Breakthrough PTSD treatment achieves 68% remission rate in clinical trial

  A new approach to treating post-traumatic stress disorder (PTSD) has received FDA clearance, offering a personalized alternative for people who have not found sufficient relief through existing treatments. Developed by California-based Wave Neuroscience in collaboration with researchers at the Texas A&M Health Institute of Biosciences and Technology, the technology uses brain activity measurements to guide targeted magnetic stimulation.

Early clinical trial findings have been encouraging. According to Wave Neuroscience, patients experienced a 52% reduction in PTSD symptoms, while 68% achieved remission. The full findings are still being prepared for public release, but researchers believe the technology could significantly expand treatment options for millions of people.

The need for more effective PTSD care is substantial. In the United States, approximately 17.5 veterans die by suicide each day, and about 7% of veterans receive a PTSD diagnosis annually.

PTSD can develop after traumatic experiences such as military combat, serious accidents, natural disasters, or violence. An estimated 6% of Americans will experience PTSD during their lifetime, with higher rates among women and veterans.

Why Current PTSD Treatments Are Not Enough

Since PTSD was formally recognized as a diagnosis in 1980, treatment has largely centered on psychotherapy and medications known as selective serotonin reuptake inhibitors (SSRIs), including sertraline and fluoxetine.

Although these approaches can help, many patients continue to experience symptoms despite receiving treatment.

A 2020 review of PTSD medications found that patients reported improvements ranging from 6.8 to 10.1 points on symptom assessments. However, remission rates reached only 10.9% at most.

Wave Neuroscience reported substantially stronger preliminary outcomes in its clinical trial. Erik Won, DO, the company's chief medical officer, described the results as a major advance over previously reported medication outcomes.

“In comparison to that study, our FDA trial reported a 52% reduction in symptoms, so more than a four-fold increase in efficacy,” Won said. “And more importantly, we saw 68% remission in our clinical trial. So, it’s really a quantum change, an inflection point in what we can offer to patients. From a clinical care perspective, that’s really meaningful.”

These findings are promising, although the results come from different studies and should not be interpreted as a direct comparison of treatment effectiveness.

How Personalized Brain Stimulation Works

The newly cleared system uses Magnetic e-Resonance Therapy (MeRT), a technology that combines measurements of brain activity with targeted magnetic stimulation.

First, an electroencephalogram (EEG) records the brain's electrical signals. This information helps guide a personalized treatment plan using transcranial magnetic stimulation, or TMS.

During TMS, a coil positioned against the scalp delivers magnetic pulses that stimulate brain activity. The technique has already been used for other psychiatric conditions, including treatment-resistant depression.

What distinguishes MeRT is its use of an AI-assisted algorithm to customize stimulation protocols based on each patient's brain activity rather than relying on a standardized approach.

“Transcranial magnetic stimulation, or TMS, was previously FDA cleared for treatment-resistant depression,” Won said. “By adding an augmented AI derived multivariate algorithm, we were able to personalize protocols that received FDA clearance for post-traumatic stress disorder, which should open up market access to about 13 million people who may be struggling with PTSD.”

Dr. Kenneth S. Ramos, a physician-scientist at Texas A&M Health with extensive experience in precision medicine, helped guide the research.

His work focuses on adapting medical care to the characteristics of individual patients instead of assuming that everyone will respond to the same treatment.

“Most clinical interventions for the treatment of PTSD do not work very well,” Ramos said. “So, this is a huge area where identifying interventions that could hopefully add quality of life to the people impacted by this disorder would be tremendously impactful.”

Wave Neuroscience CEO Fred Walke said Ramos was a natural fit for the project because of his expertise in personalized medicine.

Targeting PTSD With Greater Precision

Conventional TMS generally follows treatment protocols that are less individualized. MeRT builds on the same underlying technology but adjusts treatment according to the patient's specific brain activity.

Ramos emphasized that even small biological differences between people can have major implications for medical care. Humans are approximately 99.9% genetically alike, yet the remaining 0.1% contributes to differences that can influence how individuals respond to treatment.

Source: ScienceDaily

Poor sleep linked to migraine attacks

 A new study by researchers at the University of Arizona Health Sciences identified a link between poor sleep and migraine attacks that suggests improving sleep health may diminish migraine attacks in people with migraine.

