A group of American and Israeli researchers published a study in the journal Brain, suggesting that hits to the head, even those that do not cause an overt concussion, contribute to the chronic traumatic encephalopathy (CTE). CTE has been found in many football players, combat veterans, and other athletes who suffer from repeated head injuries.

The current study examined brains of four teenage athletes who had sustained repetitive hits to the head in the days and weeks before their death. They did not have typical symptoms of concussion – headaches, dizziness, confusion, memory difficulties, or vision problems. One of them had an early-stage CE and two had accumulation of tau protein that is implicated in CTE and Alzheimer’s disease.

These researchers proceeded to create a mouse model of repetitive and subconcussive head trauma, which also showed that relatively mild repetitive head injuries lead to degenerative changes in the brain.

These findings are not very surprising – repeatedly hitting your head cannot be good for your brain, regardless of the severity of each injury. However, many questions remain unanswered – what is the role of certain genetic traits that are known to predispose to CTE, could magnesium, which is depleted by trauma, or other supplements help reduce the damage, and what other interventions could possibly protect the brain.

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Acetylsalicylic acid, also known as aspirin, is a truly miracle drug. It is an excellent pain and fever-reducing medicine and prevents several types of cancer and cardiovascular disease.

Aspirin has been proven to be a very effective migraine medicine, especially if you take 3 regular strength (975 mg) or two extra strength tablets (1,000 mg). Aspirin works fast, but it can relieve a migraine even faster if it is taken in an effervescent form. These are more common in Europe, but in the US you can buy Alka-Seltzer, which contains aspirin and sodium bicarbonate. Sodium bicarbonate (baking soda)is an excellent antacid and reduces the risk of stomach irritation by aspirin.

Stomach irritation and peptic ulcers, along with bruising and bleeding are the main potential side effects of aspirin. These can be dangerous and even life-threatening, but are not likely to occur if aspirin is taken for an occasional migraine.

The risk of side effects goes up with taking aspirin daily, which has been proven to prevent migraines and to reduce the risk of episodic migraines becoming chronic. It definitely does not cause medication overuse headaches. Some studies suggest that as little as 81 mg a day is sufficient to prevent migraines, but 325 mg appears to be a more effective dose. Anecdotally, aspirin has been also reported to prevent migraine auras.

So, how does one decide whether to take aspirin daily. The decision is easier if you have another reason to take it, such as risk factors for coronary or cerebrovascular disease or family history of colorectal or another type of cancer. If you have a history of gastritis or peptic ulcers, bleeding disorder, or allergy to aspirin, the decision is also easy – don’t take it. If none of the above applies to you and you are in good general health, it may be worth trying, especially if you have failed to respond to Botox injections, beta blockers amd other preventive migraine drugs.

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Amantadine (Symmetrel) is a medication that has U.S. Food and Drug Administration (FDA) approval for use both as an antiviral and an antiparkinsonian medication. However, it is not an effective antiviral drug and is no longer used for this indication. However, it is used for several “off label”, that is not FDA-approved indications, including fatigue of multiple sclerosis and migraines.

Amantadine has a blocking effect on the NMDA receptor, which is involved in pain messaging in the brain. Other NMDA receptor blockers are an Alzheimer’s drug memantine (Namenda) and magnesium. There are only two case reports – one of 14 patients (10 responded to amantadine) and another report of 3 patients with migraines responding to amantadine. So, this is one of the drugs we try after the failure of many other drugs.

Amantadine does have the advantage of having few side effects, but its efficacy in migraines is purely anecdotal.

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AbobotulinumtoxinA (Dysport) is a product that is very similar to OnabotulinumtoxinA (Botox), but only Botox is approved by the FDA for the treatment of chronic migraines. Botox is the oldest of the four neurotoxins that are being used for various medical and cosmetic indications.

While AbobotulinumtoxinA (Dysport) is very similar to Botox and small clinical trials suggest that it is also effective for the treatment of migraine headaches, it is not exactly the same and should not be substituted for Botox. They differ because these are not synthetic molecules, but rather complex proteins that are produced by a slightly different strain of the Clostridium botulinum bacteria. They are also processed in a different manner. Allergan, manufacturer of onabotulinumtoxinA, or Botox holds the patent for the use of a neurotoxin to treat migraines, so other companies cannot promote their products for this indication. Other toxins are approved for cosmetic and certain other medical indications.

