The manufacturer of Petadolex brand of butterbur sent me an email saying that the FDA conducted an inspection of their manufacturing plant in Germany. However, my concerns about butterbur, which I mentioned in a previous blog post, has not been addressed. Here is my email response to the manufacturer:
“Thank you for this additional information. It is good to see that the FDA conducted a “comprehensive inspection” of the manufacturing facility in Germany. However, my concerns about the safety of Petadolex are not due to possible deficiencies in manufacturing, but are related to the extraction process. As far as I know, this is why German and UK governments still do not allow the sale of Petadolex and this is why I do not recommend Petadolex to my patients. I am also concerned that because Petadolex is fairly expensive, many patients will decide to buy a cheaper brand of butterbur, which can be truly dangerous. Once Petadolex is cleared for sale in Germany I will be happy to resume recommending it to my migraine patients”.
Bipolar disorder and other psychiatric problems are 2-3 times more common in those who suffer from migraine headaches and migraines are 2-3 times more common in patients with mental illness. Those who suffer from migraines are very familiar with the attitude of doctors, family members and employers who consider migraine to be just another headache, meaning that it is not something that should stop you from doing any activities. Some doctors still blame migraine sufferers for their condition and think that this is a problem of neurotic women. People with mental illness face even more severe discrimination from doctors and everyone else. A very good article on this topic, “When Doctors Discriminate” has appeared in the New York Times this Sunday.
Dr. Robert Shapiro of the University of Vermont recently presented a study which looked at attitudes toward patients with migraine, epilepsy and other conditions. It was an internet-based survey of 705 individuals that examined the levels of stigma by asking following questions:
How comfortable would you be with Jane as a colleague at work?
How likely do you think it is that this would damage Jane’s career?
How comfortable would you be with the idea of inviting Jane to a dinner party?
How likely to you think it would be for Jane’s husband to leave her?
How likely do you think it would be for Jane to get in trouble with the law?
Scoring ranged from 0 to 100. The mean scores were very similar for migraine, panic disorder, and epilepsy and were all significantly greater than for asthma. He concluded that migraine carries as much stigma as epilepsy or panic disorder, although he noted limitations.
Another group of researchers from Philadelphia led by Dr. William Young interviewed 123 patients with episodic migraine, 123 with chronic migraine, and 62 with epilepsy for levels of stigma as perceived by these patients.
Chronic migraine patients had much higher scores on the Stigma Scale for Chronic Illness (SSCI) than the other two groups, but that seemed to be due to chronic migraine patients’ reduced ability to work.
Dr. Young reported that migraine patients reported more “internalized” stigma, that is negative attitudes in themselves or anticipation that others would think negatively of them, and less actual discrimination on the basis of their illness, compared with the epilepsy patients.
These studies and the New York Times article indicate a great need for educating both doctors and the general public about the nature of chronic migraines and mental diseases and for combating the stigma associated with these conditions.
Read MoreSurprisingly, Botox appears to relieve hemiplegic migraines, according to a report by two neurologists from the Mayo Clinic.
They describe 5 female patients who suffered from very frequent and severe migraine headaches with four of them having chronic migraines, that is had headaches on 15 or more days each month. The headaches were preceded and/or accompanied by weakness of one side of their body. The weakness lasted only 20 minutes in one patients, but for hours and days in others. All five patients were first treated with prophylactic medications, which either did not help or caused unacceptable side effects. Botox injections were given every 3 months into the usual sites around the scalp, neck and shoulders. A total dose of 150 units was injected. Three of the patients had three sets of injections by the time of this report and they continued to respond well.
Migraine with typical visual auras has been reported to respond well to Botox injections, which is also somewhat surprising since Botox appears to work on the sensory nerves. This effect on sensory nerve endings leads to the relief of pain. It is likely that reducing painful episodes in turn leads to a calming effect on the brain in general and the brain stops generating migraines as well as symptoms associated with migraines.
I have also seen many patients with visual, sensory and motor aura respond well to Botox injections, often when prophylactic drugs had been ineffective.
