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Biomedical subjects

P Tfelt-Hansen

Publications and source records attributed to P Tfelt-Hansen.

At least 19 recordsLinked to original sources
PubMed2006

A review of evidence-based medicine and meta-analytic reviews in migraine.

The following systematic reviews and meta-analyses are presented and the results discussed: the evidence-based American guidelines, five systematic reviews on naratriptan, rizatriptan, eletriptan, sumatriptan and propranolol; a meta-analysis of sumatriptan, a meta-analysis of acute migraine therapy, a meta-analysis of triptans available in Canada and a large meta-analysis of oral triptans. The systematic reviews of several randomized trials of one drug overcome random effects in estimating treatment effect of the reviewed drug. The results from the large meta-analysis of several drugs are compared with head-to-head comparative trials. Results are generally the same in the meta-analysis and in the comparative trials, with some exceptions. Head-to-head comparisons should remain the 'gold standard' and meta-analyses are a useful supplement in cases when comparative trials are relatively small and when no comparative trials exist.

Analgesics↗
PubMed2006

The headache-inducing effect of cilostazol in human volunteers.

We have previously shown that nitric oxide (NO) and cyclic guanosine monophosphate (GMP) may cause headache and migraine. However, not all findings in previous studies can be explained by an activation of the NO-cGMP pathway. Calcitonin gene-related peptide (CGRP) causes headache and migraine in migraine patients, but CGRP receptor activation causes an increase in cyclic adenosine monophosphate (cAMP). In order to investigate the role of cAMP in vascular headache pathogenesis, we studied the effect of cilostazol, an inhibitor of cAMP degradation, in our human experimental headache model. Twelve healthy volunteers were included in a double-blind, randomized, crossover study. Placebo or cilostazol (200 mg p.o.) was administered on two separate study days. Headache was scored on a verbal rating scale (0-10) and mechanical pain thresholds were measured with von Frey hairs. The median peak headache score 0-16 h postdose was 0 (range 0-2) after placebo and 3.5 (range 0-7) after cilostazol (P = 0.003). The median headache curve peaked at 6-9 h postdose. The headaches induced were usually bilateral and pulsating. Nausea occurred in two volunteers, photo- and phonophobia were not seen. Two volunteers had a headache that fulfilled International Headache Society criteria for migraine without aura after cilostazol. No change in mechanical pain thresholds in the forehead was seen (P = 0.25). The headache after cilostazol was equal to or more severe than headache induced by glyceryl trinitrate in previous experiments. The present study thus indicates that increased levels of cAMP may play a role in headache and migraine pathogenesis.

Adult↗
PubMed2002

Sum of Pain Intensity Differences (SPID) in migraine trials. A comment based on four rizatriptan trials.

Sum of Pain Intensity Difference (SPID) is an outcome measure that summarizes treatment response over a clinically relevant period. SPID is widely reported in clinical trials of analgesics but has been little used in migraine trials. We compared SPID over 2 h with the standard migraine outcome measures of pain-free at 2 h and headache relief at 2 h using data from four published clinical trials of rizatriptan in migraine patients. In assessing treatment response (rizatriptan and sumatriptan versus placebo, rizatriptan versus sumatriptan, within-treatment dose effects), SPID usually yielded similar results to the more easily understood pain-free measure.

Humans↗
PubMed2001

Dose finding, placebo-controlled study of oral almotriptan in the acute treatment of migraine.

OBJECTIVE: To assess the efficacy and tolerability of oral almotriptan, a selective serotonin receptor (5-HT1B/1D) agonist, when used at different doses in the treatment of acute migraine. METHODS: This was a placebo controlled, double-blind, parallel-group, dose-finding study. Patients satisfying International Headache Society criteria for acute migraine were randomized to a single dose of placebo or oral almotriptan 2, 6.25, 12.5, or 25 mg at the onset of moderate or severe pain. Patients graded pain intensity on a 4-point verbal scale from 0 (no pain) to 3 (severe pain) and recorded adverse events. The primary efficacy variable was headache response at 2 hours. Data were analyzed on an intent-to-treat basis. RESULTS: Nine hundred and three patients were randomized, and 742 were included in the evaluation of the efficacy and tolerability. Headache response at 2 hours was 32.5% with placebo, and 30%, 56.3%, 58.5%, and 66.5% with almotriptan 2, 6.25, 12.5, and 25 mg doses (p < 0.05 for 6.25, 12.5, and 25 mg vs placebo). A dose-dependent decrease in the incidence of migraine-associated symptoms and the need for escape medication was observed. The incidence of adverse events with the almotriptan 2-mg, 6.25-mg, and 12.5-mg groups was comparable to that with the placebo group. CONCLUSION: Almotriptan 12.5 mg demonstrated the most favorable ratio between efficacy and tolerability, offering equivalent efficacy and better tolerability compared with the 25 mg dose. The minimum effective dose of almotriptan was 6.25 mg.

