Discuss Causes and treatment of chronic migraine

Headache Treatment Protocol Research Paper

The National Institute for Health and Care Excellence (NICE) has published a headache guideline for those aged over 12 years. The guideline, dated 2012, updated in 2015, includes treatment for migraine.Headache Treatment Protocol Research Paper

The guideline is based on scientific evidence and is intended for primary care where most headaches can safely be diagnosed and managed. If specialist advice is necessary, the guideline recommends referral to a GP with a special interest in headache or a consultant neurologist with similar interest. The guideline highlights special considerations for women with migraine including choice of contraception, management during pregnancy and management of migraine associated with the menstrual period.Headache Treatment Protocol Research Paper

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For diagnosis of headache, the guideline says that, at the first consultation, the doctor should ask for a description of the headache and any other symptoms. The doctor will want to ensure that the headache is not due to a serious underlying cause. The doctor may ask for completion of a diary over eight weeks to gather more detailed information about headaches and help them make the diagnosis.

The guideline says that, if a GP makes a diagnosis of migraine, further investigation is not usually required. A brain scan is not indicated solely to reassure the patient or the doctor. Adverse affects from scanning include exposure to radiation.Headache Treatment Protocol Research Paper

NICE guideline recommendations for migraine
The guideline recommends that for relief from a migraine attack, a healthcare professional should offer a triptan together with either a non-steroidal anti-inflammatory drug (NSAID) or paracetamol to help relieve migraine. If it is preferred to take only one drug, they may offer a trip tan, an NSAID, high‑dose aspirin or paracetamol. They may also offer you an anti-sickness medicine. All of these drugs are oral drugs. If you are unable to take oral drugs, or they do not work well, you should be offered metoclopramide or prochlorperazine which are non-oral drugs. You may also be offered a non‑oral NSAID or triptan. You should not be offered an ergot or an opioid to treat migraine, and those aged under 16 should not be offered aspirin.

The guideline recommends that for treatment to help prevent future migraine your healthcare professional should offer topiramate or propranolol. You may be offered amitriptyline as a treatment option, depending on your preferences, any other health problems and the possible side effects of the drug. Topiramate can cause birth defects and this should be discussed if there is the possibility of pregnancy. Contraception should be checked and changed if necessary, because topiramate can reduce the effectiveness of some types of contraceptive drugs. If neither topiramate nor propranolol are suitable or work well, you may be offered a course of up to 10 sessions of acupuncture.Headache Treatment Protocol Research Paper

The guideline says that women with menstrual-related migraine may be offered frovatriptan or zolmitriptan to help prevent migraine. Women with migraine with aura should not usually be offered the combined pill for contraception. During pregnancy, your healthcare professional should offer paracetamol to relieve migraine. They may offer a triptan or an NSAID after discussing the risks and benefits of taking these drugs during pregnancy.

Migraine is a primary headache disorder characterized by recurrent attacks. Acetaminophen, non steroidal anti-inflammatory drugs, trip tans, anti emetics, ergot alkaloids, and combination analgesics have evidence supporting their effectiveness in the treatment of migraine. Acetaminophen and non steroidal anti-inflammatory drugs are first-line treatments for mild to moderate migraines, whereas trip-tans are first-line treatments for moderate to severe migraines. Although trip-tans are effective, they may be expensive. Other medications such as hydroelectrically and anti emetics are recommended for use as second- or third-line therapy for select patients or for those with refractory migraine. The pharmacologic properties, potential adverse effects, cost, and routes of administration vary widely, allowing therapy to be individualized based on the pattern and severity of attacks. Several treatment principles, including taking medication early in an attack and using a stratified treatment approach, can help ensure that migraine treatment is cost-effective.

Migraine is a primary headache disorder characterized by recurrent attacks. Approximately 44.5 million U.S. adults (18% to 26% of women and 6% to 9% of men) have experienced a migraine, according to 2009 data.1 Estimated annual U.S. direct costs for migraine are more than $17 billion; the costs of lost productivity and reduced quality of life are significantly higher.2 More than one-half of migraines are treated in primary care, and they are the fourth most common cause of emergency department visits.3

Chronic migraine is a distinct and relatively recently defined sub-type of Chronic Daily Headache. The International Headache Society defines chronic migraine as more than fifteen headache days per month over a three month period of which more than eight are migrainous, in the absence of medication over use. Episodic migraine is the other migraine sub-type, which is defined as less than 15 headache days per month.1Headache Treatment Protocol Research Paper

Impact of chronic migraine
It is estimated that this condition affects fewer than 1% of the population, but this still means that there over 610,000 chronic migraine sufferers in the UK.2 Due to the nature and length of time that the sufferer is affected, people with chronic migraine experience significantly more time absent from work, school, leisure, housework and social activities than episodic migraine patients.3 Efficiency is also reduced due to chronic migraine, resulting in a more than 50% reduction in productivity from work or school.3,4 This is often described as a migraine ‘hangovers by sufferers.

The impact of chronic migraine can be very disabling.5 Being incapacitated for over half the month sometimes means that people are unable to work at all, with some claiming disability living allowance. Unfortunately, in many cases, current therapies are not enough to prevent or reduce the impact that chronic migraine has on people’s lives. This can lead to sufferers frequently becoming depressed and unable to cope.

The World Health Organization (WHO) has recognized the impact of migraine worldwide and categorized it as the same level of disability as dementia, quadriplegia and acute psychosis. Furthermore WHO classified chronic migraine as more disabling than blindness, paraplegia angina or rheumatoid arthritis.6

Some estimates put the cost of migraine, just in terms of medications at £150 million annually in the UK, but the overall cost is much more than that. An estimated 25 million working days are lost due to migraine, and at average gross weekly pay of £450, this costs the UK £2.25 billion per annul.7Headache Treatment Protocol Research Paper

Causes of chronic migraine
Just like episodic migraine there is no single cause for chronic migraine. Some people find that they have defined triggers such as caffeine, bright lights, hormone, food or sleep deprivation.

However for some people there is a steady progression in headache frequency, especially in long term sufferers. This can lead to the migraines becoming so frequent that they cross the threshold of more than 15 days per month and become defined as chronic migraine.8

Every year between 2.5 and 4.6% of people with episodic migraine experience progression to chronic migraine. The good news is that approximately the same proportion regress from chronic to episodic migraine spontaneously.8,9

Treatment for chronic migraine
Many of the therapies prescribed for chronic migraine are the same as those prescribed for episodic migraine. These include both prescription and over the counter painkillers and as well as migraine specific drugs such as trip tans. These are known as abortive or acute medications.

A combination of lifestyle changes and understanding the migraine triggers is important. There are also preventive treatments available for chronic migraine, but these are often associated with side effects, and many people cannot tolerate them for long periods of time.10Headache Treatment Protocol Research Paper

Medication overuse
It has been shown that up to 73% of chronic migraine patients over use headache medications. This may result in further complications, so it is important that if use of acute medication becomes daily, then help should be sought from their GP or neurologist.9

Currently there is no known cure for chronic migraine, although there are some new treatment options under investigation for the prevention of some types of migraine including chronic migraine.10,11

Specialist migraine/headache clinics
People with chronic migraine are three times more likely to consult their GPs compared to episodic migraine. In the UK 43% of people with chronic migraine visit a neurologist or headache specialist compared to only 18% of people with episodic migraine.12

Furthermore patients with chronic migraine are nearly four times more likely to end up visiting the accident and emergency department in any three month period, than those with episodic migraine.12

As more and more is understood about the different types of chronic daily headache and chronic migraine in particular, the role of the neurologist and specialist migraine clinics is becoming increasingly important.

