Beta blockers (Inderal or propranolol and similar drugs) are used for the preventive treatment of migraine headaches. Over the years, a few patients have told me that they take a beta blocker only when they have an attack of migraine with very good results. A report published in Missouri Medicine describes seven patients whose acute migraine headache went away with eye drops containing a beta blocker. These eye drops are used for the treatment of glaucoma. The authors argue that having medicine go into the eye allows it to get absorbed quickly into the blood stream. This is certainly true, but my first thought was that there is too little medicine in eye drops to produce an effect outside the eye. However, beta blocker eye drops can worsen asthma, lower the blood pressure and slow the heart rate, suggesting that the amount of medicine in eye drops is sufficient to cause effects beyond the eye. Oral beta blockers used daily for the preventive treatment of migraines are also contraindicated in those medical conditions. Considering that eye drops are probably safer than many oral medications used to treat an acute migraine attack and that they most likely work faster, this treatment is worth trying.

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Parkinson’s disease (PD), parkinsonian symptoms, and restless leg syndrome (RLS) are more common in people who in middle age suffered from migraines with aura. Those suffering from migraine without aura in their midlife had increased risk of having symptoms of Parkinson’s and RLS, but not PD. These are the findings of a large study of residents of Reykjavik, Iceland who were born between 1907 and 1935. These residents had been followed since 1967. Headaches were classified based on symptoms assessed in middle age. From 2002 to 2006, 5,764 participants were reexamined to assess symptoms of parkinsonism, diagnosis of PD, family history of PD, and RLS.

People who suffered from migraines, particularly migraine with aura, were in later life more likely than others to report parkinsonian symptoms and diagnosed to have PD. Women with migraine with aura were more likely than others to have a parent or sibling with PD. Late-life RLS was increased in those with headaches generally.

The authors concluded that there may be a common vulnerability to, or consequences of, migraine and multiple indicators of parkinsonism.

There are no proven ways to prevent PD, but eating more fruits and vegetables, high-fiber foods, fish, and omega-3 rich oils (or taking an omega-3 supplement, such as Omax3) and avoiding red meat and dairy may have some protective effect against PD.

Intensive research into the causes and treatment of Parkinson’s disease, supported by Michael J. Fox and Sergey Brin of Google among others, should lead to true breakthroughs in the next few years.

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Stabbing headaches can be a sign of acute multiple sclerosis, according to a report by German doctors in the journal Headache. Stabbing headache is a rare type of headache, although patients with migraines often report having occasional “ice pick” headaches. Some call these headaches “jabs and jolts”. In some people, stabbing headaches can be quite disabling. The pain lasts only a couple of seconds but can occur up to 100 times a day. Treatment usually involves indomethacin or another non-steroidal anti-inflammatory medication in the aspirin family (including our own Migralex). However, in this case where stabbing headaches were associated with MS, treating MS relieved headaches as well.

In a prior report in Clinical Neurology and Neurosurgery Italian physicians also found that of 26 patients with stabbing headaches they had seen over 10 years, more than half had autoimmune disorders, including multiple sclerosis, Sjögren’s disease, lupus, Behçet’s disease, autoimmune vasculitis, and antiphospholipid antibody syndrome. The authors speculated that stabbing headache may develop as a result of inflammation in the brain with loss of myelin around the nerve fibers, which is seen with MS and other auto-immune disorders.

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Peripheral nerve blocks can be very effective in stopping a severe migraine attack. We utilize them when a patient does not respond to oral or injected medications or when medications are contraindicated because of a coexisting disease or pregnancy.

Dr. Jessica Ailani and her colleagues at the Georgetown University in Washington, D.C. presented their experience with nerve blocks at the last annual meeting of the American Headache Society in Los Angeles. The study included 164 patients. Most patients received occipital and trigeminal nerve blocks using lidocaine or a similar local anesthetic.

Most patients were satisfied with the results, which lasted from several days up to 2 weeks. Only a small number of participants experienced side effects such as soreness at the site of injections, nausea and vomiting, and head and neck pain.

Dr. Ailani noted that more than 71% of patients rated their pain as 4 to 8 out of 10 before treatment with a nerve block. After a nerve block, nearly half (47.2%) said the pain had reduced to 1 out of 10.

“This is a very well-tolerated procedure and patients are very satisfied with the procedure,” said Dr. Ailani.

Nerve blocks can help keeps headache sufferers out of the emergency room and provide an alternative to systemic drugs, that is drugs that are injected or ingested. Systemic drugs affect the entire body while nerve blocks exert only local effects (unless one is allergic to local anesthetics).

Dr. Robert Kaniecki, a headache specialist in Pittsburgh uses nerve blocks for the prevention of chronic migraine headaches. He administers them into the same areas where Botox is injected. He finds that for some of his patients nerve blocks given every 12 weeks can be as effective as Botox. It is possible that such patients have milder migraines since the effect of nerve blocks lasts a very short time (lidocaine leaves the body after 4 hours or so) compared with the effect of Botox which lasts 3 months. Unlike Botox injections, nerve blocks have not been subjected to a rigorous scientific study comparing them to placebo (saline) injections.

