Biomedical subjects

Alan M Rapoport

Publications and source records attributed to Alan M Rapoport.

29 records · Page 2Linked to original sources

PubMed2003

New developments in migraine prophylaxis.

Migraine is a common neurological disorder that afflicts > or = 12% of the adult US population. Severe, frequent and disabling attacks require effective prophylaxis. Traditional preventive drugs such as beta-blockers, antidepressants and calcium antagonists, despite their documented efficacy, fail to offer relief for a significant proportion of migraine sufferers. Multiple threads of research over the last 15 years have led to the concept that migraine is generated from a hyperexcitable brain. This opens new perspectives in terms of preventive options, especially regarding the anticonvulsants agents. Additionally, different groups of substances, some of which nominated as non-orthodox agents, have been recently subjected to clinical trials and found to be effective. The aim of this review is to present and discuss the new options for migraine prevention.

Acupuncture↗

PubMed2003

The triptan formulations : how to match patients and products.

The 5-HT(1B/1D) receptor agonists (the 'triptans') are migraine-specific agents that have revolutionised the treatment of migraine. They are usually the drugs of choice to treat a migraine attack in progress. Different triptans are available in various strengths and formulations, including oral tablets, orally disintegrating tablets, nasal sprays and subcutaneous injections. In Europe, sumatriptan is also available as a suppository. Specific differences among the triptans exist, as evidenced by different pharmacological profiles including half-life, time to peak plasma concentrations, peak plasma concentrations, area under the concentration-time curve, metabolism and drug-drug interaction profiles. How or whether these differences translate to clinical efficacy and tolerability advantages for one agent over another is not well differentiated. However, delivery systems may play an important role in onset of action. Given that the clinical distinctions among these agents are subtle, identification of the most appropriate triptan for an individual patient requires consideration of the specific characteristics of the patient and knowledge of patient preference, an accurate history of the efficacy of previous acute-care medications and individual features of the drug being considered. The selection of an acute antimigraine drug also depends upon the stratification of the patient's migraine attack by peak intensity, time to peak intensity, level of associated symptoms such as nausea and vomiting, time to associated symptoms, comorbid diseases and concomitant treatments that might cause drug-drug interactions. Individual patient response to the triptans seems to be idiosyncratic and possibly genetically determined. Therefore, a set of specific questions can be used to determine whether a currently used triptan is optimally effective, whether the dose needs to be increased or whether another triptan should be tried. The clinician has in his/her armamentarium an ever-expanding variety of triptans, available in multiple formulations and dosages, which have good safety and tolerability profiles. Continued clinical use will yield familiarity with the various triptans, and it should become possible for the interested physician to match individual patient needs with the specific characteristics of a triptan to optimise therapeutic benefit. Use of the methods outlined in this review in choosing a triptan for an individual patient is probably more likely to lead to migraine relief than making an educated guess as to which triptan is most appropriate.

Dose-Response Relationship, Drug↗

PubMed2002

Mechanisms of action of the 5-HT1B/1D receptor agonists.

Recent studies of the pathophysiology of migraine provide evidence that the headache phase is associated with multiple physiologic actions. These actions include the release of vasoactive neuropeptides by the trigeminovascular system, vasodilation of intracranial extracerebral vessels, and increased nociceptive neurotransmission within the central trigeminocervical complex. The 5-HT(1B/1D) receptor agonists, collectively known as triptans, are a major advance in the treatment of migraine. The beneficial effects of the triptans in patients with migraine are related to their multiple mechanisms of action at sites implicated in the pathophysiology of migraine. These mechanisms are mediated by 5-HT(1B/1D) receptors and include vasoconstriction of painfully dilated cerebral blood vessels, inhibition of the release of vasoactive neuropeptides by trigeminal nerves, and inhibition of nociceptive neurotransmission. The high affinity of the triptans for 5-HT(1B/1D) receptors and their favorable pharmacologic properties contribute to the beneficial effects of these drugs, including rapid onset of action, effective relief of headache and associated symptoms, and low incidence of adverse effects.

Carbazoles↗

PubMed2002

Ethical considerations in cluster headache research.

Cluster headache is the most painful of the primary headache disorders and elucidating pathophysiology and treatment for this disorder is crucial. There is justification for studying attacks untreated, and even for precipitating these attacks. Placebo-controlled studies should only be undertaken for regulatory purposes; otherwise, active control should be used.

Cluster Headache↗

PubMed2002

Hemicrania continua: a report of ten new cases.

