Didactic migraine education in US doctor of pharmacy programs.

OBJECTIVE: To compare didactic migraine education in doctor of pharmacy (PharmD) programs in the United States with the Headache Consortium's evidence-based migraine treatment recommendations. METHODS: A self-administered survey instrument was mailed to all 90 Accreditation Council for Pharmacy Education (ACPE) approved PharmD programs in the United States. RESULTS: Seventy-seven programs responded (86%) and 69 useable survey instruments were analyzed. Fifty-five percent of programs discussed the Consortium's guidelines, 49% discussed the selection of nonprescription versus prescription agents, 45% recommended a butalbital-containing product as migraine treatment, and 20% educated students about tools for assessing migraine-related debilitation. At least 50% of programs taught information consistent with the remaining Consortium recommendations. CONCLUSION: Approximately half of the PharmD programs teach concepts about migraine headache treatment consistent with the US Headache Consortium's recommendations.

Serotonin syndrome risks when combining SSRI/SNRI drugs and triptans: is the FDA's alert warranted?

In 2006 the Food and Drug Administration (FDA) issued an alert, based on 27 case reports gathered over a 5-year span, regarding serotonin syndrome resulting from concurrent use of either a selective serotonin-reuptake inhibitor (SSRI) or a selective serotonin/norepinephrine reuptake inhibitor (SNRI) with a triptan. These diagnoses have been subsequently challenged as not meeting validated criteria for serotonin syndrome, in part because the FDA has yet to publicly disseminate important case report data. As a result of the FDA's alert, some clinicians are reluctant or refuse to provide these drugs concomitantly to patients. We believe that withholding these medications due to fears of serotonin syndrome is difficult to justify. In contrast to the small number of case reports, research shows that approximately 700,000 patients annually take SSRIs or SNRIs with triptans and that this drug combination has been effectively used by millions of individuals over the past decade. We encourage healthcare professionals to familiarize themselves with data on serotonin syndrome and to administer SSRIs/SNRIs with triptans when clinically appropriate.

Migraine-preventive medications: ensuring their appropriate use.

OBJECTIVES: To emphasize the magnitude and burden of migraine, the need for greater use of migraine-preventive medications in patients who could most benefit from them, and the role that pharmacists can play in migraine prevention. DATA SOURCES: PubMed and Medline-based literature searches were conducted to determine the need for migraine-preventive medications, the treatment of migraine, and how pharmacists can assist patients in preventing and treating migraines. The literature search included articles from the previous 6 years, as well as earlier articles for historical perspective. DATA SYNTHESIS: Migraine is a prevalent, chronic, neurologic condition that imposes substantial disability on affected patients, leading to a poor quality of life. However, migraine remains underrecognized, underdiagnosed, and under- or suboptimally treated. In particular, migraine-preventive medications are greatly underused, which contributes to avoidable disability. Community pharmacists can play important roles in identifying these and other patients with headache who are in need of medical care, referring appropriate patients to a health care provider, and educating and counseling patients with respect to abortive and preventive medications. CONCLUSION: Pharmacists are in a unique position to assist in migraine management, particularly with regard to migraine-preventive medications, because many patients may not be familiar with the benefits and use of these agents. Pharmacist involvement can have a measurable effect on patient care and improve the lives of migraine patients.

Biosimilars: illustration of scientific issues in two examples.

PURPOSE: Scientific issues and clinical implications associated with the use of biosimilars (biopharmaceuticals that are similar to an innovator product, notwithstanding minor differences) are illustrated in two examples, botulinum neurotoxins and erythropoietic agents. SUMMARY: Comparison of Botox and Dysport, products that both contain botulinum toxin type A, revealed distinct differences in physicochemical characteristics, approved indications, dosing, and frequency of adverse events. Differentiating between botulinum toxin products on the basis of immunogenicity in the clinical setting would be of value in product selection, and pharmacists could play a valuable role in collecting antigenicity rate data and reporting them to the Food and Drug Administration (FDA) and the manufacturer. Various ethical and practical considerations are associated with the use of erythropoietic agents. The desire to optimize patient care and outcomes must be weighed against the likelihood of obtaining reimbursement for erythropoietic therapy, and reimbursement policies vary from one state to another. Comparing erythropoietic agents requires the use of a consistent and valid definition of treatment response. The definition of response that FDA will accept in the future when evaluating applications for approval of new biosimilar erythropoietic agents and establishing equivalence remains to be determined. CONCLUSION: A variety of scientific and practical clinical issues are associated with the use of biosimilars, including product differences in physicochemical characteristics, reimbursement policies, and the need for valid and clinically relevant criteria for comparing the efficacy and safety of biosimilars and innovator products.

