With Swiss colleagues Drs. Caterina Podella, Livia Granata, and Reto Agosti at the headache conference held on November 4, 2021, in Zürich.
Dr. Podella presented a very comprehensive approach to the treatment of migraine headaches. Dr. Granata expertly covered the topic of cluster headaches. I spoke about the challenges of treating refractory migraine headaches and Dr. Agosti provided a lively and insightful discussion of all these topics.
I am honored to participate in a symposium on headache management,
“THE CHALLENGE OF MIGRAINE AND CLUSTER HEADACHES”. The title of my presentation is The challenge of migraine: new perspectives in refractory cases
This interactive neurological conference will be held in-person on Thursday, November 4, 2021 at the Zurich Marriott Hotel, Zurich, Switzerland
Read MoreTo gain FDA approval a drug has to be shown to be better than a placebo. The placebo effect is a well-established psychological contributor to the efficacy of most treatments.
They evaluated chronic migraine patients who were treated with erenumab (Aimovig). Erenumab is a monoclonal antibody that targets CGRP, a neurotransmitter involved in the development of migraine attacks.
Monthly erenumab injections were given for one year to 75 patients with chronic migraine who had already failed at least three other oral preventive drugs. A full psychological evaluation assessed personality disturbances, mood and anxiety disorders, as well as childhood traumas, and ongoing stressors.
After 12 months of treatment, 53 patients had at least a 50% drop in the number of headache days per month. The other 22 did not. When compared to responders, non-responders were more likely to have personality disorders with anxious-fearful, avoidant, dependent, and obsessive-compulsive features. Non-responders were also more likely to suffer anxiety disorders and had a higher number of current major stressors.
A very practical application of these findings is that doctors need to address anxiety when treating migraine and chronic pain patients. I’ve seen a number of patients whose migraines improved with an SSRI antidepressant such as fluoxetine (Prozac) or escitalopram (Lexapro). SSRIs do not possess pain-reliving properties. However, they are good at relieving anxiety and so can indirectly improve migraines. Most of the time, I prescribe SNRIs such as duloxetine (Cymbalta) or a tricyclic antidepressant such as nortriptyline (Pamelor) because they relieve anxiety and can have a direct pain-relieving effect.
The old dogma in psychology was that you cannot change your personality. We now know that such change is possible. Different types of cognitive-behavioral therapy (CBT) can be very helpful. Swedish researchers showed that even a brief internet-based CBT can produce long-term changes in personality traits.
Read MoreMany migraine sufferers report that their migraines are brought on by the weather. High humidity, high temperatures, and changes in barometric pressure are the most commonly reported triggers. I’ve seen some patients for whom changes in the weather is the only trigger. Research studies looking at this connection, however, have been contradictory.
The data from 18,000 Norwegians aged 40 years or older from the general population were examined. All of them underwent pressure pain tolerance (PPT) test using a blood pressure cuff and cold pain tolerance (CPT), tested by immersing the dominant hand in cold water.
The results showed a clear seasonal variation in CPT. Cold pain tolerance was worse during the warmer times of the year compared with January. There was no seasonal variation in PPT.
The authors also found that temperature and barometric pressure have “a causal and dynamic effect on pain tolerance, which supports the common belief that weather affects pain.”
There is not much you can do about the weather except for moving to a place with an unchanging and mild climate. Some of my patients with barometric pressure-induced headaches do respond to acetazolamide (Diamox). This is a diuretic that prevents mountain sickness in climbers. Patients do not need to constantly check the weather forecast. For more information on acetazolamide, see my previous blog post.
Read MoreTrudhesa is a new formulation of dihydroergotamine (DHE) nasal spray just approved by the FDA. It appears to be more effective than the original DHE nasal spray (Migranal) that was introduced in 1997.
Ergotamine, the first migraine-specific drug was developed in 1926. It is still available in tablet form but is not widely used because it causes nausea, constriction of blood vessels, and other side effects. DHE, approved in 1946, was the first synthetic migraine drug. It was derived from ergotamine in an attempt to reduce side effects. DHE is not effective when taken by mouth and was originally approved for intravenous use. It is still being used now – 75 years later – intravenously, intramuscularly, and subcutaneously. DHE injection is a very effective medicine, often used when no other migraine drug provides relief. It does cause nausea and vomiting in a significant number of patients. This is why it is often given along with an anti-nausea drug such as ondansetron (Zofran), prochlorperazine (Compazine), or metoclopramide (Reglan).
