Pharmacy & Therapeutics- August 2008 - (Page 483) CONTINUING EDUCATION CREDIT Other Anticonvulsant Agents Small trials with additional anticonvulsant agents reported some benefit with gabapentin (Neurontin, Pfizer) and levetiracetam (Keppra, UCB Pharma), inconsistent findings with zonisamide (Zonegran, Eisai), and a lack of efficacy with lamotrigine (Lamictal, GlaxoSmithKline). Before these agents can be recommended for migraine prophylaxis, additional studies are needed.83–89 importance of careful and slow titration of additive agents is essential because of additive side effects, potential toxicities, and drug interactions. Special Populations Women. The link between female sex hormones and migraine has been studied extensively. A phenomenon known as menstrual migraine refers to migraine associated with or occurring around a woman’s menstrual cycle. This type of migraine appears to be associated with fluctuations in estrogen levels and the resultant biochemical effects of increased prostaglandins, enhanced prolactin release, and other physiological dysregulation. Treatment has included a variety of agents, including hormonal manipulation and other therapies administered in conjunction with the menstrual cycle.131–135 The newest concept of treating menstrual migraine is the use of short-term prophylaxis with NSAIDs or triptans starting a few days before the cycle and continuing for about five to seven days.136–140 Refractory cases may respond to estrogen alone or to a combination of progesterone or testosterone in addition to the use of other hormonal manipulations.141–146 Migraine headaches usually improve during pregnancy, but treatment may be required in some patients. Simple analgesics like acetaminophen alone are the drugs of choice. Other therapies can be used with caution and in consideration of the risk–benefit ratio.147–152 Children and adolescents. The prevalence of migraine ranges from 3% to 11% in children younger than 15 years of age. Although more controlled trials are needed for evidence-based treatment of migraine in children and adolescents, the American Academy of Neurology offers some guidance. Options for abortive treatments are simple analgesics alone or triptans. The triptans, including sumatriptan (Sutent, Pfizer), rizatriptan (Maxalt, Merck), and zolmitriptan (Zomig, AstraZeneca), were reported to be safe but not superior to placebo. Fewer data are available for prophylactic treatment in children, although several agents have been proposed.153–159 Elderly Patients. New-onset headache in the elderly is considered a secondary disorder, and a comprehensive evaluation is warranted. As with pediatric patients, the safest agent for the abortive management in older adults is acetaminophen, and the use of the ergots and triptans may be limited if patients have cardiovascular or cerebrovascular disease. The selection of preventative therapies can be determined by concurrent comorbidities or contraindications.160–162 Additional Migraine-Prophylactic Agents Other agents have also been used to prevent migraine; however, many of these therapies are less effective than those discussed earlier, or they need further study. Calcium-channel blockers have had mixed success in migraine prevention,90–94 with a few small trials suggesting modest benefits with verapamil (e.g., Calan, Pfizer) (see Table 1).90–92 Although primarily used in the abortive management of migraine, the nonsteroidal anti-inflammatory agents (NSAIDs) have also demonstrated modest benefits in migraine prophylaxis. Trials with naproxen (Naprosyn, Roche), fenoprofen (Nalfon, Pedinol), tolfenamic acid (e.g., Clotam, Provalis), and ketoprofen reported decreases in duration and severity of migraine. Short-term prophylaxis with NSAIDs in menstrual migraine is discussed in the next column (Special Populations).95–102 Skeletal muscle relaxants, including baclofen (e.g., Lioresal, Novartis) and tizanidine (Zanaflex, Acorda), have been used in the prophylaxis of migraine, but the data are limited. One controlled trial and an open-label trial with tizanidine reported reduced headache frequency, duration, and intensity.103–105 Although more trials are needed, the angiotensin-converting enzyme (ACE)–inhibitors and the angiotensin II receptor blockers (ARBs) have been effective for migraine prevention and may have a future role, especially in patients with cardiovascular comorbidities.106–109 The leukotriene receptor antagonist montelukast (Singulair, Merck) was studied in migraine prevention with mixed results, suggesting that more trials may be needed to clarify its role.110,111 The association of migraine headaches and psychiatric disorders has prompted the consideration of anti psychotic agents for migraine, and some data have shown benefits with aripiprazole (Abilify, Bristol-Myers Squibb/ Otsuka) and olanzapine (Zyprexa, Eli Lilly).112,113 One of the more recent products to be studied in migraine prevention is botulinum toxin type A. Although numerous trials have been conducted, inconsistent findings have been reported, perhaps because of variable trial designs, treatment regimens, or the types of patients studied.114–120 Agents that might also be beneficial for migraine prophylaxis include antihistamines, salmon calcitonin (Miacalcin, Novartis, simvastatin (Zocor, Merck) and clonidine (Catapres, Boehringer Ingelheim).1,4,121 Other potential options include herbal products and supplements such as feverfew (Tanacetum parthenium), butterbur root (Petasites hybridus), coenzyme Q10, melatonin, riboflavin, and magnesium.122–130 Treatment Plans and Guidelines for Care As the choices for the pharmacotherapy of migraine expand, clinicians have multiple options to use for both abortive and preventative management. Various guidelines, including those of the U.S. Headache Consortium,4 have recently been revised, although updates are not yet in print.1,2,4,163–165 The available guidelines support the utility of the various pharmacological agents in migraine using a stepped-care approach, with simple analgesics or NSAIDs as first-line choices and stepping up to specific migraine therapies if the response is not sufficient. With the stratified-care approach, Combination Therapies Various combinations of prophylactic agents have been used in patients who have not responded to monotherapy. The Vol. 33 No. 8 • August 2008 • P&T® 483
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