Headache treatment:

Dr behnaz ansari

• Which kind of headache do you diagnosis?• How often was headache happened

in one month?• Which kind of drugs do you use for

treatment?• How many times do you continue

this treatment?

• Headache treatment depends upon the frequency, severity, and symptoms of your headache.

• Acute treatment refers to medicines you can take when you have a headache to relieve the pain immediately.

• Preventive treatment refers to medicines you can take on a regular (usually daily) basis to prevent headaches in the future.

Tension headache:

Tension-type headache in adults:

• Tension-type headache (TTH) is the most common headache in the population. Yearly prevalence rates for episodic TTH are approximately 80 percent in men and women. Due to its high prevalence in the population, TTH causes a high degree of disability. Despite its frequency, few placebo-controlled preventive therapeutic trials have been conducted in TTH. More research in the nonpharmacologic and pharmacologic treatment of TTH is urgently needed.

Acute treatment:

• A pain reliever may be recommended first for the treatment of tension type headache. These drugs include:

• Aspirin• Acetaminophen (eg, Tylenol®)• Nonsteroidal antiinflammatory drugs (NSAIDs) such as ibuprofen (eg, Motrin or

Advil), indomethacin, or naproxen (eg, Naprosyn or Aleve).• Pain relievers should not be used too often because overuse can lead to medication-

overuse headaches or chronic daily headaches. If you respond to a pain reliever, you should continue taking these with each headache. However:

• Do not use pain relievers more than nine days per month on average, or more than two doses per episode.

• If a pain reliever does not control your headache, talk to your healthcare provider for other suggestions.

• People with gastritis (inflammation of the stomach), ulcers, kidney disease, and bleeding conditions should not take products containing aspirin or NSAIDs.

• Pain medicine combinations — Mild pain relievers are also available in combination with caffeine, which enhances the drug's effect. As an example, Excedrin® contains a combination of acetaminophen-aspirin-caffeine. This combination may be recommended if a pain reliever alone does not relieve the headache. However, this combination is not recommended more than nine days per month due to the potential risk of developing medication-overuse headaches.

Preventive treatment:

Prophylactic headache treatment is indicated if the headaches are frequent, long lasting, or account for a significant amount of total disability . With respect to TTH, both the frequent episodic subtype (1 to 14 headache days a month) and chronic subtype (≥15 headache days a month) warrant prevention as they may be associated with significant disability, especially when

accompanied by migraine, comorbid depression, or anxiety. Therefore, preventive treatment is appropriate for most patients with chronic TTH, and is probably appropriate for many patients with frequent episodic TTH. In contrast, patients with infrequent episodic TTH (headache <1 day per month) do not require preventive treatment.

• To achieve benefit, prophylactic headache therapy requires a sustained commitment on the part of the patient and clinician .

• It is important to address patient expectations and consider patient preferences when deciding between different preventive therapies. In addition, the patient should be informed of the rationale for a particular treatment, the expected benefits of therapy, the duration of treatment that will likely be needed to achieve improvement, and the possible and likely side effects.

• PHARMACOLOGIC THERAPIES — A variety of pharmacologic therapies have been studied for the prophylactic treatment of TTH, as discussed in the sections that follow. Evidence of efficacy is limited and inconsistent , but perhaps is strongest for the tricyclic antidepressants such as amitriptyline. Other medications that may be useful include the antidepressants mirtazapine and venlafaxine, the anticonvulsants topiramate and gabapentin, and the muscle relaxant tizanidine. In contrast, the available evidence suggests that the selective serotonin uptake inhibitors are not effective for TTH prophylaxis.

• Tricyclic antidepressants are reuptake inhibitors of serotonin and noradrenaline.Amitriptyline also reduces pericranial muscle tenderness, leading to peripheral antinociception and inhibition of central sensitization .

• Patients should be informed that amitriptyline is an antidepressant agent but has an independent action on pain . The beneficial effect for TTH is not related to the presence of depression.

