Diagnosis and Treatment of Primary Headache Disorders in Older Adults

Thomas Berk, MD; Sait Ashina, MD; Vincent Martin, MD; Lawrence Newman, MD; Brinder Vij, MD

Disclosures

J Am Geriatr Soc. 2018;66(12):2408-2416. 

In This Article

Treatment of Primary Headache Disorders in Older Adults

The pharmacological treatment of primary headaches can be broadly placed into 2 categories: acute (also known as abortive) and preventive treatment. Acute treatment targets an individual episode of headache, and preventive treatment reduces the frequency of headache attacks. Education is critical in choosing the right acute treatment and setting therapeutic goals, including avoidance or overuse of acute medications. When choosing an acute medication, clinicians must consider the presence or absence of nausea or vomiting and other comorbid medical and psychiatric conditions, the adverse effect profile of the drug, and drug interactions that may occur. Preventive medications are considered when the headache disorder begins to significantly affect the person's social or professional life—a consensus among specialists is to start daily preventive therapies when a person is experiencing 1 headache per week (or 4–5 per month), although depends strongly on the preference of the individual with headache.

Acute Pharmacological Treatment

Migraine-Specific Medications. Migraine-specific medications include triptans and ergot derivatives. Triptans are serotonin agonists at 5HT 1B/1D receptors; they are considered first-line medications for acute migraine,[31] although evidence of efficacy is limited in older adults because most clinical trials have included individuals younger than 65.[32] Therapeutic benefit from triptan has been reported to increase with age,[33] but because triptans are vasoconstrictive and increase risk of cardiovascular and cerebrovascular ischemic events, they are contraindicated in individuals with documented history of stroke, coronary artery disease, and peripheral vascular disease. Expert consensus is in favor of using triptans in individuals without any documented risk of ischemic neurological or cardiac risk factors.[34] Sumatriptan 6 mg administered subcutaneously is effective for acute cluster headache attacks, as is intranasal zolmitriptan 5 mg. The role of triptans in TTH is controversial but can be useful in individuals with TTH that have some migrainous features.[35] Triptans should be avoided if there are no clear migrainous features.

Ergotamine and its derivatives are nonspecific serotonin agonists and target a wide range of serotonin (including 5HT1B/1D), dopamine, and noradrenergic receptors. This nonspecificity in their mechanism of action is what brings the association of numerous side effects such as nausea and a higher likelihood of vascular events. Although a systematic review found no significant cardiovascular safety concerns for triptan use in the absence of risk factors for such events, the frequent use of ergots has been associated with serious ischemic complications, so ergots are generally not recommended for use in elderly adults.[36] Because age is an independent cardiovascular risk factor,[37] risk stratification is critical in older adults when deciding on and discussing the use of migraine specific medications.

Simple Analgesics and Nonsteroidal Antiinflammatory Drugs. Acetaminophen is considered a safe, simple analgesic for use in older adults, and at times it is preferred over nonsteroidal antiinflammatory drugs (NSAIDs) because of a lower risk of adverse effects. Acetaminophen is available in combination with caffeine as an over-the-counter preparation for acute migraine treatment and has been shown to be more effective in the early treatment of migraine than sumatriptan.[38] These combination pills are generally well tolerated when used for brief periods for episodic migraine headache, but their long-term use can result in hepatic, renal, cardiovascular, and gastrointestinal complications in older adults, especially they contain moderate to high doses of aspirin.[39] The caffeine component of these combination analgesics is also likely to be associated with sleep disturbances[40] and anxiety.[41]

NSAIDs are generally effective for the treatment of moderate to severe migraine headache[42] and tension-type headaches,[43] and indomethacin is unique among the NSAIDs for its idiosyncratic treatment of paroxysmal hemicrania and hemicrania continua.[44] It should be used with caution, with a low starting dose of 25 mg 3 times per day and then titrated up as tolerated. Some individuals might need to titrate up to 200 to 300 mg/d in divided doses.[45] Celecoxib is an alternative to indomethacin to decrease gastrointestinal toxicity, but it is generally less effective.

Aspirin at a dose of 500 to 1,000 mg has been proven to be superior to placebo in the acute treatment of TTH,[46] as are a number of specific NSAIDs, including ibuprofen,[47] ketoprofen[48] and diclofenac,[49] but NSAIDs should be used with caution because of the high frequency of adverse effects in older adults, as well as potential interactions with other antiplatelet or anticoagulation medications, and if used for a prolonged period of time, renal function and blood pressure should be closely monitored.

Opioids and Barbiturates. Opiate and barbiturate derivatives are frequently used in the acute management of migraine despite lack of evidence of their safety and effectiveness,[50] most commonly in the use of combination pills that include acetaminophen or aspirin with caffeine and butalbital. Their use in older adults can lead to several adverse effects, including tolerance and dependence and liver and renal toxicity, and overuse of barbiturates and opiates is one of the leading causes of transformation of episodic to chronic migraine.[51,52] Because of these concerns, these medications should be used extremely rarely and cautiously and only as rescue therapy when other or conventional medications are absolutely contraindicated.

