The release of a generic substitute of the branded drug Imitrex (sumatriptan) has dramatically reduced the cost and improved the access to this uniquely effective migraine drug. The generic sumatriptan was released four years ago and now the price of one tablet is down to about $3 from over $20. The cost of two other generic triptans, Amerge (naratriptan) and Maxalt (rizatriptan) has remained very high, but it is expected to drop as more companies begin making generic copies. However, generics are not always the exact copies of the original branded drug that we expect them to be. In my previous post in 2009 I mentioned a study that showed that the generic Topamax (topiramate) does not work as well as the brand for some patients. I have also seen this with sumatriptan – my patients tell me that some generics do not work very well or at all. Out of about 10 generics of sumatriptan, I would guess that two are of poor quality. Once you find a generic that works for you, try to stick with the same generic manufacturer. The name of the manufacturer is printed on the bottle the pharmacy gives you. If one pharmacy does not have your generic, try another one. Here is a part of an email I just received from a patient (she gave me permission to share it with you):
“Just wanted to share with you that my pharmacy filled my maxalt melt prescription with yet another generic brand yesterday, which I found very unpleasant.
Previously the generic refills I’d gotten were from a company called PAR. The PAR pills resembled the original MAXALT melts in style of packaging (foil packets in plastic case) in taste and most important in melt-ability (never timed it but it always seemed to dissolve within 5 to 10 seconds–basically immediate dissolve)
But yesterday’s refill was from Mylan. These melts came in a regular prescription bottle of pills. I called the pharmacy after they were delivered thinking they accidentally gave me non-melts. They checked and told me, no, these were melts, just from a different company. They explained that this company (Mylan) packages them like any other pill (in bottles).
When I took the pill last night it felt like what i imagine it would feel like if you took a chewable vitamin and then waited for it to disintegrate in your mouth. It took minutes to “melt”, instead of seconds, and a grainy feeling remained even after that. it also made my upper palate sore, and tasted bad.
Today I called my pharmacist to double check that this was a melt and they checked again and it is. Luckily they were good enough to switch the rest of the prescription to the PAR generic brand. They also told me they would no longer carry the ones from Mylan. (They did say the Mylan generic is cheaper, though, so not sure how this will work out in the future.)”

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Pain is defined as a negative emotional experience that is affected by a variety of psychological factors. Some of the pain brain mechanisms involve endorphins (endogenous opioids) and cannabinoids (substances related to marijuana – yes, we have those in our brains) and they have been found to be involved in stress-related and placebo pain relief. A study by Italian researchers just published in journal Pain showed that when the meaning of the pain experience is changed from negative to positive through verbal suggestions, the opioid and cannabinoid systems are co-activated and these, in turn, increase pain tolerance. Healthy volunteers had a blood pressure cuff inflated over the upper arm to the point of pain and were asked to tolerate the pain as long as possible. One group was told about the negative effects of pain. The second group was told that the the pain would be beneficial to the muscles. The second group was able to tolerate pain much longer than the first one. When the researchers gave the group with the positive message opioid antidote or the antidote to marijuana, their pain tolerance worsened. Interestingly, the combined administration of these two antidotes completely eliminated their advantage over the negative message group. This study showed that a positive approach to pain reduces the global pain experience. The authors concluded that their findings may have a profound impact on clinical practice. For example, postoperative pain, which means healing, can be perceived as less unpleasant than cancer pain, which means death. Therefore, the behavioral manipulation of the meaning of pain can represent an effective approach to pain management.
This study is complementary to the study that showed the advantages of optimistic attitude mentioned in a previous post.

Art credit: JulieMauskop.com

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German researchers examined the possible connection between headaches and low back pain in a study published in the recent issue of journal Pain. They questioned 5605 headache sufferers about the frequency and type of their headaches and about the frequency of their low back pain. Of these 5605 people 255 (4.5%) had chronic headache and the rest had episodic (less than 15 headache days each month). Migraine was diagnosed in 2933 subjects, of whom 182 (6.2%) had chronic migraines. Tension-type headache was diagnosed in 1253 respondents, of whom 50 (4.0%) had chronic tension-type headaches. They also found that 6030 out of 9944 people suffered from back pains, of whom 1267 (21.0%) reported frequent low back pain. The odds of having frequent low back pain were between 2.5 times higher in all episodic headache subtypes (migraine and tension) when compared to those without any headaches. The odds of having frequent low back pain were 15 times higher in all chronic headache subtypes when compared to those without headaches. One possible explanation for this association is that having pain in any part of your body makes you more likely to develop other types of pain. We know that persistent pain makes the nervous system more excitable and this in turn may predispose to other pain syndromes. We also know that people with fibromyalgia are more likely to suffer from headaches, and those with migraines are more likely to develop painful irritable bowel syndrome.

