New drug 'ubrogepant' may work for migraine

A new study published in the November 19, 2019 issue of JAMA shows that a newly developed small molecule drug called ubrogepant may successfully fight migraine at doses of 25 and 50 mg, with pain relief at 2 hours with both doses, while the most troublesome symptom of migraine was held off at 2 hours post-dose with the 50 mg dose. This may help millions of migraine patients to achieve pain relief and function better.

Migraine is a neurological condition characterized by headache which can last for up to 72 hours, nausea, and hypersensitivity to light and sounds. It is both common and distressing, and can hamper normal life in multiple ways, including work absenteeism, loss of productivity, difficulty with relationships, career failures, financial losses and depression. The treatment and prevention of this condition has attracted much medical interest, but the rate of success is low.

Gepants
One new line of treatment is with the small molecule medications called gepants. These are antagonists at the calcitonin gene-related peptide (CGRP) receptor, which mediates the effects of CGRP in the pathogenesis of migraine. One of these is ubrogepant, an oral drug which can be used at doses of 25 and 50 mg.

An earlier phase 2b study showed that in doses of 25 mg, 50 mg and 100 mg, ubrogepant could relieve pain with the effect lasting at 2 hours after the dose.

The study

The current phase 3 ACHIEVE II trial is meant to show if doses of 25 mg and 50 mg are effective and safe in the treatment of acute migraine. There were almost 1,700 participants, 500 on placebo, about 560 on 25 mg ubrogepant, and about the same number on 50 mg. 86% completed the trial. The mean age was about 42 years. 90% were women, and about 60% had severe pain while 40% had moderate pain. 57% were most troubled by photophobia.

All patients were between 18 and 75 years, had a history of migraine for at least 1 year but were below 50 years at onset, had 2-8 attacks in each of 3 months preceding the study, reported migraine duration of 4-72 hours without treatment or with inadequate treatment, and had at least 48 hours in between acute attacks.

The study was carried out at multiple centers, with a double-blinded randomized placebo-controlled design. The participants were grouped by their previous response to commonly used migraine drugs called triptans, and the current use of other preventive drugs. All these drugs were prohibited while taking the trial drug – including opioids, triptans, ergot derivative, nonsteroidal anti-inflammatory drugs (NSAIDs), pain relievers, antiemetics, and proton pump inhibitors. Within these groups, they were randomly assigned to receive either placebo, 25 mg of ubrogepant, or 50 mg of the drug.

The participants took one tablet of assigned medication as early as possible when migraine struck, but at all costs within 4 hours of onset. If required, the patient could take a second dose or a rescue drug within 2-48 hours, if the headache continued or started again at moderate to severe levels.

However, within the group of patients who chose to take a second dose, in the ubrogepant 25 mg/ 50 mg arms, the participants were again randomized to placebo vs the previous dose of ubrogepant. In the placebo arms, all patients repeated the dose of placebo. A rescue medication could be taken if required 2 hours after the second dose, in any of the trial arms.

Patients who did not want to take the repeat dose could take another drug from 2-48 hours after the first dose.

They then reported medication efficacy – severity of headache pain, presence of nausea, vomiting, sound or light sensitivity from the time of dosing to 48 hours afterwards, at specified intervals. The primary outcome was pain absence at 2 hours from the first dose, and absence of the most troublesome symptom (as reported at the beginning) at 2 hours.

The findings

The study found that 21% of patients on 50 mg ubrogepant, and almost the same percentage on 25 mg ubrogepant, achieved pain relief at 2 hours, compared to 14% with placebo. The drug appeared to be most effective at 3-8 hours after intake.