Caffeine. Caffeine alone and caffeine-containing combination medications are commonly used acute headache treatments. Caffeine is effective as a stand-alone analgesic for headache and when combined with acetaminophen or NSAIDs for the acute treatment of migraine.[53] Caffeine has also been used as an adjunctive analgesic for TTH.[54] Hypnic headache can be prevented and treated acutely with caffeine; it is recommended that it be used before sleep.[23] Intravenous caffeine has been used for postdural puncture and other low cerebrospinal fluid–pressure headaches,[55] although caffeine overuse and withdrawal are implicated in the worsening of headaches in frequency and intensity, and the excessive use of caffeine can cause palpitations and other arrhythmias.[56]

Antiemetics. Antidopaminergic medications such as metoclopramide, promethazine, prochlorperazine, and chlorpromazine have anti-emetic and analgesic properties and are particularly effective in the treatment of acute migraine. Older adults have a greater tendency to develop anticholinergic side effects and Parkinsonism from these medications.[57] Domperidone has been thought to be a better antiemetic choice in older adults because of lower likelihood of central nervous system side effects, possibly because it does not easily cross the blood–brain barrier.[58] The QTc interval should be carefully watched under the appropriate circumstances, such as history of known QT prolongation or with concomitant use of medications that also prolong the QTc interval such as macrolide antibiotics, antifungals, and some antidepressant and antipsychotic medications.

Corticosteroids

Corticosteroids have been used in acute management of migraine with mixed success. Intravenous dexamethasone has been found to prevent recurrence of migraine when used in emergency department settings in conjunction with other intravenous medications.[59] Corticosteroids have been suggested in management of status migrainosus, although they are not universally helpful.[59,60] Corticosteroids are particularly effective in the early treatment of cluster headache and other TACs but should be used in elderly adults with caution and with close monitoring, especially in light of other comorbidities.

Oxygen

There is level A evidence for oxygen in the acute treatment of cluster headache, and it is a safe choice particularly for older adults. The exact mechanism of action of oxygen is unknown but appears to affect the parasympathetic nervous system, which becomes activated in acute cluster headache.[61] Oxygen is more effective than placebo for pain-free response and is administered through a nonrebreather mask at a rate of 10 to 12 L per minute for approximately 15 minutes with the individual sitting upright.[62] Nevertheless, oxygen therapy can be harmful in older adults with advanced chronic obstructive pulmonary disease.[63]

Preventive Treatment

Prophylactic or preventive medications can be considered in the following situations:

  1. Recurrent severe attacks of migraine occurring more than 4 to 5 times a month

  2. Acute disabling headaches despite abortive therapy.

  3. Increasing frequency of migraine attacks

  4. Contraindications to acute medications

  5. Medication overuse headache

  6. Uncommon migraine symptoms such prolonged aura (particularly pertinent to older adults)

  7. Any migraine intensity or frequency that the person feels is compromising his or her quality of life

Mechanisms of preventive medications in primary headaches include a decrease in neuronal excitability, prevention of central and peripheral sensitization, inhibition of cortical spreading depression, and pain modulation.[64] A reduction of at least 50% in headache frequency and intensity over a 3 month period is considered an effective response to migraine prophylaxis.[65] In 2012, the American Headache Society and American Academy of Neurology published guidelines for pharmacological prevention of migraine.[66] Based on level of evidence, these preventive medications have been classified as effective, probably effective, and possibly effective.[59]

A number of commonly used medications with recommended dosages and with their level of evidence for migraine prophylaxis are shown in Table 5. Practitioners should always individualize these recommended doses, especially when treating older adults; it is always a good idea to start low, go slow, and aim for the lowest effective dose.

Antiepileptics. Topiramate,[67] valproate[68,69] and gabapentin[70,71] have been studied and are recommended for migraine prevention. Although it is frequently used, the level of evidence for gabapentin use as prophylaxis for migraine prevention was recently reclassified to level U.[66] Lamotrigine has some open-label evidence of use in prolonged aura or prevention of atypical aura and is effective as a preventive for SUNCT/SUNA.[72]

Antihypertensives. Beta-adrenoreceptor blockers are frequently used for migraine prophylaxis. There is level A evidence for propranolol, metoprolol, and timolol for the prevention of episodic migraine; the Canadian Headache Society recommends atenolol and nadolol as well.[66,72] The exact mechanism of action of these medications is not clear, but beta-blockers are thought to modulate the central monoaminergic system as well as 5HT receptors.[73] The most common side effects of beta-blockers are bradycardia, hypotension, lethargy, and diminished exercise tolerance.[74] Beta-blockers might be a drug of choice for migraine prevention in elderly adults if they have concomitant hypertension or coronary artery disease.[75] Failure to respond to one beta-blocker does not necessarily predict failure of another molecule in the same category.[76]

Angiotensin-converting enzyme inhibitors have also been found to have efficacy as migraine prophylaxis in individuals with[76,77] and without[78] hypertension. Angiotensin receptor blockers have been found to reduce the frequency and severity of migraine attacks,[78,79] and candesartan (16 mg/d) in particular has been found to have similar effect when compared to propranolol (160 mg/d).[80]

Although they are commonly used to treat migraine, calcium channel blockers are not first-line treatment for migraine prevention, although they have some benefit.[81] Verapamil is particularly useful for prevention of cluster headache.[82] The mechanism of action is not clear, but possible explanations are decreasing neuronal excitability, inhibiting prostaglandin formation, and suppressing serotonin release. The target dose of verapamil for cluster headache prevention is higher (240–1,200 mg/d) than the antihypertensive dose. Common side effects to consider are constipation, dizziness, bradycardia, peripheral edema, and electrocardiographic abnormalities.