Optimizing migraine therapy: evidence-based and patient-centered care.

Migraine is a chronic, intermittently debilitating neurovascular condition that affects the physical, mental and social aspects of health-related quality of life. Primary care provider interactions with migraine sufferers are common, highlighting the need for clinicians to provide optimal therapy. A comprehensive therapy plan should encompass the whole patient, via a patient-physician partnership where goals and strategies are mutually established. Key treatments include nondrug approaches, such as education and lifestyle modifications, to reduce the occurrence of attacks, as well as acute medications to address the immediate need for relief during an attack. Routine assessment and adjustment of therapy based on data recorded by patient diaries is paramount. Clinical trials support the use of triptans and dihydroergotamine for moderate-to-severe migraine and nonsteroidal anti-inflammatory drugs (alone or in combination with antiemetics or caffeine) for mild-to-moderate migraine, as the treatments of choice to reduce pain and disability time in a cost-effective manner. Published evidence also endorses stratified care, where medication selection is geared towards disease severity, instead of step care, where nonspecific mediations are given to all patients. Thus, patients with significant migraine-induced debilitation, as assessed by tools, such as the Migraine Disability Assessment Scale or the Headache Impact Test, are prescribed migraine-specific agents from the onset of therapy, thereby avoiding the inherent failures of step care. For individuals experiencing a high frequency of attacks or routine debilitation, preventive medications are warranted.

Topiramate for migraine prevention.

Migraine is a costly, recurrent condition that affects 28 million individuals in the United States yet remains underdiagnosed and undertreated. In 2004, the U.S. Food and Drug Administration approved topiramate for the prevention of migraine in adults, joining three other agents with this indication: divalproex sodium, propranolol, and timolol. We evaluated the role of topiramate in the treatment of migraine based on published literature and our clinical experiences. A qualitative systematic search of the literature from January 1966-December 2004 was conducted by using MEDLINE, and other pertinent literature was reviewed. Three large, randomized, placebo-controlled trials of topiramate for migraine prevention in individuals experiencing 3-12 attacks/month have been published, as have several small studies and a comparator trial with propranolol. Based on the results of these studies, 100 mg/day is the optimum topiramate dosage in terms of efficacy and tolerability. Using that dosage, the number of migraine attacks/month decreased by approximately two. Several other secondary outcome measures were also significantly reduced including the number of days/month with migraine and the use of acute treatment/attack. Suboptimal efficacy was shown with 50 mg/day, whereas 200 mg/day caused considerably more tolerability issues. Paresthesia was dose related and the most common cause of attrition. Cognitive dysfunction and weight loss were also commonly reported. The reduction by two migraines/month demonstrated with topiramate in clinical trials is similar to the published results for other preventive agents, though most of those studies were small, antiquated, and poorly designed. In contrast, the topiramate trials enrolled a larger number of patients and closely adhered to the International Headache Society research recommendations, strengthening the quality of results. Topiramate 100 mg/day is an effective option in adults who require migraine prophylaxis. Although the published efficacy results of the various migraine preventive agents are comparable, the superior study design of the topiramate trials warrants consideration of topiramate as an agent of choice for migraine prevention. Future studies of any preventive agent should include more refined quality-of-life outcomes.

Migraine therapy: a survey of pharmacists' knowledge, attitudes, and practice patterns.

