Headache Treatment

Headache Disorders

• Consider using a headache diary
  
  • To record the frequency, duration, and severity of headaches
  • To monitor the effectiveness of headache interventions
  • As a basis for discussion with the patient about his headache and its impact

• Consider further evaluation and/or referral to a specialist if a patient has manifestations of red flags

Migraine Headache

• Therapy should be guided according to frequency, duration and severity of attacks, associated symptoms, degree of disability, history of treatment and patient’s preference
• Coexisting medical conditions should also be considered in migraine therapy
  
  • Myocardial infarction, stroke, epilepsy, affective and anxiety disorders are common in patients with migraine

• Goals of therapy:
  • Rapid and consistent freedom from pain and associated symptoms
  • Restoration of function
  • Significantly reduced need for repeat dosing or rescue drugs
  • Optimal self-care and reduced need for healthcare needs (eg emergency consult, diagnostic tests)
  • Minimal to no adverse effects experienced
  • Affordable treatment options
• Effective therapy should be established and promptly used to decrease pain and disability
• Non-oral route of administration should be used in patients who suffer from migraines associated with severe nausea and vomiting
• Antiemetics should be used if nausea and vomiting are likely to occur
• Educate patients about avoiding medication overuse
• Prophylactic treatment should be considered in patients whose attacks significantly interfere with daily activities despite acute therapy, with frequent attacks, with contraindication/unresponsive to ≥10 days/month treatment with ergot derivatives, triptans, opioids, or combination drugs, or ≥15 days/month treatment with non-opioid analgesics, Acetaminophen, or non-steroidal anti-inflammatory drugs (NSAIDs), with adverse events from acute therapy, or upon patient’s request
• To avoid migraine headache caused by drug overuse, simple analgesics should be taken for a maximum duration of 15 days/month while combined analgesics should be taken up to 10 days/month
• See Migraine Headache Disease Management chart for more details

Tension-Type Headache

• Episodic tension-type headache is self-limiting, non-disabling, and rarely causes anxieties about its cause or prognosis
• Many patients do not require treatment since it is usually mild to moderate in severity
• Reassurance and intermittent symptomatic treatment are often quite sufficient
• Identification of trigger factors and non-pharmacologic therapy may be helpful
• Patients with chronic tension-type headaches are more likely to require pharmacotherapy
• Underlying contributory factors are of greater potential importance in tension-type headache than in migraine
  
  • Effective therapy depends on the identification of these factors especially when headaches are frequent

• It is important to distinguish between episodic and chronic tension-type headaches because one may arise from the potential overuse of symptomatic medication wherein the long-term harm outweighs the short-term benefit
  
  • Medication overuse must always be discovered and remedied because it can mask the diagnosis, cause of illness, and markedly decrease the efficacy of treatment for all forms of headache

• Long-term remission is the objective of management of very frequent episodic or chronic tension-type headache
  
  • Not always achievable particularly in long-standing chronic tension-type headache, thus, avoidance of aggravation by medication overuse is important and treatment of contributory factors

Cluster Headache

• Treatment of cluster headache is primarily pharmacologic and it is always necessary for effective control
• Cluster headaches are very intense and patients may benefit from general pain coping strategies
• Oral medications are usually not satisfactory for acute treatment because attacks are short but build up to a very severe intensity quickly
• Prophylactic therapy is the mainstay of treatment because acute symptomatic treatment alone is rarely sufficient to provide adequate control
  
  • Exceptions are cluster periods of short duration (<2-3 weeks), when this can be anticipated from past experience, and when prophylactic treatment has failed

• Prophylactic drugs should be started as early as possible after the start of a new cluster period, since there is some evidence of their greater efficacy during that time
• Transitional medication used at the same time can be also be useful for patients with very frequent attacks
• Treatment found effective in previous attacks should be rapidly reintroduced at the start of the next attack
• Acute treatment drugs may used in addition to prophylactic drugs until the latter becomes effective and/or if there are still breakthrough attacks
• Combination drugs may be needed but there is increased risk for toxicity
• For most drugs, dosage should be escalated as quickly as tolerability permits, and often to the maximum tolerated dose
• If there is no improvement within 1 week of achieving the maximum tolerated dose of the drug, it should be stopped and changed, or supplemented
• Alcohol may trigger headache attacks and should be avoided during active cluster headache attacks
• It is also advisable to stop smoking
• Avoid analgesic, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, ergotamine tartrate, and oral triptans in acute treatment for cluster headache
  
  • Analgesics are usually not helpful

• No present curative medical intervention known
• Goal of treatment is total attack cessation or suppression but only until the next episode
• Aims to shorten the cluster period in episodic cluster headache and to lessen the frequency and/or severity of attacks in both episodic and chronic cluster headache
• Patients experiencing their first attacks will be greatly concerned and need reassurance

