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Journal of Vestibular Research :... 2011The cardinal symptom of migraine is headache pain. In this paper we review the neurobiology of this pain as it is currently understood. In recent years, we discovered... (Review)
Review
The cardinal symptom of migraine is headache pain. In this paper we review the neurobiology of this pain as it is currently understood. In recent years, we discovered that the network of neurons that sense pain signals from the dura changes rapidly during the course of a single migraine attack and that the treatment of an attack is a moving target. We found that if the pain is not stopped within 10-20 minutes after it starts, the first set of neurons in the network, those located in the trigeminal ganglion, undergo molecular changes that make them hypersensitive to the changing pressure inside the head, which explains why migraine headache throbs and is worsened by bending over and sneezing. We found that if the pain is not stopped within 60-120 minutes, the second group of neurons in the network, those located in the spinal trigeminal nucleus, undergoes molecular changes that convert them from being dependent on sensory signals they receive from the dura by the first set of neurons, into an independent state in which they themselves become the pain generator of the headache. When this happens, patients notice that brushing their hair, taking a shower, touching their periorbital skin, shaving, wearing earrings, etc become painful, a condition called cutaneous allodynia. Based on this scenario, we showed recently that the success rate of rendering migraine patients pain-free increased dramatically if medication was given before the establishment of cutaneous allodynia and central sensitization. The molecular shift from activity-dependent to activity-independent central sensitization together with our recent conclusion that triptans have the ability to disrupt communications between peripheral and central trigeminovascular neurons (rather than inhibiting directly peripheral or central neurons) explain their clinical effects. Both our clinical and pre-clinical findings of the last five years point to possible short- and long-term advantages in using an early-treatment approach in the treatment of acute migraine attacks.
Topics: Afferent Pathways; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Central Nervous System Sensitization; Cortical Spreading Depression; Drug Administration Schedule; Humans; Hyperalgesia; Inflammation; Intracranial Pressure; Ion Channels; Meninges; Migraine Disorders; Nerve Net; Nociceptors; Pain; Pain Threshold; Posterior Horn Cells; Rats; Serotonin 5-HT1 Receptor Agonists; Trigeminal Ganglion; Trigeminal Nuclei; Vasodilation
PubMed: 22348935
DOI: 10.3233/VES-2012-0433 -
The Journal of Headache and Pain Jun 2011Dose-response curves for headaches relief and adverse events (AEs) are presented for five triptans: sumatriptan, zolmitriptan, naratriptan, almotriptan, and... (Review)
Review
Dose-response curves for headaches relief and adverse events (AEs) are presented for five triptans: sumatriptan, zolmitriptan, naratriptan, almotriptan, and frovatriptan, and the CGRP antagonist telcagepant. The upper part of the efficacy curve of the triptans is generally flat, the so-called ceiling effect; and none of the oral triptans, even in high doses, are as effective as subcutaneous sumatriptan, In contrast, AEs increases with increasing dose without a ceiling effect. The optimal dose for the triptans is mainly determined by tolerability. Telcagepant has an excellent tolerability and can be used in migraine patients with cardiovascular co-morbidity. Based on the literature the triptans and telcagepant are rated in a table for efficacy and tolerability.
Topics: Azepines; Calcitonin Gene-Related Peptide Receptor Antagonists; Humans; Imidazoles; Migraine Disorders; Serotonin 5-HT1 Receptor Agonists; Tryptamines
PubMed: 21350792
DOI: 10.1007/s10194-011-0309-5 -
The Cochrane Database of Systematic... Feb 2012Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family.
OBJECTIVES
To determine the efficacy and tolerability of oral sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011.
SELECTION CRITERIA
We included randomised, double-blind, placebo- and/or active-controlled studies using oral sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or 'risk ratio') and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment.
MAIN RESULTS
Sixty-one studies (37,250 participants) compared oral sumatriptan with placebo or an active comparator. Most of the data were for the 50 mg and 100 mg doses. Sumatriptan surpassed placebo for all efficacy outcomes. For sumatriptan 50 mg versus placebo the NNTs were 6.1, 7.5, and 4.0 for pain-free at two hours and headache relief at one and two hours, respectively. NNTs for sustained pain-free and sustained headache relief during the 24 hours postdose were 9.5 and 6.0, respectively. For sumatriptan 100 mg versus placebo the NNTs were 4.7, 6.8, 3.5, 6.5, and 5.2, respectively, for the same outcomes. Results for the 25 mg dose were similar to the 50 mg dose, while sumatriptan 100 mg was significantly better than 50 mg for pain-free and headache relief at two hours, and for sustained pain-free during 24 hours. Treating early, during the mild pain phase, gave significantly better NNTs for pain-free at two hours and sustained pain-free during 24 hours than did treating established attacks with moderate or severe pain intensity.Relief of associated symptoms, including nausea, photophobia, and phonophobia, was greater with sumatriptan than with placebo, and use of rescue medication was lower with sumatriptan than with placebo. For the most part, adverse events were transient and mild and were more common with the sumatriptan than with placebo, with a clear dose response relationship (25 mg to 100 mg).Sumatriptan was compared directly with a number of active treatments, including other triptans, paracetamol (acetaminophen), acetylsalicylic acid, non-steroidal anti-inflammatory drugs (NSAIDs), and ergotamine combinations.