OBJECTIVE: Study pharmacists' knowledge, attitudes, and practice patterns with regard to migraine therapy. BACKGROUND: Pharmacists interact with headache sufferers at least 53,000 times daily, thus are well positioned to improve the less than optimal medication management of these disorders. Methods.-Two hundred self-administered surveys, distributed at a migraine symposium, assessing pharmacists' demographic characteristics and level of agreement or disagreement with treatment approaches were conducted. RESULTS: A total of 171 useable surveys (86%) were received. Of the sample, 35% were community pharmacists, 29% were hospital pharmacists, and the remainder were from other work environments. Exclusively among community pharmacists, 80% feel that headache is an important part of their practice, 85% make between one and five over-the-counter (OTC) headache product suggestions per day, and 12% make six or more daily OTC recommendations. Among all the sample's pharmacists, more than half feel migraine patients should try OTC drugs prior to prescription medications, only half ask patients about headache-related morbidity, and one-third feel migraine-specific medications should be reserved only for patients who initially fail nonspecific drugs. Few pharmacists utilize published migraine treatment guidelines. Approximately two-thirds of pharmacists do not feel migraine is a neurobiological illness. The majority is comfortable with their ability to identify people needing a physician referral. CONCLUSIONS: Our results show pharmacists, particularly those in community pharmacies, interact with headache sufferers multiple times daily. Most pharmacists were neither familiar with nor practice migraine therapies endorsed by evidence-based guidelines. Further training of pharmacists is warranted.

Pharmacology of botulinum neurotoxin serotype A.

PURPOSE: An historical perspective on the discovery and development of botulinum neurotoxin for commercial use, the differences between various botulinum toxin serotypes and commercially available products, and the structure, mechanism of action, pharmacologic effects, and immunogenicity of botulinum toxin type A are discussed. SUMMARY: Botulinum toxin was discovered several centuries ago, but its medical uses have only recently been explored. There are several botulinum toxin serotypes that differ in composition and molecular weight. The protein component of the macromolecular structure that has pharmacologic activity requires enzymatic activation, and the required enzyme varies by serotype. All serotypes interfere with muscle contraction by inhibiting acetylcholine release into the synaptic space at the neuromuscular junction, although the intracellular target varies by serotype. An antinociceptive effect may be mediated by a similar mechanism involving inhibition of pain mediator release. The effects of botulinum toxin usually are only temporary because collateral axonal sprouts that can release acetylcholine develop. The protein load and immunogenicity vary among the commercially available botulinum toxin products. The smallest protein load and longest dosing interval should be used to minimize resistance. Alternating among different serotypes is not an effective strategy for preventing or overcoming resistance because cross-resistance can occur. CONCLUSION: All botulinum toxin serotypes and products cause temporary muscle paralysis, yet vary in important ways that may affect their clinical use.

Morbidity and medication preferences of individuals with headache presenting to a community pharmacy.

OBJECTIVE: To assess the degree of debilitation and the treatment views of individuals with headache presenting to a community pharmacy. BACKGROUND: Migraine and chronic daily headache are common poorly managed illnesses. Pharmacists recommend an over-the-counter "headache product" to customers more than 53 000 times daily, thus they are well positioned to help those with headache. DESIGN: Pilot project of 22 self-administered surveys of individuals presenting to a community pharmacy with a complaint of headache. RESULTS: Thirteen persons had Migraine Disability Assessment scores of grade III or grade IV. Of the sample population, a substantial minority (41%) did not believe their headaches could be effectively managed with over-the-counter medications, 72% did not feel over-the-counter agents were safer than prescription products, 96% did not indicate that over-the-counter drugs were more effective than prescription drugs, and 50% disagreed that a physician's evaluation was not necessary. Only half of the population was satisfied with their current therapy, and individuals overwhelmingly (91%) wished they could prevent their headaches. CONCLUSIONS: The majority of individuals with headache presenting to a community pharmacy had high levels of morbidity and were in need of education regarding the proper role of over-the-counter medications, the advantages of prescription agents, and the benefits of a physician's referral. These preliminary results indicate that community pharmacies are potentially important locations for identification, education, and referral of individuals with headache.

Over-the-counter drugs for acute migraine attacks: literature review and recommendations.