Further investigations into chronic migraine may be required as well as tailored treatment plan to try to minimize the frequency and severity of attacks. People with chronic migraine also need specialist therapies that should only be prescribed whilst under the care of a neurologist.Headache Treatment Protocol Research Paper

Taking control if you have chronic migraine
Chronic migraine is a distinct type of migraine that is sometimes progressive. It is therefore important to recognize how often everyday life is disrupted by migraine and keep a record of how many days per month you have a headache. If this is more than half the month, you may well have chronic migraine and should see a neurologist, as he or she may be able to offer you a wider range of treatments to help reduce your symptoms.

Migraine is a neurovascular disorder characterized by dysfunction of the central and peripheral nervous systems and intracranial vasculature.1 Acute exacerbations of episodic and chronic migraine cause severe and disabling pain that often results in visits to an emergency department (ED) and decreased productivity and missed time from work, school, and other activities.2 In the United States, migraine and related medical issues result in costs of more than $13 billion per year due to lost productivity. In Canada, this cost has been estimated at $3,025/patient due to medical and indirect costs.3

Migraine has a negative impact on overall quality of life.4 It is associated with psychiatric and medical comorbidity including major depressive disorder, bipolar disorder, anxiety and social phobias, cardiovascular risk,5 and stroke.6 Inadequate care of migraine is common: only 56 percent of migraine patients have been diagnosed correctly, and 49 percent use only over-the-counter rather than prescription medications to treat their headache.7

Acute Exacerbation’s and Emergency Department Presentation
Migraine causes acute headaches, which typically last 4 hours to 3 days if untreated and which frequently require bed rest, pain medications, and time off from work and other activities. Although most patients with migraine function normally between attacks, for many, migraine is a pervasive disorder that interferes with work, family, and social life.1 Most individuals with migraine are able to treat their attacks at home, but this treatment is not always successful. Furthermore, when the initial oral acute treatment fails, subsequent attempts are likely to fail as well. Of Americans with migraine, 7 percent reported using an ED or urgent care center for treatment of severe headache within the previous 12 months.8 In a representative sample of adult ED visits in the United States, headaches accounted for 2.2 percent of visits or 2.1 million ED visits per year.9 In fact, a 5-month study in an American health maintenance organization found that migraine sufferers accounted for more ambulatory ED visits than patients with asthma (1.9 vs. 1.0 percent).10 In addition, migraine sufferers were more often found to have multiple ED visits.11Headache Treatment Protocol Research Paper

While headache is a common cause of presentation to the ED, there is substantial practice variability among emergency clinicians in both the United States and Canada.12-15 Twenty disparate par-enteral agents are used in U.S. EDs to treat acute migraine.12 There is substantial variability across EDs. For example, dopamine antagonists are used in 60 percent of visits in some EDs when compared with only 20 percent of visits in others.14

Acute Migraine Management
Acute headache pain and symptoms
Many agents are used to treat acute migraine, including 5-hydroxytryptamine (HT) receptor agonists (e.g., triptans), dopamine receptor antagonists (e.g., phenothiazines, metoclopramide), ergot derivatives (e.g., dihydroergotamine), intravenous nonsteroidal anti-inflammatory agents, and opioids. A variety of selective 5-HT1 receptor agonists have been developed and represent a class of drugs called triptans. These agents are indicated for the acute treatment of migraine in adults; however, reduced efficacy with delayed administration,16 the need for cardiac risk stratification prior to administration,17 and frequent adverse events18 limit their use in many EDs. Opioids are often used to treat acute migraine despite their recognized ability to cause dependence and headache relapse.11 The first objective of this comparative effectiveness review (CER) is to assess the effectiveness of various parenteral medications for adult patients with acute migraine who come to an ED for treatment.Headache Treatment Protocol Research Paper

Side effects
The second objective of this CER is to assess important immediate and longer term side effects of the different interventions. For example, opioids may be associated with drowsiness and impaired ability to function. In addition, both metoclopramide and the phenothiazines are considered to be equally efficacious, yet both agents have important immediate and subacute side effects. This CER will specifically examine the efficacy of metoclopramide and the phenothiazines and investigate their side effects, particularly akathisia and extrapyramidal events.

Prevention of Recurrence
Some patients with status migrainosus suffer a short-term recurrence that results in a return visit to a physician or ED. Research has shown that short-term or single-dose systemic corticosteroids (CSs), delivered intravenously (e.g., dexamethasone), prevent headache recurrence after treatment in an ED for acute migraine.19 However, they are infrequently used and have important short- and long-term side effects.19 A third focus of this review will be to examine the benefit and risk of using CSs for preventing recurrence of acute migraine.Headache Treatment Protocol Research Paper

Review Rationale
The research used to support current guidelines for treatment of acute migraine is dated, not adequately synthesized, insufficient, and continues to add to clinical uncertainty, resulting in wide variation of practice. Various important management trials of acute migraine headache have been completed in the past decade. The purpose of conducting this CER is to synthesize the current evidence in areas where reviews are lacking and to update reviews in areas where the data have been previously synthesized. The resulting report will provide the depth of understanding needed to inform management and policy decisions and hopefully improve migraine headache care provided in the ED.

The Key Questions
The Key Questions (KQs) were posted on the Agency for Healthcare Research and Quality (AHRQ) Effective Health Care Program Web site for public comment. Following review of the comments and discussion with the Key Informants, AHRQ, and the Eisenberg Center, no changes were made to the original KQs; however, the following comments were incorporated into the background material or inclusion criteria, as appropriate:

The importance of distinguishing between recurrent headache and recurrent visits to the ED.
The consideration of combinations of treatments.
Addressing sedation as an adverse event.
The followup period for longer term outcome studies.
Whether or not there will be sufficient information reported on subgroups to warrant their inclusion.Headache Treatment Protocol Research Paper
Tension-type headaches are the most common form of headache, occurring in about three-quarters of the general population. They can range from the occasional mild headache to daily disabling headaches in some cases.

Tension-type headaches have been called by various names over the years, including tension headache, muscle contraction headache, psychogenic headache, stress headache, ordinary headache, essential headache, idiopathic headache, and psychogenic headache. Of those names, only “tension headaches” is still fairly frequently used.

As you can see from the names that tension-type headache has been known by, it was at one time thought that the cause of tension-type headache was primarily psychological, caused by the mind or emotions. There have now been studies that strongly suggest a physical (neurobiological) cause.

Symptoms
Tension-type headaches most commonly last from 30 minutes to seven days. The pain is commonly described on both sides of the head (bilateral), as “a band around the head” or vice-like. The pain is generally mild to moderate and is not worse with routine physical activity, which means that most people with tension-type headache continue about their normal daily activities despite having their headache.Headache Treatment Protocol Research Paper

A tension-type headache is not accompanied by nausea or vomiting. It may be accompanied by increased sensitivity to light or sound, but not both. It may be associated with tenderness of the pericardial (head and neck) muscles, particularly with increased frequency of tension-type headache attacks.

