Experts Say CGRP Drugs Are First-Line Therapies for Migraine Prevention

By Pat Anson, PNN Editor

Migraine medications that block calcitonin gene-related peptides (CGRPs) are “equal to or greater” than other migraine prevention drugs and should be considered first-line therapies, according to a new guideline from the American Headache Society (AHS).

It’s the first time the organization has endorsed CGRP inhibitors for migraine prevention, despite their high cost and limited availability due to insurance requirements. Many insurers have step-therapy policies that require patients to start with cheaper first-line treatments before trying other drugs.

"Moving CGRP-targeting therapies to the first line of treatment could have a transformational impact on the prevention of migraine attacks and their associated burdens," Andrew Charles, MD, AHS president and lead author of the guideline recently published in the journal Headache. 

CGRP inhibitors block a protein that binds to nerve receptors in the brain and trigger migraine pain. Since 2018, the FDA has approved over half a dozen CGRP medications for migraine prevention and/or treatment, the biggest innovation in migraine therapy in decades.   

Older drugs that have long been used for migraine prevention were originally developed for other conditions. They include amitriptyline, a tricyclic antidepressant; simvastatin, which is used to control cholesterol; topiramate (Topamax), an antiseizure medication; and beta-blockers commonly used to control blood pressure.  

The AHS says there is growing “real world” experience that CGRP inhibitors work better than the older, repurposed medications.

“The evidence for the efficacy, tolerability, and safety of CGRP-targeting migraine preventive therapies is substantial, and vastly exceeds that for any other preventive treatment approach,” the AHS said. “The data indicates that the efficacy and tolerability of CGRP-targeting therapies are equal to or greater than those of previous first-line therapies and that serious adverse events associated with CGRP-targeting therapies are rare.”

The biggest problem with CGRP inhibitors is their cost, which can reach tens of thousands of dollars a year. Eight doses of Nurtec, a tablet taken daily, cost over $1,000; while the listed price for Emgality is $706 for a self-injectable syringe used monthly. Prices will vary, depending on insurance and whether a patient qualifies for discounts or patient assistance programs.

By comparison, amitriptyline and simvastatin are bargains. A bottle of 30 simvastatin tablets will cost about $14, while amitriptyline costs about $13 for a supply of 28 tablets. A recent study suggests that amitriptyline and simvastatin work just as well as CGRP inhibitors in reducing the need for medications to treat migraine pain, an indication that they are effective at prevention.

Despite the disparity in cost, the AHS maintains the overall benefits of CGRP inhibitors may justify the price. There are substantial hidden costs to migraine attacks, which can result in lost productivity, income, education, and personal relationships.   

“We recognize that the CGRP-targeting preventive therapies are significantly more expensive on a yearly basis than most of the previously established therapies, and some argue that this expense is a primary consideration in clinical decision-making,” the AHS said. “On the other hand, we argue that it is critically important to consider not only the direct cost of the treatment but also the substantial costs to the individual and society if effective treatment is delayed.”

Migraine affects about 39 million people in the United States and 1.1 billion worldwide. In addition to headache pain, migraine can cause nausea, blurriness, and sensitivity to light or sound. Women are three times more likely to suffer from migraines than men.  

Neurological Conditions Now Leading Cause of Chronic Illness

By Pat Anson, PNN Editor

The number of people living with neurological conditions such as migraine, diabetic neuropathy, epilepsy, stroke and dementia has risen significantly over the past 30 years, making it the leading cause of chronic illness worldwide, according to a new analysis published in The Lancet Neurology.

An international research team estimates that over 3.4 billion people – about 43% of the global population – had a neurological condition in 2021, replacing cardiovascular disease as the leading cause of poor health.

“The worldwide neurological burden is growing very fast and will put even more pressure on health systems in the coming decades,” said co-author Valery Feigin, MD, Director of the National Institute for Stroke and Applied Neuroscience at Auckland University in New Zealand.

“Yet many current strategies for reducing neurological conditions have low effectiveness or are not sufficiently deployed, as is the case with some of the fastest-growing but largely preventable conditions like diabetic neuropathy and neonatal disorders. For many other conditions, there is no cure, underscoring the importance of greater investment and research into novel interventions and potentially modifiable risk factors.”

A total of 37 disorders affecting the brain and nervous system were included in the study. Collectively, the nerve disorders are responsible for 443 million years of healthy life lost due to illness, disability or premature death, known as disability-adjusted life years (DALYs).

Tension-type headaches (about 2 billion cases) and migraines (about 1.1 billion) are the two most common neurological disorders, while diabetic neuropathy is the fastest-growing one. Painful stinging or burning sensations in the nerves of the hands and feet are often the first symptoms of diabetes.

“The number of people with diabetic neuropathy has more than tripled globally since 1990, rising to 206 million in 2021,” said co-senior author Liane Ong, PhD, from the Institute for Health Metrics and Evaluation at University of Washington. “This is in line with the increase in the global prevalence of diabetes.”

Over 80% of neurological deaths and disability occur in low- and middle-income countries, with western and central sub-Saharan Africa having the highest DALY rates. In contrast, high-income countries in the Asian Pacific and Australasia regions had the lowest rates.

“Nervous system health loss disproportionately impacts many of the poorest countries partly due to the higher prevalence of conditions affecting neonates and children under 5, especially birth-related complications and infections,” said co-author Tarun Dua, MD, Unit Head of WHO’s Brain Health unit.

“Improved infant survival has led to an increase in long-term disability, while limited access to treatment and rehabilitation services is contributing to the much higher proportion of deaths in these countries.”