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Auditory hallucinations can be associated with chronic headaches, according to a report by our own Dr. Sara Crystal and three other neurologists from the Bronx.
These four doctors reported on 7 of their own patients and also described 8 patients previously reported in the medical literature. Half of the patients had migraine with aura. Regarding hallucination content, the most common sound was distinct human voices in 8 patients, followed by hearing crickets in 2, and ringing bells in another 2, general white noise, also in 2, and repetitive beeping in 1. Regarding timing, 12 experienced hallucinations along with the headache while 3 heard sounds prior to attacks. The duration of the auditory hallucinations was less than one hour but occasionally lasted 4-5 hours or for the duration of the headache. Ten patients had either a current or previous psychiatric disorder, mostly depression. Improvement in both headaches and auditory hallucinations occurred both spontaneously and when prophylactic medications were used, which included propranolol, topiramate, and amitriptyline.
In conclusion, auditory hallucinations are uncommon, but do occur before or during migraine attacks. They usually feature the sound of human voices. Because these are unusual manifestations of migraine, doctors should consider other possible causes, such as a brain tumor, epilepsy, or schizophrenia.
Read MoreThe vascular theory of migraine suggested that changes in the blood vessel size and blood flow were responsible for the development of migraine attacks. This theory went out of fashion and for the past 20 years most headache experts thought that the process of migraine begins in the brain and not blood vessels. A new study by researchers at the University of Pennsylvania seems to again implicate blood vessels as the culprit.
Brain is supplied by four blood vessels that come up from the neck into the brain – two carotid and two vertebral arteries. At the base of the brain they connect with each other making a circle of Willis. Thomas Willis was a 17th century English physician who first described this circle. This circle ensures good blood flow to the brain even if one or even two of the four blood vessels become occluded. Only a third of the population actually has a complete circle connecting all four arteries, while in the rest the circle is incomplete.
This is not a new finding – a group of French physicians reported this discovery in 2009. However, the current study showed that having incomplete circle affected cerebral blood flow and this may be contributing to the process of triggering migraines.
This abnormality appears to be particularly common in those who have migraine with aura. The study looked at 170 people from three groups – a control group with no headaches, a group that had migraine with aura, and a group that had migraine without aura. An incomplete circle of Willis was more common in people with migraine with aura (73 percent) and migraine without aura (67 percent), compared to a headache-free control group (51 percent).
One of the authors commented that “People with migraine actually have differences in the structure of their blood vessels — this is something you are born with” and, “These differences seem to be associated with changes in blood flow in the brain, and it’s possible that these changes may trigger migraine, which may explain why some people, for instance, notice that dehydration triggers their headaches.” A very interesting observation was that “Abnormalities in both the circle of Willis and blood flow were most prominent in the back of the brain, where the visual cortex is located. This may help explain why the most common migraine auras consist of visual symptoms such as seeing distortions, spots, or wavy lines”. It is also possible that the increased risk of strokes in patients with migraine with aura is due to this anatomical defect.
It is most likely that having an incomplete circle of Willis is only one of many predisposing factors. Unfortunately, we cannot do much about this congenital abnormality, but we do have many ways to prevent migraine headaches even without fixing this problem directly.
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Increased intracranial pressure is an under-diagnosed cause of difficult to treat headaches. Persistent chronic headaches that do not respond to treatment may be due to increased pressure inside the head. These headaches may resemble chronic migraine headaches and many doctors will try treating these patients with preventive medications, such as Neurontin (gabapentin), Topamax (topiramate), amitriptyline (Elavil), or Botox injections. If these approaches do not provide relief, measurement of intracranial pressure should be considered. Most patients who suffer from increased intracranial pressure have swelling of the optic nerves (papilledema), which can be detected by examining the back of the eye, a standard part of a neurological and ophthalmological examination. However, some people with increased pressure do not have papilledema and they are the ones who present a diagnostic challenge. This condition is also called pseudotumor cerebri because tumors also raise intracranial pressure. To measure the pressure a spinal tap (lumbar puncture) is performed. The cerebrospinal fluid circulates around the brain, within its ventricles and around the spinal cord. Putting a needle into the spinal fluid at the lumbar spine level is much safer than anywhere else and gives the reading of the pressure everywhere within this enclosed space, including the brain.
