Migraine Disorders: Tfelt-Hansen P

Silberstein S, Tfelt-Hansen P, Dodick DW, Limmroth V, Lipton RB, Pascual J, Wang SJ, Anonymous00408. · Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA. [corrected] · Cephalalgia. · Pubmed #18294250 No free full text.

Abstract: 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 controlled clinical trials in migraine'. With the current trend for large multinational trials, there is a need for increased awareness of methodological issues in clinical trials of drugs and other treatments for chronic migraine. These Guidelines are intended to assist in the design of well-controlled clinical trials of chronic migraine in adults, and do not apply to studies in children or adolescents.

Russell MB, Tfelt-Hansen P. · No affiliation provided · Ugeskr Laeger. · Pubmed #10647311 No free full text.

This publication has no abstract.

Tfelt-Hansen P, Ashina M, Olesen J. · Neurologisk Afdeling N, Glostrup Hospital, DK-2600 Glostrup. · Ugeskr Laeger. · Pubmed #18940154 No free full text.

Abstract: Understanding of the pathophysiology of migraine attacks requires consideration of both symptoms and paraclinical investigations. During the aura phase, characteristic changes in regional cerebral blood flow (rCBF) can be observed. The headache is most likely a form of neurovascular pain. Nausea, photo- and phonophobia are probably elicited from the central nervous system. Positron emission tomography (PET) scans reveal specific changes in the brain stem. Allodynia, most likely caused by central sensitization, often develops during the attack. In conclusion, the migraine attack is a complex neurobiological and neurovascular process.

Edvinsson L, Tfelt-Hansen P. · Department of Internal Medicine, University Hospital, Lund, Sweden. · Cephalalgia. · Pubmed #18727638 No free full text.

Abstract: 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 substances can cross the BBB by carrier-mediated influx transport, receptor-mediated transcytosis and absorptive-mediated transcytosis. Studies of drugs relevant to migraine pathophysiology and treatment have been examined with the pressurized arteriography method. The drugs, given both luminally and abluminally, provide important notions regarding antimigraine site of action, probably abluminal to the BBB. The problems with the BBB in animal models designed to study the pathophysiology, acute treatment models and preventive treatments are discussed with special emphasize on the triptans and calcitonin gene-related peptide (CGRP). The human experimental headache model, especially the use of glycerol trinitrate (the nitric oxide model), and experiences with CGRP administrations utilize the systemic administration of the agonists with effects on other vascular beds also. We discuss how this can be related to genuine migraine attacks. Our view is that there exists no clear proof of breakdown or leakage of the BBB during migraine attacks, and that antimigraine drugs need to pass the BBB for efficacy.

Tfelt-Hansen P, Bjarnason NH, Dahlöf C, Derry S, Loder E, Massiou H, Anonymous00305. · Danish Headache Centre, Department of Neurology, University of Copenhagen, Glostrup Hospital, Copenhagen, Denmark. · Cephalalgia. · Pubmed #18498392 No free full text.

Abstract: 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 and eight such tools are presented. Finally, recommendations for reporting of adverse events are given.

Mett A, Tfelt-Hansen P. · Wolters Kluwer Health | Adis, Auckland, New Zealand. · Curr Opin Neurol. · Pubmed #18451718 No free full text.

Abstract: (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/caffeine/prochlorperazine most likely has similar therapeutic efficacy to triptan therapy, with further research needed to complete understanding of any potential differences between these treatments.(4) Multi-targeted combination therapy with a triptan plus a non-steroidal anti-inflammatory (NSAID), such as sumatriptan/naproxen sodium, is more effective in acute migraine treatment than monotherapy with either agent alone.(5) It is unclear whether triptans offer clinically relevant benefits over aspirin or NSAIDs in migraine patients. Thus NSAIDs, particularly effervescent aspirin, should be considered the first-line treatment of migraine attacks.

Tfelt-Hansen P. · Danish Headache Centre, Department of Neurology, University of Copenhagen, Glostrup Hospital, Glostrup, Denmark. · Headache. · Pubmed #18377382 No free full text.

Abstract: The introduction of triptans in migraine treatment was apparently a revolution. Comparative randomized clinical trials (RCTs) with triptan and other drugs do not give a clear-cut picture. Oral triptans are superior to oral ergotamine most likely because the bioavailability oral of ergotamine is extremely low (<1%). Compared with NSAIDs, in most cases aspirin, triptans were not superior and in several RCTs triptans caused more adverse events than aspirin plus metoclopramide. Guidelines for treatment of migraine should be evidence-based. It is suggested that based on current evidence, effervescent aspirin should be the first-line drug for the treatment of migraine. Aspirin is also much cheaper than the triptans.