The most troublesome symptom was relieved in about 39% of patients on 50 mg ubrogepant, but there was no significant difference (34% vs 27%) between the 25 mg ubrogepant and placebo arms.
Among those who took a second dose, the chances of being pain-free 2 hours after the second dose were 2.2 times higher in those who took 2 doses at 50 mg each, compared to those who took two 25 mg doses, or those who took 50 mg followed by placebo. Other secondary outcomes such as the rate of pain relief over 2-14 hours, or absence of pain over the same period, were also greater in the 50 mg group. This was also seen with respect to the absence of photophobia and phonophobia (sensitivity to light and sound, respectively). Functional improvement was also obvious at 2 and 8 hours in the 50 mg group compared to placebo.

Implications

All available evidence points to the 50 mg dose as being the most effective in the acute treatment of migraine, achieving pain relief as well as absence of the most troublesome symptom at 2 hours.
The rate of adverse effects was similar in all three groups, indicating the safety and tolerability of ubrogepant. It has no cardiovascular precautions or contraindications like the triptans or ergot derivatives. It is also free of the serious cardiovascular and gastrointestinal effects of NSAIDs. Above the age of 22, cardiovascular contraindications exist in about a fifth of all patients with episodic migraine. Thus, ubrogepant may be a good option for those who fail to achieve acute relief of migraine with current medications.

It is important to capture the full benefit of the drug using alternative outcomes such as pain relief and functional improvement at 2 hours, because it appears to be maximally effective at 3-8 hours. Moreover, participants took the drug only with moderate or severe pain, while the American Headache Society recommends that treatment begin at the first sign of headache. This was not done, so we still don’t know just how much migraine pain could be averted if ubrogepant was given early rather than relatively late, as in this study. More study over a longer term is needed to find out how ubrogepant alters nerve function during migraine, any chronic side effects, and how consistently it acts to relieve pain.

This is only for your information, kindly take the advice of your doctor for medicines, exercises and so on.     
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All the Types of Headaches and What Causes Them

I have a resident headache that accompanies me almost everywhere I go — it starts from one shoulder blade, shoots up either side of my neck, and hangs out at the base of my skull for a bit, before progressing to either temple, where it lets itself be known in rhythmic pulsations. It’s consistent, regular, painful, unwelcome — and very common.

Headaches are a ubiquitous ailment — the first symptom of most diseases as well as most minor health states; if you’re dehydrated, here take a headache; if you’re sleep deprived; a headache is awaiting your pained existence; you have a brain tumor? Headache. How do we even know when a headache needs a glass of water and a burp, or a visit to the doctor? 

The tension or stress headache
One of the most common types of headaches is the tension headache, which generally lasts for several hours and manifests as mild to moderate pain across the forehead or back of the head, a tenderness in the neck and shoulders, or a feeling of pressure behind the eyes, according to Harvard Health, Caused by contractions in the neck and shoulder muscles, its triggers can include stress, lack of sleep, fatigue, hunger, or caffeine withdrawal, or abuse of alcohol and cigarettes. They can often be cured by regular sleep, exercise and food habits, better posture, and effective management of stress triggers with therapy. When tension headaches persist for longer than a few hours, and intensify, they can resemble another common type of headache: the migraine.

The migraine(s)

While less frequent than tension headaches, migraines are more intense — they are characterized by throbbing pain in the temple, eye or back of the head, accompanied by nausea or sensitivity to light and sound. Two to three times more common in women than in men, “migraines are caused by changes in the brain’s blood flow and nerve cell activity. Genetics play a role since 70% of migraine victims have at least one close relative with the problem,” according to Harvard Health. Even migraines, however, are usually triggered by changing weather, fluctuating sleep patterns, stress, and sensory triggers such as bright lights or strong smells.

20% of migraines are accompanied by neurological symptoms called an “aura,” according to Harvard Health, which can include halos, flashing lights, wavy lines, temporary loss of vision, or numbness and tingling on either side of the body. As for its treatment, “Some people can prevent migraines simply by avoiding triggers. Others do well with prompt therapy for occasional attacks. But patients who suffer frequent migraine attacks often benefit from preventive medications,” Harvard Health delineates. 