Medical providers specializing in neurological care are unevenly distributed around the world, with wealthy countries having about 70 times the number of specialists as low-income ones.

Researchers say prevention needs to be a top priority in addressing the growth of neurological conditions. Some disorders, such as stroke and chronic headache, are potentially preventable by lowering risk factors such as high blood pressure, smoking and alcohol use.

The study was funded by the Bill and Melinda Gates Foundation.

Migraine Sufferers Rank Triptans as Most Helpful Medication

By Pat Anson, PNN Editor

A large new study that compared the effectiveness of acute migraine medications found that triptans are two to five times more helpful than ibuprofen and acetaminophen in treating migraine attacks. Triptans were also found to be more effective than Excedrin migraine, opioids, and other non-steroidal anti-inflammatory drugs (NSAIDs).

The study used a unique methodology, gathering data on over 3 million migraine attacks reported by over 278,000 people in the US, UK and Canada who used a smartphone app during a six-year period. The Migraine Buddy app allows users to monitor the frequency of their migraine attacks, triggers and symptoms, and rate how “helpful” or “not helpful” their medications are.

“There are many treatment options available to those with migraine. However, there is a lack of head-to-head comparisons of the effectiveness of these treatment options,” said lead author Chia-Chun Chiang, MD, a neurologist who specializes in Headache Medicine and Vascular Neurology at the Mayo Clinic. “These results confirm that triptans should be considered earlier for treating migraine, rather than reserving their use for severe attacks.”

Chiang and his colleagues looked at a total of 25 medications among seven drug classes. Different dosages and medication combinations were combined in their analysis. Newer drugs that inhibit calcitonin gene-related peptides (CGRP) were excluded because they were not in wide enough use during the study period.

How Patients Rated Effectiveness of Acute Migraine Drugs

NEUROLOGY

The study findings, published in the journal Neurology, ranked several triptans (eletriptan, zolmitriptan, sumatriptan, rizatriptan, naratriptan, almotriptan and frovatriptan) as the most helpful medications, with about 75% effectiveness.

By comparison, acetaminophen (paracetamol) was helpful only 37% of the time.

“Our results strongly support the use of triptans, the first class of migraine-specific medication for the acute treatment of migraine,” researchers reported. “In practice, NSAIDs and acetaminophen are generally the first-line medications utilized for mild to moderate headache, and migraine-specific medications are often reserved for moderate to severe migraine attacks, which could potentially result in under-utilization of triptans or delayed treatment during migraine attacks.”

Participants found NSAID’s more effective than acetaminophen, with ketorolac helpful 62% of the time, indomethacin helpful 57% of the time, diclofenac helpful 56% of the time and ibuprofen helpful 42% of the time.

Excedrin migraine was effective only about half the time, about the same as tramadol and codeine. Opioids are usually not recommended for migraine because they’ve been associated with medication overuse headache.

“For people whose acute migraine medication is not working for them, our hope is that this study shows that there are many alternatives that work for migraine, and we encourage people to talk with their doctors about how to treat this painful and debilitating condition,” said Chiang.

Migraine affects about 39 million people in the United States and is the second leading cause of disability worldwide, according to the American Migraine Foundation.  

Another recent study that compared migraine prevention drugs found that two medications usually used to treat depression and high cholesterol are just as effective as the new CGRP inhibitors. Amitriptyline is a tricyclic antidepressant, while simvastatin is a statin. Both drugs are used off-label for migraine prevention and cost substantially less than CGRP drugs.

Cheap Drugs May Prevent Migraine Just as Effectively as Expensive Ones

By Pat Anson, PNN Editor

Two drugs commonly used to treat depression and high cholesterol are just as effective at preventing migraine as CGRP inhibitors, according to a large new study.

They are also a heck of a lot cheaper.  

Researchers at the Norwegian Center for Headache Research analyzed the prescription drug history of over 100,000 migraine patients in Norway from 2010 to 2020. Their goal was to see if patients reduced their use of medications used to treat acute migraine pain – such as triptan – once they started taking drugs used to prevent migraine.

“When the withdrawal of acute migraine medicines changed little after starting preventive medicines, or people stopped quickly on the preventive medicines, the preventive medicine was interpreted as having little effect,” explained lead investigator Marte-Helen Bjørk, MD, a Professor in the Department of Clinical Medicine, University of Bergen.

“If the preventive medicine was used on long, uninterrupted periods, and we saw a decrease in the consumption of acute medicines, we interpreted the preventive medicine as having good effect.”

Beta blockers are often the first drugs used to prevent migraine attacks, but Bjørk and her colleagues found that three other medications were associated with lesser use of triptans: amitriptyline, simvastatin and CGRP inhibitors.

Amitriptyline is a tricyclic antidepressant that is mostly taken for depression, while simvastatin is a statin used to treat high cholesterol. Both drugs are also used off-label for migraine prevention.

CGRP inhibitors are a relatively new class of medication that block calcitonin gene-related peptides, a protein that binds to nerve receptors in the brain and triggers migraine pain. Since 2018, the FDA has approved over half a dozen CGRP medications, which are considered the biggest innovation in migraine treatment in decades.

However, CGRP drugs are not cheap. Eight doses of Nurtec, a tablet taken daily to prevent and treat migraine, can cost over $1,000, while the listed price for Emgality is $679 for a self-injectable syringe used once a month for migraine prevention. Prices will vary for patients, depending on insurance and whether they qualify for a patient assistance program.

By comparison, amitriptyline and simvastatin are screaming bargains. A bottle of 30 simvastatin tablets will cost about $14, while amitriptyline costs about $13 for a supply of 28 tablets.