Acute Disease↗
PubMed2001

The efficacy and safety of sc alniditan vs. sc sumatriptan in the acute treatment of migraine: a randomized, double-blind, placebo-controlled trial.

This double-blind, placebo-controlled, parallel-group, multicentre, multinational, phase-III trial was designed to assess the efficacy and safety of a single subcutaneous injection of placebo, 2 doses of alniditan (1.4 mg and 1.8 mg) and 6 mg of sumatriptan in subjects with acute migraine. A total of 114 investigators from 13 different countries screened 2021 subjects. In total 924 patients were treated with placebo (157), alniditan 1.4 mg (309), alniditan 1.8 mg (141) and sumatriptan 6 mg (317). The lower number of subjects in the alniditan 1.8 mg group is due to the termination of this trial arm after the incidence of a serious adverse event and a subsequent protocol amendment. The number of subjects who were pain free at 2 h (primary endpoint) was: 22 (14.1%) with placebo, 174 (56.3%) with alniditan 1.4 mg, 87 (61.7%) with alnditan 1.8 mg and 209 (65.9%) with sumatriptan 6 mg. Alniditan 1.4 mg was significantly better (P < 0.001) than placebo and sumatriptan was significantly better (P = 0.015) than alniditan 1.4 mg. The number of responders (reduction of headache severity from moderate or severe headache before treatment to mild or absent at 2 h), was 59 (37.8%) on placebo, 250 (80.9%) on alniditan 1.4 mg, 120 (85.1%) on alniditan 1.8 mg, and 276 (87.1%) on sumatriptan. Response was significantly higher (P < 0.001) with alniditan 1.4 mg than with placebo, and significantly lower (P = 0.036) with alniditan 1.4 mg than with sumatriptan. Recurrence rates were: 22 (37.3%) with placebo, 87 (34.8%) with alniditan 1.4 mg, 35 (29.2%) with alniditan 1.8 mg and 108 (39.1%) with sumatriptan. Adverse events occurred in 577/924 (62.4%) subjects, i.e. in 62/157 (39.5%) with placebo, 214/309 (69.3%) with alniditan 1.4 mg, 91/141 (64.5%) with alniditan 1.8 mg and 210/317 (66.2%) with sumatriptan 6 mg. Sumatriptan was significantly better than alniditan 1.4 mg for pain free at 2 h. The difference, however, was small and clinically not important. For alniditan, a dose-dependent adverse event relationship was seen. The safety profile of alniditan 1.4 mg was similar to that of sumatriptan.

Acute Disease↗
PubMed2001

History of headache research in Denmark.

Headache research in Denmark started with the description in 1949 by Dalsgaard-Nielsen of the percutaneous nitroglycerin test. In 1976 Jes Olesen started The Copenhagen Acute Headache Clinic and from that time modern headache research began in Denmark. Specific changes in regional cerebral blood flow during attacks of migraine with aura, spreading oligaemia, were described for the first time in 1980. The first headache classification with operational diagnostic criteria was published in 1988 and used in a Danish population study from 1989. The lifetime prevalence of migraine was 8% in men and 25% in women. An intravenous nitroglycerin test was introduced in 1989 and has been developed as an experimental headache model. In 1993 it was suggested by Jes Olesen et al. that NO supersensitivity could be a possible molecular mechanism of migraine pain. Recent genetic studies have supported the distinction between migraine with aura and migraine without aura. From the middle of the 1980s the pathophysiology of tension-type headache has been investigated and recent results indicate central sensitization in patients with chronic tension-type headache.

Denmark↗
PubMed2001

Ergotamine, dihydroergotamine: current uses and problems.

In randomized clinical trials oral ergotamine was found superior to placebo but inferior to oral sumatriptan 100mg. In contrast rectal ergotamine was found to have higher efficacy (73% headache relief) than rectal sumatriptan (63% headache relief). Intranasal dihydroergotamine (DHE) was found superior to placebo but less effective than subcutaneous and intranasal sumatriptan. In general, the use of the more specific drugs, the triptans, causing less adverse events and being more effective, is preferable to the use of the ergotamine in the acute treatment of migraine. If ergotamine is to be used the rectal route is preferable. The rectal dose of ergotamine should be tailored to the individual patient. The intranasal dose of DHE , between 1 and 2 mg, should also be tailored to the individual patient. In order to avoid drug-induced headache ergotamine and DHE should not be used daily.

Analgesics, Non-Narcotic↗
PubMed2000

Comparison of the efficacy of zolmitriptan and sumatriptan: issues in migraine trial design.