Tfelt-Hansen P, Brøsen K. · Danish Headache Centre, Department of Neurology, University of Copenhagen, Glostrup Hospital, Glostrup 2600, Denmark, · J Headache Pain. · Pubmed #18217199 No free full text.

Abstract: Pharmacogenomics is the science about how inherited factors influence the effects of drugs. Drug response is always a result of mutually interacting genes with important modifications from environmental and constitutional factors. Based on the genetic variability of pharmacokinetic and in some cases pharmacodynamic variability we mention possible implications for the acute and preventive treatment of migraine. Pharmacogenomics will most likely in the future be one part of our therapeutic armamentarium and will provide a stronger scientific basis for optimizing drug therapy on the basis of each patient's genetic constitution.

Tfelt-Hansen P. · Danish Headache Centre, Department of Neurology, University of Copenhagen, Glostrup Hospital, DK-2600, Glostrup, Denmark. · J Headache Pain. · Pubmed #17955173 No free full text.

Abstract: The clinical efficacy in migraine was compared for oral and subcutaneous sumatriptan and naratriptan. Doses of the two administration forms were chosen as resulting in comparable blood concentrations. Subcutaneous administrations of the drugs were superior for efficacy than the oral forms. This most likely due to a quicker rise in blood concentrations after subcutaneous injections.. In designing new therapies for migraine one should aim at a quick absorption of the drug, which will probably result in an increased efficacy.

Tfelt-Hansen P, Steiner TJ. · Department of Neurology, Danish Headache Centre, University of Copenhagen, Glostrup Hospital, Glostrup, Denmark. · CNS Drugs. · Pubmed #17927293 No free full text.

Abstract: In 2006, the triptans sumatriptan 50mg and naratriptan 2.5mg were approved as over-the-counter (OTC) drugs in pharmacies in the UK and Germany, respectively. Both drugs have been used in a large number of patients with migraine and are considered to have good safety profiles.The implications of OTC triptan availability for clinical practice are that more migraine patients will use a triptan and will tend to medicate early when their headache is still mild, which should be beneficial. The problem with OTC access to triptans is medication overuse; therefore, patients should be warned of this and advised to use a triptan on fewer than 10 days per month.Pharmacists should be educated regarding migraine types and symptoms and on contraindications to triptans, so they are then able to discern the patients who should receive triptans and, as importantly, those who should not.The annual cost of migraine is euro27 billion in Europe, $US1.4 billion in the UK and $US16.6 billion in the US. By far the greatest opportunity for cost-savings comes from the potential to reduce costs associated with lost productivity from migraine. OTC availability of triptans will inevitably result in easier access to these medications, which, in turn, may result in improved treatment and lower migraine-related disability. There is currently a lack of empirical evidence that treating migraine effectively does in fact recover lost productivity; well designed studies are required to show this.The availability of triptans OTC is a logical development for the better management of a common, benign, self-limiting but nonetheless burdensome disorder that is currently grossly undertreated. We welcome this development, but recognise that advice at the point of sale is crucial for effective and safe use of these drugs.

Tfelt-Hansen P, Edvinsson L. · Danish Headache Centre, Depatment of Neurology, Glostrup Hospital, DK-2600 Glostrup, Denmark. · Cephalalgia. · Pubmed #17714521 No free full text.

Abstract: 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 fourfold difference in doses will probably cover the needs of most patients.

Tfelt-Hansen P. · Dept. of Neurology, Glostrup Hospital, DK-2600, Glostrup, Denmark. · J Headache Pain. · Pubmed #17497267 No free full text.

Abstract: In most migraine patients acute therapy is needed. Migraine can be treated either with specific drugs, the triptans and ergot alkaloids, or with NSAIDs. Triptans are a major step foreward in migraine therapy. The therapeutic gain for headache relief is 50% for subcutaneous sumatriptan whereas it is 30-40% for most oral triptans. After oral triptans sustained pain free is only 30%. There is thus still ample room for improvement of acute therapy in migraine. For tension-type headache there is no specific therapy and it is treated with NSAIDs. Only 17-32% become pain free after these drugs. For attacks of cluster headache oxygen and subcutaneous sumatriptan can be used. Intranasal triptans can be an alternative.

Goadsby PJ, Dodick DW, Almas M, Diener HC, Tfelt-Hansen P, Lipton RB, Parsons B. · Institute of Neurology, London, UK. · Cephalalgia. · Pubmed #17381558 No free full text.