When it comes to reducing triptan use, amitriptyline, simvastatin and the CGRP inhibitors performed about the same. During the first 90 days of treatment, nearly 57% of patients taking simvastatin reduced their triptan use, compared to 53% of patients taking amitriptyline and 55% of those taking CGRP medicines.

The study findings, recently published in the European Journal of Neurology, show that patients taking beta blockers, topiramate or clonidine were more likely to keep taking triptans.

“Our analysis shows that some established and cheaper medicines can have a similar treatment effect as the more expensive ones. This may be of great significance both for the patient group and Norwegian health care” says Bjørk, who has already started work on a clinical trial to see if other cholesterol-lowering drugs can prevent migraine.

Migraine affects about 1 billion people worldwide and 39 million in the United States, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, blurriness or visual disturbances, and sensitivity to light and sound. Women are three times more likely to suffer from migraines than men.

Childhood Trauma and Neglect Increase Risk of Headache Disorders

By Pat Anson, PNN Editor

People who experience traumatic events during childhood, such as physical abuse, sexual abuse or neglect, are more likely to have headache disorders as adults, according to a large new study. The research adds to a growing body of evidence linking adverse childhood experiences (ACEs) to headaches and migraines in adults.

“Traumatic events in childhood can have serious health implications later in life,” says lead author Catherine Kreatsoulas, PhD, of Harvard T.H. Chan School of Public Health. “Our meta-analysis confirms that childhood traumatic events are important risk factors for headache disorders in adulthood, including migraine, tension headaches, cluster headaches, and chronic or severe headaches. This is a risk factor that we cannot ignore.”

Kreatsoulas and her colleagues reviewed 28 studies that examined the childhood histories of nearly 155,000 people in 19 countries. Their findings are published Neurology, the medical journal of the American Academy of Neurology.

About a third of the participants (31%) reported at least one traumatic childhood event. Of those, 26% were diagnosed with a primary headache disorder, compared to 12% of participants who said they experienced no childhood trauma. People who had four or more traumatic events during childhood were more than twice as likely to have a headache disorder than those who had one ACE.

Researchers also examined different types of childhood trauma. Events categorized as “threat” traumas included physical abuse, sexual abuse, emotional abuse, witnessing or being threatened with violence, and serious family conflicts.

Events categorized as “deprivation” traumas included childhood neglect, economic adversity, divorce or separation, parental death, alcohol or substance abuse, and living in a household where someone has a mental illness, chronic illness, disability or is incarcerated.

Threat traumas were linked to a 46% increase in headache disorders, while deprivation traumas were linked to a 35% increase in headaches. Among threat traumas, physical and sexual abuse were associated with a 60% increased risk for headaches. Among deprivation traumas, neglect was linked to a nearly three-fold increased risk for headache disorders.

“Threat or deprivation traumas are important and independent risk factors for headache disorders in adulthood,” said Kreatsoulas. “Identifying the specific types of childhood experiences may help guide prevention and treatment strategies for one of the leading disabling disorders worldwide. A comprehensive public health plan and clinical intervention strategies are needed to address these underlying traumatic childhood events.”

Due to the stigma and sensitive nature of childhood trauma, researchers say it’s likely the number of ACE cases is under-reported by adults.

 “Despite this, the robustness of these findings cannot be underappreciated as the studies composing this meta-analysis represent diverse global regions and the findings supersede cultural contexts,” they said.

The research does not prove that ACEs cause headaches -- it only shows an association.

Previous studies have also linked childhood trauma to an increased risk of chronic pain conditions such as fibromyalgia and lupus, as well as mood and sleep problems.

Woman Files Civil Rights Lawsuit Over Denial of Pain Treatment

By Madora Pennington, PNN Columnist

In September of 2022, millions watched Tara Rule’s emotional video on TikTok, about a doctor who refused to give her a non-narcotic pain medication because it might cause birth defects. The doctor would not even name the drug, even though Rule told him she has no intention of having children because she has Ehler's Danlos syndrome (EDS), a genetic disorder that causes severe health issues.

The 32-year old Rule recently filed a civil rights lawsuit to better establish the illegality of refusing medical treatment to women simply because they are of childbearing age.

Rule’s fight began when neurologist Jonathan Braiman, MD, steered her away from an effective treatment for her agonizing cluster migraines, a common symptom of EDS. According to Yale Medical School, cluster headaches can hurt more than childbirth.

When Rule realized she was being discriminated against by her doctor, she surreptitiously switched on her cell phone to record their discussion, which is legal in New York state. 

Brainman can be heard in the recording asking Rule intrusive questions about her sex life, while ignoring her answers. Rule explained that she was already on a medication that can cause birth defects -- known as teratogenic drug -- and wasn't well enough to have children anyway.

Brainman patronizingly told her she might change her mind if she were to become pregnant. He recommended that she bring in her boyfriend to consent to any treatment that might cause birth defects. Rule left without getting the pain relief she needed for her migraines.

In the parking lot of Albany Medical Center, where the appointment took place, a distraught and tearful Rule made the video and posted it online. Her raw emotion and disturbing story quickly went viral, not only on social media, but in news stories.

In her lawsuit against Braiman and Albany Medical, Rule alleges she was retaliated against by the hospital system. Rule says she was ejected from an unaffiliated urgent care center because Albany Medical had told other hospitals not to treat her. She believes this was a violation of her medical privacy.  

