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Egilius L H Spierings

Publications and source records attributed to Egilius L H Spierings.

At least 19 recordsLinked to original sources
PubMed2005

Part II: clinical efficacy and tolerability of zolmitriptan orally disintegrating tablet in the acute treatment of migraine.

Controlled clinical trials and extensive clinical use of conventional oral tablets of zolmitriptan, a selective agonist of serotonin1B/1D receptors, have proven the compound to be fast-acting, highly effective, and well-tolerated in the acute treatment of migraine. An orally disintegrating tablet (ODT) of zolmitriptan that dissolves on the tongue without the need for fluid intake has been developed in order to provide an acceptable, convenient alternative for patients who prefer not to, or cannot, take conventional tablets. A fast onset of effective, sustained pain relief was predicted for zolmitriptan ODT on the basis of its bioequivalence with the conventional tablet, which has been confirmed in three randomised, double-blind, placebo-controlled trials of zolmitriptan ODT in the acute treatment of migraine. Compared with placebo, significantly higher proportions of patients treated with zolmitriptan ODT responded to treatment (reduction of moderate or severe headache to mild or no pain) as early as 30 minutes after dosing. Headache response was maintained at 24 hours in significantly higher proportions of patients receiving zolmitriptan ODT compared with placebo. Zolmitriptan ODT also resulted in significantly greater pain-free rates than placebo as early as 1 hour after dosing. Zolmitriptan ODT relieved patients of other migraine-associated symptoms, including nausea, photophobia and phonophobia, and enabled >50% of patients to resume normal daily activities 2 hours after dosing. Adverse events observed with zolmitriptan ODT were similar to those associated with the serotonin1B/1D agonists as a class, and were generally transient and of mild or moderate intensity.

Acute Disease↗
PubMed2005

Migraine during pregnancy: options for therapy.

Migraine is common during pregnancy, but fortunately this combination of conditions obviously exists for only a finite period. The greatest frequency of migraine attacks occurs during the first trimester. Accurate diagnosis is a sine qua non in this setting as in any headache patient. It is in the first trimester that the fetus is at greatest risk from abortifacient and teratogenic drugs, and when very early pregnancy may be undiagnosed. Ergot alkaloids (including methysergide) should be avoided during pregnancy because of their teratogenicity, and most other drug classes should be used only when unavoidable. The use of prophylactic agents during pregnancy should be the exception, not the rule, and preferably only during the second and third trimesters; propranolol is probably safest in this situation. De novo headache during pregnancy usually requires expert review of the patient. Treatment tactics for uncomplicated migraine in pregnancy depend on the concurrent clinical situation. Paracetamol (acetaminophen) is the mainstay for the patient whose typical attacks continue into the first trimester. If paracetamol is insufficient, then partial agonist opioids may be used if typical migraine attacks persist in the second and third trimesters (which is uncommon). 'Chronic migraine' in pregnancy, i.e. >or=15 headache days per month, is rare, and is the greatest therapeutic challenge. Co-morbidities such as depression or epilepsy require specialised approaches. The complexities associated with these tactics are discussed in this article, and it is emphasised that none has the specific approval of regulatory authorities. Heightened pharmacovigilance will better inform the future pregnant migraineur. However, this type of information is less likely to be available for novel classes of neuropharmacological agents than for existing ones.

Analgesics↗
PubMed2004

The aura-headache connection in migraine: a historical analysis.

A historical analysis is presented of insights into the pathogenetic mechanisms related to the migraine aura and headache and how the mechanisms connect. In the traditional sequential concept, advanced through the work of Edward Liveing, MD, Harold G. Wolff, MD, and others, the mechanisms are considered causally connected. A noncausal, parallel concept has been proposed as well and is considered in light of the results of recent animal experimental studies.

Animals↗
PubMed2004

Consequences of transforming measures of efficacy for acute therapies: 5-HT agonists as a worked example.

