not clear. The initial FDA-approved daily dose of oral sumatriptan (Imitrex) for the treatment of an acute migraine was up to three 100 mg tablets. Several years later the maximum daily dose was reduced to 2 100 mg tablets a day, to be taken at least 2 hours apart. There was no scientific or safety reason for the reduction of the dose. Two other triptans, rizatriptan (Maxalt) and frovatriptan (Frova) are still allowed to be taken three times a day. The maximum dose of eletriptan (Relpax) is 2 40 mg tablets, however, in Europe it is 2 80 mg tablets. Some doctors are very strict in adhering to these arbitrary limits. Some patients will tell me that they always need to repeat the dose of a triptan 2 hours after the first dose. It makes sense to have them take a double dose at once and the results can be much better – the headache will go away and will not return. It is true that the higher the dose the more side effects you can expect. In patients who are sensitive to drugs or weight less than 100 lbs, it is prudent to try half of the usually dose and in everyone else the standard dose should be used at first. If the standard dose is not fully effective, another triptan can be tried, but if none provide sufficient relief and do not cause side effects I first recommend combining the standard dose of a triptan (100 mg of sumatriptan, 10 mg of rizatriptan, 40 mg of eletriptan, and so on) with an anti-inflammatory medication, such as Migralex (aspirin/magnesium), naproxen (Aleve), or ibuprofen (Advil). Only if this combination also fails would I suggest doubling the standard dose of a triptan.
What about the maximum dose of a triptan to be taken in a month? The initial studies of sumatriptan were conducted in patients who had 2 to 6 migraines a month and when the drug was approved by the FDA no monthly limit was imposed. However, the manufacturer packaged sumatriptan tablets in a blister pack of 9 tablets. This became the unofficial limit, even though no studies were ever conducted to examine the safety and efficacy of frequent sumatriptan (or any other triptan) use. Many doctors, including headache specialists believe that taking any abortive medication, including triptans too frequently will make headaches worse (so-called medication overuse headaches). We do have good scientific evidence showing that caffeine in fact can worsen headaches by causing caffeine withdrawal, or rebound headaches. People who drink large amounts of caffeine know that if they stop their caffeine intake they will develop a headache. In patients prone to headaches, as little as 2 cups of coffee, tea, or soda can worsen their headaches. We also have some evidence that barbiturates, such as butalbital (Fioricet, Fiorinal, Esgic) and opioid analgesics, such as codeine, oxycodone (Percocet), hydrocodone (Vicodin) and other can cause worsening of headaches if taken more than once a week. However, we have no evidence that triptans or NSAIDS, or non-steroidal anti-inflammatory drugs (Advil, Aleve, Motrin, Relafen, Voltaren, etc) cause worsening of headaches if taken frequently. Aspirin (such as in Migralex) in fact may prevent worsening of migraines.
I do discourage frequent use of triptans, which usually indicates poor control of migraines. Most patients with frequent migraine attacks are better off with preventive therapies, such as aerobic exercise, biofeedback, magnesium, CoQ10, Botox injections, or sometimes even preventive drugs. A common barrier to the frequent use of triptans is the insurance company. Many insurers have been reducing their monthly coverage of triptans from 9 to 12 down to 4 or 6, while increasing co-pays. This is clearly done not out of any safety concerns, but to save money.
With all of the above said, I do have about two dozen (out of thousands) patients who require very frequent or daily intake of triptans. These patients have gone through many of the preventive treatments listed above, including Botox, and they are still having daily headaches, or what we call chronic migraines. I usually try to have them stop triptans for several weeks to see if they improve with NSAIDs and prophylactic treatments, but most do not. These patients have very good control of their migraines, have no side effects, and can function normally. I am concerned about the potential cardiac side effects of these drugs, which are well documented. If a patient has some risk factors for heart disease (post-menopausal, high cholesterol, hypertension, diabetes, smoking, obesity, family history, etc), a stress test should be obtained.
What prompted this post was an article in the latest issue of journal Headache, which reports on a 49-year-old woman with 18 years of chronic cluster headaches. Injectable sumatriptan is the only treatment approved for cluster headaches. This woman has been injecting herself with 6 mg of sumatriptan anywhere from 2 to 37 times every day (on average, 20 times) for 15 years. She had no side effects or negative effects on her heart and there was no decline in the efficacy of sumatriptan over time. She failed several abortive and preventive medications. Other doctors have published articles describing patients taking triptans very frequently without loss of efficacy or side effects, but this patient has the most frequent and prolonged use ever reported.