Rule suspects she was blacklisted by other providers in her area. She tried to make an appointment with another neurologist, but was told she was “not an appropriate patient.” Her primary care provider sent a back-dated letter to Rule and her mother saying he was dismissing them as patients. That doctor gave no valid reason for the patient abandonment.

TARA RULE (TIKTOK)

Rule is on disability and lives on less than $1,000 per month. Being banned as a patient is a real hardship.

“Now I have to go to Connecticut to see physicians in a different hospital system. Or travel three and a half hours to New York City. With hotels and gas, it’s very hard. Some of these specialists outside the state are not fully covered by my insurance,” Rule said.

Traveling is made more complicated because Rule can’t stay just anywhere — she needs accessible hotel rooms. And she is accumulating thousands of dollars in debt.

After posting her video, Rule heard from many other patients who have also been discriminated against by their doctors. She felt motivated to find out what legal remedies existed.

With legal guidance, Rule wrote the civil rights complaint herself in what is known as a “federal question” lawsuit, an action that seeks to clarify a constitutional issue in US federal court. Rule has been advised that the medical care she sought does not fall under “conscience protections,” which allow doctors to refuse treatment on religious or moral grounds.  

In preparation for her lawsuit, Rule obtained her medical and insurance records, to help prove that privacy violations occurred. She discovered she had been billed for services not received, and believes her medical records were forged.

Albany Medical did not respond to a request for comment.

Rule’s lawsuit is potentially precedent-setting. It marks the first federal question case against a medical provider for refusing to provide teratogenic drugs because a woman is of “childbearing age.” Refusing to give routine medical care because a patient might get pregnant is discrimination. Patients cannot be forced into unnecessary restraints on their care.

"I am prepared for whatever happens,” says Rule, who is hopeful her lawsuit will help prevent other patients from being discriminated against by their doctors. 

Madora Pennington is the author of the blog LessFlexible.com about her life with Ehlers-Danlos Syndrome. She graduated from UC Berkeley with minors in Journalism and Disability Studies. 

'Growing Pains' in Childhood Linked to Migraine

By Pat Anson, PNN Editor

Did you experience “growing pains” as a child? An unusual ache or throbbing in your legs that occurred late in the day and kept you awake at night?

The Mayo Clinic says there’s no evidence that a growth spell actually causes physical pain, and that any discomfort may be caused by a low pain threshold or even psychological issues.

But a small new study suggests something else may be going on: Brazilian researchers say children who have growing pains are significantly more likely to develop migraines – just as their parents did.  Migraine can be hereditary, and if one or both parents have migraine, there’s a 50-75% chance that their children will also.

“In families of children with growing pains, there is an increased prevalence of other pain syndromes, especially migraine among parents,” wrote lead author Raimundo Pereira Silva-Néto. PhD, a neurology professor at Federal University of Delta do Parnaibal. “Children with migraine have a higher prevalence of growing pains, suggesting a common pathogenesis; therefore, we hypothesized that growing pains in children are a precursor or comorbidity with migraine.”

With parental authorization, Silva-Néto and his colleagues followed 78 children between 5 and 10 years of age, who were born to mothers being treated for migraine at a headache clinic. Their findings were published in the journal Headache.

After five years, about half of the children reported growing pains in their lower limbs. Headaches occurred in 76% of those children, with many meeting the criteria for migraine without aura. By comparison, only 22% of the children who did not have growing pains had headaches.

Lower limb pain was reported most often in the calf muscles (70%), usually lasted more than 30 minutes, and occurred more frequently at night.

That nocturnal connection intrigued the researchers, who noted that previous studies have found that sleepwalking, nightmares, and restless leg syndrome also occur more frequently in children who have migraines.   

“There is no definitive explanation for the nocturnal patterns of growing pains, nor for the overlap with sleep disturbances; however, the authors believe the hypothesis of a common pathogenesis with migraine,” researchers concluded. “Pain in the lower limbs of children and adolescents, commonly referred to as GP (growing pains) by pediatricians and orthopedists, may reflect a precursor/comorbidity with migraine.”

Migraine affects about 39 million people in the United States and is the second leading cause of disability worldwide, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, blurriness or visual disturbances, and sensitivity to light and sound. About one in five teens suffer from migraine.

Head-to-Head Migraine Study Ends in Tie

By Pat Anson, PNN Editor

An unusual head-to-head competition between two migraine prevention drugs has ended in a virtual tie. There were no substantial differences in effectiveness between Emgality and Nurtec, according to preliminary results from a clinical trial released by Eli Lilly, the maker of Emgality.

Emgality and Nurtec both inhibit calcitonin gene-related peptides (CGRP), a protein that causes migraine pain, but their delivery systems are different. Emgality is injected once a month, while Nurtec is an oral medication taken every other day made by Biohaven Pharamceuticals, a subsidiary of Pfizer.

Eli Lilly launched the trial in late 2021, enrolling 575 participants in a Phase 4, double-blind, placebo-controlled study evaluating the efficacy and safety of Emgality (galcanezumab) and Nurtec (rimegepant) for 3 months in adults with episodic migraine.

The so-called CHALLENGE-MIG trial was a bold and somewhat risky move by Lilly, as it seeks to gain more market share in the highly competitive $2 billion U.S. migraine market.

In a statement, Lilly said Emgality did not meet the study's primary goal, which was statistical superiority to Nurtec in achieving at least a 50% reduction in monthly migraine headache days. The response rates of patients and safety profiles of both drugs were similar.

Lilly said Emgality was superior to Nurtec in some secondary outcomes, but didn’t disclose what they were. The company would only say that Emgality helped prevent migraines, as it has in previous studies.  

