Headache medications | Headache NewsBlog

Sublingual ketamine for pain

By: Dr. Mauskop

28-11-2021

Headache medications, Headaches, Migraine, Pain

Ketamine was approved by the FDA in 1970 and was originally used for the induction of anesthesia. It has been shown to relieve depression and is also widely used to treat pain. For depression, it is approved by the FDA in a nasal spray form. For severe pain, it is often given intravenously. Oral ketamine is probably the least effective.

In a recent study, Australian researchers compared the pain-relieving effect of oral and sublingual ketamine in 16 patients. The study was double-blind. Sublingual administration of ketamine resulted in a faster onset of pain relief – 7 minutes with sublingual and 13 with oral. Side effects were also more common with the sublingual route. In all other measures, sublingual and oral administration produced similar pain-relieving effects.

Oral and sublingual ketamine are not available at regular pharmacies. It is, however, easily made up by compounding pharmacies. The sublingual ketamine is available as a lozenge which is also called troche. I usually prescribe ketamine infusions or troches only after a wide variety of other treatments do not provide relief.

Ketamine is a controlled drug with a potential for misuse. It can also cause psychiatric side effects such as hallucinations, disinhibition, delusional thinking, and depression.

Zürich headache conference

By: Dr. Mauskop

08-11-2021

Chronic migraine, Cluster headaches, Headache medications, Headaches, Migraine

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.

If you see a friend respond to treatment, you are more likely to respond as well

By: Dr. Mauskop

21-10-2021

Alternative Therapies, Headache medications, Migraine, Pain, Pain Research, Psychology of headaches

The placebo effect is a bane of clinical trials. It is, however, a great tool in clinical practice. It is unethical to prescribe an actual placebo but there is no reason not to try to enhance the placebo effect when prescribing any treatment, pharmacological or non-drug.

A new and unique study that was just published in Pain, a journal of the International Association for the Study of Pain, suggests that looking at others who respond to treatment makes people more likely to respond to that treatment as well.

German researchers decided to study what is called social observational learning (SoL). This was a double-blinded randomized controlled clinical trial in 44 patients with chronic low-back pain (CLBP). They compared the effects of observing positive treatment outcomes in a sham or pretend patient versus hearing the same sham patient report neutral effects. In the SoL group, the sham patient told study patients about his improved pain due to amitriptyline and he also demonstrated his improved mobility by bending forwards and sideways. The same sham patient told the control group only that he was taking amitriptyline. The researchers collected data before and after the intervention and two weeks later. After the intervention, pain decreased in both groups with no difference between groups. The SoL group, however, showed a significantly larger decrease in perceived disability.

The authors concluded that “The CLBP patients’ direct observation of positive treatment outcomes in the sham patient appears to have enhanced the treatment effects, while indirect verbal reports of reduced pain did not.”

These findings are not surprising. I often have patients ask for a particular treatment because their friend or relative had a very good response to it. If it is a reasonable treatment for a particular patient, I usually oblige, hoping for an enhanced placebo effect.

Response to drugs is influenced by psychological factors

By: Dr. Mauskop

11-10-2021

Alternative Therapies, Brain disorders, Chronic migraine, Headache medications, Headaches, Migraine, Psychology of headaches

To 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.

A group of Italian researchers just published an interesting study looking at other psychological factors that might influence the response to treatment.

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.

FDA approves Qulipta (atogepant), a new preventive migraine drug

By: Dr. Mauskop

02-10-2021

Chronic migraine, Headache medications, Migraine

Atogepant (Qulipta) is a new migraine drug that was just approved by the FDA for the preventive treatment of migraines. It is the third drug in the family of gepants. Gepants block the CGRP receptor. CGRP is a chemical released during a migraine attack. In the past three years, the FDA approved four injectable preventive migraine drugs that also block CGRP. Gepants are taken by mouth.

The dose of atogepant is 10 mg, 30 mg or 60 mg taken daily, once a day. The primary efficacy endpoint in clinical trials was the change from baseline in mean monthly migraine days over the 12-week treatment period. There was a drop of 3.7, 3.9, and 4.2 in the number of mean monthly migraine days in the 10 mg, 30 mg, and 60 mg doses, respectively.

Side effects – assessed in almost 2,000 patients – were infrequent and mild. Nausea occurred in 5%, 6%, and 9% on 10 mg, 30 mg, and 60 mg respectively, constipation in 6% on all three doses, and fatigue or somnolence in 4%, 4%, and 6%.

Ubrogepant and rimegepant, two other gepants, were first approved to be taken as needed, whenever a migraine strikes. Rimegepant recently was also approved for the prevention of migraines. Even though gepants are very similar they often differ in how they work in an individual patient. Some of my patients find that ubrogepant works much better than rimegepant while for others the opposite is true. I am certain that some patients will find a big difference in the way rimegepant and atogepant work for them. This is why it is useful to have a few drugs in every therapeutic category.

A new, better DHE nasal spray is approved for acute migraines

By: Dr. Mauskop

06-09-2021

Chronic migraine, Headache medications, Headaches, Migraine, New treatments

Trudhesa 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.

Placebo really works, even if you know it’s placebo

By: Dr. Mauskop

30-08-2021

Alternative Therapies, Headache medications, Headaches, Migraine, Pain, Pain Research, Psychology of headaches

The 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.

Naratriptan is the most effective triptan?