Factors that predispose to increased intracranial pressure include delayed effects of a head trauma, certain medications, excessive amounts of vitamin A, obesity, and other. One of the more recent theories suggests that narrowing of the veins that drain blood from the brain is responsible for this condition. This diagnosis is made by performing an angiogram or a magnetic resonance venogram (MRV, a test done by an MRI machine), tests that show blood vessels.
In addition to headaches, increased pressure can cause nausea, dizziness, pulsating noise in the ears, and blurred vision. If left untreated, the increased pressure can lead to loss of vision.
If no obvious causes are found the condition is called idiopathic intracranial hypertension. Its treatment begins with the attempts to lose weight if the person is overweight. Pregnant women who are more prone to develop this condition often obtain relief after the delivery. Medications that can help include acetazolamide (Diamox) and topiramate (Topamax). If medications are ineffective a neurosurgeon can place a shunt that drains cerebrospinal fluid into the abdomen. This is a relatively simple procedure, but it does carry a risk of infections and other complications. Shunting is reserved for patients who have uncontrollable headaches or are threatened with loss of vision.
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Acute treatment of episodic and chronic migraine headaches in the US leaves a lot to be desired. Results of the American Migraine Prevalence and Prevention Study lead by Dr. Richard Lipton indicates that the acute treatment of migraine headaches in patients with chronic migraines is significantly worse than in patients with episodic migraines. Chronic migraines are defined as those occurring on 15 or more days each month, while patients who have 14 or fewer migraines a month are classified as having episodic migraines.
The researchers developed a specific questionnaire to assess acute treatment of migraine headaches. The questionnaire evaluated the effect of treatment on people’s functioning, how rapid was the relief, relief consistency, recurrence risk, and tolerability or side effects. They examined responses from 8612 persons who met criteria for migraine (chronic migraine = 539; episodic migraine = 8073). The treatment scores were significantly lower for persons with chronic migraine vs episodic migraine. The conclusion was that the questionnaire was a robust tool for measuring treatment optimization and that acute treatment was suboptimal for both episodic and chronic migraines, particularly for chronic migraines, suggesting that there are opportunities for improving care.
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Stimulation of the sphenopalatine ganglion seems to relieve cluster headaches according to a study by European neurologists. The study examined the efficacy of the on-demand sphenopalatine(SPG) stimulation in chronic cluster headache patients. 43 patients in this randomized controlled study were implanted with the ATI Neurostimulator System. Chronic cluster headache is a disabling neurological disorder that often does not respond to medical therapy. A previous study showed that this stimulator was effective for acute cluster headache pain relief and in some patients made their attacks less frequent. These patients also had clinically and statistically significant improvement in quality of life and reduction in headache disability.
The 43 patients in the current study were dissatisfied with their cluster headache treatment and 32 of them completed the one-year study with 23 continuing to use the stimulator beyond one year. At enrollment, 18 (78%) of patients indicated their overall evaluation of the ATI Neurostimulation System for treating their chronic cluster headaches as good or very good. 18 (78%) found SPG stimulation a useful therapy in treating their cluster headaches. 19 (83%) found surgical effects tolerable and the implanted neurostimulator comfortable or did not notice it and 23 (100%) found the stimulation sensation tolerable. 15 (65%) did not have significant side effects after stimulation. 21 (91%) would make the same decision again to treat their CH with the ATI Neurostimulation System, and 22 (96%) would recommend the ATI Neurostimulation System to someone else. 13 (57%) of patients experienced clinically significant improvement in headache disability and quality of life compared to baseline.
These results suggest that SPG stimulation with the ATI Neurostimulator is an effective therapy with sustained benefits and a high level of
patient satisfaction. This is an experimental device and is not available in the US. Even when it becomes available it would be more reasonable to try less invasive, even if not proven treatments, such as Botox injections. My experience treating chronic cluster headaches with Botox is only “anecdotal” (as opposed to that from large clinical trials) and involves a small number of patients, but nevertheless it has been very positive.