AUTHORS' CONCLUSIONS
Oral sumatriptan is effective as an abortive treatment for migraine attacks, relieving pain, nausea, photophobia, phonophobia, and functional disability, but is associated with increased adverse events.
Topics: Acute Disease; Administration, Oral; Adult; Analgesics; Humans; Migraine Disorders; Randomized Controlled Trials as Topic; Serotonin 5-HT1 Receptor Agonists; Sumatriptan; Time Factors; Treatment Outcome
PubMed: 22336849
DOI: 10.1002/14651858.CD008615.pub2 -
Headache May 2022To gather information about prescription of triptans and to evaluate whether vascular comorbidity differs in users and nonusers of triptans over the age of 50 years.
OBJECTIVE
To gather information about prescription of triptans and to evaluate whether vascular comorbidity differs in users and nonusers of triptans over the age of 50 years.
BACKGROUND
Beyond the age of 50 years, migraine is still common-yet the incidence of vascular disorders increases. Triptans, medications for treating migraine attacks, are vasoconstrictive drugs and contraindicated in persons with vascular disorders.
METHODS
Based on a nationwide insurance database from 2011, we compared the prescription of vascular drugs (identified by Anatomical Therapeutic Chemical codes), vascular diagnoses and hospitalizations, between triptan users greater than 50 years and a matched control group.
RESULTS
Of the 3,116,000 persons over 50 years, 13,833 (0.44%) had at least one triptan prescription; 11,202 (81%) were women. Thirty percent of the triptan users (13,833/47,336 persons) were over 50 years. Of those over 50 years, 6832 (49.4%) had at least one vascular drug and 870 (6.3%) had at least one inpatient vascular diagnosis; 15.7% (2166 of 13,833 users) overused triptans. We compared triptan-users to 41,400 nonusers, using a 1:3 match. In triptan-users, prescriptions of cardiac therapies and beta blockers were significantly more common (odds ratio [OR] = 1.35, 95% confidence interval [CI] = 1.24-1.47 and OR = 1.19, 95% CI = 1.14-1.25, respectively); whereas prescriptions of calcium channel blockers and renin/angiotensin inhibitors were significantly less common (OR = 0.82, 95% CI = 0.76-0.88 and OR = 0.75, 95% CI = 0.72-0.79, respectively). The prescriptions of antihypertensive, diuretic, and antilipidemic drugs as well as platelet inhibitors and direct thrombin inhibitors did not differ in users and nonusers. Triptan users had significantly more hospital stays (OR = 1.39, 95% CI = 1.33-1.45); however, the number of days spent in the hospital and more importantly the frequency of inpatient vascular diagnoses did not differ statistically significantly between the two groups.
CONCLUSION
In persons over 50 years of age, a prescription of triptans is common. Vascular comorbidity is comparable in users and nonusers of triptans showing that triptans are prescribed despite vascular comorbidity and suggesting that triptan use does not increase vascular risk in patients with migraine over the age of 50 years. Nevertheless, regular evaluation for contraindications against triptans and for vascular risk factors is recommended in this age group.
Topics: Cohort Studies; Comorbidity; Female; Humans; Insurance; Male; Middle Aged; Migraine Disorders; Serotonin 5-HT1 Receptor Agonists; Tryptamines
PubMed: 35593784
DOI: 10.1111/head.14304 -
Tijdschrift Voor Psychiatrie 2021Current antipsychotic treatment is suboptimal. There is an urgent need for new antipsychotics with new mechanisms of action. SEP-363856 is a trace amine-associated... (Review)
Review
BACKGROUND
Current antipsychotic treatment is suboptimal. There is an urgent need for new antipsychotics with new mechanisms of action. SEP-363856 is a trace amine-associated receptor 1 (TAAR1) agonist and a serotonin 5-HT1a agonist with potential antipsychotic properties.
AIM
To describe the rationale for the development of SEP-363856, the pharmacology of TAAR1/5-HT1a agonists, and the clinical efficacy of SEP-363856.
