Multicenter prevalence of opioid medication use as abortive therapy in the ED treatment of migraine headaches

Despite a range of therapeutic options for treating acute migraine headaches, the use of opioids is still reported to be common practice. This study describes treatment practices in regards to migraines in the ED. It characterizes the prevalence of opioid orders during visits in three different settings, an academic medical center, a non-academic urban ED, and a community ED.Fourteen months of consecutive migraine visits were identified. All medications ordered were separated into first-line and rescue medications. Number of visits, length of stay, door to provider time, and total provider time were compared.A total of 1222 visits were identified. Opioids were ordered in 35.8% of these visits. By facility, opioids were ordered in 12.3% of academic medical center visits, 40.9% of urban ED visits, and 68.6% of community ED visits. This ranged from 6.9% of first-line therapies in the academic center to 69.9% of rescue therapies in the community ED. Of those who received opioids, 36.0% versus 25.1% required rescue medications. Patients who received opioids had more repeat visits, 1.79 versus 1.30. The academic center and urban ED both found greater than 30% decrease in length of stay in visits where opioids were not given.In the face of evidence against opioids for migraines, over one third of patients received them. There was a higher prevalence in the community setting. There were no significant benefits in overall throughput time, however, opioid visits required more rescue medications, increased length of stay, and resulted in more repeat visits.     

Successful use of propranolol in migraine associated with electroconvulsive therapy

To date, there have been no reports on the use of propranolol in electroconvulsive therapy (ECT)-induced migraine; we describe a 32-year-old woman who was successfully treated with propranolol for this condition. Over a course of ECT, the patient developed increasingly severe migraine which was refractory to treatment with acetaminophen, codeine, and naproxen. Sumatriptan did not relieve the headache and aggravated the nausea. Successful migraine relief was achieved with a combination of propranolol and naproxen, administered before and after ECT. Propranolol reduced blood pressure and decreased the heart rate, measured before and immediately after ECT. Propranolol, possibly in combination with naproxen, may be useful in both acute and prophylactic treatment of post-ECT migraine.     

Medication use in the treatment of migraine during pregnancy and lactation

Migraine is very common in women of reproductive age. With peak prevalence of migraine occurring during childbearing years, many women with migraine may knowingly or unknowingly use medication during pregnancy. Although migraine tends to improve during pregnancy, many women may still experience moderate to severe disabling headache and need pharmacologic treatment for the pain, nausea, and vomiting. This article explores the physiologic changes occurring during pregnancy that can affect pharmacokinetic properties of drugs and their metabolism. Acute and preventive treatment of migraine during pregnancy and lactation is discussed, with an emphasis on safety to the fetus and nursing infant. Safety and recommended use of medication during pregnancy may be different when use is considered during breastfeeding. A goal of treatment is to balance potential risk of treatment to the fetus and nursing infant with significant relief and return to normal function of the mother.     

Subcutaneous sumatriptan provides symptomatic relief at any pain intensity or time during the migraine attack

Over the years the paradigm of treating early during the migraine attack has become well established in clinical practice. It is also recommended that the 5-HT(1B/1D) agonists be administered early during the migraine attack for efficacy. This is because it has been proposed that most migraineurs are less responsive to delayed treatment, owing to the development of central sensitization of the pain transmission. The main objective of this prospective, cross-over study at a specialist clinic was to evaluate if these recommendations should also apply to the subcutaneous formulation of sumatriptan. Results are based on 20 adult International Headache Society migraineurs. Two attacks (n=40) were treated with 6 mg subcutaneous sumatriptan as early as possible after the onset of migraine headache and two attacks (n=40) as late as the patients could bear. The median intra-individual difference between the two strategies in time from first occurrence of pain to injection was 5.7 h and the median intra-individual difference in pain intensity at the time of injection was 29 visual analogue units. No significant differences were found in time to freedom from pain, pain severity at 1 and 2 h, area under the curves from injection to pain free or in headache recurrence after injection. At the end of the study, most of the patients claimed that their medication was as effective when given early as when given late in the course of the attack. The discrepancy between our present findings and retrospective analyses of trials on oral triptans probably has more to do with the less disturbed pharmacokinetics early during the migraine attack than with central sensitization. Consequently, we recommend nonoral formulations of triptans, which do not necessarily have to be administered early during the migraine attack to provide efficacy. In conclusion, it is reassuring for migraineurs that it is worthwhile taking their medication in an appropriate formulation even if they have not been able to do so early in the course of the attack.     

