Expiration date on medications does not indicate that the medication is no longer effective or safe after that date. Having had extensive experience with the production and testing of Migralex, I can reassure you that medications remain safe and effective for years after the expiration date. An article just published in the Wall Street Journal’s “Burning Question” column addresses this issue.

The FDA has conducted a study for the Department of Defense testing 122 different drugs. The conclusion of the study was that 88% of the drugs remain effective for an average of 5 and 1/2 years after the expiration date. The main problem with expired drugs is not that they become dangerous to use, but that their efficacy slowly declines. A doctor quoted in the WSJ article says that there have been no reported cases of toxicity from expired medications. But a decline in efficacy could be a problem with life-saving drugs, such as nitroglycerin for heart, EpiPen for allergies, or insulin for diabetes.

It is very important to store the medications in a dry cool place, rather than in a medicine cabinet in the bathroom, which periodically gets hot and humid. Also, do not leave drugs in a car during the summer – the temperature in a locked car left in the sun can rise to 130 degrees and higher.

I usually advise not to use drugs beyond two years of the expiration date even if they were kept in a dry and cool place. Before using an expired drug inspect the tablet to make sure it hasn’t turned colors, smells bad, or became brittle and crumbling. Obviously, if it is an inexpensive generic drug, get a fresh bottle. However, with expensive drugs, such as some triptans (Relpax, Frova, Axert) and injections of Imitrex (sumatriptan) considerable amounts of money can be safely saved. A common scenario is a patient with cluster headaches who has a bout every couple of years and has only expired injections of Imitrex. It usually takes at least a few days to be seen by a doctor and to get a new prescription, while the attacks of cluster headaches can be devastatingly severe. Again, the worst that can happen is that the injection will be less effective, but usually it will still provide some relief.

There is a difference in how long expired drugs remain effective depending on the formulation. For example, tablets are the most stable, while creams and liquid drugs, such as drops, are least likely to last past the expiration date.

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A report from the Cleveland Clinic and Case Western Reserve describes 22 patients with new daily persistent headaches (NDPH) who were treated with Botox injections.

NDPH is a condition in which the headache begins suddenly without an obvious trigger and persists continuously without a break. Because NDPH is relatively uncommon, there have been no large studies of this condition. Patients with NDPH usually do not exhibit symptoms of migraine, such as throbbing pain, nausea, sensitivity to light, noise or physical activity. Because of its sudden onset, we suspect that these headaches may be the result of a viral or another type of infection. There are no treatments that consistently relieve these headaches, but we usually try all of the drugs and approaches we use in migraines.

A group of doctors from Cleveland, Ohio discovered that while Botox seems to help, only 32% of patients with NDPH showed improvement, confirming the refractory nature of this type of headaches. Twenty one of the 22 patients underwent more than one treatment with Botox and most were given a standard migraine treatment protocol with 155 units injected into 31 sites. The improvement was modest but it did result in headache-free days, which were not observed prior to this treatment. The disability improved slightly and when the improvement did occur, it lasted about 8 weeks. Some of our chronic migraine patients also require Botox injections every 8 to 10 weeks, instead of the usual 12. Considering that we do not have any better treatments, Botox should be offered to patients with NDPH.

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A new combination of two old drugs seems to provide relief for some trigeminal neuralgia (TN) sufferers. The first line drugs for TN are epilepsy drugs, carbamazepine (Tegretol) or oxcarbazepine (Trileptal). A presentation at the last annual scientific meeting of the American Headache Society by Saudi physicians described successful use of another epilepsy/pain drug, pregabaline (Lyrica) with an antidepressant/pain drug duloxetine (Cymbalta). Both Lyrica and Cymbalta are approved by the FDA for the treatment of some pain conditions, although not TN. The doctors compared Lyrica alone with Lyrica and Cymbalta in combination in 200 patients. The combination resulted in an 80% reduction of pain, which was observed within 10 days, while Lyrica alone produced a 60% reduction that started within 20 days. The dose of Lyrica was 150 mg twice a day (after a one week build up from 75 mg twice a day) and the dose of Cymbalta was 60 mg a day.

Since both Cymbalta and Lyrica have pain relieving properties, this appears to be a rational combination of medications to use in TN and possibly other painful conditions, including various types of headaches. However, as a general rule, we try to use a single drug whenever possible to reduce the potential for side effects. TN is such a severe and debilitating condition, that it may be justified to use a combination early, especially if the first line drugs, such as oxcarbazepine fail.

In my previous posts I have described the use of intravenous medications, Botox and other invasive treatments for TN.

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Post-concussion syndrome, which often includes headaches, can persist for many months especially after a minor injury (yes, mild injury is more likely to cause post-concussion syndrome than a severe one).
However, little is known about prognosis after the injury. The symptoms fall into three categories – cognitive (such as memory, concentration difficulties), somatic (headaches, dizziness, etc), and emotional (irritability, anxiety, depression). A study by French physicians recently published in JAMA Psychiatry, also took into account the fact that injuries are often sustained during psychologically distressing events (car accidents, assaults, falls) and looked for symptoms of post-traumatic stress disorder (PTSD) in those patients.