Please refer to the International Classification of Headache Disorders 3rd edition (beta version) website for more information on the criteria used to diagnosis tension-type headache: https://www.ichd-3.org/2-tension-type-headache/

Types of Tension-type headache
Tension-type headache is broken down into three types:

Infrequent episodic type tension-type headache: one or fewer episodes per month.
Frequent episodic type tension-type headache: more than one, but fewer than 15 episodes per month for three or more months.
Chronic tension-type headache: more than 15 episodes per month for three or more months. There may be mild nausea with this type of tension-type headache.
Diagnosing Tension-type headache
There are no diagnostic tests to confirm tension-type headache. Diagnosis is accomplished by reviewing the patient’s personal and family medical history, studying their symptoms, and conducting an examination. Because of the association of tension-type headache-like symptoms with secondary headaches (due to an underlying cause or condition), doctors should consider the possibility of a secondary headache disorder when people present with presumed tension-type headache. This is particularly important if someone develops new/different headaches or has progressive headaches that are increasing in frequency. Examples of secondary causes include medication overuse or structural brain lesions.Headache Treatment Protocol Research Paper

At times, it can be difficult to distinguish between tension-type headache and a migraine attack. Tension-type headache is not made worse by physical activity. It is not accompanied by vomiting, and if nausea is present, it is mild. A migraine attack may be accompanied by increased sensitivity to both light and sound; one or neither accompanies tension-type headache. It is, however, possible for a tension-type headache to trigger a migraine attack.

Treatment of Tension-type headache
Infrequent episodic tension-type headache needs only treatment for the individual episodes (acute treatment). Simple analgesics, such as non steroidal anti-inflammatory drugs (NSAIDs) or aspirin, are reasonable choices. Sometimes combination analgesics including caffeine can be more effective; but with frequent use, side effects such as rebound headache may emerge. Use of combination therapies containing either butalbital or opioids for treatment of tension-type headache is generally not recommended because of the risk of tolerance, dependency, toxicity, and the development of medication overuse headache. Acute treatments should be limited to no more than twice per week, otherwise they can produce medication overuse headache and may cause undesirable effects on the liver, kidneys, stomach and other organs.Headache Treatment Protocol Research Paper

If tension-type headaches are frequent, long lasting, or associated with a significant amount of disability, then preventive treatment is recommended. Commonly used preventive strategies include medications such as amitriptyline and non-medication treatments for headache such as biofeedback, relaxation, and cognitive-behavioral therapy, acupuncture, massage therapy or physical therapy.

Summary
Unless they become frequent, tension-type headaches are usually more an annoyance than a big problem. They can often be treated with an over-the-counter medication and a bit of rest. Still to be on the safe side, a doctor should always diagnose headaches. More frequent tension-type headaches may require daily preventive medications or complementary therapies to restore health and quality of life.

The diagnosis of migraine headache in childhood rests on criteria similar to those used in migraine in adults. It is important, however, to appreciate several fundamental differences. These differences include the duration of attack, which is often far shorter than in an adult, and the location of the attack, which may be bilateral in many children.Headache Treatment Protocol Research Paper

The treatment of children and adolescents with migraines includes treatment modalities for acute attacks, preventive medications when the attacks are frequent, and bio behavioral modes of therapy to address long-term management of the disorder. The controlled clinical trials of medications in pediatric migraine have suffered from high placebo response rates that may be related to the sites conducting the study (ie, headache specialist vs clinical research organizations). The medications have proved to be safe in the pediatric age group.

Treatment modalities for acute migraine include over-the-counter non steroidal anti-inflammatory drugs (NSAIDs), as well as the oral trip-tans such as sumatriptan succinate, rizatriptan benzoate, and zolmitriptan and the nasal spray formulations of sumatriptan and zolmitriptan. Subcutaneous sumatriptan and parenteral dihydroergotamine have also been used limitedly.Headache Treatment Protocol Research Paper

Preventive treatment for patients with frequent or disabling migraines (or both) includes the antidepressants amitriptyline hydro chloride and nortriptyline hydro chloride, the anticonvulsants divalproex sodium and topiramate, and the antihistamine agent cyprohepatine hydro chloride. Bio behavioral approaches aimed at addressing the fundamental lifestyle issues and non pharmacologic approaches to management are fundamental to long-term success.

Headache, and more particularly migraine, is a frequent health problem in children and adolescents.1 Estimates are that headaches occur in up to 75% of adolescents and 25% of younger children.2 The greatest impact on a child and parent is from migraine, which occurs in up to 10.6% of children between the ages of 5 and 15 years,3 and 28% in children aged 15 to 19 years.4 This prevalence ranks headache and migraine in the top five health problems of childhood.
Despite its prevalence, migraine remains commonly diagnosed or misdiagnosed, just as in adults in whom migraine is often attributed to sinus disease.5 This misdiagnosis has been demonstrated in adults to result in a significant impact on treatment, disability, and quality of life. Similarly in children, frequent headaches can cause a significant impact on disability,6,7 as well as quality of life,8,9 prompting the need for early recognition and treatment.
The long-term outcome of childhood headaches and evolution into adult headaches remains largely unknown. It has been suggested that for adults migraine may represent a progressive disorder.10 In children, however, the progressive nature is unclear and further studies into longitudinal outcome and phenotypic changes in childhood headaches have yet to be identified. Headache Treatment Protocol Research Paper
Diagnosis
Historically, the diagnosis of headaches and migraine in children has been based on anecdotal experience, with only limited criteria. In 1988, the International Headache Society adopted the International Classification of Headache Disorders.11 This classification allowed for differences in childhood headaches, notably a shorter duration. However, this classification was criticized by many investigators as not sensitive or specific enough for childhood headache disorders, and revisions were suggested.12
In 2004, the second edition of the International Classification of Headache Disorders (ICHD-2)13 was released. These criteria provided improved recognition of childhood headaches in the footnotes for migraines. Among the improvements in criteria that were recognized was an expanded duration of attacks from between 1 and 72 hours, but still possessing the features of a throbbing or pulsate headache of moderate to severe intensity with exacerbation with physical activity. Children with migraine pain could have bi frontal or bi temporal pain, though exclusively occipital pain requires further investigation. Migraine-associated symptoms continued to require nausea or vomiting (or both), or light and sound sensitivity. Additionally, the criteria allowed for parental inference of these associated symptoms.
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Many treatment options are available for migraine prevention. Developing customized treatment strategies for patients is essential. At the 26th Annual Stowe Headache Symposium of the Headache Cooperative of New England, Peter Allister, MD, discussed the most efficacious migraine prevention therapies. He also gave guidance on deciding who needs preventive therapy and how to choose the right preventive treatment for each patient.Headache Treatment Protocol Research Paper
Who Needs Migraine Prevention Therapy?

Migraine prevention therapy is underutilized. Thirty-eight percent of patients could benefit from migraine prevention therapy, but only 3% to 13% are actually receiving it, according to 2012 guidelines from the AAN and the American Headache Society. Frequency of headaches and functional disability are the main criteria for deciding which patients need preventive treatment. According to the 2012 US Headache Consortium Guidelines, migraines with six or more headache days per month, four or more headache days with functional disability, or three or more headache days per month resulting in disability requiring bed rest, should be offered migraine preventive medication. The Canadian Prophylactic Guidelines Development Group 2012 recommended that prophylactic therapy be considered for patients whose migraine attacks have a significant impact on their lives, despite appropriate use of acute medications, trigger management, and lifestyle modification strategies.