Many people with migraine report having sleeping disorders, including insomnia, trouble falling or staying asleep, poor sleep quality, excessive daytime sleepiness, waking up from sleep and being forced to sleep because of a migraine headache. Until now, it was unknown whether migraine causes poor sleep or vice versa.

"It has been recognized for quite a long time that there is a relationship between sleep and migraine," said principal investigator Frank Porreca, PhD, research director for the Comprehensive Center for Pain & Addiction and professor of pharmacology at the UArizona College of Medicine -- Tucson. "The way it has been investigated in the past has been through patient-reported information, which is subjective. We quantitatively measured sleep in preclinical models and found that migraine-like pain does not influence sleep, but if you have disrupted sleep, your chances of having a migraine attack if you're a migraine patient are much higher."

Porreca led a research team that used preclinical mouse models to evaluate sleep disruption, as the sleep architecture of mice closely matches that of people, including cycles of deep sleep, REM sleep and light sleep. Sleep was assessed using electroencephalogram recordings and visual observations.

Researchers found that when mice were sleep deprived, they were more likely to experience migraine-like pain, but migraine-like pain did not disrupt normal sleep.

Porreca noted that sleep deprivation can happen for many reasons, including stress. For this study, the research team ensured they were studying the effect of sleep, and not stress, on migraine by giving mice novel objects to explore to keep them awake.

"Mice are compelled to explore novel objects. They just have to go and look," Porreca said. "It reminds me of how teenagers are often sleep deprived because they're on their phones. Anybody who studies sleep will tell you that from a sleep hygiene point of view, you don't want any devices in your bedroom where you're trying to sleep."

For people with migraine, limiting the use of electronic devices before bedtime and following other sleep health tips could be an easy way to limit the likelihood of migraine attacks.

"Early morning is one of the most common times people experience migraine attacks," Porreca said. "Migraine is highly female prevalent -- it's 3 to 1, women to men -- and almost all the women are of childbearing age. Many people with migraine probably have children. They wake up with a migraine attack and are immediately stressed. They don't have time to take care of themselves, they have to get the kids ready for school and they have to get ready for work. That migraine attack is happening in the worst time of the day for function. Improved sleep is critically important and probably would diminish the frequency of migraine attacks."

The American Migraine Foundation estimates more than 39 million people in the U.S. live with migraine, though that number is probably higher due to the number of people who do not get a diagnosis or treatment.

Source: ScienceDaily

Do astronauts experience 'space headaches'?

 Space travel and zero gravity can take a toll on the body. A new study has found that astronauts with no prior history of headaches may experience migraine and tension-type headaches during long-haul space flight, which includes more than 10 days in space. The study was published in the March 13, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"Changes in gravity caused by space flight affect the function of many parts of the body, including the brain," said study author W. P. J. van Oosterhout, MD, PhD, of Leiden University Medical Center in the Netherlands. "The vestibular system, which affects balance and posture, has to adapt to the conflict between the signals it is expecting to receive and the actual signals it receives in the absence of normal gravity. This can lead to space motion sickness in the first week, of which headache is the most frequently reported symptom. Our study shows that headaches also occur later in space flight and could be related to an increase in pressure within the skull."

The study involved 24 astronauts from the European Space Agency, the U.S. National Aeronautics and Space Administration (NASA) and the Japan Aerospace Exploration Agency. They were assigned to International Space Station expeditions for up to 26 weeks from November 2011 to June 2018.

Prior to the study, nine astronauts reported never having any headaches and three had a headache that interfered with daily activities in the last year. None of them had a history of recurrent headaches or had ever been diagnosed with migraine.

Of the total participants, 22 astronauts experienced one or more episode of headache during a total of 3,596 days in space for all participants.

Astronauts completed health screenings and a questionnaire about their headache history before the flight. During space flight, astronauts filled out a daily questionnaire for the first seven days and a weekly questionnaire each following week throughout their stay in the space station.

The astronauts reported 378 headaches in flight.

Researchers found that 92% of astronauts experienced headaches during flight compared to just 38% of them experiencing headaches prior to flight.

Of the total headaches, 170, or 90%, were tension-type headache and 19, or 10%, were migraine.

Researchers also found that headaches were of a higher intensity and more likely to be migraine-like during the first week of space flight. During this time, 21 astronauts had one or more headaches for a total of 51 headaches. Of the 51 headaches, 39 were considered tension-type headaches and 12 were migraine-like or probable migraine.