The original DHE nasal spray has been a relative disappointment. It is not very effective, although there are some patients for whom it works well. Despite being on the market for over 20 years, it is still very expensive – $100 a dose. The manufacturer of Trudhesa, which is a better product than Migranal, is promising to make their product more affordable. Nasal delivery of DHE causes less nausea than an injection.
Trudhesa is more effective despite delivering a smaller dose of DHE than Migranal. This is because Trudhesa is delivered as a fine mist into the upper reaches of the nasal cavity. It will become available in about two months. I will prescribe it to patients for whom oral medications are ineffective.
Read MoreThe placebo effect is a bane of clinical trials. A drug is considered ineffective if it is only as good as a placebo. And placebo can be quite good. Intriguingly, the placebo effect in clinical trials has been getting stronger over the past few decades. Lately, placebo has been receiving a lot of attention from researchers.
A rigorous study just published in the journal Pain looked at the effect of a placebo when patients were clearly told that they are taking a placebo. These patients were compared to those who were given a placebo in a double-blind study of peppermint oil capsules for irritable bowel syndrome (IBS). These two different types of placebo were compared to a control group of patients who were not given any pills.
Participants treated with an open-label placebo and a double-blind placebo reported similar and clinically meaningful improvements in IBS symptoms. These improvements were significantly greater than in those who were not given any pills. The results were statistically significant for the primary outcome measure (IBS Symptom Severity Scale) as well as for mean global improvement scores.
Twice as many patients in the double-blind placebo group had side effects (mostly gastrointestinal, such as heartburn) than those in the open-label placebo. It is probably because the first group was told about the possible side effects of peppermint oil.
The authors concluded that an open-label placebo “could play a role in the management of patients with refractory IBS”.
Just like migraines, IBS involves central sensitization and hypersensitivity of the nervous system. And just like with migraines, placebo response in clinical trials of IBS tend to be high. This is not to suggest that these conditions are psychological. Especially with migraines, the biological basis is well documented. Psychological factors, however, cannot be ignored. About 40% of patients with chronic pain, including migraines, have a history of emotional, physical, or sexual abuse. Post-traumatic stress disorder of other types also causes hypersensitivity of the central nervous system. Psychological factors can even be the cause of such potentially deadly conditions as broken heart syndrome (Takotsubo cardiomyopathy). It is likely that the placebo effect is stronger in conditions where psychological factors are more pronounced.
It is considered unethical to prescribe a placebo to patients without telling them that they are getting a placebo. This latest study suggests that some patients may improve even if they know that they are taking a placebo.
I do prescribe herbal supplements such as feverfew and boswellia and on a rare occasion, a homeopathic remedy, all of which lack rigorous proof of their efficacy. For that matter, many drugs we prescribe for migraines lack such definitive proof. I would suggest that we should first prescribe less harmful unproven remedies rather than unproven prescription drugs.
Read MoreThe international classification of headache disorders lists many different types of migraines – migraine with aura, hemiplegic, retinal, chronic, and others. Chronic migraine is present if a person has a headache on 15 or more days each month. If the headache is present on fewer than 15 days, the condition is called episodic migraine.
The division into chronic and episodic migraine is not based on any scientific evidence. Research by Dr. Richard Lipton and his colleagues showed that patients often cycle from chronic into episodic migraines and back. This happens even without any treatment.
They concluded: “Our data suggest that the use of a 15 headache day/month threshold to distinguish episodic and chronic migraine does not capture the burden of illness nor reflect the treatment needs of patients.”
One damaging aspect of having a category of chronic migraine as it applies to clinical practice is the fact that Botox is approved only for chronic migraines. I know from 25 years of experience injecting Botox that it works very well for some patients who have as few as four migraines a month. Unfortunately, insurance companies do not pay for Botox unless you have chronic migraine. This deprives many patients of this very effective and safe treatment.
The second very costly effect is on the research of new preventive drugs. The FDA requires a separate set of studies for chronic and episodic migraines. These additional trials of the four approved injectable CGRP monoclonal antibodies added many millions of dollars to the development costs. The trials showed good relief for both episodic and chronic migraine sufferers.