"These results bolster our knowledge of Emgality's ability to work quickly and help patients improve their quality of life with less frequent dosing," Anne White, executive vice president of Eli Lilly, said in a press release. "Reducing the frequency of migraine headache days can help people experience more freedom from the burden of this debilitating neurological disease and get back to participating in the daily activities that matter most to them."

Final result from the CHALLENGE-MIG trial won’t be posted until later this year.

“Nurtec ODT is the first and only medication approved as both an acute treatment for migraine and a preventive treatment for episodic migraine in adults. It offers flexibility to patients in treating their migraines and is the leading prescribed oral CGRP receptor antagonist,” Pfizer said in a statement. “We are confident in the efficacy and tolerability profile of Nurtec ODT as demonstrated in the clinical trials and the well-established patient preference for oral agents over injectables.

First approved by the FDA in 2018, CGRP inhibitors are the biggest innovation in migraine treatment in decades. They are also expensive, whether taken by pill or injection.

The listed cash price for Emgality is $679 for a single injection or $8,148 annually; while 8 tablets of Nurtec cost $1,011 or about $23,000 a year. Costs to patients will vary, depending on insurance coverage, copay assistance programs and rebates.

I’m Already Well Aware

By Mia Maysack, PNN Columnist

If I did not cling to my optimism for dear life, I'd scoff at the concept of an awareness month such as June being nationally recognized as Migraine & Headache Awareness Month.

That’s due to the fact I am someone who has lived with a daily reminder of intractable pain for over two decades. It isn’t those of us who can directly relate to the pain experience that are in need of awareness.

I feel many “awareness” efforts are limited or fall short in terms of gaining recognition for a specific cause or reason. People typically don’t concern themselves with issues that don’t directly affect or impact them.

Someone who hasn’t ever had a migraine couldn’t possibly understand how it differs from a regular stress headache. Furthermore, somebody who does experience an occasional migraine still cannot fathom what it would be like to have one on a more constant basis.

What transpires within and throughout our individual lenses of the world is real to us and valid, though different from others. That doesn’t lessen the next person’s experience as being anything less than our own.    

There have been some who have thought of my claims about illness are disingenuous. But the reality is that I actually learned to “fake” wellness, in an effort to create a sense of fulfillment and meaning in my life, despite the hand I’ve been dealt.

Others claim those of us who live with pain should be able to “fix” ourselves, once we acknowledge things like a childhood trauma; or that if we adopt “sufficient water intake” and “sleep hygiene” for example, all will be well.

Although I believe there’s some merit to those suggestions, and that they come from a decent, well-meaning place --- if it were that simple, I would be healed by now, along with millions of others who endure similar circumstances.

For a lot of us, we’ve had to come to terms with the fact that there may not be anything out there to give us back the life we once had or wanted. That’s because we’ve already attempted and tried just about everything in search of pain management or relief.

Often, we’re unable to obtain access to options that might ease our suffering because that process can be a grueling one and often has a ripple effect of further complications, along with a multitude of hoop jumping. That’s why I’ve mostly refrained from making it a habit to ask for professional help. Instead, I have worked on acceptance, as there are not many things that anyone else can do for me.   

Relentless and untreatable ailments in any form are going to take a toll, but I hold steady to the concept of “pain” being a worldwide experience that each and every one of us can relate to in some way or another. Each of us have had moments when we’d do just about anything to have the discomfort end.

But instead of embracing the potential for common ground, we as a society tend to label people, when the cure is to be found in seeing and treating one another as fellow human beings. We never truly know where a person may be in regards to their mental health or quality of life, and need not make this already challenging existence any more difficult for ourselves or each other.

Given the extent I’ve witnessed how our healthcare system fails us, I had to choose to not identify with the victim mentality or wait any longer for answers elsewhere.  Ultimately, I stumbled upon empowerment in owning my situation, by tending to myself in ways that I am able. That was my education in self-awareness.

Mia Maysack lives with chronic migraine, cluster headache and fibromyalgia. She is the founder of Keepin’ Our Heads Up, a Facebook advocacy and support group, and Peace & Love, a wellness and life coaching practice for the chronically ill. 

Ketamine Nasal Spray May Be Effective Migraine Treatment

By Pat Anson, PNN Editor

In recent years, ketamine has become a trendy drug for treating depression, anxiety, post-traumatic stress and some types of chronic pain. Usually administered by infusion or injection, ketamine is a non-opioid analgesic that acts on the brain by putting patients into a temporary dream-like state.

A new study at Thomas Jefferson University suggests that ketamine may also be an effective treatment for chronic migraine. Several previous trials have shown that intravenous ketamine is effective for chronic headache, but it required close monitoring by a pain specialist to adjust the dose and monitor any side effects.

In the new study, researchers gave 169 migraine patients a ketamine nasal spray that they could use at home without supervision. Over two-thirds of the participants suffered from daily headaches and nearly 85% had tried over 3 types of migraine prevention drugs, with limited success.

The study findings, published in the journal Regional Anesthesia & Pain Medicine, showed that nearly half the participants said the nasal spray was “very effective” and about 40% found it “somewhat effective.” Over a third said their quality of life was “much better.” 

Nearly 3 in 4 patients reported at least one side effect from ketamine, the most common being fatigue and double/blurred vision, followed by cognitive effects such as confusion, dissociation, vivid dreams and hallucinations. Most of the side effects were only temporary.

“In this descriptive study, intranasal ketamine served as an acute treatment for refractory chronic migraine by reducing headache intensity and improving quality of life with relatively tolerable adverse events. Most patients found intranasal ketamine effective and continued to use it despite these adverse events,” wrote lead author Michael Marmura, MD, Outpatient Director at the Jefferson Headache Center.