In the three months after return to Earth, none of the astronauts reported any headaches.

"Further research is needed to unravel the underlying causes of space headache and explore how such discoveries may provide insights into headaches occurring on Earth," said Van Oosterhout. "Also, more effective therapies need to be developed to combat space headaches as for many astronauts this a major problem during space flights."

Source: ScienceDaily

A third of women experience migraines associated with menstruation, most commonly when premenopausal

 A third of the nearly 20 million women who participated in a national health survey report migraines during menstruation, and of them, 11.8 million, or 52.5%, were premenopausal. The analysis was conducted by researchers at Georgetown University Medical Center and Pfizer, Inc., which makes a migraine medication.

Because of the underuse of medications to help treat or prevent menstrual migraines, investigators wanted to understand how common menstrual migraines were and which groups of women could most benefit from potential therapies. The study will be presented April 16, at the American Academy of Neurology 2024 Annual Meeting in Denver.

"The first step in helping a woman with menstrual migraine is making a diagnosis; the second part is prescribing a treatment; and the third part is finding treatments patients are satisfied with and remain on to reduce disability and improve quality of life," says the study author, Jessica Ailani, MD, professor of clinical neurology at Georgetown University School of Medicine and director of the MedStar Georgetown Headache Center at Medstar Georgetown University Hospital.

The researchers used the 2021 U.S. National Health and Wellness Survey, conducted by the National Center for Health Statistics, to analyze responses from women who reported their current migraine treatments, frequency and disabilities via the Migraine Disability Assessment Test (MIDAS), a five-question survey. A migraine headache can cause severe throbbing pain or a pulsing sensation, usually on one side of the head. It's often accompanied by nausea, vomiting, and extreme sensitivity to light and sound.

"Discrepancies in the incidence of who gets migraine attacks associated with menses is likely due to premenopausal women having more regular menstrual cycles and thus more menstrual-related migraines," says Ailani. "Additionally, as women move into their 40's and become peri-menopausal, there tends to be a greater shift through the month in hormone levels also leading to frequent migraine attacks."

The survey found that for all women during their menstrual periods, migraine attacks occurred as frequently as 4.5 times and that monthly only migraine headaches lasted 8.4 days, on average; 56.2 % of women had moderate-to-severe migraine-specific disabilities that ranked highest on the MIDAS scale.

When looking at treatments women in the survey used to help control their migraine symptoms, 42.4% used over-the-counter medications while 48.6% used prescription medications. Of the 63.9 % of women who used migraine treatments for acute symptoms, the most commonly used were triptans, a class of drugs developed in the 1990s to quiet overactive nerves associated with migraines and cluster headaches.

Source: ScienceDaily

Could preventative drug be effective in people with migraine and rebound headache?

 A drug used to prevent migraine may also be effective in people with migraine who experience rebound headaches, according to a new study published in the June 26, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology.

People with chronic migraine who overused pain medication had fewer monthly migraine and headache days and fewer days using pain medication when taking the migraine prevention drug atogepant.

"There is a high prevalence of pain medication overuse among people with migraine as they try to manage what are often debilitating symptoms," said study author Peter J. Goadsby, MD, PhD, of King's College London and a member of the American Academy of Neurology. "However, medication overuse can lead to more headaches called rebound headaches, so more effective preventive treatments are needed. Our findings are encouraging, suggesting atogepant may help reduce the need for pain medication among people with chronic migraine."

The study involved 755 participants who had chronic migraine, defined as having 15 or more headache days per month with eight or more qualifying as migraine.

Of this group, 66% met the criteria for medication overuse defined as taking pain medications such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen for 15 or more days in a month, triptans or ergots for 10 or more days a month, or any combination for 10 or more days.

At the start of the study, average monthly migraine days ranged from 18 to 19, and average monthly pain medication days ranged from 15 to 16.

For 12 weeks, participants were either given 30 milligrams (mg) of atogepant twice daily, 60 mg once daily, or a placebo. Atogepant is a calcitonin gene-related peptide receptor antagonist, or CGRP inhibitor. CGRP is a protein that plays a key role in starting the migraine process.

Participants recorded their migraines and headaches in an electronic diary, noting characteristics including duration and intensity, whether they experienced aura or nausea, and if they took other medications.