In this international, multicentre, double-blind, placebo-controlled, single attack study, 'triptan naive' migraine patients were randomized in an 8:8:1 ratio to receive zolmitriptan 5 mg, sumatriptan 100 mg or placebo. The all-treated analysis included 1058 patients who took study medication. The primary endpoint, complete headache response, was reported by 39%, 38% and 32% of patients treated with zolmitriptan, sumatriptan and placebo, respectively, with no significant difference between treatment groups. In patients with moderate headache at baseline, complete response was significantly greater following zolmitriptan than after placebo (48% vs. 27%; P=0.01); there was no significant difference between sumatriptan and placebo groups (40% vs. 27%). In patients with severe baseline headache (where a greater reduction in headache intensity is required for a headache response), there was no significant difference between any groups in complete headache response rates. For secondary endpoints, active treatment groups were significantly superior to placebo for: 1-, 2- and 4-h headache response (e.g. 2-h headache response rates: zolmitriptan 59%; sumatriptan 61%; placebo 44%; P < 0.01 vs. placebo); pain-free response rates at 2 and 4 h; alleviation of nausea and vomiting; use of escape medication and restoration of normal activity. The incidence of adverse events was similar between zolmitriptan and sumatriptan groups but was slightly lower in the placebo group. The lack of difference between active treatments and placebo for complete response probably reflects the high placebo response obtained, which is probably a result of deficiencies in trial design. For example, the randomization ratio may result in high expectation of active treatment. Thus, while ethically patient exposure to placebo should be minimized, this must be balanced against the scientific rationale underpinning study design.

Adolescent↗
PubMed2000

Ergotamine in the acute treatment of migraine: a review and European consensus.

Ergotamine has been used in clinical practice for the acute treatment of migraine for over 50 years, but there has been little agreement on its place in clinical practice. An expert group from Europe reviewed the pre-clinical and clinical data on ergotamine as it relates to the treatment of migraine. From this review, specific suggestions for the patient groups and appropriate use of ergotamine have been agreed. In essence, ergotamine, from a medical perspective, is the drug of choice in a limited number of migraine sufferers who have infrequent or long duration headaches and are likely to comply with dosing restrictions. For most migraine sufferers requiring a specific anti-migraine treatment, a triptan is generally a better option from both an efficacy and side-effect perspective.

Analgesics, Non-Narcotic↗
PubMed2000

Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy.

Triptans are a new class of compounds developed for the treatment of migraine attacks. The first of the class, sumatriptan, and the newer triptans (zolmitriptan, naratriptan, rizatriptan, eletriptan, almotriptan and frovatriptan) display high agonist activity at mainly the serotonin 5-HT1B and 5-HT1D receptor subtypes. As expected for a class of compounds developed for affinity at a specific receptor, there are minor pharmacodynamic differences between the triptans. Sumatriptan has a low oral bioavailability (14%) and all the newer triptans have an improved oral bioavailability and for one, risatriptan, the rate of absorption is faster. The half-lives of naratriptan, eletriptan and, in particular, frovatriptan (26 to 30h) are longer than that of sumatriptan (2h). These pharmacokinetic improvements of the newer triptans so far seem to have only resulted in minor differences in their efficacy in migraine. Double-blind, randomised clinical trials (RCTs) comparing the different triptans and triptans with other medication should ideally be the basis for judging their place in migraine therapy. In only 15 of the 83 reported RCTs were 2 triptans compared, and in 11 trials triptans were compared with other drugs. Therefore, in all placebo-controlled randomised clinical trials, the relative efficacy of the triptans was also judged by calculating the therapeutic gain (i.e. percentage response for active minus percentage response for placebo). The mean therapeutic gain with subcutaneous sumatriptan 6mg (51%) was more than that for all other dosage forms of triptans (oral sumatriptan 100mg 32%; oral sumatriptan 50mg 29%: intranasal sumatriptan 20mg 30%; rectal sumatriptan 25mg 31%; oral zolmitriptan 2.5mg 32%; oral rizatriptan 10mg 37%; oral eletriptan 40mg 37%; oral almotriptan 12.5mg 26%). Compared with oral sumatriptan 100mg (32%), the mean therapeutic gain was higher with oral eletriptan 80mg (42%) but lower with oral naratriptan 2.5mg (22%) or oral frovatriptan 2.5mg (16%). The few direct comparative randomised clinical trials with oral triptans reveal the same picture. Recurrence of headache within 24 hours after an initial successful response occurs in 30 to 40% of sumatriptan-treated patients. Apart from naratriptan, which has a tendency towards less recurrence, there appears to be no consistent difference in recurrence rates between the newer triptans and sumatriptan. Rizatriptan with its shorter time to maximum concentration (tmax) tended to produce a quicker onset of headache relief than sumatriptan and zolmitriptan. The place of triptans compared with non-triptan drugs in migraine therapy remains to be established and further RCTs are required.

Animals↗