
Peer Tfelt-HansenUniversity of Copenhagen · Department of Clinical Medicine
Peer Tfelt-Hansen
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Introduction
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Publications
Publications (179)
Background:
Cochrane Reviews are methodologically of high quality but the clinical relevance of analysed efficacy measures (EMs) should also be assessed.
Methods:
The clinical relevance of EMs used in one systematic Cochrane review of oral zolmitriptan for migraine headache was evaluated.
Results:
The following EMs were used: pain free at two...
According to a new systematic review, placebo treatment in clinical trials of migraine prophylaxis results in responder rates ranging from 0-56%, probably owing to variable combinations of spontaneous improvement and genuine placebo effects. Clinicians who treat patients with migraine should be aware of the potential nonspecific effects of any trea...
Introduction:
The development of sumatriptan, more than 20 years ago, added substantially to the characterization of 5-hydroxytryptamine (5-HT) receptors and their relevance to acute migraine therapy. Recently, 5-HT1F receptor agonists, with no vascular effects, have shown efficacy in the treatment of migraines.
Areas covered:
This evaluation re...
"Ergot alkaloids (ergotamine, dihydroergotamine) are used in patients with frequent, moderate migraine, but are less effective than triptans" [1] .
A 46-year-old male with juvenile myoclonic epilepsy was admitted to the neurological department for convulsive seizures just after lamotrigine was discontinued. On admission he was awake but had a right-sided hemiparesis with Babinski sign and ataxic finger-nose test on the left side. An MR scan showed a left-sided pontine infarction, an infarct in...
Introduction:
If a drug has a slow dissociation from the receptor this can result in a long duration of effect and a slow effect. The long duration of the antimigraine effect of dihydroergotamine (DHE) has been reported previously whereas a possible slow onset of DHE's antimigraine effect, which is the subject of this review, has only rarely been...
Peer Carsten Tfelt-Hansen, Glostrup, Denmark: According to the recent American Academy of Neurology (AAN) guideline update, a drug can be recommended as possibly effective for migraine prevention if it had demonstrated efficacy in one Class II study.(1) Eight drugs are recommended as possibly effective,(1) and there are several drugs for which I wo...
The most important question in diagnosing cluster headache is the duration (usually 15 to 180 min) of the extremely severe headache. This is illustrated with two case stories.
The effective anti-migraine drugs triptans, all bind with high affinity to three serotonin (5-HT) subtypes, the 5-HT1B, 5-HT1D and 5-HT1F. 5- HT1B mRNA is densely localized within smooth muscle, and less in the endothelium of cerebral blood vessels. This vascular distribution of 5-HT1B receptor has been shown to mediate the vasoconstrictive propert...
Background / Purpose:
To reduce study start-up time, increase data sharing, and assist investigators conducting clinical studies, the National Institute of Neurological Disorders (NINDS) embarked on an initiative to create common data elements (CDEs) for neuroscience clinical research, and is working with headache experts to develop disease-speci...
Preventive treatment is an approach that is often forgotten in the treatment of migraine: in 2007, Lipton et al. reported that 39% of patients with this condition met the criteria to be considered for or offered preventive medication, yet only 12% currently receive such treatment.¹ Therefore, the updated US evidence-based guidelines for the use of...
The prevalence of cluster headache is 0.1% and cluster headache is often not diagnosed or misdiagnosed as migraine or sinusitis. In cluster headache there is often a considerable diagnostic delay — an average of 7 years in a population-based survey. Cluster headache is characterized by very severe or severe orbital or periorbital pain with a durati...
Lasmiditan is a novel selective 5-HT(1F) receptor agonist. It is both scientifically and clinically relevant to review whether a 5-HT(1F) receptor agonist is effective in the acute treatment of migraine. Two RCTs in the phase II development of lasmiditan was reviewed. In the intravenous placebo-controlled RCT, lasmiditan doses of 2.5-45 mg were use...
Migraine is a common disorder with a female prevalence of 17% and a male prevalence of 9%. Migraine is most often disabling and the patients need treatment of the attacks. The introduction of triptans has been a revolution for many migraine patients but only a minority of patients use these specific drugs. The pharmacokinetics and efficacy and tole...
In 1991 the Clinical Trials Subcommittee of the
International Headache Society (IHS) published its
first edition of the Guidelines on controlled trials of
drugs in migraine (1). The Guidelines’ overarching
goal was to improve ‘the quality of controlled clinical
trials in migraine’, which could be achieved by using
scientifically robust methods of c...
In 92 migraine patients and 44 healthy control subjects we recorded regional cerebral blood flow (rCBF) with single photon emission computerized tomography and 133Xe inhalation or with i.v. 99mTc-HMPAO. Migraine patients were studied interictally. A quantitated analysis of right-left asymmetry indices in a fixed set of regions of interest was compa...