Acute Treatment - Migraine Headache

• Please see Migraine Headache disease management chart for further information

Analgesic

• Paracetamol may be considered for patients with acute migraine headache with contraindications to other acute therapies
  • Drug of choice for short-term alleviation of mild to moderate headache during pregnancy

Antiemetics

• Eg Metoclopramide, Prochlorperazine
• May be considered for patients with acute migraine headache, especially those presenting with migraine-associated symptoms of nausea or vomiting

Calcitonin Gene-related Peptide Monoclonal Antibodies

• Eg Rimegepant, Ubrogepant
• Treatment option for patients with migraine headache with or without aura

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

• Eg Aspirin, Celecoxib, Ibuprofen
• Recommended first-line treatment for patients with acute migraine headache

Triptans

• Eg Lasmiditan, Sumatriptan, Zolmitriptan
• Sumatriptan is the treatment of choice for patients with acute migraine headache
• Other triptans should be considered in patients unresponsive to Sumatriptan therapy
• Nasal Zolmitriptan or subcutaneous Sumatriptan should be considered in patients with severe acute migraine or early vomiting

Combination Drugs

• Combination therapy using Sumatriptan and Naproxen should be considered

Acute Treatment - Tension-type Headache

• Symptomatic treatment is appropriate for episodic tension-type headache occurring on <2 days/week
• Not used for chronic tension-type headaches because as the frequency of headache increases, the risk of medication overuse increases
• Avoid muscle relaxants, triptans, opioids, and combination analgesic with codeine for acute treatment of tension-type headache
• Acute treatment ideally be given up to 9 days per month on average, typically a maximum of 2 doses per treatment day to avoid medication overuse headache

Analgesic

• Paracetamol offers a simple and immediate relief for tension-type headache
• Less effective but less gastrointestinal side effects compared to nonsteroidal anti-inflammatory drugs

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

• Eg Aspirin, Ibuprofen, Ketoprofen, Naproxen
• Usually sufficient treatment

Combination Drugs

• Combination analgesics containing caffeine are second-line treatment of choice for acute treatment of tension-type headaches
• Combining caffeine with Ibuprofen and Acetaminophen increases efficacy but also increases the risk for developing medication overuse headache

Acute Treatment - Cluster Headache

Oxygen (O₂)

• O₂ at 100% at 10-14 L/minute for 10-20 minutes is helpful in some patients
• Highly effective when delivered at the beginning of an attack and will obtain relief within 15 minutes
• When effective, its advantage is that O₂ is safe in multiple daily uses
• High flow rate requires a special regulator and non-rebreathing mask

Sumatriptan

• Subcutaneous Sumatriptan (6 mg) is the treatment of choice unless contraindicated
• It is the only proven highly effective acute treatment
• It aborts the attack in 5-10 minutes
• Contraindicated in uncontrolled hypertension or in the presence of risk factors for coronary heart disease or cerebrovascular disease

Zolmitriptan

• Zolmitriptan 5-10 mg nasal spray has delayed bioavailability compared with subcutaneous Sumatriptan
• Effective in placebo-controlled trial but achieved lower response rates than injectable Sumatriptan
• Also contraindicated in uncontrolled hypertension and if there are risk factors for cerebrovascular heart disease or coronary heart disease
• Contraindicated in patients with Wolff-Parkinson-White syndrome

Prophylactic Treatment - Migraine Headache

• Amitriptyline, Candesartan, Propranolol, Topiramate are recommended as a first-line prophylactic treatment for patients with episodic or chronic migraine
• Other prophylactic treatment used are antiepileptic drugs (eg Valproic acid), other beta-blockers (eg Atenolol, Metoprolol, Nadolol, Timolol), monoclonal antibodies against calcitonin gene-related peptide antagonists (eg Erenumab, Fremanezumab, Galcanezumab), calcium antagonists (eg Flunarizine), Botulinum toxin A
  • Valproic acid may be considered for patients >55 years old
• Please see Migraine Headache disease management chart for further information

Botulinum Toxin A

• Recommended prophylactic treatment for chronic migraine where medication overuse has been addressed and patients have not benefitted from ≥3 oral migraine prophylactic trial treatments

Calcitonin Gene-related Peptide Monoclonal Antibodies

• Eg Atogepant, Eptinezumab, Erenumab, Fremanezumab, Galcanezumab, Rimegepant
• Recommended prophylactic treatment for episodic or chronic migraine where medication overuse has been addressed and patients have not benefitted from ≥3 oral migraine prophylactic trial treatments
  • Erenumab is not recommended as a prophylactic treatment for episodic migraine

