Biomedical subjects

Frederick G Freitag

Publications and source records attributed to Frederick G Freitag.

10 recordsLinked to original sources

PubMed2006

Oral sumatriptan for the acute treatment of probable migraine: first randomized, controlled study.

OBJECTIVE: To evaluate the efficacy and tolerability of sumatriptan tablets in adults who meet International Headache Society (IHS) criteria for probable migraine but who do not meet IHS criteria for migraine with or without aura. BACKGROUND: Headaches with some but not all of the features of migraine meet criteria for probable migraine, a form of migraine recognized by the IHS. Probable migraine attacks are also prevalent and frequently underdiagnosed. METHODS: This was a randomized, multicenter, double-blind, placebo-controlled, parallel-group study. Adults (18 to 65 years) with a 1-year history of headaches that met 2004 IHS criteria for probable migraine without aura (same operational definition as 1988 IHS migrainous disorder) were eligible for enrollment. All patients were triptan- and ergot-naïve and had never been diagnosed with migraine. Patients were randomized in a 1:1:1:1 fashion to receive sumatriptan 25, 50, or 100 mg conventional tablets or matching placebo and were instructed to treat a single moderate or severe probable migraine attack. A post hoc analysis was conducted to evaluate the population of patients who achieved headache relief sustained throughout the immediate posttreatment period. Patients who reported relief within 2 hours and subsequently lost headache relief within 4 hours were considered nonresponders. RESULTS: At 2 hours, more patients treated with sumatriptan achieved headache relief, the primary efficacy measure, compared with placebo, but differences only approached statistical significance for 100 mg (P= .053). The 2-hour headache relief rate in the sumatriptan 25 or 50 mg groups was not significantly different than placebo. The time to use of rescue was significantly shorter in the placebo group compared with the sumatriptan 100 mg group (P= .002). The time to use of rescue in the sumatriptan 25 or 50 mg groups was not significantly different than placebo. More patients treated with placebo (22%) lost headache relief within 4 hours compared with patients treated with sumatriptan 25 mg (17%), 50 mg (14%), or 100 mg (7%). A post hoc analysis demonstrated that at 2 hours, headache relief sustained through 4 hours (S 0-4 hours) was achieved in 44%, 49%, and 57% of patients treated with sumatriptan 25, 50, and 100 mg, respectively, compared with 34% of patients treated with placebo (P < .05 for sumatriptan 50 and 100 mg vs. placebo). All doses of sumatriptan were well tolerated and no serious adverse events were reported. CONCLUSION: These results suggest that oral sumatriptan may be effective and is well tolerated for the acute treatment of probable migraine without aura, however, the difference between sumatriptan and placebo was not statistically significant for the a priori defined primary endpoint.

Acute Disease↗

PubMed2005

Pain-free rates with zolmitriptan 2.5 mg ODT in the acute treatment of migraine: results of a large double-blind placebo- controlled trial.

CONTEXT: Zolmitriptan 2.5 mg orally disintegrating tablets (ODT) allow patients to take the medication without fluids, which is convenient and avoids the risk of fluid-induced exacerbation of nausea/vomiting. OBJECTIVE: To evaluate the efficacy and tolerability of zolmitriptan 2.5 mg ODT taken as soon as possible after onset of a migraine. DESIGN: Multicenter, double-blind, parallel-group, placebo-controlled two-attack trial. SETTING: Outpatient headache clinics in the US. PATIENTS: 608 patients were randomized; 566 patients treated at least 1 migraine and were included in the tolerability assessment (565 patients were included in the intent-to-treat population). INTERVENTION: Patients were randomized to either zolmitriptan 2.5 mg ODT or placebo. Patients treated up to 2 migraine attacks as soon as possible after the start of their migraine pain. MAIN OUTCOME MEASURE: Pain-free rates at 2 h. RESULTS: Zolmitriptan 2.5 mg ODT (n = 281) demonstrated a significant pain-free rate vs. placebo (n = 284) at 2 h (40% vs. 20%, p < 0.001), 1.5 h (25% vs. 15%, p < 0.001), and 1 h (13% vs. 8%, p = 0.004). Sustained pain-free rate was significantly higher than placebo (31% vs. 15%; p < 0.001). Return to normal activities favored zolmitriptan 2.5 mg ODT at 1 h (p = 0.004), 1.5 h (p < 0.001), and 2 h (p < 0.001). Adverse events associated with zolmitriptan 2.5 mg ODT were those commonly reported with the use of triptans. CONCLUSIONS: Zolmitriptan 2.5 mg ODT, taken as early as possible after onset of a migraine attack, is effective in the treatment of migraine, producing a significantly higher pain-free rate than placebo 2 h post-dose, and also at the earlier time points of 1 h and 1.5 h post-dose.

