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Biomedical subjects

Stephen Silberstein

Publications and source records attributed to Stephen Silberstein.

11 recordsLinked to original sources

Reversible anorgasmia with topiramate therapy for headache: a report of 7 patients.

OBJECTIVE: To describe 7 patients who developed new onset anorgasmia while using topiramate therapy for migraine prophylaxis. BACKGROUND: Topiramate is an effective drug for the prevention of migraine headaches. Though it is generally well tolerated, it may be associated with a dose-related anorgasmia. METHODS: Case reports. RESULTS: Seven patients (5 women, 2 men), between the ages of 40 and 62, developed anorgasmia while using topiramate for headache prevention. Four women and 2 men had migraine without aura, and 1 woman had migraine with aura. None had a prior history of anorgasmia or sexual dysfunction. Doses associated with this side effect ranged from 45 to 200 mg daily. All subjects had symptom resolution. Six patients had resolution within 7 days of discontinuing or decreasing the medication; the exact time frame of resolution for the seventh patient is unknown. CONCLUSION: In our series, anorgasmia was a reversible, dose-related adverse effect of topiramate. Physicians need to be aware of the potential for topiramate to cause sexual side effects, and should inquire about these symptoms in patients for whom this agent has been prescribed.

Adult↗

Pharmacology of dihydroergotamine and evidence for efficacy and safety in migraine.

Dihydroergotamine mesylate (DHE), an ergot alkaloid, has been extensively utilized and studied in the treatment of episodic and chronic migraine. This article reviews the pharmacokinetics, pharmacodynamics, and clinical efficacy and safety of DHE, particularly in comparison to ergotamine tartrate (ET), a similar ergot alkaloid with a long history of use in the treatment of migraine. Structural differences between these 2 compounds account for clinically important distinctions in their pharmacokinetic, pharmacodynamic, and adverse event profiles. DHE is a significantly less potent arterioconstrictor than is ET, which makes it a potentially much safer drug. In addition, DHE is associated with a markedly lower incidence of medication-withdrawal headache, nausea, and vomiting than is ET. The safety and efficacy data presented here are derived from clinical trials and case series involving DHE administered by intravenous infusion, intramuscular or subcutaneous injection, or intranasal spray.

Analgesics, Non-Narcotic↗

Central sensitization theory of migraine: clinical implications.

The clinical science of migraine headache continues to evolve. Theories of the pathophysiology of migraine have progressed from the early vascular basis of migraine to more complex current theories that emphasize the centrality of neuronal dysfunction. The most recently articulated theory of migraine is the central sensitization hypothesis, which proposes that altered processing of sensory input in the brainstem, principally the trigeminal nucleus caudalis, could account for many of the temporal and symptomatic features of migraine, as well as its poor response to triptan therapy when such treatment is initiated hours after the onset of pain. Both preclinical and clinical data support the central sensitization theory. A critical clinical implication of this theory is that drugs that are capable of either aborting or arresting the process of central sensitization, most prominently dihydroergotamine, may have a unique role in the treatment of migraine. An additional, and highly practical, implication is based upon the finding that cutaneous allodynia-pain arising from innocuous stimulation of the skin, as in hair brushing or the application of cosmetics-is an easily identifiable marker of central sensitization. Thus, the presence or absence of cutaneous allodynia can be integrated into the routine clinical assessment of migraine and utilized as a determinant of treatment. Future basic and clinical research on central sensitization is likely to be of ongoing importance to the field.

Analgesics, Non-Narcotic↗

DHE in the pharmacotherapy of migraine: potential for a larger role.

Despite a large array of currently marketed, frequently effective drugs for the acute treatment of migraine headache, comprising various classes and formulations, predictably reliable treatment for most headache types is often lacking. Dihydroergotamine mesylate (DHE) is a comparatively safe and effective therapy for migraine headache that could potentially be used for a broader range of headache types than occurs at present. The features of DHE supporting this assertion include (1) effectiveness in terminating severe, long-lasting headaches, (2) rapid onset of action, (3) very low rates of headache recurrence, (4) minimal risk of medication-overuse headache, and (5) in the nasal spray formulation, suitability for outpatients (especially patients who are very nauseated or vomiting, potentially obviating the need for an office or hospital visit for acute care). Conditions or circumstances for which there are data supporting the expanded use of DHE include menstrual migraine, migraine with central sensitization and cutaneous allodynia, medication-overuse headache, migraine recurrence, and status migrainosus. The introduction of the intranasal formulation of DHE provides both pharmacologic and patient-convenience advantages for use in migraine therapy. This article reviews the rationale for the use of DHE in these common, often difficult-to-treat migraine forms.

Analgesics, Non-Narcotic↗

Efficacy and tolerability of zolmitriptan oral tablet in the acute treatment of menstrual migraine.