Disability may be the more important of the two criteria. “If [a patient is] disabled, we really have to push and be aggressive with preventive medications,” said Dr. McAllister, Medical Director of the New England Institute for Neurology and Headache in Stamford, Connecticut. A guiding principle to consider when deciding who should receive preventive therapy is that an accurate diagnosis follows the International Headache Society, third edition (ICHD-3) guidelines. Dr. McAllister also advised doctors to make sure that patients keep headache diaries and to set realistic treatment goals. He also emphasized the importance of understanding patients medical and psychiatric conditions. In general, drug treatment should start with a low dose and slowly be tit-rated to a therapeutic dose. In addition, preventive treatment should be included as part of an overall plan that encompasses lifestyle changes, trigger reduction, and a strategy for withdrawal of medication.Headache Treatment Protocol Research Paper

Pharmacologic Options

The FDA has approved several drugs for migraine prevention, including divalproex sodium, topiramate, propranolol, timolol, and methysergide. Of all classes of migraine preventive therapy, antiseizure medications have the most support in the data. Topiramate is “a top choice” for migraine prevention because Class I evidence supports its efficacy and it is fairly well tolerated, said Dr. McAllister. Topiramate was also approved for children based on a double-blind study of participants between ages 12 and 17. Divalproex, another antiseizure medication, has high efficacy, but side effects such as weight gain, hair loss, tremor, teratogenicity, increased liver function tests, and increased risk for pancreatitis make the drug unattractive to many.

Antihypertensive medicines also may be used for migraine prevention. Much research supports the efficacy of beta blockers in migraine prevention, and doctors can help patients manage their associated side effects. Metoprolol, a beta blocker, may be more tolerable for someone with asthma or glucose issues because it is selective for β1. Although physicians have used verapamil, a calcium channel blocker, for migraine prevention, the most recent guidelines give a Level U recommendation for its use because of conflicting or insufficient evidence. Lisinopril, an angiotensin-converting-enzyme inhibitor, and candesartan, an angiotensin receptor blocking agent, have good side effect profiles. These drugs are recommended for patients with mild hypertension. American guidelines provide a Level C recommendation of clonidine, but Canadian guidelines recommend against using the drug because of insufficient evidence and concern about the side effects.Headache Treatment Protocol Research Paper

Non pharmacologic Options

Neurologists who seek to avoid pharmacologic treatments may choose options such as biologics or neurostimulators. OnabotulinumtoxinA injections are approved for patients with chronic migraine. Administered properly, the treatment has no systemic side effects and few local side effects.

In 2014, the FDA allowed the Cefaly device, which stimulates the trigeminal nerve, to be marketed for the prevention of migraine. In 2013, 67 patients with migraine were randomized to supraorbital stimulation with Cefaly or sham stimulation. The number of headache days per month decreased from seven to five among the participants randomized to Cefaly. Patients who received sham stimulation had no change in this end point.

Some patients may be interested in complementary or alternative treatment options like biofeedback. Biofeedback allows patients to monitor and change certain physiologic parameters (eg, muscle contraction and skin temperature) and is used to treat insomnia and anxiety. This therapy can be combined with a migraine preventive drug for the best results. Controlled studies indicate that biofeedback can result in a 45% to 60% headache reduction. When combined with medication, biofeedback reduces headache by more than 70%. Children and adolescents can also benefit from this treatment.

“Hormonal changes are a big contributor to the higher female incidence,” said Michael A. Moskowitz, MD, Professor of Neurology at Harvard Medical School at the Massachusetts General Hospital in Boston. “There are lines of evidence that support this from lab to clinical evidence and a decrease (although not abolished) incidence in post-menopausal females.”Headache Treatment Protocol Research Paper

Migraine headaches can vary from person to person, but they typically last from four hours up to 72 hours. Some people get them several times per month, while others experience them much less frequently. Many migraine sufferers report throbbing or pulsating pain on one side of the head, blurred vision, sensitivity to light and sound, nausea, and vomiting. Roughly one in five migraine sufferers experience an aura, or visual or sensory disturbance, before the onset of the headache. Examples of an aura include: flashes of light, loss of vision, zig-zag lines, pins and needles in an arm or leg, and speech and language problems.

Several risk factors have been identified that increase a person’s chance of having migraines:

• Family history: A significant majority of migraine sufferers have a family history of migraine attacks. For a person who has one or more first-degree relatives with migraine headaches, the likelihood rises substantially.

• Age: Migraines typically affect people between the ages of 15-55. Most people have had their first attack by 40 years old.

• Gender: Women are more likely to suffer from migraines than men.

• Certain medical conditions: depression, anxiety, stroke, epilepsy, and high blood pressure are all associated with migraine headaches.

• Hormonal changes: Women who suffer from migraines often find that the headaches have a pattern of recurrence just before or shortly after the onset of menstruation. The headaches may also change during pregnancy and/or menopause.Headache Treatment Protocol Research Paper

Migraines are vascular headaches but the exact cause is not fully understood. Some researchers believe that migraines occur when there are abnormal changes in the brain. When these changes occur, inflammation causes blood vessels to swell and press on nerves, which can result in pain.

Researchers have learned that certain triggers can set off migraine attacks. These triggers vary from person to person and can include: sleep disturbances, stress, weather changes, low blood sugar, dehydration, bright lights and loud noises, hormonal changes, foods that contain aspartame, foods that contain tyramine (fava beans, aged cheeses, soy products, etc.), caffeine, and alcohol.

Unfortunately, migraines have no known cure, but they can be managed effectively with the help of a health care provider. A variety of drugs can be used for pain relief and for prevention. Lifestyle changes are often recommended to identify and eliminate possible triggers that can set off an attack.

“Until recently there have been no treatments available to treat people who suffer from chronic migraines,” said Moskowitz. “Recently, a new medication has become available specifically to treat chronic migraine headaches, called onabotulinumtoxinA (Botox). Chronic migraine sufferers can derive significant benefit from this new form of therapy.”

Chronic migraine sufferers have also found relief in certain vitamins and other homeopathic remedies. But patients should check with their doctors for proper treatment protocols.

The management of acute and chronic migraine is an ever-changing area of focus among healthcare practitioners, especially headache specialists. A host of pharmacologic and non pharmacologic treatments to manage migraine are currently available, including rescue medications, such as non steroidal anti-inflammatory drugs and trip tans, and prophylactic options, such as antiepileptics, anti hypertensives, antidepressants, and acupuncture. Even with the large number of treatments available, many patients do not experience adequate symptom relief.1 As a result, alternative treatment modalities are ripe for exploration.Headache Treatment Protocol Research Paper

In clinical practice, many physicians utilize a procedure known as a greater occipital nerve (GON) block to treat acute migraine, despite no mention of the procedure in current migraine treatment guidelines and a scarcity of published research supporting its therapeutic benefit. The GON block procedure involves injecting a local anesthetic, with or without a corticosteroid, into the GON, which is composed of sensory fibers and originates in the C2 and C3 segments of the spinal cord, with the ultimate goal of providing relief of pain associated with migraine. Allen and colleagues conducted the present study to determine the potential benefit of using GON block in the management of acute migraine headache.1

Migraine Prevention Study
Do you suffer from migraines? If you have between 4-18 migraines per month, you could help us learn about a new investigation al medication being tested to prevent migraines.​

Bio haven Pharmaceuticals is studying a new drug to prevent migraines. If you are at least 18 years of age you may qualify.