Marmura and his colleagues are cautious about who should use ketamine because of its potential for abuse. Ketamine has a short half-life of less than two hours, meaning patients may be tempted to use it repeatedly to keep chronic headaches at bay. Patients in this study used the nasal spray an average of just 6 times a month, but a small number (13.9%) used the spray daily.

“Clinicians should only consider the use of a potentially addictive medication such as ketamine for significantly disabled patients with migraine,” they warned. “(This) should be addressed carefully and individually, as some may respond only to repeated ketamine, while some may overuse it.”

In 2019, the FDA approved the use of Spravato, a nasal spray that contains a ketamine-like substance, for severe depression. Because of the risk of abuse, Spravato can only be administered in a doctor’s office, where patients can be observed for two hours after taking a dose. The use of such a spray to treat migraine would be considered an off-label use.

In addition to its medical uses, ketamine has long been known as a party drug – “Special K” -- because it can cause hallucinations and intense, dream-like states.

It didn’t take long for drug dealers to note the increase in ketamine’s popularity. Recent research published in JAMA shows that seizures of illicit ketamine in the U.S. have risen from 55 seizures in 2017 to 247 in 2022, a 350% increase. Because much of its was seized in powder form, researchers are concerned black market ketamine could easily be adulterated with illicit fentanyl.

FDA Approves Nasal Spray That Relieves Migraine in Minutes

By Pat Anson, PNN Editor

Pfizer will soon launch a fast-acting nasal spray that can relieve migraine pain in as little as 15 minutes for some patients. The company has received FDA approval for Zavzpret (zavegepant), the first calcitonin gene-related peptide (CGRP) inhibitor formulated into a nasal spray for the acute treatment of migraine in adults with or without aura.    

“When a migraine hits, it has a significant negative impact on a person’s daily life,” Kathleen Mullin, MD, Associate Medical Director at New England Institute for Neurology & Headache, said in a Pfizer press release. “Among my migraine patients, one of the most important attributes of an acute treatment option is how quickly it works. As a nasal spray with rapid drug absorption, Zavzpret offers an alternative treatment option for people who need pain relief or cannot take oral medications due to nausea or vomiting, so they can get back to normal function quickly.”

That’s the good news. The bad news is how expensive the nasal spray is likely to be when it becomes available in July 2023. According to a Pfizer spokesperson, Zavzpret “is expected to be comparable in price to other FDA approved CGRP migraine medicines.”

CGRP is a protein that binds to nerve receptors in the brain and dilates blood vessels, causing migraine pain. Since their introduction in 2018, CGRP inhibitors have become the biggest innovation in migraine treatment in decades, although their cost is prohibitive for many patients.

Eight doses of Nurtec, a CGRP-inhibiting tablet taken daily to prevent and treat migraine, can cost over $1,000, while the listed price for Emgality, a CGRP-inhibiting solution, is $679 for a self-injectable syringe used once a month for migraine prevention. Prices will vary for patients, depending on their insurance and whether they qualify for a patient assistance program.

In a Phase 3 study involving over 1,400 patients, recently published in The Lancet Neurology, a single 10mg dose of Zavzpret relieved migraine pain in as little as 15 – 30 minutes, and provided sustained relief for as long as 48 hours.  

An important caveat is that the nasal spray did not help everyone. Only 22.5% of patients were pain free after two hours, compared to 15.5% who were given a placebo.

The 7% difference may sound like marginal improvement in a minority of patients, but in the parlance of clinical trials it’s considered “statistically significant” improvement.  

Zavzpret was well tolerated by most patients. The most common adverse reactions after ingesting the spray were taste disorders (dysgeusia and ageusia), nausea, nasal discomfort and vomiting.

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“The FDA approval of Zavzpret marks a significant breakthrough for people with migraine who need freedom from pain and prefer alternative options to oral medications,” said Angela Hwang, Chief Commercial Officer and President of Pfizer’s Global Biopharmaceuticals Business.

Migraine affects about 39 million people in the United States, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, blurriness or visual disturbances, and sensitivity to light and sound. Women are three times more likely to suffer from migraines than men.

How TMS Helped Me Feel Better Physically and Mentally

By Madora Pennington, PNN Columnist

Chronic pain is often accompanied by depression. Many clinicians used to think that pain was caused by psychological distress, so they offered patients antidepressants with the attitude that their suffering was “all in their head.”

But now it is better understood that chronic pain can cause depression. Both conditions have a similar pathology and change the brain in similar ways. That is why treatments that work on depression (like antidepressants) may reduce the brain’s sensitivity to pain.

“Regardless of the cause of the pain, anxiety and depression increase the sensation of pain. Pain increases depression and anxiety, creating a vicious cycle. Breaking that cycle can help decrease pain,” says integrative physician and pain doctor Dr. Linda Bluestein.

I have Ehlers-Danlos Syndrome (EDS). Debilitating pain has been my companion since I was 14 years old. My body makes collagen that is not structurally sound. Because I am “loosely glued together,” I get injured easily because my joints are unstable and my body has a poor sense of where it actually is in relation to itself and the outside world. My thin and stretchy connective tissue sends pain signals to my brain, even when I am not injured.

It is probably not realistic for someone with Ehlers-Danlos to expect to have a life without pain, so I welcome medical treatments that might lessen my pain, even if they don’t eliminate it. My goal is to have pain that does not incapacitate me or ruin my life by taking all my attention. Thankfully, there are modalities that do this.