Researchers found for participants with medication overuse, those taking atogepant twice daily had an average of three fewer migraine days a month and three fewer headache days when compared to those taking placebo. Those taking the drug once a day had two fewer migraine days a month and two fewer headache days compared to placebo. Both groups also had three fewer days of taking pain medications to treat their symptoms when compared to placebo. Researchers say similar reductions were found among participants without medication overuse.

In those with medication overuse, 45% of those taking the drug twice daily and 42% of those taking it once a day had a 50% or more reduction in average monthly migraine days compared to 25% taking the placebo.

The number of people meeting the criteria for medication overuse also declined by 62% among those taking the drug twice daily and by 52% among those taking it once a day.

"Based on our findings, treatment with atogepant may potentially decrease the risk of developing rebound headache by reducing the use of pain medications," said Goadsby. "This could lead to an improved quality of life for those living with migraine."

Goadsby noted more studies are needed to evaluate the long-term safety and effectiveness of atogepant, as well as to assess the potential risk of medication overuse relapse among people with migraine.

A limitation of the study was that participants recorded their headaches and medication use in electronic diaries, so it is possible some participants may not have recorded all information accurately.

The study was funded by AbbVie, the maker of atogepant. Goadsby reported that he received personal fees from AbbVie during the study.

Source: ScienceDaily

Brain fluid dynamics key to migraine mysteries, new therapies

 New research describes for the first time how a spreading wave of disruption and the flow of fluid in the brain triggers headaches, detailing the connection between the neurological symptoms associated with aura and the migraine that follows. The study also identifies new proteins that could be responsible for headaches and may serve as foundation for new migraine drugs.

"In this study, we describe the interaction between the central and peripheral nervous system brought about by increased concentrations of proteins released in the brain during an episode of spreading depolarization, a phenomenon responsible for the aura associated with migraines," said Maiken Nedergaard, MD, DMSc, co-director of the University of Rochester Center for Translational Neuromedicine and lead author of the new study, which appears in the journal Science. "These findings provide us with a host of new targets to suppress sensory nerve activation to prevent and treat migraines and strengthen existing therapies."

It is estimated that one out of 10 people experience migraines and in about a quarter of these cases the headache is preceded by an aura, a sensory disturbance that can includes light flashes, blind spots, double vision, and tingling sensations or limb numbness. These symptoms typically appear five to 60 minutes prior to the headache.

The cause of the aura is a phenomenon called cortical spreading depression, a temporary depolarization of neurons and other cells caused by diffusion of glutamate and potassium that radiates like a wave across the brain, reducing oxygen levels and impairing blood flow. Most frequently, the depolarization event is located in the visual processing center of the brain cortex, hence the visual symptoms that first herald a coming headache.

While migraines auras arise in the brain, the organ itself cannot sense pain. These signals must instead be transmitted from the central nervous system -- the brain and spinal cord -- to the peripheral nervous system, the communication network that transmits information between brain with the rest of the body and includes sensory nerves responsible for sending information such as touch and pain. The process of communication between the brain and peripheral sensory nerves in migraines has largely remained a mystery.

Fluid Dynamics Models Shed Light on Migraine Pain Origins

Nedergaard and her colleagues at the University of Rochester and the University of Copenhagen are pioneers in understanding the flow of fluids in the brain. In 2012, her lab was the first to describe the glymphatic system, which uses cerebrospinal fluid (CSF) to wash away toxic proteins in the brain. In partnership with experts in fluid dynamics, the team has built detailed models of how the CSF moves in the brain and its role in transporting proteins, neurotransmitters, and other chemicals.

The most widely accepted theory is that nerve endings resting on the outer surface of the membranes that enclose the brain are responsible for the headaches that follow an aura. The new study, which was conducted in mice, describes a different route and identifies proteins, many of which are potential new drug targets, that may be responsible for activating the nerves and causing pain.

As the depolarization wave spreads, neurons release a host of inflammatory and other proteins into CSF. In a series of experiments in mice, the researchers showed how CSF transports these proteins to the trigeminal ganglion, a large bundle of nerves that rests at the base of the skull and supplies sensory information to the head and face.