Contact one of our research sites and find out if you qualify for a clinical research study. The investigation al drug, plus all study-related assessments, will be provided at no cost to you.

Health insurance is not required to take part in this study and compensation for participation may also be provided.Headache Treatment Protocol Research Paper

What is a migraine headache?
See if You Qualify
Migraine is a chronic and debilitating disorder that affects approximately 15% of the population. Migraines are characterized by recurrent attacks lasting 4 to 72 hours with multiple symptoms, including pulsating (throbbing) headaches of moderate to severe pain that could be associated with nausea or vomiting, and/or sensitivity to sound (phonophobia) and sensitivity to light (photophobia).

Purpose of this study
This is a research study, or clinical trial, to test a new investigation al medication. An investigation al medication is one that is not approved by the United States Food and Drug Administration (FDA). The purpose of this research study is to determine the effectiveness of rimegepant as a preventive treatment for migraine. This is measured by counting the number of migraine days you have each month. About 1500 study participants will be screened and about 800 study participants will enter into the treatment phase in this study.Headache Treatment Protocol Research Paper

If you qualify, your participation in this study will last approximately 76 weeks (approximately 19 months) and will include approximately 23 study visits to the study center. The first 12 weeks of the treatment phase is the double-blind period where you may receive placebo. You may then qualify for 52 weeks of open-label medication (no placebo is given during this time; study participants are only assigned to active investigation al medication).

In the field of health psychology, discovering the connection between the physical and mental aspects of disease can be extremely beneficial for both the patient and the scientific community as a whole. For those suffering from chronic headaches, debilitating pain often interferes with daily routines. To better understand chronic headaches and their psychological connections, it is beneficial to examine the associated health issues, and psychological theories which can explain the source, the research being conducted, and the role of health psychologists in treatment.

a) What problems are often experienced by individuals and their families as a result of this illness (e.g. anxiety, depression, stigma, stress, non-adherence)?
Chronic headaches, especially migraines, can be extremely difficult for patients to deal with for many reasons. The symptoms of a headache not only affect the individual experiencing them due to the physical pain, but also affects the families who must try to comfort and support their suffering relative. Unsurprisingly, stress is a very common stress trigger and is also one of the results of having a headache. This cyclic occurrence of stress and headaches can be debilitating and difficult to overcome. Stress produces changes in the brain which can intensify the duration and magnitude of the episode, impacting the time which would normally be spent with family and friends, work duties, and even enjoyable life events.
Researchers have proposed that a mutual susceptibility to anxiety disorders, depression, and migraines may exist. Migraines and chronic daily headaches are common in people who suffer from anxiety disorders and can precede the commencement of mental illnesses, according to a 2009 study.Headache Treatment Protocol Research Paper

It is widely believed that in order for an individual to feel pain, there must be some degree of physical damage. This is one of the greatest falsehoods in the study of pain, as there are many painful experiences that are not related to any known physical damage and that do not have an evident or ultimate cause (Wall & Melzack, 2008). Migraine is one example of a disorder that affects one tenth of the population and generally does not have an evident or definite known cause at this point in the history of research. Not only is there very little known about the origins of migraine pain, but there has also been much deliberation regarding defining migraine in clinical terms. One generally acceptable definition states that an individual is said to have migraine if he or she suffers five or more headache attacks that interfere with daily living activities and that last anywhere between four and seventy-two hours straight. These headache attacks are said to be unprovoked, meaning there is no identifiable reason for headache symptoms to appear (Rothrock, 2008).
There are multiple variations of migraine such as classic migraine, common migraine, and cluster headaches; all of which can be accompanied by nausea, sensitivity to light and or sound, and aura. Aura, is a visual symptom that can sometimes accompany migraine causing the individual to see blind spots or flashes of light during a headache attack. Symptoms of migraine can vary, and unfortunately what causes these symptoms and disorder are unknown (Rothrock, 2008). Researchers in the past suspected that the origin of migraine pain was associated with changes in blood vessels which supply the brain.

Opioids are commonly prescribed for pain. An estimated 20% of patients presenting to physician offices with non cancer pain symptoms or pain-related diagnoses (including acute and chronic pain) receive an opioid prescription (1). In 2012, health care providers wrote 259 million prescriptions for opioid pain medication, enough for every adult in the United States to have a bottle of pills (2). Opioid prescriptions per capita increased 7.3% from 2007 to 2012, with opioid prescribing rates increasing more for family practice, general practice, and internal medicine compared with other specialties (3). Rates of opioid prescribing vary greatly across states in ways that cannot be explained by the underlying health status of the population, highlighting the lack of consensus among clinicians on how to use opioid pain medication (2).Headache Treatment Protocol Research Paper

Prevention, assessment, and treatment of chronic pain are challenges for health providers and systems. Pain might go unrecognized, and patients, particularly members of racial and ethnic minority groups, women, the elderly, persons with cognitive impairment, and those with cancer and at the end of life, can be at risk for inadequate pain treatment (4). Patients can experience persistent pain that is not well controlled. There are clinical, psychological, and social consequences associated with chronic pain including limitations in complex activities, lost work productivity, reduced quality of life, and stigma, emphasizing the importance of appropriate and compassionate patient care (4). Patients should receive appropriate pain treatment based on a careful consideration of the benefits and risks of treatment options.

Chronic pain has been variably defined but is defined within this guideline as pain that typically lasts >3 months or past the time of normal tissue healing (5). Chronic pain can be the result of an underlying medical disease or condition, injury, medical treatment, inflammation, or an unknown cause (4). Estimates of the prevalence of chronic pain vary, but it is clear that the number of persons experiencing chronic pain in the United States is substantial. The 1999–2002 National Health and Nutrition Examination Survey estimated that 14.6% of adults have current widespread or localized pain lasting at least 3 months (6). Based on a survey conducted during 2001–2003 (7), the overall prevalence of common, predominantly musculoskeletal pain conditions (e.g., arthritis, rheumatism, chronic back or neck problems, and frequent severe headaches) was estimated at 43% among adults in the United States, although minimum duration of symptoms was not specified. Most recently, analysis of data from the 2012 National Health Interview Study showed that 11.2% of adults report having daily pain (8). Clinicians should consider the full range of therapeutic options for the treatment of chronic pain. However, it is hard to estimate the number of persons who could potentially benefit from opioid pain medication long term. Evidence supports short-term efficacy of opioids for reducing pain and improving function in noncancer nociceptive and neuropathic pain in randomized clinical trials lasting primarily ≤12 weeks (9,10), and patients receiving opioid therapy for chronic pain report some pain relief when surveyed (11–13). However, few studies have been conducted to rigorously assess the long-term benefits of opioids for chronic pain (pain lasting >3 months) with outcomes examined at least 1 year later (14). On the basis of data available from health systems, researchers estimate that 9.6–11.5 million adults, or approximately 3%–4% of the adult U.S. population, were prescribed long-term opioid therapy in 2005 (15).Headache Treatment Protocol Research Paper