The cluster headache

According to the International Classification of Headache Disorders, cluster headaches are sudden, recurrent headaches manifesting as piercing, burning pain behind one eye. They’re characterized by a swollen eyelid, runny nose or a watery eye, and usually lasts between 15 minutes and three hours. Cluster headaches occur, well, in clusters, throughout the day, and can persist for weeks or months. Medical professionals advise avoiding alcohol and cigarettes during cluster headaches, and can prescribe medication suited to the intensity and frequency of the headache. 

The exertion headache

Arising out of extra-intensive physical activity such as running, weight lifting, or even sex, exertion headaches manifest as short-term pain throughout the head. They can be handled by using over-the-counter medication after the workout or by using beta blockers before the exertion upon prescription, according to Healthline.

The rebound headache

Headaches can also be caused by another condition in the body, such as a head injury or withdrawals. The most common is the medication-overuse or rebound headache: if you have taken painkillers for headaches for more than 15 days in a month, you’re likely to get a rebound headache characterized by restlessness, nausea, and sleep disturbance. In order to cure a rebound headache, you’ll need to drastically reduce your medication usage, which will worsen symptoms in the short term but prove helpful in weaning off of the pills in the long term, according to the Mayo Clinic.

The sinus headache

Caused by sinusitis, or sinus-swelling, sinus headaches are seasonal, and cause mild to moderate pain that manifests in the face, at the bridge of the nose, in the cheeks, or even in the teeth and jaw — mostly to people with allergies or a cold. Sinus headaches are usually accompanied by nasal symptoms such as thick discharge or a blocked nose. If nasal symptoms are not present, it may just be a migraine. Nasal sprays can help reduce sinus headaches.
The caffeine-withdrawal headache

According to John Hopkins University, consumption of caffeine can be as low as one small cup containing 100 milligrams of caffeine per day to cause a headache when stopped. Caffeine narrows blood vessels in the brain — in its absence, the blood vessels widen and facilitate increased blood flow, which can trigger a headache. Caffeine withdrawal headaches are usually accompanied by fatigue, difficulty concentrating, nausea and muscle pain.

One way to ease a caffeine withdrawal headache — as well as other headaches — is to take a pain reliever that includes caffeine as an ingredient,” Healthline reported. “Not only does caffeine help your body absorb the medication more quickly, it makes these drugs 40 percent more effective.”

The menstrual migraine

Right before a period begins, the female body experiences a drop in estrogen — the hormone that controls the chemical part of the brain associated with the sensation of pain. Many women report suffering from migraines at this time, according to the Mayo Clinic. Similar is true for any point in a woman’s reproductive cycle that experiences a drop in estrogen levels, such as perimenopause or menopause.

Over-the-counter pain medication, acupuncture, ice packs, and relaxation exercises can help ease the debilitating effects of the menstrual migraine, the Mayo Clinic advises.

The head-injury headache

Headaches resulting from any traumatic head or brain injury can manifest within seven days of the injury and can take many forms, according to the American Migraine Foundation (AMF). 85% of headaches after a head injury resemble tension headaches — maximum pain can be felt at the back of the head, either because the blow was to the back of the head, or the muscles in the shoulder and neck are pinching nerves in the region. 15% of headaches following a brain injury are migraines.

In approximately 78% of people, the headaches stay for three months after the injury; for 35%, until one year; and for 24%, even after two years. “Good sleep, exercise to tolerance, relaxation and stress management, reduced caffeine, regular healthy eating and avoidance of acute symptomatic medication overuse are recommended regardless of headache severity or type,” according to the AMF.

The concerning headache

With any headache, if the symptoms exacerbate rapidly, persist for longer than a few days, or are accompanied by loss of sleep, appetite or vision, going to a medical doctor can help identify the underlying problem. 

this is only for your information, kindly take the advice of your doctor for medicines, exercises and so on.     
https://gscrochetdesigns.blogspot.com. one can see my crochet creations  
https://gseasyrecipes.blogspot.com. feel free to view for easy, simple and healthy recipes    
https://kneereplacement-stickclub.blogspot.com. for info on knee replacement