Botox, or onabotulinumtoxinA was recently approved by the FDA for treatment of chronic migraine based on the results of two large studies. Botox is the only prophylactic therapy specifically approved for chronic migraine. Many patients and doctors alike wonder about the mechanism of action of Botox. We originally thought that Botox works by relaxing tight muscles around the scalp. Studies have shown that during a migraine attack, the muscles in the forehead, temples and the back of the head are in fact contracted. It is also typical for a person with a migraine to rub their temples or the neck, which provides some temporary relief. However, I have seen some patients who would report that injecting muscles around the head eliminated pain in the injected areas, but that they still had pain on the top of the head. There are no muscles on the top of the head and we usually do not inject Botox there, but in those patients who do have residual pain on the top, injecting Botox stops the pain. Recent research has shown that Botox in fact also exerts a direct analgesic (pain-relieving) effect. This is supported by my and other doctors’ observation that Botox also helps other types of pain, such as that of shingles or trigeminal neuralgia. These are so called anecdotal reports and cannot be relied on to make definitive conclusions – we need large trials can prove this. It appears that Botox helps by reducing pain messages sent to the brain from both muscles and peripheral sensory nerves. This explains why migraine, which is a brain disorder, can be helped by a procedure directed only at the peripheral nerves – with the reduction of the barrage of pain messages reaching the brain, the brain does not become more and more excitable, or “wound-up” and a migraine attack does not occur. Some patients tell me that after Botox treatment they sometimes feel that a migraine is about to start, but it does not.
Read MoreIntravenous infusion of magnesium for the treatment of an acute migraine is receiving more attention and is mentioned in the recent issue of journal Headache. In the first of three articles Drs. Nancy Kelley and Deborah Tepper of the Cleveland Clinic describe the use of triptans (such as sumatriptan, or Imitrex), DHE (dihydroergotamine), and magnesium for the emergency treatment of migraines. In their article they included seven reports of the use of magnesium infusion, all with positive results. We published the very first article on the use of intravenous magnesium for migraines in 1995. In the same year we published our results of the use of this treatment for cluster headaches, also a first and since that time have been promoting the use of this safe and effective treatment in many articles, lectures, and symposia. We’ve found that 50% of patients with migraines and 40% of those with cluster headaches responded to magnesium infusion. Unfortunately, many patients seen in the emergency room still do not receive magnesium, but in the best case sumatriptan or ketorolac injection, in the worse, narcotic drugs. An infusion of magnesium should be always tried first. We actually discourage our patients from going to the emergency room during office hours – instead they come to our office and are given an infusion of magnesium. If it is ineffective, then we proceed with sumatriptan, ketorolac, dexamethasone, other drugs, and sometimes nerve blocks.
Oral magnesium is not suitable for the acute treatment of a severe headache because it is absorbed too slowly. However, Migralex, a drug containing magnesium and aspirin was developed to dissolve and absorb quickly, so it can deliver magnesium (along with aspirin) to the brain within 15 – 30 minutes. Another article in the same issue of Headache recommends the use of aspirin as the first line treatment for migraine and tension-type headaches, regardless of their severity. Many doctors use “stratified” approach, which means that they recommend aspirin for milder headaches and a prescription drug, such as sumatriptan, for more severe attacks. However, the authors reviewed results of studies involving thousands of patients and concluded that aspirin can be very effective for many patients with a severe headache and should be tried first. If it is ineffective, then the patient is advised to take the prescription drug.
Acupuncture has been widely used for the treatment of migraine headaches and it has been subjected to many clinical trials. A new study published in the Canadian Medical Association Journal confirms what previous research has shown – that acupuncture in fact is effective. This study was performed by Chinese researchers and it involved 480 patients. It was a well-designed and rigorously conducted study. The doctors divided patients into 4 groups with 3 groups receiving different types of real acupuncture and the fourth one receiving sham acupuncture. Sham acupuncture group had needles inserted, but they were not manipulated to elicit a specific “qi” sensation, which was done in the real groups. Patients in all three groups receiving real acupuncture did better than those in the sham group. The benefit persisted for at least three months after the treatment. The difference was statistically significant (meaning it did not occur by chance) but not very large, mostly because the sham group also improved. In summary, this study strongly supports the results of previous clinical trials in migraines, which showed positive effects of acupuncture. It also showed that the type of acupuncture is not important, but needles need to be inserted properly and probably need to have electrical stimulation (all groups in this study had electrical stimulation). One difficulty in following the treatment used in this study is the need for doing acupuncture five days a week for 4 weeks. Many people may have difficulty finding the time (and money) for such a regimen. However, many of the previous positive studies were conducted with acupuncture treatment being performed once a week.