Abstract: 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 both to active drug and to placebo. To explore this issue, we evaluated the relationship between the CNS adverse events and treatment response following triptan or placebo treatment. We used pooled data from seven double-blind, placebo-controlled trials involving eletriptan 20 mg (E20, n = 402), eletriptan 40 mg (E40, n = 1870), eletriptan 80 mg (E80, n = 1393), sumatriptan 100 mg (S100, n = 275) and placebo (Pbo, n = 1024). Somnolence was more prevalent among 2 h headache responders than non-responders for all treatments, including E80 (8.8% vs. 5.0%; P < 0.05), E40 (6.4% vs. 5.0%; NS), E20 (4.0% vs. 2.0%; NS), S100 (4.7% vs. 3.2%; NS) and Pbo (7.6% vs. 3.0%; P < 0.05). Similarly, the incidence of asthenia was higher among patients who responded to treatment compared with those who did not respond to E80 (15.2% vs. 7.8%; P < 0.05), E40 (6.5% vs. 3.6%; P < 0.05), E20 (6.5% vs. 1.0%; P < 0.05), S100 (10.1% vs. 4.7%; NS) and Pbo (4.4% vs. 2.7%; NS). The generally higher rates of somnolence and asthenia in patients who respond to treatment suggests that these treatment-emergent neurological symptoms may represent the unmasking of CNS symptoms associated with the natural resolution of a migraine attack, rather than simply representing drug-related side-effects. The rate of somnolence in placebo responders is comparable to that in responders to E40 and E80, indicating that somnolence is related, at least in some important part, to headache relief and not treatment.

Tfelt-Hansen P. · Danish Headache Centre, Department of Neurology, University of Copenhagen, Glostrup Hospital, Glostrup, Denmark. · Cephalalgia. · Pubmed #17059433 No free full text.

Abstract: 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.

Tfelt-Hansen P, Iversen HK. · Dansk Hovedpinecenter, Amtssygehuset i Glostrup, Neurologisk Afdeling, Glostrup. · Ugeskr Laeger. · Pubmed #16756800 No free full text.

This publication has no abstract.

Tfelt-Hansen P. · The Danish Headache Center, Department of Neurology, University of Copenhagen, Glostrup Hospital, DK-2600, Glostrup, Denmark. · J Headache Pain. · Pubmed #16575501 No free full text.

Abstract: The following points are covered in this review. (1) How a randomised clinical trial in migraine is performed. The whole process from idea to publication of an article is reviewed. (2) How to understand a paper on clinical trials in migraine. The aim of the study, design of study, efficacy measures and presentation of results are reviewed. The aim of the study is often stated vaguely and it is suggested to look at the power calculations in order to understand the aim of the study. The aims and the results of the trial programmes of the triptans are reviewed. Results of the study should be presented with 95%CI. (3) How to understand meta-analyses in migraine. Relationship between meta-analyses and head-to-head comparative trials is reviewed; and it is concluded that head-to-head comparisons remain the "golden standard" with meta-analyses as a useful supplement.

Tfelt-Hansen P. · Department of Neurology, Glostrup Hospital, Glostrup, Denmark. · Curr Med Res Opin. · Pubmed #12463275 No free full text.

Abstract: 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.

Tfelt-Hansen P. · Department of Neurology, Glostrup Hospital, University of Copenhagen, Glostrup, DK-2600 Glostrup, Denmark. · Funct Neurol. · Pubmed #11200792 No free full text.

Abstract: 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 (percentage relief after active treatment minus percentage relief after placebo) of 30% and 31% for the first treated attack. These therapeutic gains are in the same range as those found for 100 mg oral sumatriptan, and in the comparative RCT the LAS + MTC combination was quite comparable to 100 mg sumatriptan, with success rates for the first attack of 57% and 53%, respectively.

Tfelt-Hansen P, De Vries P, Saxena PR. · Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark. · Drugs. · Pubmed #11152011 No free full text.

Abstract: 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.

Tfelt-Hansen P, Saxena PR, Dahlöf C, Pascual J, Láinez M, Henry P, Diener H, Schoenen J, Ferrari MD, Goadsby PJ. · Department of Neurology, Glostrup Hospital, Copenhagen, Denmark. The · Brain. · Pubmed #10611116 links to  free full text

Abstract: 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.

Tfelt-Hansen P, Block G, Dahlöf C, Diener HC, Ferrari MD, Goadsby PJ, Guidetti V, Jones B, Lipton RB, Massiou H, Meinert C, Sandrini G, Steiner T, Winter PB, Anonymous00006. · Department of Neurology, Glostrup Hospital, Denmark. · Cephalalgia. · Pubmed #11167908 No free full text.

This publication has no abstract.