Antidepressants. Antidepressants have a well-documented role in migraine prophylaxis, but they should be used cautiously in older adults because of the likelihood of elderly adults to experience central nervous system and cognitive adverse effects.[83] Amitriptyline and nortriptyline among the tricyclic antidepressants (TCAs) are arguably the best-studied medications in this category, and both have been used in a wide range of daily doses (25–150 mg/d) for migraine prevention.[66] Amitriptyline has also been found to be effective in the prevention of chronic TTH.[84] Nevertheless, the TCAs are associated with adverse effects, some potentially lethal, in older adults. The minimal effective dose should therefore be used, with frequent monitoring of adverse effects.

Of the serotonin and norepinephrine reuptake inhibitors, venlafaxine has level B evidence for migraine prevention with fewer side effects than amitriptyline, which makes it another favorable option to consider in older adults,[85] with a recommended dose of 150 mg/d.[66]

Botulinum Toxin and Other Injections

Two double-blind, controlled trials have shown the efficacy of onabotulinum toxin A therapy for chronic migraine.[86,87] Its efficacy is probably due to the indirect inhibition of central sensitization of trigeminovascular system, although the exact mechanism of action is still unknown.[88,89] Onabotulinum toxin A is given as 31 intramuscular injections in 7 head and neck regions every 3 months. It is an appealing choice for older adults because of lack of drug interactions and no problems with compliance, but it is ineffective in episodic migraine[90] and chronic TTH.[91] Onabotulinum toxin A injection treatment should be considered in individuals with refractory chronic migraine, especially when other medications are contraindicated because of drug interactions or comorbid conditions.

Greater occipital nerve block can be used safely in elderly adults. Lidocaine and bupivacaine are typically used in greater occipital nerve blocks for migraine or TTH and occipital neuralgia, whereas methylprednisolone acetate is typically used for cluster headache.[92,93] Sphenopalatine nerve block with topical anesthetics can be effective when used consistently for acute treatment or prevention of chronic migraine.[94,95] Nerve blocks are a particularly good choice when there is a need to limit the systemic effects of oral medications.

Muscle Relaxants

Tizanidine, a central muscle relaxant, has been shown to be somewhat effective in the preventive treatment of chronic TTH, alone[96] or in combination with amitriptyline.[97]

Nonpharmacological Therapies

There is some evidence of the effectiveness of nonpharmacological treatments such as cognitive behavioral therapy, relaxation, and biofeedback in the treatment of chronic headache disorders such as chronic migraine,[98] and they are an excellent addition to other preventive or acute therapies and may help optimize headache care especially in elderly adults.

Neuromodulation has been shown to be beneficial in the treatment of chronic migraine, hemicrania continua, and cluster headache[99] using various devices. Peripheral neurostimulation and occipital nerve stimulation have been found to be useful in migraine prevention,[100] and the Food and Drug Administration (FDA) has recently approved a transcutaneous supraorbital stimulation device (Cefaly, Wilton, CT) for preventive migraine treatment and a transcranial magnetic stimulation device (eNeura, Baltimore, MD) for acute migraine treatment.[101] Two transcutaneous supraorbital stimulation devices have received FDA approval—one for prevention of migraine and another to be used abortively—and are available for use in the United States with a prescription. An implanted sphenopalatine stimulator appeared to provide significant benefit in early-stage trials for chronic cluster headache. Although many of these trials did not include individuals aged 65 and older, these devices and interventions could be excellent choices for older adults who cannot tolerate acute or prophylaxis medications for migraine, cluster, and other headache disorders.

Medication Overuse: A Cautionary Tale

Headache-abortive medications can increase the risk of headache chronification.[51] Medication overuse headache (MOH) is a unique headache diagnosis defined in the ICHD-3 beta as headache occurring on 15 or more days per month developing as a consequence of regular overuse of acute or symptomatic headache medication on 10 to 15 or more days per month, depending on medication, for longer than 3 months.[8] Limiting the use of headache-abortive medication is an important preventive strategy, and all people being prescribed acute medications should be educated about this potential risk at the time of the initial consultation. Once MOH has developed, complete cessation of the offending medication is essential. Caution has to be exerted with barbiturate-containing medications such as butalbital and with opiates because a gradual taper may be necessary, and the individual may need to be monitored for acute withdrawal symptoms. As the person is being weaned off a culprit medication, preventive medications should be started. In general, people should be instructed to restrict the use of headache-abortive medications to less than 2 to 3 days per week to prevent development of MOH. An interdisciplinary approach with behavioral support may be needed in these individuals.

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