Risk of major bleeding during concomitant use of antibiotic drugs and coumarin anticoagulants

Summary.  Background:  Coumarin anticoagulants are prone to drug–drug interactions. For example, antibiotic drugs may enhance the anticoagulant effect of coumarins. However, whether such interactions are associated with an increased risk of bleeding, and if so, how frequently this occurs remains unknown. Objective:  To assess the risk of major bleeding associated with the concomitant use of antibiotic drugs and coumarin anticoagulant therapy. Methods:  We analyzed a retrospective cohort study including all users of acenocoumarol or phenprocoumon in the PHARMO Record Linkage System (age range: 40–80 years). All patients were followed up until end of last coumarin treatment, hospitalization for bleeding, death, or end of study period. For each patient, the number of days on either coumarins alone, or on coumarins in combination with antibiotic drugs was determined. From these data, the relative risks of major bleeding were calculated. Results:  A total of 52 102 users of acenocoumarol and 7885 users of phenprocoumon met the inclusion criteria of our study cohort and contributed 139 159 person-years of follow-up. During follow-up, 838 patients (1.4%) were hospitalized for a bleeding while taking coumarins. Of the 62 different antibiotics taken by study members, 19 were associated with a bleeding episode. Of these, 10 were associated with a statistically significant increased bleeding risk. The relative risk of bleeding was three to five for doxycycline, amoxicillin, amoxicillin/clavulanic acid, ciprofloxacin, cotrimoxazole, azithromycin and pheneticillin, nine for tetracycline and 43 for cefradine and neomycin. Conclusion:  Based on relative risks and incidence of use, amoxicillin (alone or with clavulanic acid) and doxycycline are the main antibiotic drugs associated with major bleeding when used in combination with coumarin.     

Prophylactic drug management of migraine

Migraine prophylaxis with drugs is still an essential part of migraine therapy. This is especially true for those patients with frequent migraines who are in danger of developing drug-induced headaches. Migraine prophylaxis should be taken in consideration in patients who suffer from 7 or more migraine days per months in spite of all non-pharmacological efforts. When choosing a prophylactic drug not only efficacy but tolerability and safety for long-term intake should be considered. Prophylactic drugs used to be classified as drugs of first, second and third choice. According to this step care model treatment was started with a drug of first choice and only in case of lack of efficacy or adverse events a drug of lower choice was selected. Today, in contrast to the traditional step care a stratified care is favored. Treatment is individualized based on an assessment of the patients' medical needs, on comorbidity, the migraine phenotype and most important the individual situation of the patient in life. The paper gives an overview of the efficacy and tolerability of drugs used in migraine prophylaxis.     

Experimental migraine models and their relevance in migraine therapy

Although the understanding of migraine pathophysiology is incomplete, it is now well accepted that this neurovascular syndrome is mainly due to a cranial vasodilation with activation of the trigeminal system. Several experimental migraine models, based on vascular and neuronal involvement, have been developed. Obviously, the migraine models do not entail all facets of this clinically heterogeneous disorder, but their contribution at several levels (molecular, in vitro , in vivo ) has been crucial in the development of novel antimigraine drugs and in the understanding of migraine pathophysiology. One important vascular in vivo model, based on an assumption that migraine headache involves cranial vasodilation, determines porcine arteriovenous anastomotic blood flow. Other models utilize electrical stimulation of the trigeminal ganglion/nerve to study neurogenic dural inflammation, while the superior sagittal sinus stimulation model takes into account the transmission of trigeminal nociceptive input in the brainstem. More recently, the introduction of integrated models, namely electrical stimulation of the trigeminal ganglion or systemic administration of capsaicin, allows studying the activation of the trigeminal system and its effect on the cranial vasculature. Studies using in vitro models have contributed enormously during the preclinical stage to characterizing the receptors in cranial blood vessels and to studying the effects of several putative antimigraine agents. The aforementioned migraine models have advantages as well as some limitations. The present review is devoted to discussing various migraine models and their relevance to antimigraine therapy.     