Opioid pain medication use presents serious risks, including overdose and opioid use disorder. From 1999 to 2014, more than 165,000 persons died from overdose related to opioid pain medication in the United States (16). In the past decade, while the death rates for the top leading causes of death such as heart disease and cancer have decreased substantially, the death rate associated with opioid pain medication has increased markedly (17). Sales of opioid pain medication have increased in parallel with opioid-related overdose deaths (18). The Drug Abuse Warning Network estimated that >420,000 emergency department visits were related to the misuse or abuse of narcotic pain relievers in 2011, the most recent year for which data are available (19). Although clinical criteria have varied over time, opioid use disorder is a problematic pattern of opioid use leading to clinically significant impairment or distress. This disorder is manifested by specific criteria such as unsuccessful efforts to cut down or control use and use resulting in social problems and a failure to fulfill major role obligations at work, school, or home (20).Headache Treatment Protocol Research Paper This diagnosis has also been referred to as “abuse or dependence” and “addiction” in the literature, and is different from tolerance (diminished response to a drug with repeated use) and physical dependence (adaptation to a drug that produces symptoms of withdrawal when the drug is stopped), both of which can exist without a diagnosed disorder. In 2013, on the basis of DSM-IV diagnosis criteria, an estimated 1.9 million persons abused or were dependent on prescription opioid pain medication (21). Having a history of a prescription for an opioid pain medication increases the risk for overdose and opioid use disorder (22–24), highlighting the value of guidance on safer prescribing practices for clinicians. For example, a recent study of patients aged 15–64 years receiving opioids for chronic non cancer pain and followed for up to 13 years revealed that one in 550 patients died from opioid-related overdose at a median of 2.6 years from their first opioid prescription, and one in 32 patients who escalated to opioid dosages >200 morphine milligram equivalents (MME) died from opioid-related overdose (25).

This guideline provides recommendations for the prescribing of opioid pain medication by primary care clinicians for chronic pain (i.e., pain conditions that typically last >3 months or past the time of normal tissue healing) in outpatient settings outside of active cancer treatment, palliative care, and end-of-life care. Although the guideline does not focus broadly on pain management, appropriate use of long-term opioid therapy must be considered within the context of all pain management strategies (including non opioid pain medications and non pharmacologic treatments). CDC’s recommendations are made on the basis of a systematic review of the best available evidence, along with input from experts, and further review and deliberation by a federally chartered advisory committee. The guideline is intended to ensure that clinicians and patients consider safer and more effective treatment, improve patient outcomes such as reduced pain and improved function, and reduce the number of persons who develop opioid use disorder, overdose, or experience other adverse events related to these drugs. Clinical decision making should be based on a relationship between the clinician and patient, and an understanding of the patient’s clinical situation, functioning, and life context. The recommendations in the guideline are voluntary, rather than prescriptive standards. They are based on emerging evidence, including observational studies or randomized clinical trials with notable limitations. Clinicians should consider the circumstances and unique needs of each patient when providing care.

Rationale
Primary care clinicians report having concerns about opioid pain medication misuse, find managing patients with chronic pain stressful, express concern about patient addiction, and report insufficient training in prescribing opioids (26). Across specialties, physicians believe that opioid pain medication can be effective in controlling pain, that addiction is a common consequence of prolonged use, and that long-term opioid therapy often is over prescribed for patients with chronic non cancer pain (27). These attitudes and beliefs, combined with increasing trends in opioid-related overdose, underscore the need for better clinician guidance on opioid prescribing. Clinical practice guidelines focused on prescribing can improve clinician knowledge, change prescribing practices (28), and ultimately benefit patient health.

Professional organizations, states, and federal agencies (e.g., the American Pain Society/American Academy of Pain Medicine, 2009; the Washington Agency Medical Directors Group, 2015; and the U.S. Department of Veterans Affairs/Department of Defense, 2010) have developed guidelines for opioid prescribing (29–31). Existing guidelines share some common elements, including dosing thresholds, cautious tit ration, and risk mitigation strategies such as using risk assessment tools, treatment agreements, and urine drug testing. However, there is considerable variability in the specific recommendations (e.g., range of dosing thresholds of 90 MME/day to 200 MME/day), audience (e.g., primary care clinicians versus specialists), use of evidence (e.g., systematic review, grading of evidence and recommendations, and role of expert opinion), and rigor of methods for addressing conflict of interest (32). Most guidelines, especially those that are not based on evidence from scientific studies published in 2010 or later, also do not reflect the most recent scientific evidence about risks related to opioid dosage.

This CDC guideline offers clarity on recommendations based on the most recent scientific evidence, informed by expert opinion and stakeholder and public input. Scientific research has identified high-risk prescribing practices that have contributed to the overdose epidemic (e.g., high-dose prescribing, overlapping opioid and benzodiazepine prescriptions, and extended-release/long-acting [ER/LA] opioids for acute pain) (24,33,34). Using guidelines to address problematic prescribing has the potential to optimize care and improve patient safety based on evidence-based practice (28), as well as reverse the cycle of opioid pain medication misuse that contributes to the opioid overdose epidemic.Headache Treatment Protocol Research Paper

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Scope and Audience
This guideline is intended for primary care clinicians (e.g., family physicians and internists) who are treating patients with chronic pain (i.e., pain lasting >3 months or past the time of normal tissue healing) in outpatient settings. Prescriptions by primary care clinicians account for nearly half of all dispensed opioid prescriptions, and the growth in prescribing rates among these clinicians has been above average (3). Primary care clinicians include physicians as well as nurse practitioners and physician assistants. Although the focus is on primary care clinicians, because clinicians work within team-based care, the recommendations refer to and promote integrated pain management and collaborative working relationships with other providers (e.g., behavioral health providers, pharmacists, and pain management specialists). Although the transition from use of opioid therapy for acute pain to use for chronic pain is hard to predict and identify, the guideline is intended to inform clinicians who are considering prescribing opioid pain medication for painful conditions that can or have become chronic.

This guideline is intended to apply to patients aged ≥18 years with chronic pain outside of palliative and end-of-life care. For this guideline, palliative care is defined in a manner consistent with that of the Institute of Medicine as care that provides relief from pain and other symptoms, supports quality of life, and is focused on patients with serious advanced illness. Palliative care can begin early in the course of treatment for any serious illness that requires excellent management of pain or other distressing symptoms (35). End-of-life care is defined as care for persons with a terminal illness or at high risk for dying in the near future in hospice care, hospitals, long-term care settings, or at home. Patients within the scope of this guideline include cancer survivors with chronic pain who have completed cancer treatment, are in clinical remission, and are under cancer surveillance only. The guideline is not intended for patients undergoing active cancer treatment, palliative care, or end-of-life care because of the unique therapeutic goals, ethical considerations, opportunities for medical supervision, and balance of risks and benefits with opioid therapy in such care.Headache Treatment Protocol Research Paper