Triptans

• Eg Frovatriptan, Naratriptan, Zolmitriptan
• Frovatriptan should be considered as a prophylactic treatment in women with perimenstrual migraine 2 days prior up to 3 days after bleeding starts
• Zolmitriptan or Naratriptan are prophylactic options to Frovatriptan

Prophylactic Treatment - Tension-type Headache

Tricyclic Antidepressants

• Eg Amitriptyline, Nortriptyline, Protriptyline
• Amitriptyline is the drug of choice for frequently recurring episodic tension-type headache or chronic tension-type headache
• Nortriptyline and Protriptyline may be tolerated better but their usefulness is less certain
• Withdrawal may be attempted after improvement has been maintained for 4-6 months
• Failure of tricyclic treatment may be due to subtherapeutic dosage, insufficient duration of treatment or non-compliance

Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)

• Eg Mirtazapine, Venlafaxine
• Mirtazapine and Venlafaxine are the second drugs of choice for prophylactic treatment of tension-type headache

Selective Serotonin Reuptake Inhibitor (SSRI)

• No evidence that it decreases severity in chronic tension-type headache
• May be indicated for underlying depression

Drugs to Avoid in Tension-type Headache

• Codeine and Dihydrocodeine are not indicated and there is no place for stronger opioids
• Botulinum toxin is ineffective for tension-type headache

Prophylactic Treatment - Cluster Headache

Verapamil

• First-line of choice for both episodic and chronic cluster headache
• Usually well tolerated
• Side effects are constipation, flushing, and gingival hyperplasia
• Electrocardiogram (ECG) should be checked for atrioventricular block before the dosage reaches 480 mg/day and whenever it is increased beyond that
• Beta-blockers should not be given concomitantly

 Corticosteroids

• Prednisolone may be preferred if commenced in high dosage of 60-100 mg per day for 2-5 days
• Most often produce marked and almost immediate relief
• Only limited to a very short and intensive course because of the potential for serious side effects
• Dose reduction is started after 2-5 days and continued in 10 mg decrements every second or third day so that treatment is discontinued after 2-3 weeks
• Relapse may occur during dosage reduction
  • Second or third courses, administered with caution, can consolidate efficacy of the first following relapse
• May be used as an initial add-on therapy to other prophylactic drugs until the latter are effective
• Side effect is gastric upset

 Lithium Carbonate

• Should be considered in episodic or chronic cluster headache if Verapamil is not effective
• In the episodic form, with short duration treatment courses (<12 weeks), higher doses of 800-1600 mg/day may be necessary and serum concentrations may reach 1.0-1.4 mmol/L
• Tolerance may occur and efficacy may be lost after 2-3 cluster periods of Lithium therapy
• Lower daily dose of Lithium at 600-900 mg and serum concentrations of 0.3-0.8 mmol/L may be beneficial in patients with chronic cluster headache needing long-term therapy
• Serum concentrations must be frequently monitored to check adequacy of dosage in the absence of symptom remission and to prevent overdosage
• Occurrence of symptoms of early toxicity such as nausea, diarrhea, polyuria, or polydipsia without benefit from Lithium warrants discontinuation of therapy
• Serious long-term adverse effects are tremor, edema, electrolyte imbalance, muscle weakness, central nervous system disturbance, ECG abnormality, hypothyroidism, and hyperthyroidism
• Renal, cardiac, thyroid functions monitoring should be done
• Nonsteroidal anti-inflammatory drugs (NSAIDs) should not be taken concomitantly

 Methysergide

• An effective treatment option in patients with episodic cluster headache
• Tolerance may develop after 2-3 treatment periods
• Drug-free interval of at least 1 month should follow each 6-month course of Methysergide treatment to prevent side effects
• Short term side effects include nausea, abdominal discomfort, and leg cramps
• Long term side effects are retroperitoneal, endomyocardial, or pulmonary fibrosis
• Avoid concomitant use with Ergotamine because of increased risk of ergotism
• No evidence of risk when used with triptans

 Ergotamine tartrate

• Ergotamine tartrate given rectally is still useful in short-term therapy of episodic cluster headache when attacks occur predictably
  • Nocturnal attacks are prevented by taking it at bedtime
  • Daytime attacks may be prevented by a dose at least 1 hour before they are due
• Treatment should be omitted from time to time (eg every seventh day) to establish continued need
• Rarely suitable prophylactic drug in chronic cluster headache
• Patients with cluster headache are relatively resistant to the toxic effects of Ergotamine
• Contraindicated in patients with vascular disease, hypertension, and those with multiple risks for vascular disease
• Should not be used concomitantly with beta-blockers, Methysergide, and Sumatriptan