Other toxins are a little cheaper than Botox, but I almost exclusively inject Botox because I’ve been using it for over 25 years with excellent results and very few side effects, because it has been extensively tested in thousands of migraine patients, and because it is the toxin that is usually covered by insurance companies.

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Many migraine sufferers do not find acetaminophen (Tylenol) to be strong enough to treat migraine headaches and it does not have an official FDA approval for migraines (ibuprofen does). However, it is one of the most popular drugs for all kinds of pain, including migraines. And, in fact, double-blind placebo controlled trials have proven that acetaminophen does relieve pain and associated symptoms of migraine headaches.

One such study published in 2000 in the Archives of Internal Medicine by Dr. R. Lipton and his colleagues compared 1,000 mg of acetaminophen with placebo in 351 migraine sufferers. After 2 hours, 58% in the acetaminophen group and 39% in the placebo group reported relief. Twice as many had no pain at all after 2 hours in the acetaminophen group compared to placebo – 22% vs 11%. No side effects were reported in either group.

This study does not prove that acetaminophen is as strong as prescription drugs, such as sumatriptan (Imitrex), because the authors excluded patients with very severe attacks – those who needed to lie down and those who had vomiting more than 20% of the time.

So, while acetaminophen can help some patients with milder migraines, it can be a useful adjunct to a prescription drug, such as sumatriptan, especially if ibuprofen, naproxen, and other NSAIDs are contraindicated or cause upset stomach or other side effects. Acetaminophen is better tolerated than NSAIDs, but it should not be used at a high dose for long periods of time because it can cause liver damage.

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Almotriptan (Axert) belongs to the family of triptans, which are, by far, the most effective drugs for the acute treatment of migraine headaches.

The first drug in this category, sumatriptan (Imitrex) was introduced in 1992 as an injection. Sumatriptan injection remains the most effective treatment – it works for 80% of migraine sufferers. The tablets of sumatriptan and other triptans are a bit less effective, but still provide good relief for over 60% of patients. For some, combining a triptan with 400 mg of ibuprofen (Advil, Motrin) or 500 mg of naproxen (Aleve, Naprosyn, Anaprox) makes it much more effective.

Almotriptan is one of the five relatively fast-acting triptans. The other four are sumatriptan, rizatriptan (Maxalt), zolmitriptan (Zomig), and eletriptan (Relpax). Naratriptan (Amerge) and especially frovatriptan (Frova) take longer to begin helping, but their effect tends to last longer.

In Europe, many triptans are sold without a prescription, which indicates that these are very safe drugs. There is no evidence that triptans cause medication overuse headaches (unlike caffeine and opioid/narcotoc drugs). See my post on daily use of triptans and a recent article debunking the myth of medication overuse headaches.

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This is the first in a 100-part series of blogs on various migraine drugs. Yes, we do use that many drugs to treat migraines, although only a handful are FDA-approved for migraines. Many of these drugs are in the same family, but they are all somewhat different from each other.

Acetazolamide (Diamox) is a diuretic (water pill), which is used to treat mountain sickness. Unlike other diuretics, it is somewhat selective in removing extra fluid from the brain and the lungs, rather than equally from all parts of the body.

Migraine sufferers whose migraines are triggered by traveling to high altitudes can sometimes prevent these migraines by taking acetazolamide the day before their ascent and then throughout their stay at high altitude. A handful of my patients continued to take acetazolamide even after they returned to the sea level because they found it to be effective in preventing all of their migraines. These patients tended to have barometric pressure changes as their main migraine trigger. For people who get only occasional weather-related headaches, taking acetazolamide daily is not necessary. However, they can often prevent an attack by taking the drug the day barometric pressure drops and for as long as the pressure fluctuates.

To avoid having to constantly watch the weather forecast, a couple of apps can send you a warning whenever barometric pressure drops (it usually takes a drop of 20 millibars of pressure to trigger a migraine). One such free app is MigraineX.

Interestingly, people who live at high altitudes tend to have more migraines than those living aa the sea level.

Acetazolamide is also used to treat headaches due to increased intracranial pressure (pressure inside the skull).

