An oral tablet is the most convenient way to take medicine. However, many migraine sufferers wake up with a headache that is in full bloom and severe nausea or vomiting makes it difficult to take oral medications. Others find that tablets are ineffective or take too long to work.

Sumatriptan (Imitrex), the miracle migraine drug which has changed lives of millions of migraine and cluster headache sufferers, was first released in an injection. The injection is still available and is the most effective way to stop a migraine. The injection comes in a variety of pre-filled syringes and cartridges, which are very easy to self-inject. The problem with injections is that some people don’t like the idea of injecting themselves, which is surprising, considering how much pain and suffering they endure from migraine. Another problem is the cost – even in a generic form a shot costs $35 (see for cheapest prices). The biggest reason why injections are underutilized is that doctors fail to offer this option to patients, many of whom would be happy to use it.

Nasal sprays offer a middle ground option – not as fast or effective as an injection, but faster and sometimes more effective than a tablet. There are several medications available in a nasal spray. The same triptan medication, sumatriptan comes in a nasal spray. However, another triptan, zolmitriptan (Zomig NS) in my experience is more effective. The disadvantage of Zomig is that it is very expensive if not covered by insurance (over $200 a spray) because it is not available in a generic form.

Another nasal spray approved for migraine headaches is Migranal. It contains dihydroergotamine, which is one of the strongest injectable migraine drugs. However, it is much less effective in a nasal spray form. It is also very expensive – $200 a dose. Dihydroergotamine is about to be released in an inhaler. It will be called Levadex and will deliver the medicine into the lungs. Its efficacy should be as good as that of an injection, but with fewer side effects. Hopefully, it will not be more expensive than the generic sumatriptan injection. Otherwise, just like with Migranal, insurance companies will not cover it.

Sprix is a nasal spray containing ketorolac. In a tablet form (Toradol) ketorolac is no more effective than aspirin and is more irritating to the stomach. But it is a very effective drug for migraines when it is injected and to a lesser extent, when sprayed into the nose. It is very popular as an injection in the ERs and at our New York Headache Center. Sprix can sometimes irritate the nasal passages. It costs about $35 a dose.

Stadol (butorphanol) is a narcotic (opioid) pain killer, which costs about $30 a dose in a generic form. It does relieve pain well and is approved for migraine headaches. However, just like other narcotics, it is potentially addictive. Also, many migraine sufferers find that narcotics do not help their migraine and often makes them feel sicker. It also costs over $30 a dose.

There are several over-the-counter nasal sprays containing hot pepper extract, capsaicin. There is no good scientific evidence that these capsaicin products sprayed into the nose relieve migraines or cluster headaches. On the other hand, besides burning and irritation of the nasal passages, they have few side effects and are inexpensive.

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Sleep deprivation is a very common trigger of migraine and tension-type headaches. Scientists have always wondered about the purpose of sleep. We know that sleep helps strengthen our memories. New research suggests that sleep is also needed for other housekeeping chores, such as cleaning junk out of our brains. Literally, the brain rids itself of damaged proteins during sleep. It appears that poor sleep quality leads to accumulation of these proteins, which can lead to a higher risk of Alzheimer’s disease.

Another recent study showed that people with insomnia tended to have smaller brain volume in certain regions of the brain, particularly frontal lobes.

Other research showed that a variety of psychiatric illnesses also lead to a reduced brain volume. The frontal lobes are necessary for planning our actions, mood, and affect.

Veterans with post-traumatic stress disorder (PTSD) frequently complain about sleep difficulties and have documented high rates of sleep disorders

In the latest study, the researchers scanned the brains of 144 veterans using magnetic resonance imaging (MRI).

The participants with poor sleep quality had less frontal lobe gray matter than vets who reported sleeping well.

These veteran had other psychological disorders, in addition to the sleep disorder. Half of them abused alcohol, 40 percent had depression and 18 percent had PTSD.

The connection between sleep disorders and the brain volume was not affected by psychiatric medications.

The researchers speculated that these findings are not necessarily limited to veterans. However, they were careful to stress that their findings do not prove that there is a cause and effect relationship between sleep quality and brain volume. It is possible that something else is causing both sleep problems and shrinkage of the brain or that shrinking of the brain causes sleep disturbances and not the other way around.

What is indisputable is that we all need good night’s sleep to function normally, avoid headaches, accidents, and be happy. Most people need 7 hours of sleep, but there are some who need only 5 or 6 and others, 8 to 9 hours. A very small percentage of people function perfectly well with 3 or 4 hours of sleep. On the other hand, some people do not feel rested no matter how long they sleep. Those usually suffer from a sleep disorder, such as sleep apnea, restless leg syndrome, narcolepsy, and other. The diagnosis is made through a sleep study. Treating the underlying sleep disorder often leads to a dramatic improvement in the quality of life, including an improvement in migraine and tension-type headaches.

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There is no debate about the fact that there is an epidemic of vitamin D deficiency in the United States – it affects about two thirds of the population. However, it is bewildering why scientists are still debating if people should be taking vitamin D supplements. You would think that this is a pretty obvious, common sense conclusion. But common sense is far from common, especially in academia (and obviously not just in medicine – it is much worse in the “soft” social sciences).

