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New treatments

Merck discontinued the development of telcagepant, a promising new drug which represents a new class of migraine drugs, so-called CGRP antagonists. These drugs appear to be as effective as sumatriptan (Imitrex) and other triptans in aborting a migraine attack, but do not carry an increased risk of strokes and heart attacks which can occur, albeit very rarely, with triptans. Telcagepant was also tested as a daily preventive drug for migraines and in those trials some patients developed minor liver abnormalities. At first, Merck continued to pursue the development of telcagepant for abortive treatment, but recently decided that the risk of not getting it approved by the FDA because of the liver problems was to high. This again demonstrates that part of the reason why new drugs are so expensive – for every one that makes it to the market there are many that after an investment of hundreds of millions of dollars do not. It is likely that Merck and other companies will continue to do research to find a CGRP antagonist without serious side effects.

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Chronic cluster sufferers may benefit from sodium oxybate (Xyrem), according to a report in the leading neurology journal,Neurology. Xyrem is a drug approved for the treatment of narcolepsy but it is also being evaluated for the treatment of pain of fibromyalgia, chronic fatigue, and other conditions. It is well established that patients with cluster headaches often suffer from sleep disorders and cluster attacks often wake patients from sound sleep in the middle of the night. It is logical to consider drugs that affect sleep in the treatment of cluster headaches. However, traditional sleeping medications do not help cluster sufferers. Approximately 10% of patients with cluster headaches suffer from chronic clusters, which means that they have headaches for years without a break, while the other 90% have cluster periods lasting a few weeks to a few months every year or every several years. The article in Neurology describes 4 patients with chronic clusters who were treated with Xyrem with excellent long-term results. In one patient relief lasted 8 months while in the other three for up to two years. Side effects consisted mostly of dizziness, some memory difficulties, vomiting, and weight loss, however they were not severe enough to stop taking this medication. Xyrem is a controlled drug with potential for abuse and is dispensed only through a single centralized pharmacy.

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Botox has been shown to relieve headaches of low spinal fluid pressure in a case reported at the last annual scientific meeting of the American Headache Society in Washington DC. Low spinal fluid headache usually occurs after a spinal tap (lumbar puncture) or rarely without an obvious cause. The diagnosis is made by doing a spinal tap which normally shows low pressure and by a characteristic appearance of the MRI scan of the brain. The woman who was treated by doctors from the Mayo Clinic had a spontaneous leak of the spinal fluid and did not respond to blood patches which is the first-line treatment for this condition and consists of injections of person’s own blood into the area around the leak. She also did not respond to a variety of medications. Botox injections provided her with relief for the first time in 20 years. She has continued to receive Botox injections for three years now with sustained results. It somewhat surprising that Botox would help because the cause of low pressure headaches is thought to be tugging on the nerves due to sagging of the brain, which normally is floating in the spinal fluid. It is possible that Botox just stops pain sensations regardless of the cause, whether it is due to migraine, shingles or other nerve disturbance.

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Trigeminal neuralgia is an excruciatingly painful disorder which affects about one in a thousand people. Patients describe the pain of TN as an electric shock going through the face. The pain is brief, but can be so frequent as to become incapacitating. Eating and talking often triggers the pain, so some patients become malnourished and depressed. The good news is that most people can obtain relief from this condition by taking medications, such as Tegretol (carbamazepine), Trileptal (oxcarbazepine), Dilantin (phenytoin), or Lioresal (baclofen). Patients who do not respond to medications have several surgical options available. According to a new Dutch nationwide study of three invasive treatments for trigeminal neuralgia published in journal Pain shows that every year about 1% of those suffering from TN undergo surgery. Of the three most common types of surgery, percutaneous radiofrequency thermocoagulation (PRT) is by far most popular – in  a three year period in Holland, 672 patients underwent PRT, 87 underwent microvascular decompression (MVD), and 39 underwent partial sensory rhizotomy (PSR). The latter two procedures a performed by neurosurgeons (MVD requires opening of the skull), while PRT is usually done by anesthesiologists (a probe is inserted through the cheek to the nerve ganglion under X-ray guidance). MVD was most effective, but caused more complications than PRT, although fewer than with PSR. More patients having PRT had to have a repeat procedure, but it was still safer than the other two. Very often the physician under-treats during the first treatment of PRT in order to avoid complications. Overall, the best initial procedure for those suffering with TN is PRT and if repeated PRTs fail, MVD can sure this condition.