Acetazolamide is available in 125 mg, 250 mg, and an extended release, 500 mg tablets. The usual starting dose is 250 mg once a day. Potential side effects include tingling of your face and extremities, dizziness, altered taste (carbonated beverages have a very unpleasant taste), and with long-term daily use, kidney stones.

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Several drugs are often used to treat symptoms of concussion, including an epilepsy drug, gabapentin (Neurontin), amitriptyline (Elavil) and other antidepressants.

A recent study by doctors at the University of Utah in Salt Lake City examined the role of medications in the treatment of concussions. They studied 277 patients who suffered a concussion and were seen at the local sports medicine clinic. Patients were evaluated for 22 symptoms including headaches. The patients were divided into three groups: those prescribed amitriptyline or nortriptyline, those who were prescribed gabapentin, and those who were not prescribed any medication at all.

Patients who were prescribed medications tended to have more severe headaches and other symptoms. However, headaches and other symptoms decreased significantly within days after the initial visit equally in all three groups.

This study does not prove that all treatments for postconcussion syndrome are ineffective. A recent presentation by Dr. Bert Vargas of the Sports Neurology and Concussion Program at the University of Texas Southwestern Medical Center in Dallas stressed that many migraine treatments can be very effective for postconcussion headaches and other symptoms. The features of postconcussion headaches often resemble migraines and migraine medications, such as triptans (sumatriptan, or Imitrex, and other) can be very effective. Unfortunately, only 2% – 5% of patients with posttraumatic headaches receive migraine drugs. The vast majority are treated with acetaminophen or NSAIDs, such as ibuprofen or naproxen.

Botox injections have also been reported to be very effective for postconcussion headaches, which has been my experience as well. Botox injections are approved by the FDA only for the treatment of chronic migraines. However, if headaches are accompanied by migraine features a diagnosis of posttraumatic chronic migraine can validly be made and then many insurance companies will pay for this treatment.

Dr. Vargas also noted that topiramate (Topamax), which is an epilepsy drug approved for the prevention of migraines, is not a good choice for posttraumatic headaches. Topiramate often causes cognitive side effects which can worsen the concussion-related cognitive problems, including impaired memory and concentration.

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Last month Allergan reported that their oral CGRP receptor antagonist, ubrogepant was safe and effective in the acute treatment of migraine attacks (see my post). Today, results of a phase 3 trial of a similar drug, rimegepant were reported. Biohaven is the company developing rimegepant, which it licensed from Bristol-Myers Squibb. Rimegepant was shown to be about as effective as ubrogepant with very few side effects, confirming that one of more of these “gepants” will make it to the market. These drugs are expected to be approved some time in 2020.

One piece of information that was not initially released by Allergan is that 5 patients on ubrogepant developed liver function abnormalities on blood tests, compared to only 1 on placebo. None of the patients taking rimogepant had liver function abnormalities. This could spell trouble for the Allergan drug, as it did for the original Merck drug, telcagepant.

Both Allergan and Biohaven have additional oral CGRP antagonists in development for the preventive treatment of migraines.

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The first of the four CGRP monoclonal antibodies developed for the prevention of migraines is expected to be approved by the FDA in the next 2-3 months. The other three should be approved within a year. All four will be given by an injection (three subcutaneously and one, intravenously).

Most people prefer tablets to injections and two companies are developing three drugs with the same mechanism of action as the monoclonal antibodies (blocking CGRP), but in a tablet form. The original CGRP drug in a tablet form was developed by Merck and it was very effective for the prevention and acute treatment of migraines, but a few patients developed liver side effects. The side effects were not serious, just abnormal blood tests, which returned to normal once the drug was stopped, but nevertheless Merck stopped the development of telcagepant in 2009. This led pharma companies to shift to the development of monoclonal antibodies, which bypass the liver, but can be given only by injection.

Allergan and Biohaven are two companies that are developing oral CGRP drugs in the hope that they can achieve good efficacy without the side effects. Allergan just released the results of the first phase 3 study of ubrogepant. The study included 1327 U.S. adult patients who were given placebo, ubrogepant 50 mg or 100 mg. They treated a single migraine attack of moderate to severe headache intensity. Both doses were significantly better than placebo in achieving pain freedom at 2 hours after the initial dose. Sensitivity to light, noise, and nausea also significantly improved with the drug, but not placebo. The side effect profile of ubrogepant was similar to placebo without serious liver problems.