The recommendations address the use of opioid pain medication in certain special populations (e.g., older adults and pregnant women) and in populations with conditions posing special risks (e.g., a history of substance use disorder). The recommendations do not address the use of opioid pain medication in children or adolescents aged <18 years. The available evidence concerning the benefits and harms of long-term opioid therapy in children and adolescents is limited, and few opioid medications provide information on the label regarding safety and effectiveness in pediatric patients. However, observational research shows significant increases in opioid prescriptions for pediatric populations from 2001 to 2010 (36), and a large proportion of adolescents are commonly prescribed opioid pain medications for conditions such as headache and sports injuries (e.g., in one study, 50% of adolescents presenting with headache received a prescription for an opioid pain medication) (37,38). Adolescents who misuse opioid pain medication often misuse medications from their own previous prescriptions (39), with an estimated 20% of adolescents with currently prescribed opioid medications reporting using them intentionally to get high or increase the effects of alcohol or other drugs (40). Use of prescribed opioid pain medication before high school graduation is associated with a 33% increase in the risk of later opioid misuse (41). Misuse of opioid pain medications in adolescence strongly predicts later onset of heroin use (42). Thus, risk of opioid medication use in pediatric populations is of great concern. Additional clinical trial and observational research is needed, and encouraged, to inform development of future guidelines for this critical population. The recommendations are not intended to provide guidance on use of opioids as part of medication-assisted treatment for opioid use disorder. Some of the recommendations might be relevant for acute care settings or other specialists, such as emergency physicians or dentists, but use in these settings or by other specialists is not the focus of this guideline. Readers are referred to other sources for prescribing recommendations within acute care settings and in dental practice, such as the American College of Emergency Physicians guideline for prescribing of opioids in the emergency department (43); the American Society of Anesthesiologists guideline for acute pain management in the preoperative setting (44); the Washington Agency Medical Directors Group Inter agency Guideline on Prescribing Opioids for Pain, Part II: Prescribing Opioids in the Acute and Sub acute Phase (30); and the Pennsylvania Guidelines on the Use of Opioids in Dental Practice (45). In addition, given the challenges of managing the painful complications of sickle cell disease, readers are referred to the NIH National Heart, Lung, and Blood Institute’s Evidence Based Management of Sickle Cell Disease Expert Panel Report for management of sickle cell disease (46).Headache Treatment Protocol Research Paper Cluster headaches are associated with cranial autonomic symptoms in addition to severe unilateral head pain. Pharmacotherapy is often required in the form of both abortive and prophylactic therapies to help manage symptoms. High-flow oxygen and non oral trip-tans are abortive treatments of choice. Prophylactic therapy to prevent symptom recurrence is typically achieved with verapamil or lithium carbonate. Corticosteroids and nerve blocks are used as bridge treatment until prophylactic therapy is effective. It is important for pharmacists to recognize the symptoms of cluster headache because this headache disorder has limited self-care management and often requires referral to specialists. Cluster headache is a rare headache disorder characterized by severe, unilateral head pain that presents with cranial autonomic symptoms including conjunctiva l redness, lacrimation (tearing of the eye), rhinorrhea (runny nose), and drooping of the eyelid. The autonomic symptoms present ipsilaterally, occurring on the same side of the head as the pain. Cluster headache is one of five primary headache disorders categorized as trigeminal autonomic cephalgias (TACs).1 TACs are generally considered the most debilitating of all primary headache disorders owing to their high level of pain combined with autonomic symptoms.2Headache Treatment Protocol Research Paper Effective pharmacotherapy exists for targeting pain associated with cluster headache, and treatment should be implemented after a correct diagnosis has been made to reduce pain burden and improve quality of life. Pharmacologic treatment for cluster headaches is divided into three phases: abortive treatment (i.e., medications used acutely to immediately terminate the pain of a cluster headache); prophylactic treatment (i.e., medications given daily to prevent future headaches); and bridge treatment (i.e., medications used for brief intervals until prophylactic treatments reach peak efficacy).3 The scope of this article is to review the pharmacologic management of cluster headache. Epidemiology The lifetime prevalence of cluster headache is 124 per 100,000 based on pooled epidemiological studies.4 Onset of symptoms is typically seen by the early third decade of life, and women often have an earlier onset of symptoms compared with men. Most data regarding cluster headaches have primarily been in Caucasian populations, so it is difficult to determine if there are differences in prevalence across race and ethnicity.5 Cluster headache occurs more predominantly in men, with rates quadrupled in males versus females.4 Familial studies indicate that first-degree relatives have a five-to-18-fold greater risk of developing cluster headache compared with the general population.6 Although not a definitive risk factor, smoking is more prevalent in patients with cluster headache.5 Diagnosis and Clinical Features A diagnosis of cluster headache is based primarily on patient history, presenting symptoms, and diagnostic criteria. Severe headache pain presenting with autonomic symptoms (e.g., runny nose, facial flushing, lacrimation) and restlessness or agitation are the cornerstone symptoms associated with cluster headache. The diagnostic criteria for headache disorders are based on the International Classification of Headache Disorders 3rd edition (ICHD-3). The diagnostic requirements for cluster headache are noted in TABLE 1.1 The headache attacks occur in cycles or bouts lasting weeks or months, often referred to as a cluster attack period. These attack periods correlate with circadian changes, as attacks are often more severe with changes in daylight hours, most notably around the start and end of daylight saving time.7 Attacks often occur during sleep, and the onset of pain can become drastic quickly. Owing to the circadian implications and timing of symptoms, cluster headaches can be further divided into two categories: episodic cluster headache and chronic cluster headache. Episodic cluster headache is more common compared with chronic cluster headache, the latter occurring in roughly 10% of the population with cluster headache. An episodic cluster headache diagnosis is made in patients who have had two cluster headache attacks lasting 7 days up to 1 year and separated by a pain-free remission period of at least a month. Patients with chronic cluster headache do not have a remission period or have remission periods lasting less than a month for at least a year.1 Most patients have a cluster attack period annually; however, patients can have periods of remission lasting for years. MRI is often utilized to rule out other causes of severe head pain. Laboratory and other tests are often not indicated. Because of the specificity of symptoms and severity of headache pain seen in cluster headache, few other disease states are compatible with the features present in cluster headache. The differential diagnosis of cluster headache includes other TACs (e.g., paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks), trigeminal neuralgia, and headache pain secondary to another cause (e.g., trauma, malignancy, aneurysm).8Headache Treatment Protocol Research Paper Other common headache disorders, such as migraine headache and tension headache, do not typically match the presentation seen in cluster headache. Tension headaches present with less headache pain compared with cluster headache and are devoid of autonomic symptoms. Additionally, tension headaches present with bilateral pain, compared with unilateral pain seen in both migraine and cluster headaches. Migraine headaches are primarily associated with nausea, vomiting, photophobia, and phonophobia, which occur infrequently with cluster headaches. Withdrawal to a noiseless and dark setting is often required to alleviate symptoms in migraine patients, whereas cluster headache patients typically move and pace to relieve restlessness. Migraine headaches may also present with aura, which are rare in cluster headache. The short duration of attacks and male predominance are also key differences between cluster headaches and migraine headaches, as patients with migraine headaches have a female predominance