The authors conducted a study of patients seen at an emergency department for a mild head injury. They checked on these patients for persistent symptoms three months after the concussion. The study included 534 patients with head injury and 827 control patients with non-head injuries.

The study showed that three months after the injury, 21.2 percent of head-injured and 16.3 percent of nonhead-injured patients had post-concussion syndrome, while 8.8 percent of head-injured patients met the criteria for PTSD compared with only 2.2 percent of control patients.

Their conclusion was that it is important to differentiate post-concussion syndrome from PTSD because it has important consequences, in terms of treatment, insurance resource allocation and advice provided to patients and their families. They also stressed the importance of considering PTSD in all patients with mild traumatic brain injury who suffer persistent symptoms.

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Botox is FDA-approved only for chronic migraine headaches, however, it is being used “off-label” for other types of headaches as well. We find that frequent episodic migraines, cluster headaches, numular, and cervicogenic (neck-related) headaches improve with Botox. In our practice, post-traumatic headaches also seem to respond to Botox.

A report by neurologists from Stony Brook University describes five patients suffering from post-traumatic headaches, who responded to Botox. These patients sustained a traumatic brain injury and had suffered from post-traumatic headaches for years, despite trials of various prophylactic medications. After treatment with Botox, all of their five patients had greater than 50% improvement of their disability as measured by the MIDAS (MIgraine Disability Assessment Scale) questionnaire.

This is not a surprising observation because in many patients with a traumatic brain injury headaches have migraine features, suggesting similar underlying mechanisms. People with a family history of migraines who sustain a head injury seem to be more likely to develop post-traumatic headaches than those without such family history, which also suggests a link with migraines. Some patients with post-traumatic headaches and especially those with overt whiplash injury (almost all head injuries, to a varying degree, involve a whiplash neck injury) may respond to Botox because Botox relaxes tight muscles. We no longer think that this is the reason Botox helps migraines because there is evidence that in migraines Botox works by blocking sensory nerve endings rather than by relaxing muscles.

Because of the cost, insurance companies are often unwilling to pay for Botox to treat anything but chronic migraines. However, headaches that begin after a head injury and are accompanied by some migraine features can be correctly classified as post-traumatic chronic migraines, thus avoiding difficulties with the insurance companies.

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Acetaminophen is what most obstetricians recommend pregnant women take for their headaches. However, it is not very effective for migraine headaches and it is not as safe as we thought (see my recent post). Fioricet is another drug favored by some obstetrician and it is also not very effective and not very safe.

Sumatriptan (Imitrex) was introduced 20 years ago and the manufacturer has maintained a registry of women who took the drug while pregnant. The final results of this registry were just published in the journal Headache. The registry included 626 women who were exposed to sumatriptan during their pregnancies. They also followed women who took two other migraine drugs, naratriptan (Amerge) and a combination of sumatriptan with naproxen (Treximet). However, there were too few women in those groups to make any conclusions about the drugs’ safety.

As far as sumatriptan, the risk of major birth defects was not increased. The authors also reviewed several other large studies which assessed the risk of taking migraine medications during pregnancy. One of the studies were from the Swedish Medical Birth Register, which included 2257 births following first trimester sumatriptan exposure. No risk was found in this study either.

In summary, pregnant women suffering from severe migraines should be prescribed sumatriptan. Most women respond to an oral form (tablet), but those with very severe attacks should be offered an injection.

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Skipping meals, for some people, is a sure way to get a migraine headache. Even those who do not suffer from migraines can get a headache from not eating breakfast and lunch. However, fasting has remained popular for the treatment of various conditions. Migraine sufferers who suspect that some foods may be triggering their headaches are sometime advised to try an elimination diet. This diet often begins with a fast and then one type of food is introduced at a time to see if it triggers a negative reaction. Anecdotal reports describe relief of migraine headaches with fasting for periods of up to five days. Some programs recommend five-day fasts twice a year, while others are advocating five days each month. A 5:2 diet involves eating a normal amount of calories for five days and the following two days eating 1/4 of that amount. The problem is that some people will have worsening of their headaches in the first day or two. However, most patient reports that after having headaches for a day or two the head becomes very clear.

It is not clear if fasting helps various medical conditions, if indeed it does, which remains an open question. One potential mechanism may involve stem cells. Recent studies suggest that fasting causes proliferation of stem cells. The study was published in the journal Cell Stem Cell. The research was done in mice and showed that prolonged fasting protects against immune system damage and induce immune system regeneration. The researchers speculated that fasting induces stem cells from a dormant state to a state of proliferation.

One of the authors of the study said that “We could not predict that prolonged fasting would have such a remarkable effect in promoting stem cell-based regeneration of the hematopoietic system. When you starve, the system tries to save energy, and one of the things it can do to save energy is to recycle a lot of the immune cells that are not needed, especially those that may be damaged. What we started noticing in both our human work and animal work is that the white blood cell count goes down with prolonged fasting. Then when you re-feed, the blood cells come back. ”

Fasting and induction of stem cells seems to reduce an enzyme which has been linked to aging, tumor progression and cancer. Fasting also protected against toxicity in a small human trial where patients fasted for 72 hours prior to chemotherapy.