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Candesartan (Atacand) is a relatively new blood pressure medication in the family of ACE receptor blockers (ARBs), which is also effective in the preventive treatment of migraine headaches. Another ARB, Benicar, or olmesartan has also been shown to be effective in preventing migraine headaches. Propranolol (Inderal), a beta blocker, is one of the oldest preventive drugs for migraines and many doctors often use it first. A recent study by Norwegian doctors compared candesartan with propranolol and placebo. They conducted a triple-blind, double crossover study, with 72 adult patients with episodic or chronic migraine, recruited in an outpatient clinic and through advertisements. Participants underwent three 12-weeks’ treatment periods on either candesartan (Atacand) 16 mg, propranolol slow release (Inderal LA) 160 mg, or placebo. The primary outcome measure was days with migraine headache in a 4 week period. They also looked at days with headache, hours with headache, proportion of responders (50% reduction of migraine days from baseline), and side effects.
Their analysis showed that candesartan and propranolol were equally effective and both were superior to placebo. Both drugs had more side effects than placebo, but side effects were different. The researchers concluded that candesartan should be included in the arsenal of drugs recommended for migraine prevention. The advantage of ARBs, such as Atacand and Benicar, is that unlike beta blockers they do not slow down the heart rate, which can be a problem during exercise. During exercise heart rate increases to deliver more blood to the muscles and lungs, but propranolol prevents this increase in the heart rate, which makes people feel tired, short of breath and not able to exercise as hard as they’d like. This is a significant problem since I recommend regular aerobic exercise as the first and the most important preventive treatment for migraine (and tension-type) headaches.
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Half of the kids seen by pediatric headache specialists suffer from chronic migraines. Dr. Hershey and his colleagues at the Cincinnati Children’s Hospital presented results of a study that compared cognitive behavioral treatment combined with amitriptyline (an antidepressant used to treat migraine and other pains) with amitriptyline alone in children aged 10 to 17 who suffered from chronic migraines. This was a first randomized clinical trial in childred with chronic migraines. Combined psychological & pharmacological treatment has been reported to be effective in adults and children with chronic pain other than migraine. Psychological intervention was cognitive behavioral therapy (including biofeedback); pharmacological intervention was amitriptyline (goal dose of 1 mg/kg/day). The control group was taught attention control with equal to psychological intervention in terms of contact frequency and face-to-face time, and involved education and support. They enrolled 135 children with mean age of 14 years; 15% minority; 79% female. Mean baseline headache frequency was 21 days and mean baseline disability score was 68 (severe disability grade). There were no differences between groups at baseline.
For the combined group, a greater than 50% headache frequency reduction was seen in 66% at post-treatment (20 weeks later), 86% at 12-month follow-up. And most impressively, 71% no longer had chronic migraines at the end of treatment and 88% were not chronic at 12-month follow-up. The disability score dropped to below 20 (mild to no disability) in 75% at post-treatment and 88% at 12-month follow-up. These results were significantly better than in the control group of children. The authors concluded that the combined psychological and medication treatment in youth with chronic migraine shows clinically significant reductions in headache frequency and migraine-related disability. At 12-month follow-up, almost 9 out of 10 children no longer had chronic migraines and were mild to no disability grade. They also felt that the results of this study should immediately impact practice of headache medicine in children. However, they could be wrong speculating that based on the published studies in adults, cognitive-behavioral therapy with amitriptyline may be better than other medications and Botox injections. In order to prove this, they need to do a study directly comparing Botox injections with cognitive-behavioral therapy and amitriptyline. One other factor that is not mentioned by the authors is that chronic migraines often subside on their own, which was shown in a study of 122 Taiwanese adolescents.
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A non-steroidal anti-inflammatory (NSAID) drug naproxen (Aleve) alone seems to be more effective than naproxen combined with sumatriptan (Treximet), according to a study by Dr. Roger Cady and his colleagues from Missouri, which was presented at the International Headache Congress in Boston.