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Expectation of relief can enhance pain relief, according to a new study published in The Journal of Pain by Canadian researchers. This is not a new discovery, but provides additional confirmation of this important clinical observation. The current study was performed in 60 healthy volunteers, 15 of whom expected relief of experimental pain, 15 expected worsening of pain from the procedure, 15 had no expectations, and 15 were in a control group. Pain was induced by electrical stimulation of right leg, while applying an ice pack to the left arm (counterstimulation) was tested as a treatment to reduce pain in the leg. Those who were told that the pain will worsen from the ice pack in fact felt more pain, while those who were expecting relief, experienced less pain. A study published in 2009 by Harvard researchers showed that expectation of relief from acupuncture also translated into stronger relief experienced by volunteers subjected to experimental pain. Their clinical observation was confirmed by functional MRI scans showing stronger activation of pain relieving structures in the brain. The researchers concluded that while acupuncture provides pain relief by sending blocking messages up to the central nervous system, messages regulating pain perception from the brain down can affect pain perception depending on person’s expectations.
This suggests that having a positive expectation when seeing doctors and undergoing various treatments may improve the outcome of these treatments.

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Many people report that sex relieve their migraine and tension-type headaches. We also know that sexual activity can trigger severe headaches. A group of German researchers conducted an observational study among patients of a headache clinic. They sent out a questionnaire to 800 unselected migraine patients and 200 unselected cluster headache patients. They asked about their experience with sexual activity during a headache attack and its impact on headache intensity. 38% of the migraine patients and 48% of the patients with cluster headaches responded. In migraine, 34% of the patients had experience with sexual activity during an attack; out of these patients, 60% reported an improvement of their migraine attack (70% of them reported moderate to complete relief) and 33% reported worsening. In those with cluster headaches, 31% of the patients had experience with sexual activity during an attack; out of these patients, 37% reported an improvement of their cluster headache attack (91% of them reported moderate to complete relief) and 50% reported worsening. Some patients, in particular male migraine patients, even used sexual activity to treat their headaches.
Obviously, the majority of patients with migraine or cluster headache do not have sexual activity during headache attacks. However, the doctors concluded that sexual activity can lead to partial or complete relief of headache in some migraine and a few cluster headache patients. Some of my patients report that masturbation is as good as having sex in relieving their migraine attacks.


Art Credit: JulieMauskop.com

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Optimists appear to tolerate pain better than pessimists, an old discovery that is supported by a new study published in The Journal of Pain. The study by researchers at the Universities of Florida and Alabama involved 140 older individuals with osteoarthritis. They were subjected to experimental pain (heat was repeatedly applied to the forearm) and also had a variety of psychological tests. Those elderly who were judged to be optimists (based on an established and validated test) had lower pain perception. The study also showed that optimism was associated with lower levels of catastrophizing. Catastrophizing was also measured by validated scale, which includes questions such as “I feel it is never going to get better” and “I can’t stand it anymore”. The good news is that studies have shown that cognitive-behavioral therapy can reduce catastrophizing and improve pain. So, if you are a pessimist, do not give up – see a psychologist and your pain may be easier to control.


Photo credit: JulieMauskop.com

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Cambia (diclofenac) is a prescription anti-inflammatory drug (NSAID) which is approved by the FDA for the treatment of migraine headaches. It is sold as a licorice-tasting powder that has to be dissolved in water before being ingested. This drug belongs to the same family as Advil or Motrin (ibuprofen), Aleve (naproxen), and prescription drugs, such as Relafen (nabumetone), Celebrex (celecoxib), and other. One of the drugs in this category, Viox (rofecoxib) was taken off the market because it increased the risk of heart attacks and strokes. A recent study published in an online medical journal, PLOS Medicine and translated into lay language in an NPR article indicates that diclofenac is as dangerous as Vioxx in causing heart attacks and strokes. The study also indicates that diclofenac unfortunately is one of the most popular NSAIDs in the world. It is probably safe to take Cambia a few times a month to treat migraine headaches, however, it should be avoided by people with other risk factors for heart disease and strokes. These risk factors include migraine with aura, high blood pressure, high cholesterol, diabetes, smoking, oral contraceptives, family history of heart disease, and other. Aspirin (in Migralex and other products), on the other hand, is the only NSAID that has been shown to prevent strokes, heart attacks, and several forms of cancer.
Cambia
Photo credit: CambiaRx.com