• We suggest the use of amitriptyline for patients with frequent episodic TTH or chronic TTH. Exceptions include patients with obesity, bipolar disease, or cardiac conduction defects. This recommendation is best suited for patients who have a preference for pharmacologic treatment rather than behavioral or other nonpharmacologic therapies. Our recommendation is in agreement with 2010 guidelines from the European Federation of Neurological Societies for the treatment of TTH, which conclude that amitriptyline has a clinically relevant prophylactic effect in patients with chronic TTH and should be the drug of first choice.

●Start the drug at the lowest dose, and increase the dose gradually until therapeutic benefit is achieved, the maximum dose of the drug is reached, or side effects become intolerable.

●Give the prophylactic medication an adequate trial in terms of duration and dosage. Benefit is often first noted only after four to six weeks of therapy . In addition, benefit may continue to accrue for three months.

●Avoid overuse of analgesic medications. Ongoing analgesic overuse must be eliminated, or preventive therapy will likely be ineffective.

●Once effective, maintain drug therapy for at least three to six months. Thereafter, a slow taper off the medication can be performed

• With these principles in mind, we start amitriptyline at 10 to 12.5 mg nightly and increase the dose in 10 to 12.5 mg steps every two to three weeks as tolerated and as needed for sleep, until there is improvement in headache or until a maximum dose of 100 to 125 mg nightly is reached.

• Tricyclic medications are associated with an increased risk of cardiac conduction abnormalities and arrhythmias. Before initiating treatment with any of the cyclic antidepressants, patients should be screened for cardiac conduction system disease, which precludes the use of these medications.

• We and others suggest that patients age 40 years and older have a baseline ECG for this purpose. Patients younger than age 40 can be screened by history for evidence of cardiac disease. They do not require an ECG if the history is negative. Patients who have a normal ECG before starting a tricyclic antidepressant do not need additional ECG monitoring while on the antidepressant, unless symptoms arise suggestive of cardiac toxicity.

• Other antidepressants — Limited data from small randomized controlled trials suggest that mirtazapine (a noradrenergic and specific serotonergic antidepressant) and venlafaxine (a serotonin-norepinephrine reuptake inhibitor) may be effective for the treatment of chronic TTH in patients without depression.

• Anticonvulsants — Limited evidence suggests that topiramate and gabapentin may be beneficial for patients with chronic TTH.

• Tizanidine — There is limited and conflicting data regarding the effectiveness of tizanidine, a muscle relaxant and antispasticity agent, for the prophylaxis of TTH

Trigger point injections — Trigger point injections require more research, but limited data from small randomized controlled trials suggest that lidocaine injections may reduce headache frequency and, thereby, total acute medication

use for patients with frequent episodic or chronic TTH. Botulinum toxin injections — In a 2012 meta-analysis, eight placebo-controlled trials evaluated botulinumtoxinA (botulinum toxin type A) for patients with chronic TTH . Botulinum toxin injections led to a small reduction in the number of headaches per month, but the result was not statistically significant.

Trigger point injection:

• BEHAVIORAL THERAPIES —European guidelines for the treatment of TTH published in 2010 state that non-drug management should be considered for all patients with TTH even though the scientific evidence is sparse and contradictory.

 

●Regulation of sleep, exercise and meals●Cognitive-behavioral therapy

●Relaxation●BiofeedbackAcupuncture — The available evidence regarding acupuncture for TTH suggests that any benefit is likely to be modest.

Migraine headache:

Migraine treatment:

• Abortive Therapy• Numerous abortive medications are used for

migraine. The choice for an individual patient depends on the severity of the attacks, associated symptoms such as nausea and vomiting, comorbid problems, and the patient's treatment response.

Moderate Severe Extremely Severe

NSAIDs Naratriptan DHE (IV)

Isometheptene Rizatriptan Opioids

Ergotamine Sumatriptan (SC,NS) Dopamine antagonists

Naratriptan Zolmitriptan

Rizatriptan Almotriptan

Sumatriptan Frovatriptan

Zolmitriptan Eletriptan

Almotriptan DHE (NS/IM)

Frovatriptan Ergotamine

Eletriptan Dopamine antagonists

Dopamine antagonists

• The 2 categories of migraine-specific oral medications are triptans and ergot alkaloids. The specific ergot alkaloids include ergotamine and dihydroergotamine (DHE).The specific triptans include the following] :

• Sumatriptan• Rizatriptan• Zolmitriptan• Naratriptan• Almotriptan• Eletriptan• Frovatriptan• All the triptans are most effective when taken early during a migraine and all may be

repeated in 2 hours as needed, with a maximum of 2 doses daily. • Triptans should not be used more than 3 days weekly, to avoid transformed migraine and

medication overuse headache.