Read MoreHow 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.
Swearing is a common response to pain. A study just published in The Journal of Pain examines whether swearing can actually help pain. Oxford English Dictionary defines swearing as the use of offensive or obscene language. Prior studies by the same researchers at the Keele University in the UK showed that for most people swearing produces a pain lessening effect. In this new study Richard Stephens and Claudia Umland looked at the effect of repeated daily swearing on experimental pain. They took 71 healthy undergraduate students (who else?) and subjected them to pain using a standard research procedure – submerging subjects’ hand into cold water. They again showed that swearing reduces pain and increases heart rate. The latter suggests that swearing reduces pain not only by distraction, but through physiologic effect on the body. They also found that people who tended to swear frequently throughout the day had less of a pain relieving effect from swearing when subjected to pain. So, listen to your mother and don’t swear all the time – save it for when it can do some good for you.
Read MoreLikeable patients may receive better care for their pain, according to a study by Belgian researchers. The researchers asked 40 doctors to look at photos of six different patients. Each photo was accompanied by a description such as friendly, egoistic, arrogant, honest, faithful, hypocritical, or reserved. Then the doctors were asked to evaluate the severity of pain in these six patients after they watched a video in which the patients were being evaluated for shoulder pain. Patients with positive descriptions were thought to have more pain than those with negative ones. Most doctors are probably convinced that they treat all patients equally, but this is clearly not true. Doctors and medical students should be informed of these findings so that they constantly remind themselves of the potential bias.
Read MorePregnant 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.
Read MoreThe FDA approved Botox for the treatment of chronic migraine because of the two large double-blind and placebo controlled trials which involved close to 1,400 patients (in which we, at the NYHC also participated). These studies showed that Botox reduced the number of days with headaches and it also improved many other related aspects. A study just published in Neurology looked at the effect of Botox on the quality of life of patients that participated in these trials. It is possible to have a treatment that reduces the number and even the severity of migraines without improving patients’ quality of life because of its side effects. This is seen with some patients who take topiramate (Topamax) – their headaches may be much better but the quality of life is not because of memory impairment or fatigue, which makes them unable to function. The same is true with other medications, such as antidepressants. However, the quality of life of patients receiving Botox in these two studies was significantly better than in those receiving placebo injections. This is because their headaches improved dramatically and because Botox rarely caused any side effects. Unfortunately, many insurance companies will pay for Botox only after the patient fails to improve on 2 or 3 prophylactic medications, even though these medications are not approved by the FDA for chronic migraines.
Read MoreHypertension appears to increase the risk of trigeminal neuralgia, according to a new study published in Neurology by Taiwanese researchers. They looked at 138,492 people with hypertension and compared them to 276,984 people of similar age and sex who did not have hypertension. The risk of trigeminal neuralgia was one and half times higher in those with high blood pressure. Trigeminal neuralgia is an extremely painful condition with electric-like pain in one or more branches of the trigeminal nerve, which supplies sensation to the face. The likely cause of trigeminal neuralgia is compression of the trigeminal nerve by a blood vessel at the site where the nerve is coming out of the brainstem. Persistently elevated blood pressure tends to make blood vessels harder and more tortuous. Hypertension has been show to be a factor in a similar condition – hemifacial spasm, which results from the compression of the facial nerve by a blood vessel. The usual treatment of trigeminal neuralgia starts with medications, such as oxcarbazepine (Trileptal), carbamazepine (Tegretol), phenytoin (Dilantin), baclofen (Lioresal) and other. If medications are ineffective, invasive treatments are recommended. Botox injections have been reported to provide some patients with good relief, although Botox is probably more effective for hemifacial spasm. ANother procedure is the destruction of the tigeminal nerve ganglion with heat from a radiofrequency probe. This is done under X-ray guidance. Radiofrequency ablation is often effective, but the pain may recur and the procedure may need to be repeated. A more drastic but also more effective approach involves opening the skull and placing a Teflon patch between the nerve and the offending blood vessel. Obviously, this procedure carries a higher risk of serious complications, but in experienced hands it is relatively safe. You can determine the experience of the neurosurgeon by asking how many procedure he or she has performed. Ideally, pick a surgeon who has done it hundreds of times.