Hemicrania continua (HC) is an uncommon primary headache first described as a syndrome in 1984. Being quite unusual, its clinical characterization still demands better description. The aim of this study is to present the main clinical characteristics of 10 patients with the diagnosis of HC seen in a tertiary center, critically discussing their main features. All subjects had strictly unilateral headache without side shift and absolute response to indomethacin. Seven patients (70%) presented autonomic features during pain exacerbations. Four (40%) had migrainous symptoms during the exacerbations and one presented partial relief with dihydroergotamine. One patient had pain excruciatingly severe during the exacerbations. Although the cardinal features of HC - continuous, unilateral, indomethacin responsive, remain strongly reliable, a refinement on the clinical characterization is needful and desired.

Adult↗

PubMedDate not supplied

Chronic daily headache: identification of factors associated with induction and transformation.

BACKGROUND: Chronic daily headache (CDH) is one of the more frequently encountered headache syndromes at major tertiary care centers. The analysis of factors related to the transformation from episodic to chronic migraine (CM) and to the de novo development of new daily persistent headache (NDPH) remain poorly understood. OBJECTIVES: To identify somatic factors and lifestyle factors associated with the development of CM and NDPH. METHODS: We used a randomized case-control design to study the following groups: 1) CM with analgesic overuse (ARH), n = 399; 2) CM without analgesic overuse, n = 158; and 3) NDPH, n = 69. These groups were compared with two control groups: 1) episodic migraine, n = 100; and 2) chronic posttraumatic headache (CPTH); n = 65. Associated medical conditions were assessed. We investigated the case groups for any association with somatic or behavioral factors. Data were analyzed by the two-sided Fischer's exact test, with the odds ratio being calculated considering a 95% confidence interval using the approximation of Woolf. RESULTS: When the active groups were compared with the episodic migraine group, the following associations were found: 1) ARH: hypertension and daily consumption of caffeine; 2) CM: allergies, asthma, hypothyroidism, hypertension, and daily consumption of caffeine; and 3) NDPH: allergies, asthma, hypothyroidism, and consumption of alcohol more than three times per week. The following associations were found when comparing the active groups with CPTH: 1) ARH: asthma and hypertension; 2) CM: allergies, asthma, hypothyroidism, hypertension, and daily consumption of caffeine; and 3) NDPH: allergies, asthma, hypothyroidism, and consumption of alcohol more than three times per week. CONCLUSIONS: Several strong correlations were obtained between patients with specific types of CDH and certain somatic conditions or behaviors; some have not been previously described. Transformation of previously episodic headache or development of a NDPH thus may be related to certain medical conditions and behaviors beyond the frequently incriminated precipitant analgesic overuse. As similar results were obtained when CPTH was used as a control, the correlation is more complex than simple comorbidity.

Adult↗

PubMedDate not supplied

Burden of migraine in Brazil: estimate of cost of migraine to the public health system and an analytical study of the cost-effectiveness of a stratified model of care.

BACKGROUND: The search for rationality in health expenses in developing countries collides with the lack of effectively conducted epidemiologic studies. PURPOSE: To present an estimate of the impact and costs of migraine in the Brazilian public health system and to estimate the impact on these costs and the effectiveness of a model of stratified care in the management of migraine. METHODS: An analytical model of utilization of the Brazilian public health system was constructed. Data refer to 1999 and were obtained in accordance with the following steps: (1) Brazilian demographic characteristics; (2) characteristics of the public health system related to its 3 hierarchical levels-primary, secondary, and tertiary care, the last being subdivided into emergency department and hospital care; and (3) estimation of the number of migraine consultations at each complexity level. In Brazil, migraineurs seen in the public health system are most often discharged with an acute treatment, usually a nonspecific medication. We compared this treatment with a proposed stratified care model that uses a triptan as an acute care medication. We have made the following assumptions: (1) 15% of the patients would fall into the Migraine Disability Assessment (MIDAS) grade I category, 25% would fall into the MIDAS grade II category, 30% into the grade III category, and 30% into the MIDAS grade IV category; (2) the mean number of migraine attacks per year are: MIDAS I, 7.49; MIDAS II, 8.02; MIDAS III, 12.22; and MIDAS IV, 27.01. The annual costs of the treatment were calculated according to the following equation: AC = P x N x C + P x Cp + P x Cat x AMA, where P is the number of patients; N, the number of consultations per patient; C, the cost of consultation per level; Cp, the cost of preventive drugs; Cat, the cost of acute therapy drugs; and AMA is the number of migraine attacks per year. Results.-The public health system resources included 55 735 ambulatory units (primary and secondary) and 6453 emergency department and public hospital units, with a corresponding budget of US $2 820 899 621.26. The estimated cost of a consultation on the primary care level was US $11.53; on the secondary care level, US $22.18; in the emergency department, $34.82; and for hospitalization, US $217.93. The total estimated public health system expenses for migraine were US $140 388 469.60. The proposed model would imply a cost reduction of 6.2% (US $7 514 604.40) with an improvement in the quality of the public health system from the actual 18.2% to an estimated 84.5%. CONCLUSION: Migraine seems to pose a huge burden on the Brazilian public health system. The implementation of a stratified care model of treatment that would include specific acute migraine therapies could result in a dramatic increase in the quality of migraine care and a significant reduction in cost.