OBJECTIVE: To determine the efficacy and tolerability of zolmitriptan 2.5 mg oral tablet as an acute treatment for menstrual migraine attacks. METHODS: This was a two-phase, multicentre, randomised, double-blind, placebo-controlled, parallel-group outpatient study (Phase I is reported here). The study was conducted at 27 sites in the USA. Eligible women were randomised (1 : 1) to receive either zolmitriptan 2.5 mg oral tablet or placebo, and instructed to acutely treat up to two menstrual migraine attacks per menstrual period for up to three menstrual cycles with a single dose of study medication. Menstrual migraine was operationally defined as an attack occurring within the time period of 2 days prior to the expected onset of menses to 5 days after the onset of menses. Participants were asked to treat migraine headaches of moderate or severe intensity only that occurred >24 hours after the end of the last migraine attack and that had not been acutely treated with other medications. Information regarding each migraine attack was recorded by patients in treatment diary cards. The primary efficacy variable was 2-hour headache response (defined as a 2-point drop on a 4-point scale) for all attacks treated. Secondary variables included 1- and 4-hour headache response rate; 1-, 2- and 4-hour headache response based on a 100 mm visual analogue scale (VAS); pain-free rate at 1, 2 and 4 hours; use of escape medication; the proportion of patients with recurrence within 24 hours of initial treatment; and tolerability. RESULTS: The intention-to-treat population comprised 334 patients (zolmitriptan [n = 174]; placebo [n = 160]). Patients treated 625 attacks with zolmitriptan and 529 attacks with placebo. Twice as many patients who took zolmitriptan achieved a 2-hour headache response compared with placebo recipients (65.7% vs 32.8%; p < 0.0001). Furthermore, a significantly higher headache response was observed with zolmitriptan than placebo at all timepoints assessed. Significantly more zolmitriptan recipients were pain-free 2 hours post-dose compared with placebo recipients (p < 0.0001). The use of escape medication was considerably lower in zolmitriptan recipients (42.6% vs 71.3%; p < 0.0001). Based on the reduction in VAS score of > or = 30 mm from baseline, significantly more zolmitriptan recipients achieved headache response compared with placebo recipients at 1, 2 and 4 hours post-dose (all p < 0.0001). Recurrence was reported in 29.1% of zolmitriptan-treated attacks versus 45.1% of placebo-treated attacks (p = 0.0009), with median time to recurrence of 8.5 and 4.0 hours, respectively. Zolmitriptan was well tolerated. CONCLUSION: Oral zolmitriptan is effective and well tolerated for the acute treatment of menstrual migraine attacks. The results are similar to those seen with zolmitriptan in studies of the general migraine population.

Acute Disease↗

Can allodynic migraine patients be identified interictally using a questionnaire?

OBJECTIVE: The gradual development of cutaneous allodynia during the course of a migraine attack is commonly detected by quantitative sensory testing (QST) in migraineurs seeking secondary and tertiary medical help. In this study, the authors developed a questionnaire that tested the recollection of the patients on their skin sensitivity during past migraine attacks. METHODS: The authors devised a series of questions regarding skin sensitivity during migraine and posed them to 89 migraineurs when they were free of migraine (Visit 1). To validate their recollections, the authors determined the patients' pain thresholds to mechanical and thermal skin stimuli in the absence of migraine (Visit 1) and during an attack (Visit 2), using QST. RESULTS: Whereas 75.3% of the patients testified to at least one type of skin hypersensitivity during migraine, 24.7% were unaware of any abnormal skin sensitivity. The questionnaire correctly identified 84.8% of the 66 patients classified as allodynic by QST and mislabeled the remaining 15.2% as nonallodynic (false negatives). Among the 23 patients classified as nonallodynic by QST, 47.8% were mislabeled as allodynic using the questionnaire (false positives). Among the total number of 89 patients studied, the questionnaire produced 62.9% true positives and 13.5% true negatives (= 76.4% correct labeling) vs 12.4% false positives and 11.2% false negatives (= 23.6% mislabeling). CONCLUSION: The reliability of the questionnaire as a diagnostic tool of allodynia varies with the proportion of allodynic patients in a given clinic. The major source of variability is the misconception of nonallodynic patients that their skin is hypersensitive during migraine.

Adult↗

Consensus statement: cardiovascular safety profile of triptans (5-HT agonists) in the acute treatment of migraine.

BACKGROUND: Health care providers frequently cite concerns about cardiovascular safety of the triptans as a barrier to their use. In 2002, the American Headache Society convened the Triptan Cardiovascular Safety Expert Panel to evaluate the evidence on triptan-associated cardiovascular risk and to formulate consensus recommendations for making informed decisions for their use in patients with migraine. OBJECTIVE: To summarize the evidence reviewed by the Triptan Cardiovascular Safety Expert Panel and their recommendations for the use of triptans in clinical practice. PARTICIPANTS: The Triptan Cardiovascular Safety Expert Panel was composed of a multidisciplinary group of experts in neurology, primary care, cardiology, pharmacology, women's health, and epidemiology. EVIDENCE AND CONSENSUS PROCESS: An exhaustive search of the relevant published literature was reviewed by each panel member in preparation for an open roundtable meeting. Pertinent issues (eg, cardiovascular pharmacology of triptans, epidemiology of cardiovascular disease, cardiovascular risk assessment, migraine) were presented as a prelude to group discussion and formulation of consensus conclusions and recommendations. Follow-up meetings were held by telephone. CONCLUSIONS: (1) Most of the data on triptans are derived from patients without known coronary artery disease. (2) Chest symptoms occurring during use of triptans are generally nonserious and are not explained by ischemia. (3) The incidence of serious cardiovascular events with triptans in both clinical trials and clinical practice appears to be extremely low. (4) The cardiovascular risk-benefit profile of triptans favors their use in the absence of contraindications.