Two major studies published in the highly respected British Medical Journal reviewed studies that involved data on more than a million people. Both studies showed that vitamin D provided significant benefits. Vitamin D appears to protect against major diseases. Adults with lower levels of vitamin D had a 35% increased risk of dying from heart disease,14% greater risk of dying from cancer, and a higher risk of dying from any cause. Taking vitamin D reduced the risk of dying from all causes by 11%. The authors estimate that 13% of all deaths in the US are due to low vitamin D levels. This is an astonishing discovery, on the par with the discovery that aspirin dramatically reduces the risk of different types of cancer.

So, a reasonable person would expect the medical community to begin recommending vitamin D supplementation, at least for those with low levels. But here is what one of the authors said:: “Based on what we found, we cannot recommend widespread supplementation”. He called for more clinical trials to prove beyond any doubt that taking vitamin D is a good idea. These trials usually cost many millions of dollars and take many years to complete. How much does it cost to take 2,000 units of vitamin D3 daily? One dollar a month. And what are the potential side effects of taking 2,000 units of vitamin D? None.

The bottom line is, if your vitamin D level is below 40, take 2,000 units a day. Some people may need higher doses if their levels remain low, which is not unusual. The normal range is considered to be between 30 and 100, but there are studies indicating that you are safer with a higher level. One such study showed that attacks of multiple sclerosis are less likely if you have high normal rather than low normal levels. We do not know if taking vitamin D prevents migraines and other types of headaches (such a study does need to be done), but we do recommend to everyone whose vitamin D level is low to get it up to normal range.

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A good predictor of response to Botox injections in chronic migraine patients has been found by Spanish researchers.

While Botox is a very effective treatment for chronic migraines and possibly other types of headaches and pain, it does not help everyone. Approximately 30% of patients with chronic migraine headaches do not respond to Botox. We usually try at least two sets of injections three months apart before considering the patient to be a non-responder. Considering that Botox is an expensive treatment, it would be very useful to know beforehand which patients will respond and which will not. Besides the cost, it would also save patients time, during which they could be trying other treatments.

Some studies show that having a constricting headache or pain in the eye is usually a positive predictor of response to Botox. On the other hand, exploding headache (that is when the pain is felt pushing from the inside out), is less likely to respond to Botox injections. However, these are very subjective descriptions and predictions based on them are not that reliable.

A new study by Spanish researchers just published in the journal Headache reported that the levels of CGRP (calcitonin gene-related peptide) and VIP (vasoactive intestinal peptide) in patients’ blood are good predictors of response to Botox in chronic migraine sufferers. These two chemicals, which circulate in the blood and perform various important functions in the brain have long been the subject of scientific research. Actually, we think that Botox works by blocking the release of CGRP from the peripheral nerve endings. Dr. Julio Pascual and his colleagues measured the levels of these two chemicals in chronic migraine patients before they were treated with Botox. Botox was administered according to the standard protocol every 12 weeks for at least two treatment cycles. A patient was considered a moderate responder when both: 1) moderate-severe headache episodes were reduced by between 33 and 66%; and 2) subjective benefit on a visual scale from 0 to 100 was recorded by the patient of between 33-66%. Patients were considered to be excellent responders when both items improved by more than 66%. Those without improvement of at least one-third in the two items were considered as nonresponders.

The study involved 81 patients with chronic migraine and 33 healthy controls. CGRP and VIP levels were significantly increased in the chronic migraine population vs controls. CGRP and, to a lesser degree, VIP levels were significantly increased in responders vs nonresponders. The probability of being a responder to Botox was 28 times higher in patients with a CGRP level above the threshold.

The measurement of CGRP and VIP is done only by research institutions and is not yet offered by commercial laboratories. However, considering how much money can be saved by not giving Botox to those who are unlikely to respond, these tests should become widely available once these findings are confirmed by other researchers.

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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
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The beneficial effect of Botox on mood has been reported for years. I mentioned this in one of my blog posts in 2011. Now, a new and highly scientific study (double-blind, placebo-controlled) which is about to be published in the Journal of Psychiatric Research confirms that Botox relieves depression. The study is described in today’s New York Times.

I have also heard from many of my own patients who receive Botox for chronic migraines that their mood improves, although in their case it could be to a great extent because their headaches improve.

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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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Cefaly, a TENS unit specifically developed for the treatment of migraine headaches, was cleared for sale in the US. It was available last year for a short time on, but because it was not yet approved, it was taken off the market. I mentioned in my previous post that TENS units have been in use for muscle and nerve pain for decades. TENS has good proof of efficacy in musculo-skeletal pain, but studies in migraines have been relatively small. Even Cefaly was tested in only 67 migraine patients. So, while it is not definitely proven effective, TENS is safe and is worth a try if usual treatments do not help. Cefaly is easy to use but it is expected to cost around $300. The old-fashioned TENS units are not as convenient to use, but sell for as little as $50. Both Cefaly and regular TENS units require doctor’s prescription, although many websites sell TENS units without one. These devices are usually powered by a 9 volt battery and, unless you have a pacemaker or another electrical device in your body, the risk of side effects is low.

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Imbalance of many hormones produced by our endocrine system can lead to headaches. Here is a brief summary of the hormones linked to headaches.

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Trigeminal neuralgia (TN) 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. Eating and talking often triggers the pain, so some patients become malnourished and depressed. The pain is brief, but can be so frequent and severe that it causes severe disability, weight loss, severe anxiety, and depression. The good news is that most people can obtain relief by taking drugs, such as Tegretol (carbamazepine), Trileptal (oxcarbazepine), Dilantin (phenytoin), or Lioresal (baclofen). I have successfully treated several patients who did not respond to these medications with Botox injections.

Patients who do not respond to medications or Botox injections 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 often cure this condition.

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