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Pregnant women who take NSAIDs such as naproxen (Aleve), ibuprofen (Advil), diclofenac (Volaren, Cambia), celecoxib (Celebrex), and other are two and a half times more likely to have a miscarriage. This is a finding of Canadian researchers who examined the records of 4,705 women who had a miscarriage. Surprisingly, they did not find that the risk was higher with a higher dose of NSAIDs. NSAIDs are particularly dangerous in the third trimester, when they can also cause heart problems in the fetus. Instead of NSAIDs pregnant women can try taking acetaminophen (Tylenol), which unfortunately is not a very effective pain killer. Narcotic or opioid drugs, such as codeine, Vicodin and similar drugs are not safe in pregnancy either, but can be used occasionally, although they are not very effective for migraine headaches. Triptans, such as sumatriptan (Imitrex), rizatriptan (Maxalt), eletriptan (Relpax) and other while not approved for pregnant women, may be safer and much more effective than either NSAIDs or narcotics. If a pregnant woman has frequent headaches, prevention with intravenous magnesium, biofeedback, and Botox injections should be tried before resorting to daily preventive drugs.

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Risk of irregular heart beat, heart attacks, and death increases in people taking NSAIDs, such as ibuprofen (Advil), naproxen (Aleve), diclofenac (Cambia, Voltaren, Cataflam), and celecoxib (Celebrex). The risk with these drugs in people who suffer from hypertension and heart failure is well-known, but two recent large studies provide additional information on this risk. A study in the British Medical Journal that reported on 32,602 patients with atrial fibrillation suggested that patient who developed atrial fibrillation (dangerous irregular heart beat, which is often called A fib) were more likely to have been taking NSAIDs (but not aspirin) when this heart condition occurred. Another study conducted by Danish doctors and published in the journal Circulation looked at 83,677 patients who suffered a heart attack. They discovered that taking an NSAID drug (but again, not aspirin) for as little as one week increased the risk of having a second heart attack and dying by 45%. Taking NSAIDs for three months increased the risk by 55%. It is particularly unfortunate for heart patients who suffer from migraine headaches because they are also not allowed to take migraine drugs, such as sumatriptan (Imitrex), rizatriptan (Maxalt), and other triptans. This leaves them with aspirin (or Migralex – a combination of aspirin with magnesium, developed by Dr. Mauskop) and pain drugs that can make headaches worse (Fioricet, codeine, Vicodin, and other). Another option for these patients is to use preventive treatments, such as magnesium (which is also very beneficial for heart conditions), CoQ10, biofeedback, Botox injections, acupuncture, and as a last resort, preventive medications.

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Aspirin is the first-line treatment for migraine and tension-type headaches regardless of headache intensity, according to a report published by three leading headache experts (from Austria, Germany, and Norway) in the journal Headache. Some headache expert advise using a prescription drug such as sumatriptan (Imitrex) or another triptan (Maxalt, Zomig, Relpax, etc) from the outset if the headache is severe and to use aspirin or similar drugs when the headache is less severe. However, this review of published data from large clinical trials suggests that aspirin works equally well for both moderate and severe headaches. This is true for both migraine and tension-type headaches. The six migraine trials reviewed included 2,079 patients (1165 with severe and 914 with moderate attacks) treated with 1,000 mg of aspirin and one tension-type headache trial had 325 patients (180 with moderate and 145 with severe attacks) treated with 500 mg and 1,000 mg of aspirin. Prior studies have also shown that 1,000 mg of aspirin is as effective as 100 mg of sumatriptan in the treatment of migraine headaches and aspirin had fewer side effects. Disclosure: I have patented and developed Migralex, an over-the-counter drug which contains (in 2 tablets) 1,000 mg of aspirin and 150 mg of magnesium.

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Migraine and epilepsy drug Topamax is being recalled by its manufacturer, Ortho-McNeil Neurologics, a division of Johnson and Johnson. This recall affects only two lots of 100 mg tablets. This recall does not affect topiramate, generic copies of this brand. Since the generic form is much cheaper, most patients have switched to it from branded Topamax. This adds another problem to this beleaguered drug. It was recently reclassified by the FDA from pregnancy category C to category D, which means that it is much more dangerous for the fetus than originally thought. Topiramate is also associated with a high incidence of kidney stones (20%) and can cause other serious problems. This is why we always emphasize non-drug approaches (exercise, acupuncture, biofeedback magnesium, Botox, etc), which can be more effective and are much safer than drugs.

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Topiramate (Topamax) increases the risk of birth defects, such as cleft lip and palate, warned the Food and Drug Administration (FDA). Topiramate is an epilepsy drug which is also approved for the preventive treatment of migraine headaches. It is a very popular drug, in part because it can cause weight loss in some patients. In clinical trials only half of migraine patients who started taking this drug remained on it for more than a few months because it was ineffective for some and caused intolerable side effects in others. One of the main side effects which makes people stop taking this drug is difficulty speaking and thinking. Topiramate is also known to cause kidney stones and the initial data suggested that less than 1% of patients taking it developed kidney stones. However, a recent report suggested that up to 20% of people taking topiramate for a period of two years will develop kidney stones. Half of the patients who developed kidney stones were not aware of it. Kidneys stones not only can be very painful, but in severe cases can impair kidney function.
These two newly discovered dangers are additional reasons to avoid taking topiramate and if possible, to avoid taking any medications. While we do prescribe many medications, including topiramate, we always begin with life style modification (diet, sleep, exercise), biofeedback or meditation, magnesium, CoQ10, and other supplements, acupuncture, and Botox injections.

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