OBJECTIVES: To examine whether the distributions of active and placebo response rates change after transformation into therapeutic gains, numbers needed to treat, and therapeutic ratios for 51 published clinical trials of 5-HT(1B/1D) agonists in the acute treatment of migraine. BACKGROUND: Acute migraine therapies have been compared using meta-analysis. Before pooling the results of noncontemporaneous clinical trials for meta-analysis, reconciliation of active response rates with concurrent placebo controls is done because of fluctuations in placebo response rates. The 3 common methods of reconciliation are to find for each clinical trial the therapeutic gain, the number needed to treat, or the therapeutic ratio. METHODS: Raw active and placebo response rates were tabulated and displayed as histograms. The distributions of the therapeutic gains, numbers needed to treat, and therapeutic ratios were similarly plotted. These distributions were then compared with normal distributions using chi-squared goodness-of-fit methodology. RESULTS: The distribution of active response rates was consistent with a normal distribution (passing a goodness-of-fit test). Placebo response rates were not normally distributed. The distribution of therapeutic gains failed a test of normality (P=.018), as did the numbers needed to treat (P <.001); the skews of these distributions were toward opposite ends of the scale for relative efficacy. The therapeutic ratios also failed a test for normality, but passed a test for log-normal distribution. CONCLUSIONS: Choice of transformation is a potential source of bias in meta-analysis of acute migraine therapies.

Acute Disease↗
PubMed2004

Acute treatment of migraine with zolmitriptan 5 mg orally disintegrating tablet.

OBJECTIVE: To determine the speed of onset of headache response and duration of response with zolmitriptan 5 mg orally disintegrating tablet (ODT) in the acute treatment of migraine. BACKGROUND: Rapid pain relief is important for migraine sufferers. The early efficacy (30 minutes) of the 5 mg dose of the zolmitriptan ODT formulation was evaluated. METHODS: In this double-blind, parallel-group trial, 670 patients were randomised to receive either zolmitriptan 5 mg ODT (n=329) or matching placebo (n=341) to treat two migraine headaches of moderate or severe intensity. RESULTS: Zolmitriptan 5 mg ODT was significantly more effective than placebo in achieving a headache response (reduction in migraine headache intensity from moderate or severe to mild or no pain) at 30 minutes (16.5% vs 12.5%; p=0.048; primary endpoint), 1 hour (p <0.0001), and 2 hours (p <0.0001). Significantly more patients achieved a sustained headache response for 24 hours with zolmitriptan 5 mg ODT than with placebo (42.5% vs 16.4%; p <0.0001). Zolmitriptan 5 mg ODT also produced a higher pain-free rate than placebo at all timepoints (0.5, 1 and 2 hours post-dose), with the differences becoming significant at 1 hour. Adverse events were reported by 37.7% of the patients treated with zolmitriptan 5 mg ODT and 18.1% of the patients treated with placebo. Those that occurred most often for the patients treated with zolmitriptan 5 mg ODT were tightness (7.0%), dizziness (6.7%), somnolence (6.7%) and paraesthesias (6.1%). CONCLUSIONS: A significant headache response as early as 30 minutes post-dose and good maintenance of this headache response at 24 hours makes zolmitriptan 5 mg ODT an excellent acute treatment for migraine. Together with the relatively low adverse event rate, these data demonstrate that zolmitriptan 5 mg ODT is a valuable therapy for migraine sufferers.

Acute Disease↗
PubMed2003

Headache following cervical sympathectomy and results of a blood flow study in the cat.

BACKGROUND: A patient developed severe, continuous, unilateral headache that was "vascular" in nature, following cervical sympathectomy. OBJECTIVE: To determine the changes in cranial blood flow in the cat following lesioning and stimulation of the cervical sympathetic nerve. METHOD: Carotid blood flow was determined by electromagnetic flowmetry and its tissue distribution by intra-arterial injection of 15-microm radioactive microspheres. RESULTS: Following sympathetic lesioning, an increase in carotid blood flow was observed and reversed with stimulation. The distribution of carotid blood flow changed for the brain only, maintaining relatively constant tissue perfusion. CONCLUSION: An increase in cerebral blood flow could not have accounted for the sympathectomy-induced headache. Dilation of major cerebral arteries and cranial noncerebral vasodilation probably constitutes its mechanism.

Animals↗
PubMed2002

Mechanism and management of migraine.

Migraine is a condition that affects 10%-15% of the population. Abortive treatment is always indicated because the intense headaches interfere with normal functioning. Preventive treatment is indicated when the headaches exceed 3-4 per month.