Acute Disease↗

Inpatient treatment of headache: an evidence-based assessment.

OBJECTIVE: To evaluate inpatient treatment of headache in the United States. PARTICIPANTS: Participants were selected by the meeting chairpersons, Drs. Diamond and Silberstein as well as Dr. Freitag. Criteria for selection included participation in an inpatient treatment program, headache specialists not affiliated with an inpatient treatment program, clinician with interest in headache but not affiliated with a dedicated headache treatment program. The single meeting held in New York was by invitation only. All invitees were provided with opportunity to present their views and participate in the recommendations of the Consortium. The list of participants at the meeting were: Harvey Blumenthal, MD, Roger Cady, MD, James Couch, MD, Seymour Diamond, MD, Frederick G. Freitag, DO, R. Michael Gallagher, DO, Al Lake III, PhD, Richard Lipton, MD, NinanMathew,MD, Alan Rapoport, MD, Jay Rosenberg, MD, Joel Saper, MD, Stephen Silberstein, MD. Funding for theproject was provided by the US Headache Guidelines Consortium Project through the American Academy of Neurology and the National Headache Foundation. EVIDENCE: Each of the authors were part of the writing committee each with specific areas that they were responsible for conducting the literature reviews and submitting a portion of the original document for editing and review. Dr. Freitag coordinated this process and assembled the first draft of the article for circulation and review among the authors and chairpersons. In the absence of class I evidence consensus expert opinion was fundamental to the process. CONCLUSIONS: The treatment of headache is commonly delivered in the outpatient office environment. There exists a group of patients who have been refractive to outpatient treatment and in whom in patient care may be appropriate. The factors that determine the optimal treatment setting, the methodology of the treatment and the results of such treatment have come under increasing scrutiny secondary to the cost of treatment in the hospital. The US Headache Consortium guidelines project in conjunction with the national headache foundation believed that the need existed to objectively examine the issues surrounding inpatient treatment. The epidemiology of chronic headache is important to understand in this context since essentially all patients that are treated in hospital have high frequency headache often associated with significant disability. This severity of illness produces both health care costs but also is responsible for significant impact on businesses and the economy. The method of treatment of headache in the hospital environment can follow several paths based on the accessibility of the resources specific to headache treatment. While there exist these differing paths of treatment only treatment in a dedicated headache treatment unit has been investigated in depth here in the US though reports from other countries that do not have dedicated inpatient treatment lends support to options in headache treatment. Some have suggested that inpatient treatment is not required even in recidivist patients and limited reports have examined aggressive outpatient treatment as an option in headache management. None of the studies reported to date provide class one evidence for efficacy either inpatient or outpatient. Recommendations are made to assess headache treatment in patients with high frequency headaches to garner better scientific evidence for differing treatment approaches.

Adult↗

Cardiovascular tolerability and safety of triptans: a review of clinical data.

Triptans are not widely used in clinical practice despite their well-established efficacy, endorsement by the US Headache Consortium, and the demonstrable need to employ effective intervention to reduce migraine-associated disability. Although the relatively restricted use of triptans may be attributed to several factors, research suggests that prescribers' concerns about cardiovascular safety prominently figure in limiting their use. This article reviews clinical data--including results of clinical trials, postmarketing studies and surveillance, and pharmacodynamic studies--relevant to assessing the cardiovascular safety profile of the triptans. These data demonstrate that triptans are generally well tolerated. Chest symptoms occurring during use of triptans are usually nonserious and usually not attributed to ischemia. Incidence of triptan-associated serious cardiovascular adverse events in both clinical trials and clinical practice appears to be extremely low. When they do occur, serious cardiovascular events have most often been reported in patients at significant cardiovascular risk or in those with overt cardiovascular disease. Adverse cardiovascular events also have occurred, however, in patients without evidence of cardiovascular disease. Several lines of evidence suggest that nonischemic mechanisms are responsible for sumatriptan-associated chest symptoms, although the mechanism of chest symptoms has not been determined to date. Importantly, most of the clinical trials and clinical practice data on triptans are derived from patients without known cardiovascular disease. Therefore, the conclusions of this review cannot be extended to patients with cardiovascular disease. The cardiovascular safety profile of triptans favors their use in the absence of contraindications.

Chest Pain↗