Lassen LH, Jacobsen VB, Haderslev PA, Sperling B, Iversen HK, Olesen J, Tfelt-Hansen P. · Department of Neurology, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark. · J Headache Pain. · Pubmed #18437288 links to  free full text

Abstract: 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 investigate its mechanism of action in patients with migraine. We here investigate the effects of intravenous human alpha-CGRP (halphaCGRP) on intracranial hemodynamics. In a double-blind, cross-over study, the effect of intravenous infusion of halphaCGRP (2 mug/min) or placebo for 20 min was studied in 12 patients with migraine without aura outside attacks. Xenon-133 inhalation SPECT-determined regional cerebral blood flow (rCBF) and transcranial Doppler (TCD)-determined blood velocity (V (mean)) in the middle cerebral artery (MCA), as well as the heart rate and blood pressure, were the outcome parameters. No change of rCBF was observed at the end of infusion [1.2% +/- 1.7 with halphaCGRP, vs. -1.6% +/- 3.1 with placebo (mean +/- SD)] (P = 0.43). V (mean) in MCA decreased to 13.5% +/- 3.6 with halphaCGRP versus 0.6% +/- 1.8 with placebo (P < 0.005). Since rCBF was unchanged, this indicates a dilation of the MCA. halphaCGRP induced a decrease in MAP (12%) (P < 0.005) and an increase in heart rate (58%) (P < 0.0001). CGRP dilates cerebral arteries, but the effect is so small that it is unlikely to be the only mechanism of CGRP-induced migraine.

Diener HC, Tfelt-Hansen P, Dahlöf C, Láinez MJ, Sandrini G, Wang SJ, Neto W, Vijapurkar U, Doyle A, Jacobs D, Anonymous00001. · Department of Neurology, University Essen, Hufelandstr 55, 45122 Essen, Germany. · J Neurol. · Pubmed #15316798 No free full text.

Abstract: 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 with and without aura were randomised to TPM 100 mg/d, TPM 200 mg/d, PROP 160 mg/d (active control), or placebo. The primary efficacy measure was the change in mean monthly migraine frequency from the baseline phase relative to the double-blind treatment phase. Five hundred and seventy-five subjects were enrolled from 61 centres in 13 countries. TPM 100 mg/d was superior to placebo as measured by reduction in monthly migraine frequency, overall 50% responder rate, reduction in monthly migraine days, and reduction in the rate of daily rescue medication use. The TPM 100 mg/d and PROP groups were similar with respect to reductions in migraine frequency, responder rate, migraine days, and daily rescue medication usage. TPM 100 mg/d was better tolerated than TPM 200 mg/d, and was generally comparable to PROP. No unusual or unexpected safety risks emerged. These findings demonstrate that TPM 100 mg/d is effective in migraine prophylaxis. TPM 100 mg/d and PROP 160 mg/d exhibited similar efficacy profiles.

Tfelt-Hansen P, Seidelin K, Stepanavage M, Lines C. · Department of Neurology, Bispebjerg Hospital, Copenhagen, Denmark. · Br J Clin Pharmacol. · Pubmed #12100223 links to  free full text

Abstract: AIMS: To compare the peripheral vasoconstrictor effects of ergotamine, rizatriptan, and their combination, in normal subjects. METHODS: This was a double-blind, four-way, crossover study. Sixteen young male volunteers, selected as responders to the vasoconstrictor effect of 0.5 mg ergotamine i.v., were administered 10 mg oral rizatriptan, 0.25 mg i.v. ergotamine, 10 mg oral rizatriptan+0.25 mg i.v. ergotamine, and placebo. The vasoconstrictor effect on peripheral arteries was measured with strain gauge plethysmography up to 8 h after dosing. The 8 h assessment period was divided into two 4 h intervals to assess the immediate (0-4 h) vs sustained effect (4-8 h) of treatment. RESULTS: For the 0-4 h interval, the decreases in peripheral systolic blood pressure gradients were: placebo (-1 mmHg [95% CI: -3, 1])<rizatriptan (-5 mmHg [95% CI: -7, -3])<ergotamine (-15 mmHg [95% CI: -16, -13])=rizatriptan+ergotamine (-15 mmHg [95% CI: -17, -13]). For the 4-8 h interval, the decreases were: placebo (-5 mmHg [95% CI: -8, -3])=rizatriptan (-8 mmHg [95% CI: -11, -5])<ergotamine (-26 mmHg [95% CI: -29, -24])=rizatriptan+ergotamine (-28 mmHg [95% CI: -31, -26]). CONCLUSIONS: In normal subjects, rizatriptan 10 mg orally had only a small transient vasoconstrictor effect on peripheral arteries compared with the sustained and more pronounced effect of 0.25 mg i.v. ergotamine. Furthermore, rizatriptan exerted no additional effect on ergotamine-induced constriction of peripheral arteries when the two drugs were given in combination.

Dahlöf C, Tfelt-Hansen P, Massiou H, Fazekas A, Anonymous00137. · Gothenburg Migraine Clinic, Gothenburg, Sweden. · Neurology. · Pubmed #11723269 No free full text.

Abstract: 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.