Results of the second phase 3 trial are expected in the first half of 2018. Allergan plans to file these results with the FDA in 2019, after which the FDA has a year to review the data and will hopefully approve the drug.

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The news headlines are filled with stories of professional football players suffering from brain damage, but you do not to have to participate in sports to sustain a concussion – it is an everyday occurrence. In the US, in 2013 there were 2.8 million concussion-related emergency room visits and hospitalizations with 50,000 people dying from brain injuries. Three out of four concussions are mild. However, even mild concussion can cause impaired thinking or memory, poor concentration and emotional problems.

The U.S. Food and Drug Administration has recently approved the first blood test to evaluate concussion in adults. The diagnosis of concussion or in medical lingo, mild traumatic brain injury (mTBI), has been based purely on the description of symptoms by the patient, neurological examination, including the 15-point Glasgow Coma Scale, and brain imaging, such as CT scan to detect brain damage or bleeding. The majority of patients with a concussion have normal MRI and CT scans. This new blood test will help health care providers decide if a CT scan is necessary. This will avoid unnecessary scans which expose patients to radiation. It should also save money.

The Brain Trauma Indicator developed by Banyan Biomarkers, Inc. works by measuring levels of proteins, known as UCH-L1 and GFAP, that are released from the brain into blood and measured within 12 hours of head injury. Levels of these blood proteins after mTBI can help predict which patients may have brain lesions visible by CT scan and which won’t. Test results can be available within 3 to 4 hours.

The FDA based their approval on the data from a study of 1,947 patients with a suspected concussion. The Brain Trauma Indicator was able to predict the presence of intracranial lesions on a CT scan 97.5 percent of the time and those who did not have intracranial lesions on a CT scan 99.6 percent of the time.

It is not clear how this test will be used in the real world. If someone is sick enough to be brought to an ER, they are likely to get a CT scan, which is faster and avoids the 3-4 hour wait for the blood test results and the added cost of the blood test. People with a mild concussion who are not taken to an ER will not need the test because they are very unlikely to have visible brain injury on the CT scan. If symptoms persist for a while and the patient comes to our headache clinic, we obtain an MRI scan, which is more informative and avoids radiation, although it is more expensive.

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Lidocaine is an effective local anesthetic that is injected for dental procedures, minor surgeries, as well as nerve blocks, including nerve blocks for migraines, cluster, and other types of headaches. Since it is a numbing medicine, lidocaine has been also given intravenously in the hope of relieving widespread pain or pain that does not respond to local injections. Unfortunately, it is not as effective intravenously as it is for local injections and nerve blocks for either headaches or other pain conditions.

A controlled study of intravenous lidocaine for pain was just published by Korean researchers in the Regional Anesthesia and Pain Medicine“Efficacy and Safety of Lidocaine Infusion Treatment for Neuropathic Pain: A Randomized, Double-Blind, and Placebo-Controlled Study“.

The researchers decided to examine whether pain relief from intravenous lidocaine can be sustained through repeated lidocaine infusions. This was a randomized, double-blind, placebo-controlled study of infusions of lidocaine (3 mg/kg of lidocaine administered over 1 hour) vs infusions of normal saline, given once a week for 4 consecutive weeks in patients with postherpetic neuralgia or complex regional pain syndrome (formerly called RSD, or reflex sympathetic dystrophy). The results were assessed by the change in pain score from baseline to after the fourth infusion and then again, 4 weeks later.

Forty-two patients completed this study and the percentage reduction in pain scores after the final infusion was significantly greater in the lidocaine group compared with the saline group. However, this pain reduction was not detectable at the 4-week follow-up. None of the study participants experienced serious complications from the treatment.

So, while repeated lidocaine infusions did provide effective short-term pain relief, the effect did not persist.

I have had several of my patients with severe chronic migraines respond to intravenous lidocaine, but their experience was similar – they had to get weekly infusions to maintain good relief. Because intravenous lidocaine can cause irregular heart beat (arrhythmia), cardiac monitoring is required. This makes weekly intravenous lidocaine infusions even more expensive and impractical for most pain and headache sufferers.

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