Acute Disease↗

PubMed2004

Cluster headache.

Cluster headache is a relatively rare episodic headache disorder.Although traditionally it is believed to be a male-related disorder,the sex ratios are changing toward a more even balance. The disorder is characterized by bouts of daily headaches with pain-free remissions for extended times. Though attacks are brief, they are severe and typically are associated with autonomic symptoms. Medical therapies are the mainstay of treatment, with the goal being prevention of headaches in a cycle. Acute therapies, although effective, may be limited in usefulness because of attack frequency. Intractable cases may benefit from histamine desensitization and surgical treatments.

Adaptation, Psychological↗

PubMed2004

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↗

PubMed2003

Preventative treatment for migraine and tension-type headaches : do drugs having effects on muscle spasm and tone have a role?

Baclofen, tizanidine and botulinum toxin A, agents used to treat disorders of muscle tone, have been studied as potential preventative treatments for migraine, tension-type headache and other related disorders. The most extensive work has been completed with botulinum toxin A. However, there is still a paucity of well controlled, clinical trials with this agent, and overall there have been conflicting and oftentimes equivocal results: studies of its use in migraine headache have suggested efficacy, whereas those of tension-type headache have not shown significant evidence of efficacy. There were few significant adverse events associated with the use of botulinum toxin A in these trials. The mechanism by which botulinum toxin A may work to prevent headache is not clear. Although changes in muscle tone may play a role in the effect of the drug, central mechanisms such as effects on neuropeptides involved in the pathogenesis of migraine may also be relevant. Further clinical trial work is in progress to help determine optimal administration schedules and choice of injection locations with botulinum toxin A for specific headache disorders. There has been limited study of the use of baclofen, an agent that acts centrally via GABA(A) receptors, in migraine and cluster headache, with only two open trials conducted to date. Both of these studies support the use of baclofen in the preventive treatment of headache.Tizanidine, which may have both a peripheral and a central mechanism in the locus ceruleus in migraine headache, has been studied in several clinical trials. Although the primary mechanism of action of this agent is, like clonidine, as an alpha-adrenoceptor agonist, it has little antihypertensive effect. Open trials of tizanidine have shown it to be useful in chronic headache. One well controlled trial, conducted as a follow-up to an open-label trial in the preventive treatment of chronic daily headache, reported tizanidine as having a statistically significant benefit over placebo. Also of interest is its use in conjunction with a long-acting NSAID to aid in the treatment of rebound headache accompanying the discontinuation of overused acute migraine therapies. In conclusion, though limited, the studies suggest the efficacy of botulinum toxin A, baclofen and tizanidine in primary headache disorders.

Baclofen↗

PubMed2003

Divalproex in the treatment of migraine.

Valproic acid has been used in the treatment of migraine headache for nearly 20 years. During this period of use several additional delivery modes have been developed to either improve tolerability or patient compliance with the divalproex sodium formulation and the extended-release formulation of divalproex sodium. Additionally, an intravenous formulation has become available which permits rapid achievement of therapeutic levels of the drug. There have been a number of reports on the use of valproic acid in migraine and other headache disorders, suggesting it to be an efficacious treatment. This paper reviews the results of the published reports of valproic acid in migraine and other headache disorders, including open-label studies, comparator trials, and double-blind, placebo-controlled trials. These studies have been conducted with the various formulations of valproic acid that have been on the market. The papers utilized in this study were obtained though Medline searches on valproic acid and divalproex sodium coupled with the various headache disorders. Additionally, the CD-ROM of past issues of Headache and Cephalalgia was reviewed for similar keywords. Lastly, the indices of the journal Headache Quarterly were reviewed for additional articles on valproic acid and divalproex sodium. Valproic acid in its various formulations has been demonstrated to be an efficacious and well-tolerated agent for the preventive treatment of migraine, chronic daily headache, and cluster headache. Additionally, it has been demonstrated to be efficacious and well tolerated in treating acute migraine attacks when given as an intravenous solution.

Animals↗

PubMed2002

A randomized trial of divalproex sodium extended-release tablets in migraine prophylaxis.