Optimal vasopressor drug therapy during resuscitation

Optimal vasopressor support during resuscitation should theoretically enhance aortic diastolic and coronary perfusion pressure as well as coronary and cerebral blood flow/oxygen delivery without increasing cellular oxygen demand. Intravenous vasopressor support, using 1 mg doses of epinephrine every 5 minutes in adults or vasopressin 40 IU, is recommended by American Heart Association Advanced Cardiac Life Support Guidelines to maximize oxygen delivery to the heart and brain and increase cellular high energy phosphate levels. Vasopressin offers theoretical advantages over epinephrine in that it does not increase myocardial oxygen demand significantly and its receptors are relatively unaffected by acidosis. However, unlike epinephrine, it is not a myocardial stimulant. Despite these differences in physiologic actions, two large randomized clinical trials yielded virtually identical overall survival to hospital discharge when these agents were compared during inhospital or out-of-hospital resuscitation in Canada and Europe, respectively. More recent clinical and experimental evidence suggests that a combination of vasopressin and epinephrine used during resuscitation can improve hemodynamics and perhaps survival. The verdict on a combination vasopressor strategy may soon come from a large (>2,000 patients) prospective clinical trial that is underway in France to clarify the role of combination vasopressin/epinephrine therapy in out-of-hospital resuscitation.     

The use of questions to determine the presence of photophobia and phonophobia during migraine

Objective.— To investigate whether the use of more detailed close‐ended questions as part of the routine headache history is helpful when patients initially deny that they are sensitive to light and noise during migraine headaches. Background.— According to the International Headache Society 2004 criteria, the diagnosis of migraine requires the presence of at least one of the following during a headache: (1) nausea and/or vomiting, (2) photophobia and phonophobia. Evans anecdotally noted that many patients answer the question, “does light or noise bother you during a headache,” with a “no” when the answer is really “yes” if they are asked more detailed close‐ended questions. Methods.— Consecutive patients fulfilling International Headache Society 2004 criteria for migraine or probable migraine presenting to a headache clinic and a neurology clinic were asked the following questions: “does light bother you during a headache?” If “no,” they were then asked, “during a headache, would you prefer to be in bright sunlight or in a dark room?”“does noise bother you during a headache?” If “no,” they were then asked, “during a headache, would you prefer to be in a room with loud music or in a quiet room?” Results.— Eighty‐five consecutive patients with migraine or probable migraine were questioned, 71 females (83.5%) and 14 males (16.5%). There was denial of light and sound sensitivity in 24% of patients with routine questioning and then awareness of sensitivity in 93% with the further questioning. A total of 7.1% of the patients were diagnosed with probable migraine. However, if the additional questions were not asked, 8% more of the patients with definite migraine would have been incorrectly diagnosed as probable migraine. Conclusion.— When patients initially deny light and noise sensitivity during migraine headaches, additional questions should be asked to ensure that their answer is accurate. Not asking the additional questions may result in the over‐diagnosis of probable migraine.     

A double-blind controlled study of nifedipine as an abortive treatment in acute attacks of migraine with aura

Patients with migraine with aura treated each of six acute attacks with either nifedipine or vehicle administered in double-blind, randomized form. Two modes of administration were studied. Both increased the intensity of headaches compared to vehicle. We conclude that nifedipine is not useful as an abortive treatment of migraine with aura.