• However, triptans should not be taken by patients with known or suspected coronary artery disease, as they may increase risk of myocardial ischemia, infarction, or other cardiac or cerebrovascular events. Do not administer vasoconstrictors, such as ergots or triptans, to patients with known complicated migraine; treat their acute attacks with one of the other available agents, such as NSAIDs or prochlorperazine.

• The dose of rizatriptan must be reduced to 5 mg in patients taking propranolol. Sumatriptan, zolmitriptan, and rizatriptan are primarily metabolized by monoamine oxidase (MAO) and should be avoided in patients taking MAO-A inhibitors.

• The first combination product of a triptan and an NSAID, Treximet, was approved by the FDA in 2008. Treximet contains sumatriptan and naproxen sodium.

ANTIEMETICS

• Intravenous (IV) metoclopramide and IV or intramuscular (IM) chlorpromazine, prochlorperazine, and droperidol can be used as monotherapy for acute migraine headache. These medications act as antiemetics mainly because they are dopamine receptor antagonists. In addition, they are effective for reducing migraine headache pain.

• Of note, most of these drugs (ie, chlorpromazine, prochlorperazine, droperidol, and diphenhydramine) are associated with a risk of QT interval prolongation and torsades de pointes.

• For initial treatment of patients who present to the hospital emergency department with moderate to severe migraine, particularly if the migraine is accompanied by vomiting or significant nausea, we suggest initial treatment with either subcutaneous sumatriptan 6 mg or a parenteral antiemetic agent rather than other migraine-specific drugs (Grade 2C); reasonable antiemetic choices are intravenous (IV) metoclopramide (10 mg) or prochlorperazine (10 mg).

• IV dihydroergotamine (DHE 45) 1 mg combined with IV metoclopramide 10 mg is also a reasonable alternative for treatment of intractable severe migraine in the emergency department, and it can be used if metoclopramide monotherapy is ineffective

Comorbid Condition Medication

Hypertension Beta blockers

Angina Beta blockers

Stress Beta blockers

Depression Tricyclic antidepressants, SSRIs

Overweight Topiramate, protriptyline

Underweight Tricyclic antidepressants (nortriptyline, protriptyline)

Epilepsy Valproic acid, topiramate

Mania Valproic acid

• we recommend adjunctive treatment with a single dose of parenteral dexamethasone (10 to 25 mg) to reduce the risk of early headache recurrence for patients who are treated with standard abortive therapy for migraine headache in the emergency department or clinic. However, frequent use of adjunctive dexamethasone for headache increases the risk of glucocorticoid toxicity and should be avoided.

• Opioids and barbiturates should not be used for the treatment of migraine

Complementary and Alternative Treatments:

• A guideline from the American Academy of Neurology and the American Headache Society (AAN/AHS) recommends offering butterbur to patients with migraine to reduce the frequency and severity of migraine attacks (level A recommendation).Patients on butterbur require monitoring of liver enzymes.

• The AAN/AHS found moderate evidence of effectiveness for riboflavin (vitamin B2), magnesium, and feverfew. A 3-month, randomized, controlled trial of high-dose riboflavin (400 mg) found that riboflavin was superior to placebo in reducing attack frequency and headache days.

• A randomized, controlled trial of coenzyme Q10 (CoQ10) documented that CoQ10 is effective and well tolerated for migraine prophylaxis.Results of a trial in children and adolescents suggested that prophylaxis with CoQ10 may lead to earlier improvement in headache severity than does placebo-based prophylaxis, but the trial found no long-term difference in headache outcomes between the CoQ10 and placebo groups.[117]

• Melatonin has also been used for migraine prevention.