OBJECTIVE: To evaluate the efficacy and safety of extended-release divalproex sodium compared with placebo in prophylactic monotherapy treatment of migraine headache. METHODS: This was a double-blind, randomized, placebo-controlled, parallel-group study. Subjects with more than two migraine headache attacks during a 4-week baseline were randomly assigned in a 1:1 ratio at each center to receive either extended-release divalproex sodium or matching placebo once daily for 12 weeks. Subjects initiated treatment on 500 mg once daily for 1 week, and the dose was then increased to 1,000 mg once daily with an option, if intolerance occurred, to permanently decrease the dose to 500 mg during the second week. Reduction from baseline in 4-week migraine headache rate was the primary efficacy variable. Migraine headaches separated by a < 24-hour headache-free interval were counted as single migraines in calculating migraine headache rates. Tolerance and safety were also evaluated. RESULTS: The mean reductions in 4-week migraine headache rate were 1.2 (from a baseline mean of 4.4) in the extended-release divalproex sodium group and 0.6 (from a baseline mean of 4.2) in the placebo group (p = 0.006); reductions with extended-release divalproex sodium were significantly greater than with placebo in all three 4-week segments of the treatment period. No significant differences were detected between treatment groups in either the overall incidence or in the incidence of any specific treatment-emergent adverse event; 8% of subjects treated with extended-release divalproex sodium and 9% of those treated with placebo discontinued for adverse events. CONCLUSION: Extended-release divalproex sodium is an efficacious, well-tolerated, safe, and easy-to-use once-a-day prophylactic antimigraine medication.

Adolescent↗

PubMed2002

Do over-the-counter medications help the physician manage migraine headache?

The use of over-the-counter-medication in migraine treatment is commonplace. They are often used in addition to physician-prescribed medications and may be used without the full knowledge of the physician. Although considerable evidence suggests their efficacy in migraine treatment, they are rarely used to maximal levels of efficacy and safety. A review of the evidence for these treatments is important for cost effective, well-tolerated, and specific treatment of migraine headache.

Clinical Trials as Topic↗

PubMed2002

Divalproex sodium in the treatment of migraine and cluster headaches.

The discovery of a new class of effective migraine-abortive medications, the triptans, has sparked a new interest in the study of vascular headache. Over the past few years, the Food and Drug Administration (FDA) has approved six new abortive pharmacologic therapies, with several others in various stages of clinical trials. Unfortunately, concurrent pharmacologic changes in headache prophylaxis have not kept pace with their abortive counterparts. However, divalproex sodium (Depakote), which is approved by the FDA as a migraine prophylactic agent, is the first in the anticonvulsant class of medication for migraine headache and has expanded the options in headache treatment. The objective of this retrospective multicenter study of 284 patients with migraine or cluster headaches was to examine the clinical efficacy and safety of divalproex sodium as prophylaxis in monotherapy and in polytherapy. Sixty-one percent of migraineurs and 73% of cluster patients noted a decrease in pain with divalproex sodium and continued that therapy for more than 3 months. Reported negative side effects included weight gain, nausea, somnolence, tremor, alopecia, dysequilibrium, and rash. However, only 14% of subjects discontinued therapy due to these side effects. Overall, divalproex sodium was found to be an effective and generally well-tolerated prophylactic treatment option as monotherapy or in polytherapy for migraine and cluster headache.

Cluster Headache↗

PubMedDate not supplied

Tramadol/acetaminophen for the treatment of acute migraine pain: findings of a randomized, placebo-controlled trial.

OBJECTIVE: To compare tramadol/acetaminophen (APAP) and placebo for the management of acute migraine pain. BACKGROUND: Tramadol/APAP tablets reduced moderate-to-moderately severe acute pain in controlled studies of other painful conditions. METHODS: This randomized, double-blind, placebo-controlled, parallel group study enrolled adults with migraine pain as per International Headache Society criteria. Subjects took tramadol/APAP (total dose, 75 mg/650 mg) or placebo for a typical migraine with moderate-to-severe pain. Severity of pain and migraine-related symptoms were recorded before study medication and at 0.5, 1, 2, 3, 4, 6, and 24 hours after study medication. RESULTS: Efficacy analyses included 305 subjects (154 tramadol/APAP and 151 placebo). Treatment response was higher for tramadol/APAP than a placebo at 2 hours after dosing (55.8% vs. 33.8%, P < .001) and at every other assessment from 30 minutes (12.3% vs. 6.6%) through 6 hours (64.9% vs. 37.7%) (all P< or = .022). Subjects in the tramadol/APAP group were more likely than those in the placebo group to be pain-free at 2 hours (22.1% vs. 9.3%), 6 hours (42.9% vs. 25.2%), and 24 hours (52.7% vs. 37.9%) (all P< or = .007). Two hours after dosing, moderate-to-severe symptoms that were less common for tramadol/APAP than placebo included photophobia (34.6% vs. 52.2%, P= .003) and phonophobia (34.3% vs. 44.9%, P = .008), but not migraine-related nausea (38.5% vs. 29.4%, P= .681). Treatment-related adverse events included nausea, dizziness, vomiting, and somnolence. CONCLUSIONS: Tramadol/APAP reduces the severity of pain, photophobia, and phonophobia associated with migraine headache, but does not reduce migraine-associated nausea. Tramadol/APAP might be an appropriate option for the management of moderate-to-severe migraine headache.

Acetaminophen↗