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Frequent attacks of migraine are best treated with preventive measures. Several categories of medications have been shown to be effective for the prevention of migraine headaches. These include Botox injections (for chronic migraine), epilepsy drugs (gabapentin, topiramate, divalproex), blood pressure medications (propranolol, atenolol, lisinopril, losartan, and other), as well antidepressants.

Antidepressants, like most other preventive drugs, were discovered to be effective for pain and headaches by accident. We have good scientific proof that you do not need to be depressed to obtain pain and headache relief from these drugs. The effect on pain and on anxiety or depression are independent of each other. However, many patients who have pain and headaches have higher rates of depression and anxiety and these drugs can relieve both conditions.

The oldest category of antidepressants are tricyclic antidepressants. Elavil or amitriptyline was introduced in the US in 1961. Amitriptyline has been extensively tested for a variety of painful conditions, including low back pain, neuropathy pain, migraines, and other. The main side effects of amitriptyline are dry mouth, drowsiness, constipation, and sometimes, weight gain. Other drugs in the family of tricyclic antidepressants often have fewer side effects. Many doctors always begin with nortriptyline or Pamelor, which is a derivative of amitriptyline and may have fewer side effects. Amitriptyline is broken down in the body into nortriptyline, which is less sedating. We also prescribe other tricyclics, desipramine (Norpramine), doxepin (Sinequan), and protriptyline (Vivactil), which also tend to have fewer side effects. When a patient has insomnia and is not prone to gaining wait, amitriptyline may be the better choice since it will also improve sleep.

The starting dose of amitriptyline, nortriptyline, doxepin, and desipramine is 10 or 25 mg taken at night. Then, if this starting dose is ineffective, the dose is gradually increased to 50 mg, then 75, and sometimes higher. Besides being very effective, tricyclics have another advantage – there is a blood test to measure how much of the medicine is absorbed and is circulating in the body. When a patient takes more than 75 – 100 mg without obtaining relief, we do a blood test to see if the blood level is low and we need to increase the dose or if the level is high and the drug is just ineffective. With protriptyline, the least sedating drug, the starting dose is 10 mg and the highest dose is around 30 mg. Treatment of pain and migraines usually requires a much lower dose of a tricyclic than for depression. All of the tricyclics are available in a generic form and are inexpensive.

Another category of antidepressants that relieve pain and headaches is serotonin and norepinephrine reuptake inhibitors, or SNRIs. Some of the SNRIs are FDA-approved for various painful conditions, such as neuropathy, shingles, fibromyalgia, and back pains. Most popular SNRIs are Effexor (venlafaxine), which is available in a generic form, Cymbalta (duloxetine), Pristiq (desvenlafaxine), Savella (milnacipran), and Fetzima (levomilnacipran). These drugs have fewer side effects than tricyclics, although they are sometimes difficult to stop because they can cause heightened anxiety and other withdrawal symptoms.

Nardil (phenelzine) is an antidepressant in the family of MAO inhibitors and it has also been used for the preventive treatment of migraine headaches. However, this drug has many potential serious drug-drug and drug–food interactions and most doctors avoid this medicine. Other MAOI drugs are Parnate (tranylcypromine), Emsam patch (selegiline) and other.

SSRIs are the most popular drugs for the treatment of anxiety and depression, but they are ineffective for the treatment of pain, migraines, and other headaches. These drugs include Prozac (fluoxetine), Paxil (paroxetine), Lexapro (escitalopram), Zoloft (sertraline) and other. They are very popular because they have fewer side effects than other antidepressants, although they probably cause higher rates of sexual dysfunction.

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Severe persistent migraines can affect emotional, interpersonal, social, and work-related functioning. It is difficult to learn how to cope with pain and improve your functioning on your own. Cognitive-behavioral therapy (CBT) has been proven to improve lives of people with pain, including migraine headaches and not only in adults, but also in children. One major problem with CBT is that it is not readily available in many areas and when available, it is expensive.

I’ve written about two online programs for CBT, which offer help to patients with anxiety and depression. Another online service painACTION.com offers free resources that have been shown to improve coping with pain, to decrease anxiety and depression, and to provide other benefits. The site offers help to patients with migraine, as well as cancer pain, back and arthritis pain, and neuropathic pain. The migraine section has five modules: communication skills, emotional coping, self-management skills, knowledge base, and medication safety.

I do have a problem with their medication safety section in that it does not mention caffeine and caffeine-containing drugs when describing rebound, or medication overuse headaches. These drugs include Excedrin, Anacin, Fiorinal, Fioricet, Esgic, and other. At the same time, they list aspirin, which actually may prevent medication overuse headaches and triptans, which rarely cause such headaches (one of my most popular posts is devoted to daily intake of triptans, which is not something I encourage, but which is the only solution for some patients).

But overall, this is a very useful resource for headache sufferers. To take full advantage of this site you need to go through multiple modules, preferably on a regular basis, say twice a week. It is also useful to keep going back to the old material since it is not easy to change faulty thought processes. The site has enough material to keep you engaged for many sessions. And if you do visit the site regularly you will find that your headaches may become more manageable and that they may have less of an impact on your life.

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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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