Brazil↗

PubMedDate not supplied

Patterns of use of triptans and reasons for switching them in a tertiary care migraine population.

OBJECTIVE: To assess the reasons for switching triptans within migraine patients presenting to a specialty clinic. DESIGN AND METHODS: We reviewed data of migraineurs who (1) were currently using a triptan as acute treatment medication for migraine, and (2) had previously used at least one other triptan, or a different triptan formulation. All subjects were followed for at least 1 year. For every triptan/formulation used, the reasons for discontinuation were obtained. RESULTS: Our sample consisted of 386 patients, 339 of whom (87.8%) were females. Sumatriptan was first used by 349 (90.4%); zolmitriptan, by 238 (61.5%); rizatriptan, by 195 (50.5%); naratriptan, by 137 (35.4%); and almotriptan, by 31 (8.0%). Almotriptan was excluded from this analysis because of our small sample. We found significant differences among those who wanted to try another triptan to see if it would be better in those who first used sumatriptan 25 mg, compared to those first using sumatriptan 50 mg (P = .01), sumatriptan 100 mg (P < .001), sumatriptan nasal spray (NS) (P < .001), sumatriptan subcutaneous (SC) (P < .001), zolmitriptan 5 mg (P < .001), rizatriptan 10 mg (P < .001), and naratriptan (P = .001). Patients using rizatriptan, sumatriptan NS, and sumatriptan SC had significantly lower rates of reporting this answer. Subjects first using naratriptan were less likely to report recurrence than those using sumatriptan 25 mg (P = .004), sumatriptan 50 mg (P = .0005), sumatriptan 100 mg (P = .003), zolmitriptan (P = .02), and rizatriptan (P = .006). Incomplete relief was more frequently reported by those first using sumatriptan 25 mg and naratriptan. Inconsistency was a reason for switching in those initially using sumatriptan NS, sumatriptan 25 mg, and naratriptan and less frequently reported in those using zolmitriptan and sumatriptan SC. Side effects were major factors for those first using sumatriptan 100 mg, NS, and SC, and less for those using naratriptan and sumatriptan 25 mg. From those subjects that initially used sumatriptan SC and were switched to a different triptan or formulation, 19.5% returned to sumatriptan SC; for the other triptans/formulations, the percentages were: sumatriptan 25 mg, 7.8%; sumatriptan 50 mg or 100 mg, 42.3%; sumatriptan NS, 17.7%; zolmitriptan, 17.6%; rizatriptan, 16.5%; naratriptan, 9.4%. For those who used more than three triptans/formulations, the last triptan used was: sumatriptan, 29.5%; zolmitriptan, 31.8%; rizatriptan, 25.0%; naratriptan, 12.5%. CONCLUSIONS: A variety of treatment attributes are important in determining the reasons involved in switching a triptan. To assess this attributes can provide additional information to supplement the traditional tests of efficacy provided by randomized clinical trials.

Adolescent↗

PubMedDate not supplied

Chronic daily headache: correlation between the 2004 and the 1988 International Headache Society diagnostic criteria.

BACKGROUND: In a previous study, we compared the 1988 International Headache Society (IHS) criteria and the Silberstein-Lipton criteria (S-L) in a subspeciality clinic sample of 638 patients with chronic daily headache (CDH) assessed both clinically and with headache diaries. Both systems allowed for the classification of most patients with CDH. The 1988 IHS classification required multiple diagnoses and was more complex to apply. OBJECTIVES: The aim of this study was to revisit the same database, now comparing the prior classification systems with the new 2004 IHS classification. In contrast with the 1st edition, the 2nd edition includes criteria for chronic migraine (CM), new daily persistent headache (NDPH), and hemicrania continua (HC). METHODS: We reviewed the clinical records and the headache diaries of 638 patients seen between 1980 and 2001 at a headache center. All patients had primary CDH according to the S-L criteria. RESULTS: Using the S-L criteria as a reference, of the 158 patients with transformed migraine (TM) without medication overuse, just 9 (5.6%) met 2004 IHS criteria for CM. Most of the subjects were classified using combinations of migraine and CTTH diagnoses, much like the 1988 IHS classification. Similarly, using the new IHS system, just 41/399 (10.2%) subjects with TM with medication overuse were classified as probable CM with probable medication overuse. Most patients with NDPH without overuse were easily classified using the 2004 criteria (95.8%). Regarding NDPH with medication overuse, the diagnostic groups were much like results for the 1st edition. All patients with chronic tension-type headache (CTTH) and hemicrania continua (HC) according to the S-L system were easily classified using the 2004 IHS criteria. CONCLUSIONS: We conclude that the 2004 IHS criteria facilitate the classification of NDPH without medication overuse and HC. For subjects with TM according to the S-L system, the new IHS criteria are complex to use and require multiple diagnoses. Very few patients with TM in the S-L system could be classified with a single diagnosis in the 2004 IHS classification. In fact, CM was so rare that it would be virtually impossible to conduct clinical trials of this entity using the 2004 IHS criteria. Clinical trials of this entity should therefore be conducted using the S-L criteria. Finally, we propose that in the 3rd edition of the IHS classification, the diagnosis of NDPH be revised so as not to exclude migraine features.