Adrenergic beta-Antagonists↗
PubMed2002

Evidence-based assessment of pregnancy outcome after sumatriptan exposure.

OBJECTIVE: Assessment of best available evidence for tolerability of sumatriptan after inadvertent exposure during pregnancy. BACKGROUND: Migraine's demography suggests that inadvertent exposure to acute therapies is likely during the earliest undiagnosed stages of pregnancy. The tolerability of such therapies under these conditions is not amenable to clinical trial for ethical reasons. In the United States, sumatriptan is currently labeled pregnancy category C (ie, not recommended for use during pregnancy unless the potential benefit justifies the potential risk to the fetus). METHODS: Three types of adverse events were studied: spontaneous abortion, fetal abnormality, and obstetric complications. Traditional evidence-based criteria were used to assess a search-protocol product of four clinical studies and two case reports. RESULTS: The single positive finding ("preterm delivery" without low birth weight) was in the smallest study; this study was retrospective and the finding was externally inconsistent with the other three larger studies, all of which were prospective. No study followed children for more than 4 years, which is the period needed to identify the maximum number of congenital anomalies. Rigorous teratological technique was generally not employed. Post hoc power calculations were used to provide parameters of the hazard detectable by these studies in aggregate. CONCLUSIONS: Pregnancy categories B and C both seem feasible for sumatriptan. Within the limits of the examined studies, there is no evidence for any specific effect of sumatriptan on pregnancy outcome. Patients inadvertently exposed to sumatriptan during an early stage of pregnancy should be reassured by these data.

Abnormalities, Drug-Induced↗
PubMed2002

Headache of gastrointestinal origin: case studies.

Three patients with headache of gastrointestinal origin are described. Reflux, dyspepsia, and constipation caused the headaches, which responded promptly to treatment of the respective gastrointestinal disorders.

Adult↗
PubMed2002

Tolerability and safety of frovatriptan with short- and long-term use for treatment of migraine and in comparison with sumatriptan.

OBJECTIVE: To evaluate the tolerability and safety of frovatriptan 2.5 mg in patients with migraine. BACKGROUND: Frovatriptan is a new, selective serotonin agonist (triptan) developed for the acute treatment of migraine. Dose range-finding studies identified 2.5 mg as the dose that conferred the optimal combination of efficacy and tolerability. METHODS: The tolerability and safety of frovatriptan 2.5 mg were assessed during controlled, acute migraine treatment studies, including a study that compared frovatriptan 2.5 mg with sumatriptan 100 mg, as well as a 12-month open-label study during which patients could take up to three doses of frovatriptan 2.5 mg within a 24-hour period. Safety and tolerability were assessed through the collection of adverse events, monitoring of heart rate and blood pressure performance of 12-lead electrocardiogram, hematology screen, and blood chemistry studies. RESULTS: In the short-term studies, 1554 patients took frovatriptan 2.5 mg and 838 took placebo. In the 12-month study, 496 patients treated 13 878 migraine attacks. Frovatriptan was well tolerated in the short- and long-term studies with 1% of patients in the short-term studies and 5% of patients in the long-term study withdrawing due to lack of tolerability. The incidence of adverse events was higher in the frovatriptan-treated patients than in the patients who took placebo (47% versus 34%) and the spectrum of adverse events was similar. When compared to sumatriptan 100 mg, significantly fewer patients taking frovatriptan experienced adverse events (43% versus 36%; P=.03) and the number of adverse events was lower (0.62 versus 0.91), there were also fewer adverse events suggestive of cardiovascular symptoms in the frovatriptan group. Analysis of the entire clinical database (n=2392) demonstrated that frovatriptan was well tolerated by the patients regardless of their age, gender, race, concomitant medication, or the presence of cardiovascular risk factors. No effects of frovatriptan on heart rate, blood pressure, 12-lead electrocardiogram, hematology screen, or blood chemistry were observed. No patient suffered any treatment-related serious adverse event. CONCLUSIONS: Short- and long-term use of frovatriptan 2.5 mg was well tolerated by a wide variety of patients. Frovatriptan treatment produced an adverse events profile similar to that of placebo, and in a direct comparison study was better tolerated than sumatriptan 100 mg.

Acute Disease↗