By: Dr. Mauskop

26-07-2021

Chronic migraine, Headache medications, Migraine

In the US, we are lucky to have seven different triptans available in the pharmacies. Five of them – sumatriptan, rizatriptan, zolmitriptan, eletriptan, and almotriptan are considered to be more effective than the other two – naratriptan and frovatriptan. Frovatriptan has the longest duration of effect because its half-life is 26 hours. Its initial efficacy, however, is not as good as that of other triptans. Naratriptan has a half-life of 6 hours, while the leading five triptans, only 2-4 hours. Naratriptan is also considered to be less effective but it could be because the marketed dose is too low.

In an article in the latest issue of Cephalalgia Peer Tfelt-Hansen argues that naratriptan is as effective as sumatriptan. In fact, if you inject an adequate dose of naratriptan it works better than an injection of sumatriptan. Naratriptan, however, is not available as an injection, only sumatriptan is.

Naratriptan (Amerge) was introduced by the same company that made sumatriptan (Imitrex), the very first triptan. They decided to market it as a “gentle” triptan and selected a relatively low dose of 2.5 mg that had as few side effects as the placebo.

In clinical trials, 2.5 mg of oral naratriptan is less effective than 100 mg of oral sumatriptan. However, clinical trials have shown that 10 mg of naratriptan has similar efficacy to 100 mg of sumatriptan. Naratriptan, 10 mg had slightly fewer side effects than sumatriptan, 100 mg.

The author also mentions the conclusion of the 2004 review by the American Triptan Cardiovascular Safety Expert Panel: “Incidence of triptan-associated serious cardiovascular adverse events in both clinical trials and clinical practice appears to be extremely low”. For more than a decade now, all European countries have at least one of the triptans available without a prescription.

The practical implication of this information is that it is safe to exceed the FDA-approved dose of naratriptan. If taking one 2.5 mg tablet provides some relief, taking two or three at once will not result in dangerous side effects. I’ve also had patients tell me that they need to take a double dose of sumatriptan – 200 mg instead of 100 or 20 mg of rizatriptan instead of the maximum recommended single dose of 10 mg. In the US, eletriptan is available only in 20 and 40 mg strength. Some European countries have 80 mg tablets as well.

Since all triptans are now available in a generic form, three of them are very inexpensive and patients can bypass the insurance limits and pay out-of-pocket for additional tablets. That is if your doctor is willing to prescribe a larger number of tablets – many erroneously believe that triptans are a common cause of medication overuse, or rebound headaches. You can find naratriptan, rizatriptan, and sumatriptan in some pharmacies for less than $2 a pill.

Erenumab relieves trigeminal neuralgia – another case series

By: Dr. Mauskop

07-06-2021

Headache medications, Headaches, Pain, Trigeminal and other neuralgias

Trigeminal 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”.

The first case series was reported in 2019 by the Cleveland Clinic doctors. They found that six out of eight TN patients had a good response to erenumab (Aimovig).

A group of Israeli physicians published another case series in the current issue of Neurology. They found that nine out of ten TN patients obtained very good relief from erenumab.

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.

Dr. Allan Purdy’s review of my new book

By: Dr. Mauskop

02-06-2021

Alternative Therapies, Blocks, Botox, Chronic migraine, Headache medications, Headaches, injections, Migraine, post-traumatic headache, Psychology of headaches, Science of Migraine

A 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.

Nurtec is the first drug approved for acute and preventive treatment of migraines.

By: Dr. Mauskop

27-05-2021

Chronic migraine, Headache medications, Migraine, New treatments

Biohaven, the manufacturer of rimegepant (Nurtec ODT) just received FDA approval to market this drug for the prevention of migraines. Rimegepant was approved in January of 2020 for the acute treatment of migraine headaches. It is the first drug to be approved for both acute and preventive therapy of migraines.

Rimegepant is one of six drugs that block the action of calcitonin gene-related peptide (CGRP). CGRP has many important functions in the body but the release of excessive amounts of it in the brain can trigger a migraine. Four of the CGRP migraine drugs are given by injection and they are used only for the prevention of migraine attacks. Rimegepant and ubrogepant (Ubrelvy) are taken by mouth as needed, whenever a migraine strikes. These are truly novel drugs that have dramatically improved the lives of many migraine sufferers.

Rimegepant stays in the body longer – it has a half-life of 10-12 hours, while ubrogepant’s half-life is 7-8 hours. Another difference is that rimegepant dissolves in your mouth (ODT after Nurtec stands for orally disintegrating tablet), while ubrogepant is a solid tablet that is swallowed.

In clinical trials, rimegepant was noticed to provide relief of migraine that persisted for up to 48 hours. Because of this sustained effect, the researchers decided to test this drug for the prevention of migraine attacks by giving it every other day. And rimegepant passed this test. The official FDA-approved label says that for the prevention of migraines, one tablet of rimegepant should be taken every other day. For the acute treatment of migraines, the directions say to take 1 tablet a day, as needed.

The insurers typically pay for 8 tablets a month, although a few of my patients have been able to get 16. Now, with its approval for the prevention, patients will be able to get 16 tablets a month. It is possible that some patients may be able to get an additional 8 tablets for acute therapy. For most, however, 16 tablets a month should be sufficient.

The safety profile of rimegepant (as well as ubrogepant) is truly remarkable. The new rimegepant label states that “The most common side effects of NURTEC ODT were nausea (2.7%) and stomach pain/ indigestion (2.4%).” It also states that these are not the only possible side effects but their frequency is very low. Just like with any drugs, an allergic reaction is also possible.

The pendulum swings and hits hard patients on opioid drugs

By: Dr. Mauskop

17-05-2021

Brain disorders, Chronic migraine, Headache medications, Headaches, Migraine, Pain, Pain Research

The 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.

A study just published in the journal Pain looked at the difficulties patients taking opioid drugs have in finding a primary care doctor.

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.