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Obese people are more likely to suffer from more frequent and severe migraine headaches. The question that remained unanswered was whether losing weight helps relieve headaches. A new study just published in the leading neurology journal, Neurology suggests that this may be the case. Researchers from Brown University in Providence, RI examined 24 severely obese patients before and after bariatric (weight reduction) surgery. Their mean body mass index (BMI) was 46 and their mean age was 39. A direct correlation between the amount of weight loss and the reduction in the number of headache days was observed. Weight loss was also associate with reduced disability. This study gives scientific support to the idea that weight loss may improve migraine headaches.

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Taking two different triptans (drugs such as Imitrex, or sumatriptan, Maxalt, or rizatriptan and other) within 24 hours of each other is contraindicated according to the FDA. However, there is no scientific reason for such prohibition. You are allowed to take a second dose of the same triptan 2 hours after the first dose, so it makes no sense why you could not take a different one. Most of the triptans (five out of seven) get washed out from the body within 2 – 3 hours, so even if there was an interaction between different triptans (and there is absolutely no evidence for that) it would be safe to give a different one 3 hours later. A report in the latest issue of the journal Headache by Dr. Rothrock studied 200 patients who “mixed triptans”, that is took a shot of sumatriptan and two hours before or after a tablet of either rizatriptan (Maxalt, zolmitriptan (Zomig), almotriptan (Axert), or eletriptan (Relpax). He found that not only there were no problems, patients were highly satisfied with this approach. I also hear from my patients that sometimes they know that one tablet of a triptan will not be enough for their severe attack and they will take two at once. Many doctors strongly advise their patients against it, but there is no evidence of any great danger from a higher dose. These dosages were arrived at by looking for an optimal dose which provides good relief and few side effects and for most people the standard dose will suffice. But some people need higher amounts. In case of eletriptan (Relpax), 20 mg and 40 mg are available in the US, but in some European countries it is available in 80 mg. It is clear that some patients benefit from a higher than recommended dose without an increase in side effects.

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Botox is now approved for chronic migraine headaches. However, it may help you feel happier not only because your headaches improved. Several studies suggest that the inability to frown caused by Botox makes people happier too. Psychologists at the University of Cardiff in Wales showed that healthy people (not headache sufferers) who had cosmetic Botox injections were happier and less anxious than those who hadn’t. Another study published in the Journal of Pain showed that people who grimaced during a painful procedure felt more pain than people who did not. In an experiment by German researchers, healthy people were asked to make an angry face while their brains were being scanned by a functional MRI. Those who received Botox injections had much less activation in areas of the brain that process emotions than those who had no injections. My patients who receive Botox for headaches also report that because they cannot make an angry face they feel less angry. We need a large study of the effect of Botox injections on the mood, so that if this finding is confirmed, Botox can be recommend for the treatment of mood disorders.

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Melatonin does not seem to be effective for the prevention of migraine headaches, according to a study published in Neurology. The researchers from Norway gave 2 mg of extended release melatonin every night for 8 weeks to 46 migraine sufferers. All 46 received also received 8 weeks of placebo and neither the doctors nor the patients knew whether the first treatment was with melatonin or placebo (so called double-blind crossover trial). Migraine frequency did improve from an average of 4.2 a month to 2.8, but the same results were observed while on melatonin as on placebo. This study confirms a well established observation that taking a placebo helps, or perhaps that what helps is just keeping track of your headaches and seeing a medical provider on a regular basis.
One argument against the validity of the study is that the dose of melatonin might have been too low because one small trial of 10 mg of melatonin in cluster headache sufferers did show benefit. Another possibility is that the dose was too high. There is a study that suggests that taking 0.3 mg (or 300 mcg) helps insomnia, while 3 mg does not. Anecdotally, I find that for me and many of my patients 0.3 mg works better for insomnia and jet lag than 3 mg.

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Botox, which was recently approved for the treatment of chronic migraine headaches, was originally thought to relieve migraine headaches by relaxing tight muscles around the scalp.  However, several recent studies determined that besides relaxing muscles, Botox also stops the release of several neurotransmitters from the nerve endings.  These neurotransmitters are released by messages sent from the brain centers that trigger a migraine attack.  In turn the released neurotransmitters send pain messages back to the brain completing a vicious self-sustaining cycle.  A meticulous study just published in the journal Pain by Danish researcher confirmed that injections of Botox stop the release of neurotransmitters and reduce sensitivity of rat’s chewing muscles.  Not knowing the exact way how Botox works makes many doctors skeptical about its efficacy.  However, we have no idea how preventive medications, such as beta blockers, antidepressants and epilepsy drugs prevent headaches either.  These drugs, like Botox, were also discovered to help headaches by accident.  This does not and should not stop us from using them.  Botox is more effective and safer than medications taken by mouth and is an excellent option for over 3 million Americans who suffer from chronic migraines.