“Chemotherapy causes significant collateral damage to the immune system. The results of this study suggest that fasting may mitigate some of the harmful effects of chemotherapy.”

So, how long do you need to fast to induce your stem cells and to get beneficial results? Some advocate suggest one or two days a week. Others promote twice yearly five-day fasts. The bottom line, we have no research on this topic.

Fasting may help protect against brain disease. Researchers at the National Institute on Aging have found evidence that fasting for one or two days a week can prevent the effects of Alzheimer and Parkinson’s disease. Research also found that cutting the daily intake to 500 calories a day for two days out of the seven can show clear beneficial effects for the brain. It is possible that fasting helps by inducing proliferation of stem cells in the brain.

Fasting cuts your risk of heart disease and diabetes:
Regularly going a day without food reduces your risk of heart disease and diabetes. Studies show that fasting releases a significant surge in human growth hormone, which is associated with speeding up metabolism and burning off fat. Shedding fat is known to cut the risk of heart disease and diabetes. Doctors are even starting to consider fasting as a treatment.

3. Fasting effectively treats cancer in human cells:
A study from the journal of aging found that cancer patients who included fasting into their therapy perceived fewer side effects from chemotherapy. All tests conducted so far show that fasting improves survival, slow tumor growth and limit the spread of tumors. The National Institute on Aging has also studied one type of breast cancer in detail to further understand the effects of fasting on cancer. As a result of fasting, the cancer cells tried to make new proteins and took other steps to keep growing and dividing. As a result of these steps, which in turn led to a number of other steps, damaging free radical molecules were created which broke down the cancer cells own DNA and caused their destruction! It’s cellular suicide, the cancer cell is trying to replace all of the stuff missing in the bloodstream that it needs to survive after a period of fasting, but can’t. In turn, it tries to create them and this leads to its own destruction.

This post contains direct quotes from collective-evolution.com

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Botox is a very effective treatment for chronic migraines and possibly other types of headaches and pain. However, Botox is an expensive and somewhat unpleasant treatment. Even though Botox helps a high percentage of patients (about 70%) it would be useful if we could predict who is going to respond and who is not.

One of the predictors seems to be the directionality of pain. That is, if patients with migraine who have constricting (imploding) pain or pain localized to the eye seem to respond better than those who have pain that seems to be pushing from inside out (exploding). This is not a very reliable predictor because some people have difficulty categorizing their pain in that way and because even if they do describe it clearly one way or another, this predictor is far from 100% accurate.

In a study just published in the journal Headache a group of Spanish neurologists claim that they have found a predictor with 95% accuracy. They measured blood levels of calcitonin gene-related peptide (CGRP) and found that those with levels of CGRP above a certain number were 28 times more likely to respond to Botox than those with levels below that level.

CGRP has been shown to be very involved in the process of migraine and several drugs and antibodies which block the CGRP receptor appear to be very promising (see my recent blog post on such antibodies). So, it is not very surprising that this correlation between the response to Botox and blood level of CGRP was found. However, this finding needs to be confirmed in a larger group of patients (this study involved 81 patients) and this test needs to become available commercially since now it can be done only in research laboratories.

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Besides many other mental and physical problems, bullying in school causes headaches. This is the conclusion of a group of psychologists at the University of Padua in Italy who published their findings in the last issue of the journal Headache. They looked at 20 published studies on bullying, which included 173,775 children, and found that 14 of these studies recorded the presence of headaches. While 19% of kids who were not bullied suffered from headaches, this number was 33% in those who were. There was no difference in the incidence of headaches between kids in Europe compared to other countries.

This study confirms what has been reported for health problems in bullied kids in general. It is well known that psychological stress causes physical symptoms. Social pain is a term that psychologists use to describe the effect of peer rejection, ostracism, or loss. Recent studies have shown that physical and social pain share many physiological mechanisms in the brain. The authors also speculate that lack of coping skills, low self-esteem or lack of assertiveness may lead to more psychological and physical problems. They also call on pediatricians, school nurses and others to become more aware of the physical symptoms, such as headache, as a manifestation of bullying.

I have seen a number of children with severe persistent headaches, which required home schooling. In some of these kids bullying was a definite contributing factor, although many children are reluctant to admit this even to their parents.

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The introduction of Levadex has been delayed again, this time for a year. It seems like deja vu all over again – I wrote the same thing on this blog in April of last year. Levadex, which the manufacturer (Allergan) just renamed as Semprana, is an inhaler containing DHE. DHE, or dihydroergotamine is one of the most effective injectable drugs for migraine. It should be even better in an inhaled form because it works faster and causes much less nausea than the injection. The FDA is again delaying the launch because of manufacturing problems. Apparently, the particle size of the drug when it comes out of the inhaler is not uniform enough. Many patients are unhappy, but I am sure that the Allergan is very unhappy too since they spent almost a billion dollars to acquire this drug from a small company that developed it.

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