Migraines affect 28 million people in the United States, and most of these individuals experience attack-related morbidity. Six of every 10 patients with migraine treat their headache exclusively with over-the-counter (OTC) products. Overreliance on OTC agents contributes to preventable morbidity and drug-induced headaches. To evaluate the role of OTC drugs in the management of migraine headaches, we performed a qualitative systematic literature search by using MEDLINE (January 1966-April 2002), analyzed the references of articles returned by the MEDLINE search, and reviewed other pertinent literature. In the studied populations, acetaminophen, aspirin, ibuprofen, and an aspirin-acetaminophen-caffeine combination product were shown to be more effective than placebo at reducing moderate or severe migraine pain to mild or no pain by 2 hours after administration. However, published trials of OTC agents have systematically excluded patients enduring morbidity with 50% or more of attacks and/or vomiting with 20% or more of attacks. Patients who experience disability during the predominance of their attacks are poor candidates for OTC-exclusive therapy and should seek a physician's help for migraine-specific prescription drugs. For those with migraine who encounter disability with less than 50% of attacks and/or vomiting with less than 20% of attacks, sole treatment with OTC products is a feasible option. Patients who fail to obtain acceptable relief after an adequate trial of OTC agents also should be referred to a physician. Pharmacists are well positioned to assess whether patients could benefit from OTC agents or should seek a physician's assistance.

Evaluation of pharmacists' services for hospital inpatients.

Patient satisfaction with pharmacist-conducted weekly medication-education classes and the underlying factor structure of the evaluation items are described. The pharmacist service consisted of weekly, one-hour classes for headache sufferers in a tertiary headache clinic's hospital unit. One pharmacist taught all of the classes and conducted them in the same manner each week, using the Indian Health Service patient-counseling technique. The classes included both lecture and one-on-one interactions. Any patient admitted to the hospital's headache unit was eligible to participate in the study. Patients were asked to complete a survey at the end of the class, evaluating the service in terms of performance, disconfirmation of expectations, affect, equity, and self-efficacy by rating three statements about each of these on a 7-point scale, where 1 = very strongly disagree and 7 = very strongly agree. Exploratory factor analysis was used to investigate the degree to which these five evaluation areas were distinct constructs. A total of 157 patients attended a medication-education class during the study period. Of these, 153 (97%) provided usable data. Respondents favorably evaluated the pharmacist service, as the means were significantly greater than the scales' midpoint scores (p < 0.001). Factor analysis results suggested that covariation in the data was best described by four factors rather than five: (1) performance, (2) disconfirmation of expectations, (3) equity, and (4) self-efficacy. Inpatients attending pharmacist-conducted weekly medication-education classes favorably evaluated the pharmacist service. Four different conceptualizations of patients' evaluations were identified.

Do butalbital-containing products have a role in the management of migraine?

STUDY OBJECTIVE: To evaluate the role of butalbital-containing products in the management of migraine. METHODS: Qualitative systematic search using MEDLINE (January 1966-November 2001), review of the United States Headache Consortium's evidence-based guidelines for migraine treatment, and review of other pertinent literature. RESULTS: Over 28 million people suffer with migraine, yet this illness is less than optimally diagnosed and managed. Between 14% and 36% of diagnosed migraineurs are prescribed butalbital-containing products, often as initial therapy. However, the only identified controlled trial of these drugs for migraine treatment showed that butalbital-containing products were inferior to butorphanol. The consortium's guidelines specifically discourage administration of butalbital-containing products for migraine. In addition, other published literature highlights the frequent adverse consequences of butalbital-containing products for migraineurs, such as poor migraine control, disability, drug-induced headaches, and withdrawal symptoms. CONCLUSION: Although butalbital-containing products commonly are prescribed for migraine, no evidence in the literature demonstrates their benefit over other agents or placebo. Drugs with proven migraine efficacy, as listed in the consortium's evidence-based guidelines, should be prescribed instead.

Headache education in colleges of pharmacy.

OBJECTIVE: To assess primary headache education in colleges of pharmacy during the 2000-2001 academic year. DESIGN: A survey seeking to quantify students' primary headache education was mailed to all 82 American Association of Colleges of Pharmacy member schools. RESULTS: A usable response was obtained from 65 of 74 answering schools. Per professional year, the average pharmacy student receives 1 headache core course contact hour and no headache elective course contact hours. Two schools offer clerkships devoted exclusively to headaches. Six schools offer clerkships in which a student could expect to focus on headache therapy at least 25% of the time. Seven schools plan to alter their current curriculum to include more headache education, all via additional lectures. CONCLUSIONS: Few opportunities exist for students to learn about primary headaches in colleges of pharmacy. Given the high prevalence and poor medical management of primary headache disorders along with the commonality of pharmacist-headache patient interactions occurring in practice, pharmacy schools should evaluate and alter their curriculum to include more primary headache education.