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Daily and prolonged intake of high doses of triptan medications (sumatriptan, or Imitrex, rizatriptan, or Maxalt, eletriptan, or Relpax and 4 others) has been shown to be safe in at least three clinical reports. I also have a few patients who have good control of their headaches and no side effects after many years of taking high doses of triptans daily. (I am not suggesting that it is healthy to take any medicine daily for years, but some people have no other choice because without this treatment they are disabled). A report just published in The Journal of Clinical Pharmacy and Therapeutics describes a patient who also was taking high doses of triptans daily (zolmitriptan or Zomig and frovatriptan or Frova tablets and sumatriptan injections), but who developed severe depression on two occasions when the triptans were stopped suddenly. The first bout of depression was very difficult to treat despite trials of several antidepressant drugs (amitriptyline, or Elavil, mirtazapine, or Remeron, and duloxetine, or Cymbalta, with addition of quetiapine, or Seroquel). All these antidepressants work through the serotonin system. His second bout of depression responded very well to bupropion (Wellbutrin), an antidepressant that works on norepinephrine and dopamine, rather than serotonin. This report suggests that while it may be safe to take triptans daily for a long time, they can affect the serotonin mechanisms in the brain and that they should never be stopped suddenly. Another important lesson is that if depression does develop after stopping daily triptans, the preferred drug may be bupropion.

Photo credit: JulieMauskop.com

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A recently published study by neurologists at the Military Medical Center in San Antonio led by Dr. Grogan tried to find predictors of response to botulinum toxin injections in chronic migraine sufferers. They looked at the records of 128 patients who received injections of botulinum toxin, although they did not receive Botox (onabotulinumtoxinA), but a similar product, Myobloc (rimabotulinumtoxinB). It has been previously reported (and mentioned in this blog) that patients with headaches who experience constricting pain or pain in the eye are more likely to respond than those who have an “exploding” headache or pain with pressure felt going from inside out. This new study confirmed this observation, originally made by Dr. Rami Burstein and his colleagues at Harvard Medical School. Dr. Grogan and his colleagues’ patients received an average of 7 and a half treatments over a period of 22 months. Treatment results showed that 80% of their patients who received injections of Myobloc had at least a 50% improvement and 57% had a greater than 75% reduction in their headache frequency. This is similar to the 70% response rate we see with Botox injections. Patients who had migraine with aura were more likely to respond to Myobloc injections. Just like with Botox side effects were few and mild and only 4% of patients decided to stop this treatment due to side effects. More patients who received Myobloc (82%) complained of pain during injections. I have also observed this and the reason is that Myobloc is very acidic, while Botox is non-acidic.
There are two other botulinum toxin products on the market, but only Botox is approved by the FDA for the treatment of chronic migraine headaches. These other two products are Dysport (abobotulinumtoxinA) and Xeomin (incobotulinumtoxinA) and they are more similar to Botox than Myobloc because they are also type A botulinum toxins, while Myobloc is type B. Only Botox is approved by the FDA for the treatment of chronic migraine headaches, while the other three are approved for movement disorders such as dystonia as well as for cosmetic use.


Dysport

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Tension and migraine headaches are the 2nd and 3rd most common medical problem in the world after dental caries (cavities), according to a new study conducted by the World Health Organization (The Global Burden of Disease Survey 2010) and reported in the journal Headache. Tension-type headaches affects 20.1% of the world’s population and migraine, 14.7%. Migraine is the 7th most disabling of all medical conditions. Migraine sufferers spend more than 5% of all of their time having pain and other symptoms of this condition. Migraine is by far the most disabling of all neurological condition. Hundreds of millions of people in the world suffer unnecessarily from headaches. This is in part due to lack of awareness of the extent, the severity, and the impact of headaches, but also due to limited resources. The National Institutes of Health in the US allocates very little money to researching headache disorders and a disproportionally large amounts on neurological conditions such as epilepsy, MS, Parkinsons, and other. I am not suggesting that these other condition do not deserve to be studied, but suffering by many more people would be relieved by investing more money in headache research.

Art credit: JulieMauskop.com

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A typical visual aura which precedes the headache in about 20% of migraine sufferers usually lasts 20 to 60 minutes. A small number of patients suffer prolonged auras, which can last for hours. While we have many medications to treat the pain of migraine, we have no effective way to stop a prolonged aura. The only possible exception is intravenous magnesium, which I have found to help some patients for prolonged visual and other types of aura. Researchers at UCSF led by Dr. Peter Goadsby conducted a rigorous blinded study of intranasal ketamine for prolonged auras. They compared ketamine to a strong tranquilizer, midazolam. The results of the study published in Neurology showed that ketamine but not midazolam can make aura milder, but it did not shorten it. Ketamine is a drug given intravenously for anesthesia, but it has been also widely tested for the treatment of pain, albeit with mixed results.

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I failed to mention in my two previous posts that there is a difference in the type of electrical current used in transcutaneous electrical nerve stimulation (TENS) and transcranial direct current stimulation. The former uses alternating current, while the latter is a direct current (AC vs DC). Cefaly device uses AC, while tDCS devices use DC. It is possible that both types of stimulation are equally effective for chronic migraine headaches and other conditions. We would need to have a blinded trial comparing these two types of stimulation to see if one is superior to the other.

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