METHOD
A narrative review of the literature using PubMed, Embase and PsychINFO.
RESULTS
Six publications were identified, one of which was a phase 2 clinical trial with SEP-363856. This phase 2 study shows that SEP-363856 is an effective and well-tolerated antipsychotic; positive, but also negative symptoms decreased; motor side effects (akathisia) and prolactin increase did not occur, while metabolic side effects hardly occurred. Reported side-effects were somnolence and nausea. The antipsychotic activity of SEP-363856 appears to be (pre)clinical not based on D2 antagonism, but on TAAR1 and 5-HT1a agonism.
CONCLUSION
TAAR1 and 5-HT1a agonists such as SEP-363856 may be a treatment option for psychosis. Hopefully they can be further developed into an antipsychotic with a favorable effectiveness and tolerability profile.
Topics: Antipsychotic Agents; Humans; Psychotic Disorders; Receptors, Dopamine; Serotonin 5-HT1 Receptor Agonists; Treatment Outcome
PubMed: 34851520
DOI: No ID Found -
The Cochrane Database of Systematic... Apr 2010Cluster headache is an uncommon, but severely painful and disabling condition, with rapid onset. Validated treatment options are limited, and first-line therapy includes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cluster headache is an uncommon, but severely painful and disabling condition, with rapid onset. Validated treatment options are limited, and first-line therapy includes inhaled oxygen. Alternative therapies such as intranasal lignocaine and ergotamine are not as commonly used and are less well studied. Triptans are successfully used to treat migraine attacks and, because of this, they may also be useful for cluster headache.
OBJECTIVES
To determine the efficacy and tolerability of triptans for the acute treatment of cluster headaches.
SEARCH STRATEGY
We searched Cochrane CENTRAL, MEDLINE and EMBASE for studies through 22 January 2010.
SELECTION CRITERIA
Randomised, double-blind, placebo-controlled studies of triptans for acute treatment of cluster headache episodes.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study quality and extracted data. Numbers of participants with different levels of pain relief, requiring rescue medication and experiencing adverse events and headache-associated symptoms in treatment and control groups were used to calculate relative risk and numbers needed to treat (NNT) and harm (NNH).
MAIN RESULTS
All six included studies used a single dose of triptan to treat an attack of moderate to severe pain intensity. In total 231 participants received zolmitriptan 5 mg, 223 received zolmitriptan 10 mg, 131 received sumatriptan 6 mg, 88 received sumatriptan 12 mg, and 326 received placebo. Zolmitriptan was administered either orally or intranasally, and sumatriptan either subcutaneously or intranasally.Overall, the triptans studied were better than placebo for headache relief and pain-free responses, with an NNT of 2.4 for 15 minute pain relief with subcutaneous sumatriptan 6 mg (75% with sumatriptan and 32% with placebo), and 2.8 for 30 minute pain relief with intranasal zolmitriptan 10 mg (62% with zolmitriptan and 26% with placebo). Fewer participants need rescue medication with triptan than with placebo, but more experienced adverse events.
AUTHORS' CONCLUSIONS
Zolmitriptan and sumatriptan are effective in the acute treatment of cluster headaches and may provide a useful treatment option, potentially offering convenience over oxygen therapy and a better safety and tolerability profile than ergotamine. Non-oral routes of administration are likely to provide better and more rapid responses.
Topics: Cluster Headache; Humans; Oxazolidinones; Randomized Controlled Trials as Topic; Serotonin Receptor Agonists; Sumatriptan; Tryptamines
PubMed: 20393964
DOI: 10.1002/14651858.CD008042.pub2 -
Current Opinion in Supportive and... Jun 2012We highlight the recent clinical trials for the management of acute and chronic migraine. (Review)
Review
PURPOSE OF REVIEW
We highlight the recent clinical trials for the management of acute and chronic migraine.
RECENT FINDINGS
In women with menstrual migraine, triptans seem to be well tolerated irrespective of whether or not patients are taking oestrogen-containing contraceptives or have comorbidities that indicate increased cardiovascular risk. The new acute drug, telcagepant, a calcitonin gene-related peptide (CGRP) antagonist, is safe for long-term use (up to 18 months) in migraine patients with stable coronary artery disease in whom the use of triptans is not advisable. From the pooled analysis of the two Phase III Research Evaluating Migraine Prophylaxis Therapy studies of onabotulinumtoxinA (BOTOX) in chronic migraineurs, it clearly emerged that efficacy increases overtime (up to 56 weeks) and paralleled self-perceived improvement in quality of life. Effectiveness was also observed in patients with severely disabling headaches, who met criteria for triptan abuse and were refractory to several prophylactic treatments. Finally, combination of preventive pharmacological agents with different action mechanisms may be the next frontier in therapeutic advancements for treating migraine.