 Anticonvulsants

• Studies suggest that Topiramate ≥100 mg daily may be effective
• Other anti-epileptic drugs such as Sodium valproate, Gabapentin, and Carbamazepine are of little or no value

 Melatonin

• Single small randomized-control trial suggests potential benefit from Melatonin
• Offers a natural way to support restful sleep

 Combination Therapy

• Combination of drugs are recommended to prevent resistance to monotherapy
• Verapamil should be the basic drug to which Ergotamine or Methysergide is added
• Lithium can be combined with Verapamil but with caution because of increased risk of toxicity
• Verapamil, Lithium, and Ergotamine can be used in severe chronic cluster headache but with high potential for toxicity
• Therapeutic delay as Verapamil is up-titrated can be avoided by early short term concomitant use of Prednisolone
  • Used when rapid control is a high priority because of frequent severe attacks

Duration of Use

• Prophylaxis, except for Prednisolone, should be continued in episodic cluster headache until the patient has been headache-free for at least 14 days to minimize risk of relapse
• Withdrawal of drugs should be progressive dosage reduction and not abruptly discontinued
• Treatment must be resumed if relapse occurs but control is not quickly re-established
• Prophylaxis sometimes converts chronic cluster headache into the episodic subtype and can be withdrawn according to the same criterion of 14 days symptom-free
• Treatment may be continued indefinitely

Predisposing Factors Recognition Trigger Avoidance

• Patient should be educated about the many influences that can lead to a migraine attack
• Identify and differentiate between predisposing and precipitating or trigger factors
  
  • Some predisposing factors cannot always be avoided but can be treated
  • Factors triggering an acute attack in one patient may not trigger an attack in another patient

• Predisposing factors: Stress, depression, anxiety, menstruation, menopause, head or neck trauma
  
  • Lifestyle changes to decrease stress is beneficial to stress-related illnesses

• Trigger factors:
  
  • Environmental triggers: Weather changes, bright lights, loud noise, motion, high altitude, odors (eg fumes or perfumes)
  • Lifestyle triggers: Disturbance in sleep patterns, long distance travel, poor diet, skipping meals, smoking, stress, physical strain, fatigue
  • Hormonal triggers: Menopause, puberty, menstruation
  • Medication triggers: Glyceryl trinitrate, oral contraceptives, hormone therapy
  • Dietary triggers: Caffeine, chocolate, aspartame, alcohol, monosodium glutamate, tyramine-containing food and nitrate-containing food

• Most patients benefit from regular eating patterns and sleep schedules, regular aerobic exercise and stress reduction
• Patients also prefer to stay in a dark and quiet room during the attacks

Cognitive Behavioral Therapy, Biofeedback and Relaxation Training

• Relaxation therapy and cognitive training to develop stress-coping mechanisms are the mainstays of nonpharmacologic treatment of tension-type headache
• Electromyography biofeedback helps patient recognize muscle tension
• Also considered in patients with frequent tension-type headache and migraine headache
• Yoga and medication are used to enhance stress management in some patients

Physiotherapy

• May be appropriate and treatment of choice for musculoskeletal symptoms
• May include massage, mobilization, manipulation, and correction of posture
  
  • However, mobilization and manipulation sometimes worsen the symptoms before they improve
  • Cervical spine manipulation is not risk-free

• Regular home exercises are usually given
• Not effective in stress-related illnesses

Acupuncture

• Acupuncture may be tried in the absence of other options for tension-type headache
• No proven efficacy but detection of tender muscle nodules on palpation, with needling aimed at these nodules offer a good prospect of limited success
• Symptoms may at first be aggravated by acupuncture
• Consider a course of up to 10 sessions for 5-8 weeks for prophylactic therapy in patients with chronic tension-type headache

Noninvasive Neuromodulatory Devices

• Eg transcutaneous electrical nerve stimulation (TENS), remote electrical neuromodulation (REN), noninvasive vagus nerve stimulation (nVNS), single-pulse transcranial magnetic stimulation (sTMS), caloric vestibular stimulation, percutaneous mastoid electrical stimulator (PMES)
• May be offered in patients with tension-type headache or migraine headache
• Helps induce conditioned pain modulation and activates analgesia

Occipital Nerve Blockade

• Transitional therapy using occipital nerve blockade is often used in patients with cluster headache, but no evidence of good efficacy, when prophylaxis is started and until the dose is therapeutic

Deep Brain Stimulation

• Used only for refractory chronic cluster headache
• Effect is not related to direct hypothalamic stimulation
• Side effects are micturition syncope, subcutaneous infection, and transient loss of consciousness