Hopefully, the next, fourth classification of headache disorders will eliminate the category of chronic migraines.
Read MoreTrigeminal neuralgia (TN) is an extremely painful and often debilitating condition. Many people respond to the standard therapy with epilepsy drugs such as carbamazepine (Tegretol) or oxcarbazepine (Trileptal). Botox injections can be helpful as well. A significant minority of patients, however, do not respond to these treatments and sometimes require brain surgery.
Fortunately, we have a new class of drugs that has allowed some of my patients to avoid having an operation. These drugs are CGRP monoclonal antibodies (mAbs). They have been approved by the FDA only for the prevention of migraine headaches, so their use for TN is considered to be “off-label”.
Erenumab was the first CGRP mAb. It was approved in May of 2018. Another two, galcanezumab (Emgality) and fremanezumab (Ajovy) were approved about six months later. These are given by a monthly subcutaneous injection. About a year ago, an intravenous CGRP mAb, eptinezumab (Vyepti) was also approved. These four drugs are very similar. However, some patients find one to be more effective than others. I’ve found this to be true not only in migraine patients but also in those with TN. Erenumab is slightly different in its mechanism of action and it is the only one that has a warning about the potential for causing severe constipation and increased blood pressure. Since TN patients tend to be older and more prone to these side effects, I prefer galcanezumab or fremanezumab. Unlike eptinezumab, they can be self-administered.
Off-label use is totally legitimate. However, insurance companies are not likely to pay for an expensive drug that is not explicitly approved by the FDA for a specific indication. And these drugs are not cheap – about $600 to $700 for each monthly shot. Because of the competition among pharmaceutical companies, they provide us with plenty of free samples (except for eptinezumab). TN is a relatively rare disorder so we can provide free samples to all of our TN patients who respond to these drugs. This is true for most neurologists’ private offices. This may not be true in big hospitals where sampling is not allowed.
Read MoreA publication of the American Headache Society, Headache, The Journal of Head and Face Pain, has just published Dr. Allan Purdy’s most generous review of my new book, The End of Migraines: 150 Ways to Stop Your Pain.
I am very grateful to Dr. Purdy and to my many colleagues who wrote endorsements for this book.
Self-publishing allows me to set a low price of $3.95 for the ebook version. It also makes it easy for me to regularly update it. Self-publishing, however, means that, unlike my previous three books, this one does not have the promotional help of a big publisher. If you read the book, please write a review on Amazon and spread the word to other migraine sufferers.
Read MoreThe opioid epidemic has claimed many lives. Overprescribing by doctors has certainly played a role. The push to use opioids more liberally started in the late 1980s. This promotion by many pain experts even led to pain being adopted as the fifth vital sign. One impetus for this push was the mistaken belief in the low rates of addiction when opioids are used to treat pain. Another was the results of surveys of patients being discharged from hospitals. Poor pain control was the main complaint of 40% of such patients. Centers for Medicare & Medicaid Services (CMS) got into the act as well and included good pain control as one of the measures required for the recertification of hospitals. In January 2018, however, the three survey questions about pain management were replaced by three questions about communication about pain. In October of 2019, even these three items about communication about pain were completely removed from the CMS’ HCAHPS Survey. So hospitals and doctors no longer need to worry about relieving pain and the suffering that goes with it. Doctors have to worry more about losing their license or even being put into jail. I’ve testified in front of a disciplinary panel on behalf of a doctor who was at risk of losing his license. An adult patient’s mother complained to the state health department about her son getting prescriptions for opioid drugs. In this case, the doctor was exonerated but the financial and the emotional toll will certainly make him very unlikely to continue prescribing opioids drugs.
These drugs, despite their potential for causing addiction and other side effects, are life-savers for many people. When used judiciously and as part of a multidisciplinary approach, they can provide not only improved quality of life but can make a difference between disability and normal functioning.
