“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.
Read MoreMany headache sufferers take over-the-counter medications which can cause upset stomach and heartburn due to reflux. Many will then resort to taking acid lowering drugs. These drugs reduce acidity which also impairs absorption of various vitamins and minerals, including vitamin B12, D, magnesium, and other. Magnesium deficiency is known to worsen migraine and cluster headaches.
The most popular drugs for indigestion, reflux, and stomach ulcers are so called proton-pump inhibitors, or PPIs (Prilosec, Protonix, Nexium, and other), and histamine 2 receptor antagonists (Zantac, Tagamet), and they are available by prescription and over the counter. Over 150 million prescriptions were written for PPIs alone last year.
A new study, published in The Journal of the American Medical Association by Dr. D. Corley and his colleagues shows that people who are taking these medications are more likely than the average person to be vitamin B12 deficient.
The study was performed at Kaiser Permanente. It involved 25,956 adults who were found to have vitamin B12 deficiency between 1997 and 2011, and who were compared with 184,199 patients without B12 deficiency during that period.
Patients who took acid lowering drugs for more than two years were 65 percent more likely to have a vitamin B12 deficiency. Higher doses of PPIs were more strongly associated with the vitamin deficiency, as well.
Twelve percent of patients deficient in vitamin B12 had used PPIs for two years or more, compared with 7.2 percent of control patients. The risk of deficiency was less pronounced among patients using drugs like Zantac and Tagamet long term: 4.2 percent, compared with 3.2 percent of nonusers.
The new study is the largest to date to demonstrate a link between taking acid suppressants and vitamin B12 deficiency across age groups. Earlier small studies focused primarily on the elderly.
The surprise was that the association was strongest in adults younger than age 30, since in the past only elderly were suspected to be at risk.
Vitamin B12 deficiency has been very common even in people not taking PPIs. This is in part due to healthier diets, which are often low in vitamin B12 which is found in high amounts in meat and liver. Vegetarians are particularly at risk.
Vitamin B12 deficiency is a serious condition, which in severe cases can be fatal. It can present with fatigue, memory impairment, tingling, weakness, dizziness, worsening headaches, anemia, and other symptoms.
Dr. Corley and his colleagues do not recommended stopping PPIs or similar drugs in people with clear need for these drugs. However, studies have found that the drugs are often overused or used for longer than necessary. One reason for this is that stopping PPIs often causes “rebound” increase in reflux making people think that they must continue taking these drugs. The way to get off PPIs is to first switch to Zantac and antacids, such as Tums or Mylanta. After a few weeks, stop taking Zantac and continue only antacids. Avoid eating foods that worsen reflux, such as chocolate, alcohol, and other, and you may need the antacids only occasionally.
Besides vitamin B12 deficiency, prolonged use of PPIs leads to other problems, including increased risk of bone fractures, pneumonia, and a serious gastro-ointestinal infection with C. difficile.
To see whether study patients were not just low in vitmain B12 but also had symptoms of deficiency, researchers reviewed the charts of 20 randomly selected PPI-using patients to determine why they had their vitamin B12 levels tested. Twenty five percent of that small sample had also been tested for anemia and 15 percent for memory loss. This indicates that many people with this deficiency have symptoms. However, because the symptoms are vague and not specific for this deficiency, doctors often ignore them and do not order any tests.
To complicate matters, when doctors do test for vitamin B12 deficiency, the test they use is not very accurate. Many laboratories list normal levels being between 200 and 1,000. However, many patients with levels below 400, and some even with levels above 400 still have a deficiency. If a deficiency is strongly suspected, additional tests are needed – homocysteine and methylmalonic acid levels.
Art credit: JulieMauskop.com
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.
Read MoreStrenuous mental activity seems to delay recovery after a head injury, according to a new study published in Pediatrics .
Doctors have always recommended rest after a head injury, but it has never been clear how much to limit activities, what kind to limit (physical, mental, or both), and for how long.
Dr. William P. Meehan III, director of the Micheli Center for Sports Injury Prevention in Waltham, Massachusetts and his colleagues studied 335 patients (62% were males), aged 8 to 23 who came to a sports concussion clinic within three weeks of their injury between 2009 and 2011. Most of the concussions were sustained while playing ice hockey, football, basketball or soccer. The researchers asked them about their symptoms and how often they were reading, doing homework or playing games at each of their appointments.
Those with minimal cognitive activity were not reading or doing homework, and spent less than 20 minutes on the Internet or playing video games each day. They could have watched TV or movies or listened to music. Those with moderate or significant cognitive activity did some reading and some homework, but less than usual. Others had not limited their cognitive activities at all since their last clinic visit.
On average, patients took 43 days to fully recover from their concussions. Those with more minor concussions tended to get over their symptoms faster. So did those who did less with their brains while recovering.
Results showed that only those engaging in the highest levels of cognitive activity had a substantial increase in their symptom duration, while those at all lower activity levels seemed to recover at about the same pace.
According to Dr. Meehan, “This would suggest that while vigorous cognitive exertion is detrimental to recovery, milder levels of cognitive exertion do not seem to prolong recovery substantially”
In general, Meehan said, doctors recommend almost complete brain rest for three to five days after a concussion, followed by a gradual return to normal activities.
Athletes suspected of having a concussion should be seen by the most immediately available medical personnel, like an athletic trainer or team doctor, he said, with a follow-up visit to their primary care doctor.
I would also emphasize the importance of physical rest and complete avoidance of any activities that could result in another head injury before completely recovering from the first one. Complete recovery means no symptoms at all, including headaches, dizziness, mental fog, fatigue, difficulty concentrating, insomnia, anxiety, depression, and other. Taking a magnesium supplement can also help since animal studies show magnesium depletion following an injury. If rest alone does not lead to a complete recovery, cognitive behavioral therapy, medications (for anxiety, depression, and irritability), and Botox injections (for persistent headaches) are sometimes needed.
Read MoreMany people who experience severe headaches are often concerned about having a brain aneurysm. What prompted this post is a patient I just saw who was found to have a small (3 mm) aneurysm on a routine MRI scan as well as a new article just published in The Lancet Neurology.
Considering that over 36 million Americans suffer from migraine headaches, this is by far the most common cause of severe headaches. However, aneurysms are not rare – more than 7 million Americans have them. The vast majority of these people do not know that they have an aneurysm and in 50 to 80 percent they never cause headaches or any other problems. Every year, more than 30,000 people do suffer a rupture of the aneurysm. The rupture of an aneurysm is what causes a very severe headache and about one in seven people with a rupture die before reaching the hospital. In addition to a severe headache, the hemorrhage from a ruptured aneurysm can cause a stiff neck, drowsiness, weakness or numbness on one side, difficulty speaking and other symptoms of a stroke.
Dutch researchers analyzed the available data, trying to find predictors of aneurysm rupture. They discovered that the risk goes up with age, high blood pressure (hypertension), history of a previous brain hemorrhage, aneurysm size, its location and the geographic region. There is nothing one can do about age and other factors, but blood pressure is one factor that can be controlled.
If the aneurysm is less than 5 mm, as in my recent patient, the risk of a rupture is very low. However, if the aneurysm is larger, surgical treatment is usually indicated, especially if other risk factors are present.
It is not clear why, but people living in Finland and Japan are about 3 times more likely to have an aneurysm rupture than those in the rest of Europe and North America.
Art credit: JulieMauskop.com
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.
Art credit: JulieMauskop.com
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