Sometimes the observations by one astute clinician of one patient lead to new treatments. In 1966, Rabin et al. in a study of propranolol to prevent angina noted that a 59-year old man reported that his migraines and angina improved on propranolol but the migraines returned after a crossover to placebo medication. Since then, propranolol has become a first-line agent for migraine prevention with increasing caveats, some real, others questionable.
Clinical History: A 38-year old woman has had migraine without aura of moderate to severe intensity for 15 years. For the last 2 years, the headaches have been occurring about 1-2 times per week with an inconsistent response to triptans. She is otherwise healthy except for a history of moderate depression 3 years previously when she got divorced. She occasionally feels 'down'. She walks for exercise and does some weight training. Her examination is normal except for a sitting blood pressure of 146/98 with a pulse of 76.
Would propranolol be a good choice for prevention of her migraines and treatment of her hypertension? Are other beat-blockers effective for migraine prevention? What titration schedule do you recommend? What are the lower limits of blood pressure and pulse at which you will initiate treatment with a beta-blocker for migraine prevention? Does propranolol have an increased risk of stroke when used for the treatment of hypertension? Is propranolol contraindicated in migraine with prolonged aura? Are there other contraindications for beta-blocker use? Is propranolol use associated with weight gain? Depression? Is propranolol still a first-line treatment for migraine prevention?
Expert Opinion: This patient is experiencing 4-8 headaches a month, a frequency well above the threshold of 2-3 attacks per month beyond which preventive headache treatment is encouraged. Traditional reasons for preferring beta-blockers in this case might include the fact that 2 beta-blockers, propranolol and timolol, are FDA-approved for migraine prophylaxis, a status that reflects the level of evidence supporting their efficacy in migraine treatment. Additionally, this patient has stage 1 hypertension, making it attractive to choose a possible "two-fer" drug that might benefit both hypertension and headache.
This patient does not have one of the few conditions historically considered contraindications to the use of beta-blockers, such as asthma, congestive failure, or aura.
Because new information has emerged regarding the long-term risks and benefits of beta-blockers, it is worth re-examining the evidence, or lack of evidence, that underlies many commonly held beliefs and assumptions about beta-blocks.
Assumption # 1: Beta-blockers are a first-line treatment for hypertension.
Current treatment guidelines do include beta-blockers among the first-line choices for treatment of hypertension, but this has recently come under considerable fire.
Assumption # 2: Beta-blockers only cause reversible, nuisance side effects like fatigue, but have few or no serious side effects. Evidence is emerging that beta-blocker use many be associated with some important health risks, including diabetes, weight gain, and ischemia stroke in patients who have migraine with aura.
Assumption # 3: Beta-blockers might cause or exacerbate depression. An association between the use of beta-blockers and major depression has been suggested, based on case reports and clinical observation, but has never been validated in well-conducted clinical trials.
Assumption # 4: Beta-blockers are absolutely contraindicated in patients with asthma, chronic obstruction pulmonary disease, or congestive heart failure. Randomized clinical trials show that cardioselective beta-blockers prolong life in patients with CHF, and they are now indicated for that condition in all but the most seriously compromised patients.
Applying the Evidence to our Patient: What is the bottom line for this patient and others like her? Many longstanding beliefs about the harms, benefits, and contraindications of beta-adrenergic blocker therapy have been flatly contraindicated or called into serious question over the past decade.
Several possible complications of beta-blockers arguably should not weight heavily in the decision about this patient's treatment. Her body mass index is well with the normal range, so there is little need to worry about a possible risk of beta-blocker-induced diabetes or weight gain. Similarly, she does not have a chronic respiratory condition or heart failure. She may be depressed, and it would be prudent to evaluate this possibility carefully.
In addition to headache, this patient's most pressing medical concern is hypertension. There is now considerable controversy about whether beta-blockers are an appropriate first-line choice for treatment of hypertension.
In making this decision, several drawbacks of treating 2 conditions with a single drug should be considered. Despite these, if the physician and patient are aware of potential problems, a beta-blocker is a reasonable treatment choice for this patient.
There is not always a clear correlation between dose and efficacy, or dose and side effects. Thus, trial and error may be necessary to determine the effective and tolerated dose for each patient.