MADORA GETTING TREATMENT AT UCLA’S tms CLINIC

The last one I tried was transcranial magnetic stimulation (TMS), which stimulates the brain through a magnetic pulse which activates nerve cells and brain regions to improve mood.

TMS treatments are painless and entirely passive. The patient just sits there and lets the machine do the work. A magnetic stimulator rests against the head and pulses, which feels like tapping or gentle scratching.

TMS has been around for almost 40 years. The first TMS device was created in 1985 and the FDA approved it for major depression in 2008. Since then, its use has been expanded to include migraine, obsessive compulsive disorder, and smoking cessation.

While other medical procedures work on an injured body part, TMS targets the brain, where pain is processed. This helps the brain shift away from perceiving pain signals that are excessive and have become chronic.

“Many people are surprised to learn that stimulating the brain can help alleviate pain that is felt in an arm, leg or some other part of the body. We explain to patients that because pain is perceived in the brain, it is possible to reduce or sometimes even eliminate it by stimulating specific brain regions,” says Andrew Leucther, MD, a psychiatrist who heads UCLA’s TMS clinic, where I was treated. In addition to depression, the clinic also treats fibromyalgia, neuropathy, nerve injury, and many other causes of pain.

“Most patients are much less bothered by pain after treatment and report that they are functioning better in their work and personal lives,” Leucther told me.

Many insurers cover TMS for depression, but it is not generally covered for pain alone — although many doctors will add protocols for pain when treating depression. This is how I got my 36 sessions of TMS treatment, the usual number that insurance will cover and is thought to be effective.

Repetitive TMS stimulation to the primary motor cortex of the brain has robust support in published studies for the treatment of pain. It seems to work particularly well for migraines, peripheral neuropathic pain and fibromyalgia. Like all treatments, it may not work for everyone.

TMS practitioners recommend four or five sessions per week, gradually tapering off toward the end. My body is so sensitive, about three per week was all I could tolerate comfortably. The appointments lasted a brief 10 -15 minutes. A downside of the TMS machine is that it puts pressure against the head, which could be too much for Ehlers-Danlos patients who have uncontrolled head and neck instability.

TMS gave me relief in different ways than other methods have.  One of the first things I noticed was less negativity and rumination. It was like getting a nagging, negative person out of the room -- or rather, my head. I felt less heartbroken over the major losses of my life, such as having spent so much of it totally disabled.

I also noticed a big difference in my PTSD triggers. I found myself shrugging off situations that normally would put me in a very uncomfortable, perturbed state. Keep in mind, I was getting TMS applied to various points on my scalp for pain, depression and anxiety.

Since having TMS, I notice that my body is less sensitive to touch. From spa treatments to medical procedures, it does not hurt as much to be poked at or pressed on. The extra comfort TMS had given me, both mentally and physically, is a lot for someone with medical problems like mine that are so difficult to treat.

Madora Pennington is the author of the blog LessFlexible.com about her life with Ehlers-Danlos Syndrome. She graduated from UC Berkeley with minors in Journalism and Disability Studies. 

FDA Approves Wearable Device for Migraine Prevention

By Pat Anson, PNN Editor

A wearable neuromodulation device has been approved by the Food and Drug Administration as a preventative treatment for migraine. In a recent study, the Nerivio device significantly reduced the number of migraine days per month in patients with episodic and chronic migraine.

Nerivio is worn on the upper arm and controlled by a smartphone app. It uses mild electrical pulses to disrupt pain signals in the brain without the use of drugs. The device has previously received clearance from the FDA as an acute treatment for migraine in adults and children over age 12.

"Nerivio already has a well-established efficacy and safety profile in acute migraine treatment," said Andrew Blumenfeld, MD, Director of the Los Angeles Headache Center and co-author of the study published in the journal Headache. "Effective preventive treatment is key to managing migraine, but it is often underutilized.”

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The randomized, placebo-controlled trial involved 248 migraine sufferers who used either Nerivio or a placebo device for 45 minutes every other day. Those who used Nerivio experienced a mean reduction of 4 migraine days per month, compared to a reduction of 1.3 days in the placebo group. Participants also experienced statistically significant reductions in the number of days they required acute migraine medication.

“The trial data demonstrates Nerivio can now cover the full treatment spectrum and provide access to migraine prevention and relief, especially for the adolescent population, who have a strong preference for clinically effective, drug-free treatment solutions. With FDA clearance of the device, its availability and potential use for preventive and acute treatment is welcome news for both physicians and patients," Blumenfeld said in a statement.

Like most new migraine treatments, Nerivio can be expensive, with the wholesale price currently listed at $599 for a 12-treatment unit. Out of pocket costs will be less if the device is covered by insurance or if patients enroll in Nerivio’s Patient Savings Program. A prescription is required.

With Nerivio’s new dual-use indication, patients may use the device more often to proactively prevent migraines. To better support existing and new users, the number of treatments per unit is being expanded from 12 to 18 treatments.

The Nerivio app allows patients to customize their treatment, receive reminders for preventive treatment, track their migraine patterns, and share migraine data with their doctor. The app can also leads users through a Guided Intervention of Education and Relaxation, using techniques such as diaphragmatic breathing, muscle relaxation and guided imagery.

Nerivio is made by Theranica, a medical technology company based in Israel, which estimates the device has over 40,000 users in the United States. The company is investigating whether the device may help treat other chronic pain conditions besides migraine.