• Body work - Eg, chiropractic, massage, and craniosacral therapy

• Nutritional/herbal supplements - Eg, vitamins and herbs

• Yoga• Acupressure and acupuncture

• Biofeedback

Status Migrainosus Treatment :

• an intractable migraine attack (status migrainosus), that is, an attack lasting longer than 72 hours, should be addressed in an urgent care or emergency department. In rare cases, patients may need to be hospitalized for a short period and may need to be treated with intravenous valproate or dihydroergotamine(intravenously/subcutaneously/intramuscularly) for a few days.

Treatment of Menstrual Migraine:

• Abortive therapy for menstrual migraine is the same as for nonmenstrual migraine. Patients with frequent and severe attacks may benefit from short-term, perimenstrual use of preventive agents (eg, frovatriptan).

• Patients with menstrual and nonmenstrual migraine who are receiving continuous preventive therapy and experiencing breakthrough menstrual migraine headaches may benefit from perimenstrual elevation of the dose of the preventive medication.

• Patients who do not respond to standard preventive measures may benefit from hormonal therapy. Perimenstrual estrogen supplementation with estradiol (0.5 mg orally twice a day, or a 1-mg transdermal patch) may be beneficial.

Cluster headache:

Cluster headache::

ACUTE TREATMENT — Subcutaneous sumatriptan and oxygen inhalation are first-line treatments for acute cluster headache attack . Other agents with some evidence of effectiveness include ergots, lidocaine, and octreotide.

Oxygen — Although controlled trial evidence is limited , oxygen therapy is considered to be safe and effective for aborting cluster headache.

Octreotide appears to be effective and well tolerated in the treatment of acute cluster headaches.

PREVENTIVE TREATMENT :

— Preventive therapy should be started as soon as possible at the onset of a cluster episode. Verapamil is the drug of choice for prophylaxis of episodic and chronic cluster headache Other agents that may be effective include glucocorticoids(, We suggest using prednisone 60 to 100 mg once a day for at least five days, and then tapering by decreasing the dose 10 mg every day. Intravenous and oral administration of glucocorticoids can be successfully combined), lithium(The initial dose of lithium should be 20 mg/kg, usually 300 mg two or three times daily, with dose increases every four to five days based upon lithium levels; the typical maintenance dose is 900 to 1200 mg/day given in three to four divided doses of the regular formulation, or in two divided doses of the sustained release formulation. The lithium plasma level should be monitored and kept between 0.6 and 1.2 mmol/L ), topiramate, and methysergide.

Pizotifen – The antiserotonergic drug pizotifen (3 mg daily) was effective in cluster headache prophylaxis in a

single-blind, placebo-controlled trial. ●Valproic acid – Evidence regarding the utility of valproic

acid in cluster headache prophylaxis is limited and conflicting. Valproic acid can be used in a dose between 5 and 20 mg/kg daily.

●Capsaicin – Repeated ipsilateral intranasal application of capsaicin was reported to be effective in approximately two-thirds of patients with cluster .headache in two open-label studies

Ergotamine – Some experts advocate the combination drug caffeine (250 mg) and ergotamine (2 mg) given as a rectal suppository to prevent cluster headache attacks during the night

●Melatonin – Oral melatonin (10 mg) was more effective than placebo in double-blind, randomized controlled study involving 20 patients, but the response rate was relatively low (5 of 10 patients)

●Indomethacin – Although short-term indomethacin treatment is considered ineffective for cluster headache, there are reports of occasional patients meeting diagnostic criteria for cluster headache who have responded to indomethacin

when used for several weeks at higher doses (≥225 mg daily). ●Triptans – A multicenter placebo-controlled trial of 169 patients found that oral

sumatriptan was not effective in preventing cluster headache attacks . However, limited data from small uncontrolled studies and case reports suggest that treatment with two longer-acting triptans – oral naratriptan and frovatriptan is beneficial for cluster headache prevention.

For patients with episodic cluster headache prophylactic medications should be tapered after the expected duration of the cluster has passed. The drugs can be restarted at the lowest effective dose if symptoms recur.

For patients with chronic cluster headache who have a good response to preventive pharmacotherapy, we suggest a dose reduction trial of preventive medications every other month.

Medication overuse headache: Treatment :

• Medication overuse headache (MOH) is a common problem in clinical practice that needs to be properly managed in order to increase the likelihood of successful chronic daily headache treatment.