This was a small study involving 39 patients who suffered with moderate to severe attacks of migraine. The researchers looked at possible effect of acute medications on frequency of headaches. As migraine frequency increases, so too can the risk of medication overuse, which leads to more headaches. On the other hand, frequent administration of acute medications may act both as an acute and prophylactic treatment. The patients in the study were 18 to 65 years of age, with frequent episodic migraine with or without aura, in Stage 2 migraine (3 to 8 headache days per month) or Stage 3 migraine (9 to 14 headache days per month). Patients were asked to treat their migraines with sumatriptan/naproxen (Group A) or naproxen alone (Group B) for 3 months. Patients in Group B had a statistically significant reduction in migraine headache days at month 3 compared to baseline. Group A also had a reduction of migraine headache days but this decrease did not reach statistical significance over baseline. In addition, subjects in Group B had a statistically significant reduction of migraine attacks at all three months of the study compared to baseline. A greater than 50% reduction in the number of migraine days at month 3 occurred in 43% (6/14) of subjects in Group B compared to 17% (3/18) of subjects in Group A. Sumatriptan/naproxen was statistically superior to naproxen at 2 hours in reducing the migraine headache severity. The amount of acute medication used decreased from baseline to months 1-3 for both groups. Both treatments were well tolerated. The authors concluded that naproxen provides headache relief at 2 hours and reduces frequency of headache days and migraine attacks. Despite both groups using similar quantities of naproxen, this was not seen in sumatriptan/naproxen group, but sumatriptan/naproxen is more effective as acute treatment at 2 hours in reducing headache severity but does not significantly reduce attack frequency or the number of headache days.
If confirmed by larger studies, this is a very surprising discovery because there is little evidence indicating that triptans, like sumatriptan in this study, cause increased frequency of migraines due to medication overuse. In fact, this study did not show that sumatriptan did that, but only that naproxen alone was better at preventing migraine headaches. We also know from Dr. Richard Lipton’s large studies that aspirin has a preventive effect and naproxen and other NSAIDs do not, although they do not worsen headaches either. The large and multi-decade Framingham study showed that 81 mg of aspirin taken daily also has small but statistically significant beneficial effect in preventing migraine headaches. As far as acute treatment of migraines, in a review by an independent organization, Cochrane Reviews, the extra strength dose of aspirin (1,000 mg) was shown to be as effective as 100 mg of sumatriptan.
Nausea of migraines responds to an acupressure device, according to two German doctors who presented their findings last week at the International Headache Congress in Boston. I spoke to one of the authors, Dr. Zoltan Medgyessy about his study. The study included 41 patients, whose average age was 47 years. They had been suffering from migraines for on average 26 years and had experienced an average of 33 migraine
days over the previous three months. The average migraine pain intensity was 7 on a scale from 0 to 10; the average intensity of nausea was 6 on a 1-10 scale. Patients were instructed to use the device (Sea Band) instead of taking nausea medication during their next migraine attack and to complete and return a migraine attack diary. After using the acupressure band, 34 (83%) patients noticed a reduction of nausea and 18 (44%) reported a significant improvement in nausea. The average intensity of nausea after therapy was 3. The relief of nausea was reported after an average of 29 minutes. The average duration of the migraine attacks was 22 hours. The Sea Bands were worn on average for 18 hours. Forty patients (98%) reported that they would use Sea Band during migraine attacks again. The authors concluded that the use of an acupressure band can reduce migraine-related nausea. The advantage of this therapy is that it is drug-free and has no risks
or side-effects such as dizziness, fatigue, or restlessness seen with drugs. Its effect is rapid, and it is easy and it is inexpensive to use (in the US, $6 to $10). To prove that this method works beyond just placebo effect we need a blinded trial comparing anti-nausea medication with Sea Bands. I do recommend Sea Bands or a similar device, Psi Band for my migraine patients. A controlled trial in 60 women showed that Sea Bands relieve morning sickness of pregnancy (nausea and vomiting of pregnancy), which suggests that the relief we see in migraine patients is also real and not just due to placebo.
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