This study examined if primary care clinics “are more or less willing to accept and prescribe opioids to patients depending on whether their history is more or less suggestive of aberrant opioid use”. They conducted an audit survey of primary care clinics in 9 states from May to July 2019. They had simulated patients call the clinics and give one of two scenarios for needing a new provider: their previous physician had either (1) retired or (2) stopped prescribing opioids for unspecified reasons. Of 452 clinics responding to both scenarios (904 calls), 193 (43%) said their providers would not prescribe opioids in either scenario, 146 (32%) said their providers might prescribe in both, and 113 (25%) responded differently to each scenario. Clinics responding differently had greater odds of willingness to prescribe when the previous doctor retired than when the doctor had stopped prescribing.
The authors concluded that “…primary care access is limited for patients taking opioids for chronic pain.” and that “This denial of care could lead to unintended harms such as worsened pain or conversion to illicit substances.”
Hopefully, the pendulum will soon begin moving closer to the middle. Another hope is that the researchers will finally discover the holy grail of pain management – a non-addictive pain medicine with few other side effects.
Read MoreAlmost 1.5 million Americans visit emergency rooms every year for the treatment of head trauma. Headache, not surprisingly, is one of the most common symptoms of head trauma. What is very surprising is that until now, there have been no controlled studies of acute therapies for posttraumatic headaches.
Dr. Benjamin Friedman and his colleagues at the Montefiore Hospital in the Bronx just published a “Randomized Study of Metoclopramide Plus Diphenhydramine for Acute Posttraumatic Headache” in the journal Neurology. Emergency rooms often use metoclopramide (Reglan) as the first-line drug for the treatment of migraines. Diphenhydramine (Benadryl) was added to reduce the chance of side effects from metoclopramide. These side effects of restlessness and involuntary movements can be very unpleasant.
The study involved 160 patients. Their pain severity was measured on a 0 to 10 verbal scale. Patients who received a placebo reported a mean improvement of 3.8, while those receiving two medications improved by 5.2 points. Side effects occurred in 43% of patients who received medications and 28% of patients who received placebo.
My recent post was devoted to a study that showed dramatic similarities between migraines and posttraumatic headaches. The outcome of Friedman’s study, therefore, is not unexpected.
The overall efficacy of metoclopramide is fairly modest. It provides only partial relief that often does not last. And some patients get no relief at all. It also causes unpleasant side effects.
It is puzzling why emergency room doctors are not using a migraine-specific drug, sumatriptan for both migraines and posttraumatic headaches. An injection of sumatriptan works well within an hour for 70% of migraine patients. It has significantly fewer side effects than metoclopramide. Vials of sumatriptan (but not autoinjectors) are relatively inexpensive.
As far as the use of sumatriptan for posttraumatic headaches, we have only a few anecdotal reports. One of the reports, however, describes seven patients who did not respond to other drugs and had very good relief of their posttraumatic headaches with sumatriptan.
Read MoreWe know that physical emotional, and sexual abuse in childhood increases the risk of developing chronic pain and migraines later in life. Dutch researchers looked at several other potential predisposing factors. The results of their study were published in the May issue of the journal Pain.
This study was a part of the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohort study. It included 3,064 children who were evaluated at the ages of 11, 14, 17, and 20. The researchers assessed headache prevalence and incidence in girls and boys and explored associations with early life, environmental, lifestyle, health, and psychosocial factors.
From age 11 to 20 years, the prevalence of headaches increased from 9% to 20% in girls and remained in 6% to 8% range in boys. Eighty-eight percent of the girls and 76% of boys with headaches also reported at least one of the following at age 17: sleeping problems, asthma, hay fever, musculoskeletal complaints, fatigue, low mental health, or worrying. They also found that lower educational achievement, skipping breakfast on two or more days per week, and in boys, exposure to tobacco smoke in infancy, increased the risk of developing headaches. In girls, sleeping problems and musculoskeletal complaints were associated with a higher chance of having headaches. Interestingly, residential greenness reduced the chance of developing headaches.
The risk factors are usually divided into modifiable and non-modifiable. Sex, age, and genetic factors are some of the non-modifiable ones. The factors mentioned in the study, except for sex, are all theoretically modifiable. In practice, however, they are very difficult to fix. Eating breakfast every morning is probably the easiest to achieve for most families. But even that can be difficult for the very poor. Moving to suburbs for greener surroundings, improving educational opportunities, and avoiding second-hand smoke in infancy are even harder to achieve.
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