Medicine Cabinet Migraine Prophylaxis in Adult Patients
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Medicine Cabinet Migraine prophylaxis in adult patients INTRODUCTION Dikran Parsekyan Summary points Migraine headaches can be debilitating if patients cannot Ralph’s Pharmacy control or minimize the symptoms, and they can substan- 14049 Ventura Blvd •Not all patients are candidates for prophylactic Sherman Oaks, CA tially impair the quality of life. However, migraines can therapy for migraine; physicians must evaluate 91403 often be successfully controlled by the avoidance of triggers, whether prophylaxis is indicated in a patient lifestyle changes, and abortive treatment. In patients in •Prophylaxis of migraines is not a cure; abortive Correspondence to: whom these measures prove insufficient or unsatisfactory, measures will still be necessary in most patients Dr Parsekyan prophylactic measures to prevent migraines may be need- •A headache diary is essential to identify and avoid [email protected] triggers and to evaluate therapy ed.1 A common preventive measure is the use of prophy- •For prophylactic drug therapy, choose the agent that Competinginterests: lactic drugs, which will be the focus of this article. I will has the potential for the highest benefit and lowest None declared briefly mention nonpharmacologic or alternative measures. risk to the patient •Although their efficacy is questionable, alternative West J Med SEARCH METHODS therapies may have some role in migraine prophylaxis 2000;173:341-345 ......................................................................... The information given here is based on a MEDLINE search from 1966 to the present using the terms “migraine uled according to predetermined triggers, such as the onset prevention” and “migraine prophylaxis.” The search was of menses. The physician should evaluate previous prophy- limited to English-language review articles and studies lactic measures, if any, for adequacy and appropriateness. with human subjects. I also searched the Internet using the Women of childbearing age should be treated with caution key word “migraine” to link to the Web sites of the Jour- because of the teratogenicity of most prophylactic drugs.2 nal of the American Medical Association Migraine Informa- Patients must also understand the goals, limits, and tion Center and the American Academy of Neurology. risks of migraine prophylaxis. The goals are to reduce the BEFORE STARTING PROPHYLAXIS duration, frequency, and severity of the attacks to improve 5 Patients for whom prophylactic therapy is indicated have the patient’s quality of life and minimize disability. Pro- the following migraine features: phylactic therapy is rarely curative; therefore, abortive therapies continue to be necessary in most patients, al- • More than 2 headaches per month, but fewer than 8 though their effectiveness is usually increased when used (>8 attacks per month usually indicate overuse of with prophylactic drugs.6 A 50% reduction in the fre- 2 abortive therapy) quency of migraines is generally deemed successful.8 • Headaches less frequent but more prolonged (>2 days’ Compliance is a major issue because patients experience duration) or severe attacks leading to substantial medication side effects before any benefit from prophy- disability1,3 lactic drugs.3 • Migraines are refractory to abortive treatment measures CHOOSING AN AGENT • Therapies for acute attacks are intolerable, contraindi- Many drugs have proven efficacy in preventing migraine. cated, or overused (>2 per week)2-4 Based on patient-specific indices, the agent with the high- • Migraines are predictable in occurrence est risk-to-benefit ratio should be used. The efficacy, con- • The patient has other migraine conditions such as mi- traindications, precautions, side effects, concurrent disease graine with prolonged aura or hemiplegic migraine5 states of the patient (“special indications”), compliance issues, and cost should all be considered.1,5,9 Side effects Before prophylaxis is appropriate, the physician must must be given special consideration because migraine suf- evaluate whether proper and adequate abortive therapies ferers have an increased frequency of adverse effects com- have been instituted. Some patients overuse abortive mea- pared with other patients.2,3 sures, leading to rebound headaches. In these patients, the drug should be withdrawn before preventive therapy is Guidelines for migraine prophylaxis initiated.2,6 • Initiate the chosen drug at a low dose and titrate up A headache diary is essential for all patients who suffer (usually every 2-4 weeks) until benefits occur or side from migraine headaches.7 If migraine triggers can be effects prevent any further increase in dose. Long- identified, prophylactic therapy may be unnecessary. If, acting formulations may improve compliance2,5 however, the triggers are unavoidable or undetermined, drug therapy is indicated to try to prevent the migraines. • A 2- to 3-month trial is needed to assess the efficacy of If prophylactic therapy is initiated, a 2- to 3-month trial is a regimen generally needed to assess the efficacy of the regimen.5 • After 1 year, try to withdraw the drug, even if it has Prophylaxis may be daily on a continuous basis or sched- been effective. Volume 173 November 2000 wjm 341 ............................................ Medicine Cabinet • Use a drug that may benefit any comorbid conditions -Blockers in migraine prophylaxis the patient has5 • Prophylaxis should be monotherapy whenever pos- Daily dose range (the most effective dose or dose range sible. Combinations of drugs have not shown substan- is shown in parentheses) tial benefit except in some patients with multiple co- • Propranolol hydrochloride (should be specifically 2 considered as first-line agent)*: 40 to 320 mg (80-240 morbid conditions. mg) • Timolol maleate (should be specifically considered as DRUGS WITH AN ESTABLISHED ROLE IN first-line agent)*: 20 to 30 mg MIGRAINE PROPHYLAXIS • Nadolol: 40 to 240 mg First-line agents • Metoprolol tartrate: 50 to 300 mg (200 mg) The first-line agents with the greatest efficacy are -block- • Atenolol: 50 to 200 mg (100 mg) ers, tricyclic antidepressants, and divalproex sodium or val- proic acid. I have not considered agents unavailable in the Side effects 1 United States, such as flunarizine, lisuride, and pizotifen. • Fatigue I have also excluded agents that have proved to be inef- • Bradycardia fective or for which proof of efficacy is limited. • Dizziness • Depression -Blockers • Impotence The scientific and clinical evidence supports -blockers as • Bronchospasm the drugs of choice for the prevention of migraines.7 The • Nausea (adverse effects are less frequent than with most commonly used agent is propranolol hydrochloride. the other first-line agents) Generally, if 1 agent fails, another in its class may be tried, and this change may prove to be effective. It is imperative Precautions 2  that abrupt stoppage of therapy is avoided. -Blockers • Asthma 7 are not effective in reducing aura. In general, response to • Chronic heart failure these agents is gradual, and it may take at least a month to • Diabetes mellitus see an effect.10 The use of -blockers with intrinsic sym- • Peripheral vascular disease pathomimetic activity (such as pindolol) should be • Conduction defects or heart block avoided.11 The daily dose range for -blockers in migraine • Depression prophylaxis, together with their side effects, precautions, • and special indications, are given in the first box.5-7,10 Raynaud’s disease • Hypotension Tricyclic antidepressants Tricylic antidepressants are another class of medication Special indications considered as first-line treatment in migraine prophylaxis. • Concurrent hypertension Even without the presence of depression, these agents are • Angina effective in preventing migraines, and the response is usu- • Post myocardial infarction ally more rapid (within 4 weeks) than with -block- • Tremor 10,12,13 ers. Combined use with -blockers does not reduce • Anxiety or panic attacks (specifically propranolol) the incidence of migraines, but it may reduce that of ten- 7 sion-type headaches. Although the entire class is consid- *Approved by the Food and Drug Administration for migraine prevention ered useful in prophylaxis, tertiary amines, such as ami- 5,7 triptyline, are more effective than the secondary amines, 250 mg daily, titrated up to 1,500 mg. If no benefit is 15 such as nortriptyline.6 Amitriptyline hydrochloride is the seen at low doses, dose escalation is usually not helpful. first-line agent of choice among the tricyclic antidepres- A serum drug concentration of 50 to 120 mg/L is con- sants.5 Physicians need to consider the differences in side- sidered to be in the therapeutic range, but it is unclear effect profiles of the various drugs when deciding which whether such monitoring is necessary or, indeed, indica- 10,16,17 one to use (second box).5-7,10,14 tive of efficacy. Other anticonvulsants either have no efficacy or have not proved effective at this time.5 Divalproex sodium or valproic acid Divalproex and valproic acid are also first-line agents in Second-line agents migraine prevention, and the former has been approved Calcium channel blockers by the Food and Drug Administration (FDA) for this Calcium channel blockers are effective second-line agents indication (third box).5-7 The initial dose is usually from (fourth box).5-7,10 They are usually slower in onset than 342 wjm Volume 173 November 2000 ............................................ Medicine Cabinet Tricyclic antidepressants in migraine prophylaxis Daily