In a randomized, multi-centre, double-blind, placebo-controlled, parallel group study, the efficacy of 100 mg oral sumatriptan was compared with that of placebo in the treatment of episodic tension-type headache. The patients were recruited from the general population in the vicinity of the study centres, by randomly mailed invitations. One or more...
There is a striking similarity between the migraine-provoking effect of the nitric oxide (NO) donor glyceryl trinitrate (GTN) and that of calcitonin gene-related peptide (CGRP). We tested the hypothesis that NO releases CGRP to cause the delayed migraine attack after GTN.
In a double-blind-cross-over study, 13 migraine without aura (MO) patients we...
The Clinical Trials Subcommittee of the International Headache Society published its first edition of the guidelines on controlled trials of drugs in tension-type headache in 1995. These aimed ‘to improve the quality of controlled clinical trials in tension-type headache’, because ‘good quality controlled trials are the only way to convincingly dem...
Several personal descriptions of migraine with aura from 1870 onwards reported a slow, gradual progression of symptoms. Lashley in 1941 meticulously chartered his own auras and concluded that the symptomatology reflected a cortical process progressing with a speed of 3 mm/min across the primary visual cortex. Leão described cortical spreading depre...
Provoking delayed migraine with nitroglycerin in migraine sufferers is a cumbersome model. Patients are difficult to recruit, migraine comes on late and variably and only 50-80% of patients develop an attack. A model using normal volunteers would be much more useful, but it should be validated by testing the response to drugs of known efficacy in a...
Glyceryl trinitrate (GTN) induces delayed migraine attacks in migraine patients. The purpose of this study was to investigate whether pre-treatment with prednisolon could decrease this effect of GTN.
In this double-blind, randomized and placebo-controlled, crossover study 15 migraineurs with migraine without aura were pre-treated with 150 mg of pre...
A 31-year-old man with acute-onset of left-sided weakness following the sniffing of cocaine was admitted with rhabdomyolysis. Neurophysiological studies showed axonal degeneration in 4/10 sensory and 3/8 motor nerves, and conduction block outside the typical compression-sites in 3/8 motor nerves. The findings are consistent with a diagnosis of mult...
Stress is a provoking factor for both tension-type headache and migraine attacks. In the present single-blind study, we investigated if stress induced by norepinephrine (NE) could elicit delayed headache in 10 healthy subjects and recorded the cranial arterial responses. NE at a dose of 0.025 microg kg(-1) min(-1) or placebo was infused for 90 min...
No new preventive drugs specific to migraine have appeared for the last 20 years and existing acute therapies need improvement. Unfortunately, no animal models can predict the efficacy of new therapies for migraine. Because migraine attacks are fully reversible and can be aborted by therapy, the headache- or migraine-provoking property of naturally...
Systematic prospective records of aura symptoms were obtained from 50 patients, who filled in report forms during the aura phase of two attacks. The pattern of the various aura symptoms was remarkably constant during two attacks. Visual aura was recorded by 94% of the patients, somato-sensory aura symptoms by 40%, motor disturbances by 18% and spee...
Harold Wolff's theory of vasodilation in migraine is well-known. Less known is his search for a perivascular factor that would damage local tissues and increase pain sensitivity during migraine attacks. Serotonin was found to be among the candidate agents to be included. In the same period, serotonin was isolated (1948) and, because of its actions,...
Salient aspects of the anatomy and function of the blood-barrier barrier (BBB) are reviewed in relation to migraine pathophysiology and treatment. The main function of the BBB is to limit the access of circulating substances to the neuropile. Smaller lipophilic substances have some access to the central nervous system by diffusion, whereas other su...
Tolerability of a drug should be regarded as important as its efficacy. In all four phases of drug development evaluation of adverse events is important. Recommendations for assessment of adverse events in acute and prophylactic clinical drug trials in migraine are given. Tolerability may be indirectly assessed using measures of general well-being...
The efficacy of triptans in the treatment of migraine was recently contested. How high is then the maximum effect of a triptan?
After subcutaneous naratriptan 10 mg a 88% pain-free response was observed. This result was obtained despite the fact that more half of the patients had a migraine duration of > 4 h. These results indicate that subcutaneou...
In cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), one-fifth to one-third of patients have migraine with aura (MA), and this is often the first symptom of CADASIL (1-3). In one German CADASIL family, all had migraine and dementia (4); and in an Italian family dominant MA was associated with the...
Arteriovenous anastomoses (AVAs) may open up during migraine attacks. In studies with anaesthetized and bilaterally vagosympatectomized pigs, triptans reduce AVA blood flow and increase the arteriovenous O2 difference (AVDO2). To investigate whether subcutaneous sumatriptan 6 mg could induce changes in the AVDO2, we measured the AVDO2 in the extern...