• Withdrawal of the overused medication as soon as possible is the treatment of choice for medication overuse headache (MOH) . It is also important to educate patients about the detrimental effects of analgesic overuse.

• Bridge (transitional) therapy may be useful during drug withdrawal to provide symptomatic relief. For most patients, a preventive (prophylactic) medication aimed at the suspected background primary headache disorder (eg, migraine) should be initiated either during or immediately following withdrawal

PATIENT EDUCATION:

• Clinicians must educate patients about the detrimental effects of analgesic overuse . Patients need to understand that analgesics have the potential to cause MOH, and that analgesic overuse can negate the effectiveness of headache preventive measures

WITHDRAWAL OF THE OVERUSED MEDICATION :

—Withdrawal of overused acute medications can be accomplished on an outpatient or inpatient basis . Most patients can be managed as outpatients. Outpatient withdrawal is particularly appropriate for patients who are highly motivated and do not take barbiturates or

tranquilizers. Significant complications may occur as a consequence of drug dependency when withdrawing from opioids, benzodiazepines and barbiturates, and the choice between outpatient and inpatient withdrawal of these agents remains an area of debate . Some experts favor inpatient withdrawal with close observation and medical monitoring in the first several days . However, it is often reasonable to try outpatient treatment first unless serious withdrawal problems develop or are considered likely.

With overuse of barbiturates, opioids, or benzodiazepines, the pace of withdrawal depends on the amount and frequency of usage. Abrupt outpatient withdrawal is routinely done in clinical practice if intake of the offending agent is not very high. However, we suggest a gradual taper when these agents (particularly barbiturates

or benzodiazepines) are being used frequently or at high doses .The taper can usually be accomplished in two to four weeks.

For patients withdrawing from butalbital, we recommend phenobarbital taper for seizure prophylaxis, particularly when butalbital is stopped abruptly or when high doses are being used. Our suggested regimen is phenobarbital 30 mg twice daily for two weeks, followed by 15 mg twice daily for two weeks.

When there is concern for opioid withdrawal symptoms, treatment with a once-weekly transdermal clonidine patch (0.1 to 0.2 mg/24 ; alternatively, clonidine can be given as needed for withdrawal symptoms (0.1 to 0.2 mg three times daily, titrated up or down based on symptoms).hours) for one to two weeks may help.

Withdrawal symptoms — During the period of analgesic withdrawal, the headaches are likely to exacerbate before subsequently improving . In addition to increased headache, withdrawal symptoms can include nausea, vomiting, restlessness, anxiety, nervousness, and disturbed sleep . Withdrawal symptoms typically last 2 to 10 days , but

occasionally can persist for as long as two to four weeks .The duration and severity of withdrawal headache depends on the type of overused analgesic. In one prospective study of 95 patients, the mean duration of withdrawal headache was 4.1 days for triptans, 6.7 days for ergots, and 9.5 days for analgesics (most of which were combined with codeine, caffeine, or barbiturates) . Overall, withdrawal from triptan-induced MOH was less severe than withdrawal from other analgesics.

Bridge therapy :

• Bridge therapy, also known as transitional therapy, is used to provide symptomatic relief for patients with MOH during withdrawal of the offending medication. Bridge therapy strategies that appear to have some merit include the short-term use of certain oral (naproxen, tizanidine, glucocorticoids) and intravenous (dihydroergotamine, prochlorperazine, lidocaine, valproic acid, aspirin) medications.

we suggest use of bridge therapy during outpatient withdrawal of the offending medication using either long-acting NSAIDs(naproxen 550 mg twice daily for two to four weeks while the overused acute medication is withdrawn . An alternative is naproxen 550 mg twice daily for one week, and then naproxen once daily for one week), prednisone, or subcutaneous DHE. Antiemetics are also frequently needed in clinical practice.

For inpatient withdrawal, we suggest intravenous bridge therapy using dihydroergotamine plus metoclopramide, prochlorperazine, valproate sodium, or methylprednisolone

Case Presentation: Part I

• A 25-year-old female with no significant past medical history is referred to the neurology clinic by her primary care office for headaches.