Adolescent↗

PubMedDate not supplied

Assessment of adverse events associated with triptans--methods of assessment influence the results.

BACKGROUND: A recent study conducted in triptan-naive migraine patients showed that tolerability was the second most important attribute of an acute treatment. However, the proportion of patients reporting side effects after any acute treatment may vary with regard to the method of assessment. OBJECTIVES: To contrast two methods of assessing adverse events (prompted and unprompted) in those with headache using triptans. METHODS: This study was conducted in two sites, a headache center in the United States, and a neurology office focusing on headache in Italy. We prospectively surveyed 415 adults with headache, who had been using the same triptan for at least 3 months. Participants were asked about their headache and treatment history. Subjects then completed a standardized questionnaire, assessing adverse events in two different ways. First, subjects were asked if they had any adverse events when using the triptan. After returning the first part of the questionnaire, subjects received a second form, where 49 possible adverse events were listed. We contrasted and correlated both sets of answers. RESULTS: Most patients (U.S.=74.9%, Italy=65.5%) reported no side effects in the unprompted questionnaire. However, most of them (U.S.=62.9%, Italy=54.1%) reported at least one side effect in the prompted questionnaire. Most patients that reported side effects in the unprompted questionnaire said they had just one adverse event, while most reported two or more side effects in the prompted questionnaire. Both in the unprompted and in the prompted questionnaires, most side effects were rated as mild or moderate. Interestingly, 31 (7.5%) subjects (pooling data from both sites together) graded their adverse events as severe in the prompted questionnaire, but had not self-reported them. CONCLUSIONS: (1) When assessing adverse events, the method of data collection may dramatically influence the results. (2) From those subjects who did not self-report adverse events after using a triptan, most of them will report positively if presented with a list of side effects.

Adult↗

PubMedDate not supplied

Naratriptan in the preventive treatment of refractory transformed migraine: a prospective pilot study.

OBJECTIVE: To assess the efficacy, safety, and tolerability of daily naratriptan in the preventive treatment of transformed migraine (TM) refractory to previous first line therapies. BACKGROUND: Limited evidence suggests that the triptans can be used in the preventive treatment of refractory headaches. DESIGN/METHODS: We included subjects from 18 to 65 years old, with TM, with or without medication overuse (Silberstein and Lipton, 1996). All participants had previously failed at least two preventive medications. Concomitant, preventive medications were allowed if on a stable dose. After the baseline period, all patients received naratriptan 2.5 mg bid. The treatment phase lasted 3 months. The primary endpoint was change in headache frequency per month. Safety assessment included monthly ECGs, complete ophthalmologic exam, and monthly blood tests. Statistical analyses were performed using the intent-to-treat (ITT) population. We also conducted per-protocol (PP) analyses. RESULTS: Our ITT population consisted of 30 subjects (79% female, mean age of 46.5 years). Mean headache frequency per month at baseline was 27.1 days and a significant reduction of headache frequency was obtained in 1 month (20.4, P < .001), 2 months (18.9, P < .001), and 3 months (19.0, P < .001). HIT scores were 64.3 at baseline, 57.4 after 1 month (P < .001), 55.7 after 2 months (P < .01), and 60 at 3 months (P < .05). The mean number of days using rescue medication was reduced from 17.7 at baseline, to 9.7 at 3 months (P < .001). Our PP population consisted of 22 subjects, and 54% had fewer than 15 headaches per month at the end of the study (converted to an episodic pattern). No serious adverse events were reported. No significant changes were observed in blood pressure or in heart rate. ECGs and ophthalmologic exam were unchanged from baseline. CONCLUSIONS: (1) Daily use of naratriptan provided good preventive efficacy in an important subset of subjects with TM refractory to other preventive treatments. (2) The tolerability of this treatment was excellent. (3) Over a short period of time (3 months), no serious adverse events were reported, nor significant changes were found in the ECG or ophthalmologic evaluation.

Adolescent↗