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Intranasal sumatriptan powder seems to be a new and very promising way to deliver a migraine drug.  Sumatriptan (Imitrex) nasal spray has been available for many years, however it is not very effective or at least is not consistently effective.  The liquid tends to leak out of the nose, get swallowed, or just not get absorbed.  Nasal spray of Zomig (zolmitriptan) appears to be more effective, perhaps because of the smaller volume of the liquid and a finer spray particles.  The new product, OptiNose nasal powder seems to be even more effective.  It is a sophisticated device which does not allow for the powder to enter the lungs and deposits the medicine only in the nasal cavity.  In a study of 117 patients, 57% were pain-free and 80% had pain relief 2 hours after receiving 20 mg of sumatriptan powder, which was very significantly better than with placebo.  The nasal powder seems to be three times more effective than the nasal spray and almost as effective as an injection.  We hope that the FDA will approve this product in the near future.

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Botox was just approved by the FDA for the treatment of chronic migraine headaches.  This is great news to the more than 3 million chronic headache sufferers in the US (people who have more than 15 days with headaches each month).  In Dr. Mauskop’s opinion Botox is one of the most effective treatments for frequent and severe headaches and it is the first treatment approved FDA for chronic migraines. Dr. Mauskop was one of the first headache specialists to begin using this treatment more than 15 years ago. He has published several scientific articles and book chapters on the use of Botox for headaches. His most recent chapter on Botox for headaches was just published a month ago in the 97th volume of the Handbook of Neurology (Elsevier).  Dr. Mauskop has trained over 200 doctors from all across the US, Canada and Europe who traveled to the New York Headache Center to learn this technique.  Initial reports of the use of Botox for headaches were met with disbelief, while strong skepticism about the efficacy of this treatment persisted for many years. The main reason for this skepticism was the fact that migraine headaches are known to originate in the brain, while Botox affects only muscles and nerves on the outside of the skull. A large amount of research led to our current understanding of how Botox works: while the brain begins the headache process, it requires feedback from nerves and muscles on the surface of the head. By blocking activation of the nerves and muscles the feedback loop remains open and the headache does not occur. After the first few treatments some patients still develop a migraine aura or just a sensation that the headache is about to start, but it does not. After repeated treatments even the auras and this sensation stops occurring. Botox seems to be effective in 70% of patients, which is a rate significantly higher than with any preventive migraine medications, such as Topamax (topiramate), Depakote (divalproex sodium), Inderal (propranolol), or Neurontin (gabapentin). These drugs are effective in less than 50% of patients who try them. The other 50% do not respond or develop unacceptable side effects. Lack of serious side effects is another big advantage of Botox over medications. Botox can cause cosmetic side effects, such as a surprised look, droopy eyelids, or one eyebrow being higher than the other. These and other side effects become less common as the doctor who performs them becomes more experienced. Occasionally, patients develop a headache from being stuck with a needle. This is also uncommon because the needle is very thin and if done correctly, the procedure usually causes very little pain. The effect of Botox begins about 5-6 days after the injections, but the improvement continues to occur for 3 months, at which point the second treatment is given. Some patient require Botox injections at 2 month intervals. Published studies have shown that the second treatment is usually more effective than the first and the third one is better than the second. After several treatments some people improve completely (a small percentage of patients stop having all of their headaches after the first treatment). Dr. Mauskop’s experience suggests that children as young as 10 who suffer from daily headaches also respond well to Botox injections. The major drawback of Botox is its cost. However, several insurance companies have been paying for this treatment and with the FDA approval most of them will have to cover this treatment for patients with chronic (more than 15 days a month) headaches.

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A new treatment for motion sickness in patients with migraines was reported by a group of doctors from Pittsburgh.  Giving migraine sufferers who are prone to motion sickness a migraine drug, rizatriptan (Maxalt) prevented motion sickness . There were 25 subjects in the study and 15 of them developed motion sickness after being rotated in the darkness. Of these 15 patients, 13 showed decreased motion sickness after being pretreated with rizatriptan. This was a small study and not all patients benefited, but this is an option that should be considered in patients who suffer from severe motion sickness.  It is likely that the effect is not specific to rizatriptan, but that sumatriptan (Imitrex), eletriptan (Relpax) and other triptans are also effective.  However, just like when treating migraine attacks, it is possible that some patients will respond better to one triptan and others to another.

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