The present chapter focuses on general information necessary for the physician to advise patients about the choice of prophylactic drugs. For general recommendations on when to use prophylactic treatment, on the use of headache diaries, and on tailoring the dose to the individual patient, consult Chapter 47 on the general and pharmacologic approach to migraine management.

The first priority is to use the drug that has the highest benefit-risk ratio. At first glance, this task might seem easy based on numerous publications about pharmacologic prophylaxis of migraine. Review of these studies and clinical trials show, however, that most prophylactic drugs have an approximate 40% advantage over placebo in reducing attack frequency (see Chapters 54, 55, 56, 57, and 58). In part, this may be artifactual, as a result of publication bias occasioned by authors, industrial companies, and editors having a preference for positive results. If a trial of an active drug does not produce better results than placebo, or if the new drug has inferior benefits compared with those of an established drug, the trial often remains unpublished. In addition, comparability is seldom substantiated by narrow confidence intervals. Even in small trials with grossly inadequate power, the lack of significance is often confused with lack of difference (see Chapter 7). Side effects are often reported as infrequent for active drugs as for placebo in controlled clinical trials, probably because of either the inclusion of too few patients in the trial or an inadequate system for reporting adverse events (see Chapter 7). In clinical practice, prophylactic antimigraine drugs often have side effects that limit their use.

In addition to these limitations in transferring results from controlled trials to clinical practice, it should be kept in mind that migraine patients recruited for controlled trials are often hard-core patients from specialized clinics who have participated in multiple trials. Controlled trials are probably not a true reflection of general practice.

Our ranking of prophylactic drugs (summarized in Table 59-1) is based on a combination of our judgment of the publications and our personal experience and may differ from the experience of others. The table gives a ranking, from + to ++++ (see Table 59-1), for clinical efficacy, scientific validity of the drug trials, and potential for side effects. The table also includes side effects and contraindications. For a more extensive review of side effects and contraindications, the reader should consult the individual chapters. Drug contraindications should be known before a drug is considered for use. The potential for side effects is an important factor in the choice of prophylactic drug, because use may be prolonged over months to years. Side effects may cause noncompliance with a drug that is otherwise effective. The potential side for effects ranges from verapamil (+), candesartan (+) and clonidine (+), which have few side effects, to methysergide (++++), which potentially have serious fibrotic complications after long-term treatment. Accordingly, methysergide can never be the drug of first choice despite its effectiveness.

Physicians also should consider the scientific proof for efficacy when choosing a drug; the contemporary patient is often inquisitive. The literature is extremely varied with regard to the scientific support of drugs used in migraine prophylaxis (see Table 59-1). Some old, well-established drugs (e.g., methysergide, ranked ++) have not been evaluated using contemporary methods (see Chapter 55); for verapamil (+), results for only 41 patients in three controlled trials have been published (see Chapter 56). In contrast, the β-blockers, especially propranolol (++++), the calcium antagonist flunarizine (++++), and sodium valproate/divalproex (+++) and topiramate (++++) were evaluated extensively in controlled clinical trials and found superior to placebo (see Chapters 54, 56, and 57).