(1) A wide array of data regarding acute migraine treatment are available, but few trials strictly adhere to International Headache Society guidelines for patient inclusion criteria.(2) Triptans appear to have similar efficacy profiles, but among newer triptans, almotriptan offers improved tolerability over sumatriptan.(3) Combination indomethacin/...
The mechanisms of glyceryl trinitrate (GTN)-induced headache are not fully elucidated. In this study we administered GTN 0.5 microg/kg/min i.v. for 20 min in six healthy volunteers. Before, during and 60 min after the infusion, we investigated regional cerebral blood flow (rCBF), cerebral blood volume (CBV), both estimated with SPECT, and blood flo...
Dale showed in 1906 in a seminal work that ergot inhibits the pressor effect of adrenaline. Stoll at Sandoz isolated ergotamine from ergot in 1918. Based on the belief that migraine was due to increased sympathetic activity, ergotamine was first used in the acute treatment of migraine by Maier in Switzerland in 1925. In 1938 Graham and Wolff demons...
Calcitonin gene-related peptide (CGRP)-containing nerves are closely associated with cranial blood vessels. CGRP is the most potent vasodilator known in isolated cerebral blood vessels. CGRP can induce migraine attacks, and two selective CGRP receptor antagonists are effective in the treatment of migraine attacks. It is therefore important to inves...
In 1991 the Clinical Trials Subcommittee of the International Headache Society (IHS) developed and published its first edition of the Guidelines on controlled trials of drugs in episodic migraine because only quality trials can form the basis for international collaboration on drug therapy, and these Guidelines would 'improve the quality of control...
To identify clinical variables associated with risk of headache recurrence within 22 hours of initial successful treatment of a migraine attack (2-hour headache response), and to analyze the effect of eletriptan in reducing the incidence of recurrence.
Data were pooled from 10 randomized, double-blind, placebo-controlled trials evaluating eletripta...
The pharmacokinetics of antimigraine drugs zolmitriptan and sumatriptan varied considerably with a fourfold to 10-fold variation in plasma levels. In addition, the pharmacodynamics of triptans as investigated in vitro also varied considerably. In theory, there should probably be a 10-fold variation in doses available, but in clinical practice a fou...
If treatment-emergent central nervous system (CNS) symptoms following triptan therapy represent direct pharmacological effects of the drug, they should occur independent of response to active drug. However, if they represent unmasking of neurological symptoms of the migraine attack after pain is relieved, they should be more common in responders bo...
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 a...
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 cause...
Topiramate (TPM) has shown efficacy in migraine prophylaxis in two large placebo-controlled, dose-ranging trials. We conducted a randomised, double-blind, multicentre trial to evaluate the efficacy and safety of two doses of topiramate vs placebo for migraine prophylaxis, with propranolol (PROP) as an active control. Subjects with episodic migraine...
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...
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.
This was a placebo controlled, double-blind, parallel-group, dose-finding study. Patients satisfying International Headache Society criteria for acute migraine were randomi...
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...
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...
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 sc...
Sumatriptan and the newer triptans (zolmitriptan, naratriptan, rizatriptan, eletriptan, almotriptan, frovatriptan and donitriptan)
display high agonist activity at 5-HT1B and 5-HT1D receptors. Most triptans, but not all (donitriptan, frovatriptan and rizatriptan), also have a high affinity at the 5-ht1F receptor. In anaesthesisted animals, triptans...
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...
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 co...
In this chapter we will discuss experiences with randomised controlled trials (RCTs) in the acute treatment of migraine. With the introduction of the new 5-hydroxytryptamine (5HT)1B/1D receptor agonist sumatriptan [1], the first drug developed specifically for migraine, and recently other triptans, the focus in RCTs in migraine has overwhelmingly b...
The introduction in 1991 of sumatriptan succinate, the first approved 5-HT1B/1D receptor agonist, represented a significant advance in the treatment of acute migraine. The approval of three additional 5-HT receptor agonists, including rizatriptan, has further expanded the options for migraine treatment. Four randomized clinical trials have compared...
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 r...
In two, double-blind, randomised, clinical, trials (RCTs), oral lysine acetylsalicylate (1620 mg, equivalent to 900 mg aspirin) combined with metoclopramide (10 mg) (LAS + MTC) was compared with placebo, and with oral sumatriptan (100 mg) in one of these RCTs. In both RCTs the LAS + MTC combination was superior to placebo with therapeutic gains (pe...
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 p...
Rizatriptan is a potent, oral, 5-HT1B/1D agonist with more rapid absorption and higher bioavailability than oral sumatriptan. It was postulated that this would result in more rapid onset of effect. This randomized, double-blind, triple-dummy, parallel-groups study compared rizatriptan 5 mg, rizatriptan 10 mg, sumatriptan 100 mg, and placebo in 1268...