and the headache often lasts longer and is exacerbated by physical activity. Although infrequent with migraine headaches, autonomic symptoms may be present and are not absolute differentiating features of these headaches.1,8 Pathophysiology The pathophysiology of cluster headache is complex and is not fully understood. Neuroimaging has identified the posterior hypothalamus and the trigeminovascular system as key areas for modulation of the pain and autonomic symptoms present in cluster headache. During acute cluster attacks, positron emission tomography scans have shown activation of the ipsilateral hypothalamic gray area, demonstrating a possible role for the hypothalamus to modulate cluster attacks.9,10 The cyclic nature of cluster attack periods and the correlation with symptom reemergence with change in daylight hours imply that the posterior hypothalamus is involved, as it is responsible for controlling circadian rhythms. Additionally, neuroendocrine activity associated with circadian changes, including concentrations of melatonin, cortisol, testosterone, and prolactin, has altered secreting patterns in patients with cluster headache, further inducing hypothalamic activity.Headache Treatment Protocol Research Paper The posterior hypothalamus is interconnected with the trigeminovascular system, the major set of neurons in the trigeminal nerve that innervate the cerebral blood vessels. Although the mechanism is not fully elucidated and conflicting theories exist for the generation of pain symptoms associated with cluster headache, it is proposed that a disruption between these systems leads to activation of the trigeminal-autonomic reflex, resulting in both the pain and the autonomic symptoms seen in cluster headache.10,11 Although a direct trigger for the pain in cluster headache has not been identified, the activation of the trigeminovascular system leads to the release of pronociceptive neuropeptides, including calcitonin gene-related peptide, neurokinin A, and substance P.11 Afferent pain pathways from the trigeminovascular system project to the trigeminocervical complex and then to the thalamus, relaying pain signals to cortical areas, which results in pain in an individual with cluster headache. Autonomic symptoms in cluster headache are produced through reflex activation of parasympathetic pathways from afferent trigeminovascular nociceptive input.10,11 These pathways may also be innervated and controlled by the posterior hypothalamus. When activated, the parasympathetic pathways innervate the cerebral blood vessels and meninges. This innervation causes further irritation and also results in autonomic symptoms (i.e., lacrimation, rhinorrhea).10,11 Genetic risk factors may also play a role in the pathophysiology of cluster headache. The G1246A polymorphism of the hypocretin 2 receptor, or orexin receptor type 2, is associated with a higher incidence of cluster headache. Hypocretin (or orexin) is a neuropeptide located in the lateral and posterior hypothalamus that is involved in the sleep-wake cycle and energy homeostasis. The degree of involvement of hypocretin neuropeptides in cluster headache is not known, and further research is needed to understand their interplay in cluster headache.5,6,12Headache Treatment Protocol Research Paper Pharmacologic Therapy Pharmacologic treatment of cluster headaches is divided into three categories: abortive therapy, prophylactic therapy, and bridge therapy. The goal of abortive therapy is to quickly terminate individual attacks. Abortive therapy should be used as soon a cluster headache begins in order to quickly terminate the attack. Abortive therapy should be provided to all patients with cluster headache, provided there are no contraindications to treatment.13 Prophylactic therapy is given daily and is indicated at the start of a cluster period to shorten the frequency and severity of episodic cluster attacks. Prophylactic therapy is generally indicated for patients with frequent, severe attacks and in those whose attack periods last a month or longer. Additionally, patients are candidates for prophylactic therapy if they might overuse abortive treatments, especially triptans and ergot derivatives. Patients treated with prophylactic therapy for episodic cluster headache should receive continuous treatment for at least 2 weeks after being symptomfree. Prophylactic therapy should then be slowly tapered and may be reintroduced at the beginning of the next cluster period. Patients with chronic cluster headache will require indefinite treatment with prophylactic therapy.13 Prophylactic therapies often require low starting doses to prevent adverse effects, and they necessitate ascending titration to achieve an effective dose. Prophylactic therapy has a delayed onset of action, which is often not seen for 2 to 3 weeks. Owing to the delay in onset of prophylactic medications, bridge therapy is often used in addition to other treatments to help decrease pain burden until prophylactic medications reach full effect.3 Bridge therapy is used only as transitional treatment, and its duration spans the course of a few weeks.14 ORDER HERE NOW Making headway into migraine: assessment of subcutaneous lignocaine and ketamine use in the management of chronic (transformed) migraine and development of a biomarker of headache.Headache Treatment Protocol Research Paper Migraine is the most prevalent disabling neurological disorder and has a major impact on health resources. Prevalence of migraine is more common than asthma and diabetes combined, affecting 16% of the population (18% of women and 6% of men) . In the Global Burden of Disease Survey of 2010, migraine ranked as the 3rd most prevalent disorder and 7th highest specific cause of disability worldwide. Migraine carries a significant economic burden of disease, incorporating loss of productivity and work absenteeism, long term need for medications and recurrent visits to health professionals. There are several different theories as to what causes migraine. To name a few, spasm of blood vessels is often implicated; or activity of different neurotransmitters, or abnormal electrical activity of pain nerves. Reflecting this, medications used for treatment of migraine differ in their mechanisms of action: there is no ‘one drug suits all’. While there have been major advances in understanding physiology of migraine in recent decades, there is no consensus on the assessment of the condition and no clinical tool to serve as a bio marker of disease or treatment response. The burden of disease is amplified in patients with transformed or chronic migraine, which represents 7.7% of the total migraine population. Patients who experience sub optimal headache control may overuse short acting analgesics (especially codeine and tryptophan), and are at risk of an additional component of analgesic rebound headache which may perpetuate migraine. This study focuses on patients with chronic migraine. It seeks to obtain pilot data for use of subcutaneous lignocaine and ketamine infusion in treatment of transformed (chronic) migraine in use at St Vincent’s Private Hospital and to evaluate nerve excitability studies as an in vivo bio marker of migraine psychophysiology and treatment response.Headache Treatment Protocol Research Paper In work leading up to this project, Dr Susan Tomlinson has (with the support of Brain Foundation Research Gifts) established proof-of-principle that nerve excitability studies can be used to detect changes in peripheral nerve excitability in patients with neurological conditions affecting the central and peripheral nervous system or both (see Chief Investogtors publications 1,3, 7,9, 10). Studies to date have largely involved patients with single-gene ion channel disorders including epilepsy and ataxia. This has laid the ground work to apply the principles to more common conditions in which the cause is not known; specifically, neuropathic pain and idiopathic epilepsy; and studies are due to complete in 2017. As a result of current projects, it has emerged that application of nerve excitability studies to migraine is highly relavent, as the genetic models of migraine pertain to single-gene ion channel disorders and many medications used to treat migraine modulate ion channel function. Futhermore, A/Prof Raymond Garrick has developed a protocol to treat patients with chronic migraine which appears to be highly effective and anecdotally is transformative in the lives of this cohort of patients. The collaboration of the coinvestigators would enable us to obtain objective evidence for a new treatment to a very challenging problem. We hypothesise that patients with transformed migraine/chronic daily headache have complex physiology. The chronicity of the headache is perpetuated by sensitized, neutrally driven pathways. Inpatient management with a prolonged (approx. 10 day) subcutaneous infusion of lignocaine and ketamine may provide adequate analgesia and stabilization of these entrenched pathways to break the cycle of pain, enable withdrawal of medications that perpetuate headache (e.g. codeine and triptans) and allow introduction of preventative agents.Headache Treatment Protocol Research Paper