It was assumed that the trigeminal ganglion, like the rest of the peripheral nervous system, rested outside the blood-brain-barrier, which tightly controls what molecules enter and leave the brain. However, the researchers identified a previously unknown gap in the barrier that allowed CSF to flow directly into the trigeminal ganglion, exposing sensory nerves to the cocktail of proteins released by the brain.

Migraine-Associated Proteins Double During Brain Wave Activity

Analyzing the molecules, the researchers identified twelve proteins called ligands that bind with receptors on sensory nerves found in the trigeminal ganglion, potentially causing these cells to activate. The concentrations of several of these proteins found in CSF more than doubled following a cortical spreading depression. One of the proteins, calcitonin gene-related peptide (CGRP), is already the target of a new class of drugs to treat and prevent migraines called CGRP inhibitors. Other identified proteins are known to play a role in other pain conditions, such as neuropathic pain, and are likely important in migraine headaches as well.

"We have identified a new signaling pathway and several molecules that activate sensory nerves in the peripheral nervous system. Among the identified molecules are those already associated with migraines, but we didn't know exactly how and where the migraine inducing action occurred," said Martin Kaag Rasmussen, PhD, a postdoctoral fellow at the University of Copenhagen and first author of the study. "Defining the role of these newly identified ligand-receptor pairs may enable the discovery of new pharmacological targets, which could benefit the large portion of patients not responding to available therapies."

The researchers also observed that the transport of proteins released in one side of the brain reaches mostly the nerves in the trigeminal ganglion on the same side, potentially explaining why pain occurs on one side of the head during most migraines.

Source: ScienceDaily

New drug to prevent migraine may start working right away

 A drug recently approved to prevent migraine may start working right away, according to a study published in the December 23, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study looked at the drug atogepant, which is a calcitonin gene-related peptide (CGRP) receptor antagonist taken by mouth.

"With many current drugs to prevent migraine, it takes time to find the right dosage for the individual and it can take weeks or even months for it to be most effective," said study author Richard B. Lipton, MD, of Albert Einstein College of Medicine in the Bronx, New York, and a Fellow of the American Academy of Neurology. "Some people give up and stop taking the drugs before they reach this point. Plus, many people experience side effects with current treatments. Developing a drug that works both effectively and quickly is critical."

In the study, people taking the drug atogepant were less likely to have a migraine on the first day of taking the drug compared to those taking a placebo. They also had fewer migraines per week during each of the first four weeks of the study and fewer migraines during the study overall than those taking a placebo.

For this study, researchers looked at the data from three trials on the safety and effectiveness of atogepant over 12 weeks to focus on how rapidly improvements appeared. The ADVANCE trial, which enrolled people with episodic migraine, had 222 people taking the drug and 214 taking placebo. The ELEVATE trial, which enrolled people with episodic migraine who had previously not responded well to other oral preventive treatments, had 151 on the drug and 154 on placebo. The PROGRESS trial, which enrolled people with chronic migraine, had 256 on the drug and 246 on placebo.

People with episodic migraine experience up to 14 migraine days per month. People with chronic migraine experience at least 15 days with headache per month, with at least eight days being characteristic of migraine.

On the first day of the study, 12% of those taking the drug in the first trial, the ADVANCE trial had a migraine, compared to 25% of those taking placebo. In the second trial, the ELEVATE trial, the numbers were 15% and 26%. For the third trial, the PROGRESS trial, the numbers were 51% and 61%.

When researchers adjusted for other factors that could affect the rate of migraine, they found that people taking the drug were 61% less likely to have a migraine in the first trial, 47% less likely in the second trial, and 37% less likely in the third trial.

For the first two trials, the people taking atogepant had an average of one fewer day with migraine per week, compared to an average of less than one-half day fewer per week for those taking the placebo. For the third trial, average migraine days per week declined by about 1.5 days for those taking the drug compared to about one day for those taking the placebo.

The people taking atogepant also showed improvement on assessments of how much migraine impaired their activities and their overall quality of life compared to people taking the placebo.

"Migraine is the second-leading cause of disability in the overall population and the leading cause of disability in young women, with people reporting negative effects on their relationships, parenting, career and finances," Lipton said. "Having a treatment that can act quickly and effectively addresses a key need."

A limitation of the study is that it involved mostly female and white participants, so the results may not apply to the overall population.

The study was supported by AbbVie, the maker of atogepant.

Source: ScienceDaily