Why Women Are More Likely to Suffer Migraines

By Pat Anson, PNN Editor

German scientists may have finally proven a link between hormones and migraines, and why women suffer migraines at triple the rate that men do. In studies on animals and humans, researchers found that calcitonin gene-related peptides (CGRPs) increase in females during menstruation.

CGRP is a protein that binds to nerve receptors and dilates blood vessels in the brain, causing migraine pain. Several medications are now on the market that inhibit CGRP, one of the biggest innovations in migraine treatment in decades.

“This elevated level of CGRP following hormonal fluctuations could help to explain why migraine attacks are more likely during menstruation and why migraine attacks gradually decline after menopause,” says Bianca Raffaelli, MD, of Charité – Universitätsmedizin Berlin in Germany. “These results need to be confirmed with larger studies, but we’re hopeful that they will help us better understand the migraine process.”

Raffaelli and her colleagues measured CGRP levels in the blood and tear fluid of 180 women during their menstrual cycles, and found that those who suffer from episodic migraines had significantly higher concentrations of CGRP during menstruation, when estrogen levels are low.

“This means that when estrogen levels drop immediately before the start of a menstrual period, migraine patients release more CGRP,” said Raffaelli, lead author of a study published in the journal Neurology. “This could explain why these patients suffer more migraine attacks just before and during their monthly period.”

In women who take oral contraceptives, there were hardly any fluctuations in their estrogen or CGRP levels. The same was true for postmenopausal women.

“Taking birth control pills and the end of menopause do in fact bring relief for some female migraine patients. But as our study also shows, there are women who suffer from migraine even without any hormonal fluctuations. We suspect that other processes in the body play a role in triggering attacks in those patients. After all, CGRP isn’t the only inflammatory peptide that can cause a migraine attack,” said Raffaelli.

The study also suggests that measuring CGRP levels in tear fluid is feasible and warrants further investigation, because accurately measuring CGRP in the blood is challenging due to its short half-life.

The research team now plans to study how other physical processes are influenced by the menstrual cycle, such as blood vessels and brain function. They also plan to take a closer look at CGRP levels in men of varying age groups.

Migraine affects more than 37 million people in the United States, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, blurriness or visual disturbances, and sensitivity to light and sound.

New Test Predicts Effectiveness of CGRP Drugs for Migraine

By Pat Anson, PNN Editor

CGRP inhibitors have been one of the biggest innovations in migraine treatment in decades. CGRP stands for calcitonin gene-related peptides, a protein that binds to nerve receptors in the brain and triggers migraine pain. Since 2018, the FDA has approved over half a dozen CGRP inhibitors for migraine prevention and treatment.

The problem with anti-CGRP therapies – besides their high cost – is that they only work for about half the people who take them.

A new test may take some of the guesswork out of CGRP therapy, by predicting with about 80% accuracy which patients will respond to CGRP inhibitors before treatment begins.  In a small study published in the journal Cephalalgia, Harvard Medical School researchers found that most migraine patients with non-ictal cephalic allodynia -- pain sensitivity experienced in-between migraine attacks – did not respond to CGRP treatment. Conversely, most patients without non-ictal cephalic allodynia did respond to CGRP therapy.  

Determining which patients have or don’t have cephalic allodynia is relatively easy, through a novel Quantitative Sensory Testing (QST) algorithm that measures how sensitive patients are to heat, cold and being poked in the skin with a sharp object. The test identified CGRP responders with nearly 80% accuracy and non-responders with nearly 85% accuracy.

“Detection of non-ictal cutaneous allodynia with a simplified paradigm of QST may provide a quick, affordable, non-invasive, and patient-friendly way to prospectively distinguish between responders and non-responders to the prophylactic treatment of migraine with drugs that reduce CGRP signaling,” wrote lead author Rami Burstein, MD, Professor of Anesthesia, Harvard Medical School.

Burstein helped develop the QST test in collaboration with CGRP Diagnostics. The test can be done in about five minutes in a doctor’s office.

“This is all about improving outcomes for people suffering from migraines and so we strongly recommend that all potential anti-CGRP recipients have the test done prior to prescription,” said Mark Hasleton, PhD, CEO of CGRP Diagnostics. 

“This will help provide migraine sufferers with either the best chance for treatment success for likely responders, or to enable rapid transition for likely non-responders to other treatment strategies, thus avoiding the misery of treatment failure. CGRP Diagnostics is currently in discussions with multiple key pharma and payor players in this area, with the expectation that such a test will become a prerequisite prior to anti-CGRP prescription.”

A surprise finding from the study is that cutaneous allodynia may be related to genetic factors that cause pain sensitivity, rather than the frequency or severity of migraines.

“This study unveils the mechanism of physiological response to anti-CGRP therapy and could fundamentally change the anti-CGRP therapy field,” said Iris Grossman, PhD, Founding Scientific Advisor at CGRP Diagnostics. “We now have an objective tool to tailor early and effective therapy to migraine sufferers. This novel test holds the potential for earlier access to anti-CGRP therapy, reduced need for prior treatment failures with generics, and enhanced formulary access. It also enables non-responders to rapidly transition to other treatment strategies, preventing a great deal of suffering and frustration for all.”

A 2020 survey of migraine patients by Health Union found that 52% of those who tried a CGRP therapy switched brands because the treatment didn’t work or because they didn’t like the side effects, such as constipation and weight gain.

CGRP medications are not cheap. Eight doses of Nurtec, the migraine treatment endorsed by Khloe Kardashian, can cost over $1,000 without insurance.

Migraine affects more than 37 million people in the United States, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, blurriness or visual disturbances, and sensitivity to light and sound. Women are three times more likely to suffer from migraines than men.