Read MoreCyclic vomiting in childhood is often a precursor of migraines in adulthood. Usually a child has attacks of vomiting with or without a headache that can occur 10 – 20 times in a 24-hour period. Most children have family history of migraines and as they get older they develop migraines themselves. A study from the Cleveland Clinic led by Dr. David Rothner (a regular speaker at our annual headache symposium) shows that one third of these children may actually have a metabolic disorder and not just migraine. Most children feel perfectly fine between these episodes of vomiting. If these attacks are frequent Dr. Rothner recommends amitriptyline (Elavil), cyproheptadine (Periactin), and ondansetron (Zofran) to treat this condition. Some of the metabolic disorders could be possibly treated with supplements such as CoQ10, riboflavin (vitamin B2), as well as magnesium.
Read MoreHigh blood pressure is not a common cause of chronic headaches. The pressure has to suddenly increase (from say 100/70 to 150/90) or to be very high (like 170/110, or higher) to cause a headache. Mild hypertension is called a silent killer because it does not cause headaches or any other symptoms for many years. Doctors have been debating for a long time what to consider normal blood pressure. A study by University of California researchers just published in Neurology looked at 12 previous studies that involved over half a million people. They determined that what was considered normal blood pressure in the past (130-139 systolic and 85 to 89 diastolic, sometimes called “prehypertension”) in fact is associated with a significant increase in the risk of strokes. This has a practical application in people suffering from migraine headaches. One of the three categories of drugs used for preventive treatment of migraines is drugs used to treat high blood pressure. So, someone with blood pressure is 130/85 may want to request that the doctor prescribes a blood pressure medication rather than a drug from two other categories – epilepsy drugs (Topamax, Depakote, Neurontin) or antidepressants (Elavil, Pamelor, Effexor, Cymbalta, etc). Fortunately, in most cases blood pressure medications tend to have fewer side effects than drugs in the other two categories. Some of the blood pressure medications that have been shown to be effective for the prevention of migraines are beta blockers, such as propanolol (Inderal), timolol (Blocadren), atenolol (Tenormin), nebivolol (Bystolic), and ACE receptor blockers (ARBs), such as candesartan (Atacand) although other ARBs, such as olmesartan (Benicar) may be also effective. Not all blood pressure drugs are equally effective for the prevention of migraine headaches. Calcium channel blockers, such as verapamil (Calan) and amlodipine (Norvasc) and diuretics are probably less effective.
Read MoreCluster headaches are relieved by steroid injections in the back of the head, according to a study by French doctors, published in The Lancet. 43 patients with chronic and episodic cluster headaches were recruited into this blinded study where some patients received a steroid (cortisone) injection and some received saline water. The injections were given in the back of the head under the skull, on the side of headache. Injections were repeated every 2 – 3 days for a total of 3 injections. There was a significant improvement in patients who received cortisone. This study supports the wide use of a similar procedure, an occipital nerve block to relieve cluster headaches. In this study patients were allowed to take oxygen and sumatriptan (Imitrex) as needed. They were also started on verapamil for the prevention of cluster headaches and the injections were used for short-term relief while awaiting for the effect of verapamil to kick in. In my experience, some patients, especially those with episodic cluster headaches, may have complete resolution of their headaches just from the nerve block. Sometimes a single block is sufficient, but occasionally it helps for only a few days and needs to be repeated. It is likely that the injection technique and doctor’s experience can make a difference. Another option to stop cluster headaches is to take an oral steroid medication, such as prednisone, but taking it by mouth is more likely to cause side effects. Verapamil is an effective preventive drug, but it usually needs to be taken at a high dose – starting with 240 mg and going up to 480, 720 mg, and even higher. Verapamil is a blood pressure medication and before starting it and before increasing the dose an EKG is usually taken as it is contraindicated in people with some heart problems. In addition to verapamil, topiramate (Topamax), lithium, other drugs, and even possibly Botox injections can prevent attacks.
Read More
Recent Comments