• The patient notes that approximately 6-months ago she started to develop throbbing bifrontal headaches that were associated with nausea and photophobia. When she has these headaches, she must sit in a dark room and try to sleep. After she wakes up, she usually feels better, but on some occasions the headaches persist. For these headaches, she used over-the-counter ibuprofen, which initially helped. At the start, the headaches occurred only once every few weeks and responded to ibuprofen. However, the headaches have progressed to the point where she has them every day. She has been taking the ibuprofen every day and multiple times a day with no relief. More recently, she has had to miss work for these headaches.

• There is no associated visual blurring, premonitory aura, diplopia, slurred speech, numbness, or weakness. The headaches do not awaken her from sleep. She does not drink caffeine. She denies any chance that she could be pregnant.

• Her past medical history includes an appendectomy in childhood. Otherwise, she denies any chronic illness. There is no history of kidney stones or asthma.

• Her only medication is the daily ibuprofen, which she takes multiple times a day. She is not on any oral contraceptives.

• She has no known drug allergies. • She does not smoke, drink alcohol, or use illicit substances. She

is an elementary school teacher. • She has a strong family history of migraine headaches on her

maternal side. There is no history of any other neurologic diseases.

• On physical examination, she is a well-developed and well-nourished female in mild distress. She appears bothered by the light in the examination room. She is afebrile. Her blood pressure is 110/70, pulse is 75, and respiratory rate is 12.

• She has no tenderness to palpation over her shoulders, neck, or occiput. No bruits are heard over her neck. There are no murmurs or abnormal heart sounds.

• Neurological examination and her imaging were normal.

Treatment??• You discuss with the patient that her original headaches were consistent with

migraine headaches. However, more recently you suspect her headaches have evolved into daily medication-overuse headaches from excessive abortive analgesia use. You counsel her that her normal neurologic examination and unremarkable imaging are reassuring that there is not a more sinister underlying etiology to these complaints.

• As she is having headaches daily, you feel she would benefit from a preventive migraine medication. After reviewing the AAN guideline “Update: Pharmacologic Treatment of Episodic Migraine Prevention in Adults,”1 you select propranolol, as it has a Level A recommendation. You start the patient on propranolol 80 mg extended release once daily and discuss potential side effects, including dizziness. You have asked her to limit her ibuprofen use. You also discuss nonpharmacologic strategies for migraine prevention, such as good sleep, exercise, and regular meals. Finally, you ask the patient to keep a headache diary to assess therapeutic response and identify common triggers.

Case Presentation: Part II

• The patient returns to the neurology clinic in 3 months. She feels the propranolol helped her headaches, as her headache frequency decreased to twice a week. Furthermore, these migraine headaches responded well to ibuprofen. Unfortunately, she has had problems with dizziness since starting the propranolol. The dizziness has not passed despite the fact she has been on the medication for a few months. She denies any new neurologic symptoms. She has not had to miss any work in the last 3 months. After keeping a diary, she suspects that pepperoni might trigger some of her headaches.

• You discuss with her that, although you are happy she has improved, it is important to strive for better control of her headaches. As she is having side effects from the propranolol, you do not feel this medication should be increased. You decide to taper her off the propranolol over the course of a week. She will then start topiramate, which also has a Level A recommendation in the AAN guideline. The topiramate will be started at 25 mg daily and titrated over 4 weeks to 50 mg twice a day. You discuss potential side effects, including kidney stones, cognitive changes, and paresthesias. She is encouraged to continue the ibuprofen, which aborts her headaches nicely. She will continue her headache diary.

Case Presentation: Part III

• The patient returns to the neurology clinic in another 3 months. She is doing very well and has had no headaches in over 1 month. In fact, she has not required any ibuprofen in over a month. She is tolerating the topiramate without difficulty .

• You discuss that you are happy that she has such good headache control on topiramate. She is encouraged to continue the medication as written and is given refills. You review the previously discussed nonpharmacologic strategies for migraine prevention. Finally, you advise the patient to make you aware if she is currently pregnant or is planning on becoming pregnant, as this medicine has a Category D pregnancy risk factor. She is scheduled for a routine follow-up in the future.