SUMMARY
Although triptans are safe and well tolerated, CGRP antagonists may be an option for nonresponsive patients or those in whom the use of triptans is not advisable. New drugs and combinations of old therapeutic options may help patients with severe forms of headache.
Topics: Acute Disease; Azepines; Botulinum Toxins, Type A; Calcitonin Gene-Related Peptide Receptor Antagonists; Chronic Disease; Humans; Imidazoles; Migraine Disorders; Randomized Controlled Trials as Topic; Tryptamines
PubMed: 22406987
DOI: 10.1097/SPC.0b013e3283521dc3 -
CNS Drug Reviews 2005The basic CNS neuropharmacology of naratriptan is reviewed here. Naratriptan is a second-generation triptan antimigraine drug, developed at a time when CNS activity was... (Review)
Review
The basic CNS neuropharmacology of naratriptan is reviewed here. Naratriptan is a second-generation triptan antimigraine drug, developed at a time when CNS activity was thought not to be relevant to its therapeutic effect in migraine. It was, however, developed to be a more lipid-soluble, more readily absorbed and less readily metabolized variant on preexisting triptans and these variations conferred on it a higher CNS profile. Naratriptan is a 5-HT(1B/1D) receptor agonist with a highly selective action on migraine pain and nausea, without significant effect on other pain or even other trigeminal pain. Probable sites of therapeutic action of naratriptan include any or all of: the cranial vasculature; the peripheral terminations of trigeminovascular sensory nerves; the first-order synapses of the trigeminovascular sensory system; the descending pain control system; and the nuclei of the thalamus. Naratriptan may prevent painful dilatation of intracranial vessels or reverse such painful dilatation. Naratriptan can prevent the release of sensory peptides and inhibit painful neurogenic vasodilatation of intracranial blood vessels. At the first order synapse of the trigeminal sensory system, naratriptan can selectively suppress neurotransmission from sensory fibers from dural and vascular tissue, while sparing transmission from other trigeminal fibers, probably through inhibition of neuropeptide transmitter release. In the periaqueductal gray matter and in the nucleus raphe magnus, naratriptan selectively activates inhibitory neurons which project to the trigeminal nucleus and spinal cord and which exert inhibitory influences on trigeminovascular sensory input. Naratriptan has also a therapeutic effect on the nausea of migraine, possibly exerting its action at the level of the nucleus tractus solitarius via the same mechanisms by which it inhibits trigeminovascular nociceptive input. The incidence of naratriptan-induced adverse effects in the CNS is low and it is not an analgesic for pain other than that of vascular headache. In patients receiving selective serotonin uptake inhibitors (SSRIs) naratriptan may cause serotonin syndrome-like behavioral side effects. The mechanism of action involved in the production of behavioral and other CNS side effects of naratriptan is unknown.
Topics: Analgesia; Animals; Cardiovascular Diseases; Humans; Migraine Disorders; Piperidines; Serotonin Receptor Agonists; Tryptamines
PubMed: 16389295
DOI: 10.1111/j.1527-3458.2005.tb00048.x -
The Cochrane Database of Systematic... Feb 2012Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. Subcutaneous administration may be preferable to oral for individuals experiencing nausea and/or vomiting
OBJECTIVES
To determine the efficacy and tolerability of subcutaneous sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults.
SEARCH METHODS
We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011.
SELECTION CRITERIA
We included randomised, double-blind, placebo- and/or active-controlled studies using subcutaneous sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or 'risk ratio') and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment.
MAIN RESULTS
Thirty-five studies (9365 participants) compared subcutaneous sumatriptan with placebo or an active comparator. Most of the data were for the 6 mg dose. Sumatriptan surpassed placebo for all efficacy outcomes. For sumatriptan 6 mg versus placebo the NNTs were 2.9, 2.3, 2.2, and 2.1 for pain-free at one and two hours, and headache relief at one and two hours, respectively, and 6.1 for sustained pain-free at 24 hours. Results for the 4 mg and 8 mg doses were similar to the 6 mg dose, with 6 mg significantly better than 4 mg only for pain-free at one hour, and 8 mg significantly better than 6 mg only for headache relief at one hour. There was no evidence of increased migraine relief if a second dose of sumatriptan 6 mg was given after an inadequate response to the first.Relief of headache-associated symptoms, including nausea, photophobia, and phonophobia, was greater with sumatriptan than with placebo, and use of rescue medication was lower with sumatriptan than placebo. For the most part, adverse events were transient and mild and were more common with sumatriptan than placebo.Sumatriptan was compared directly with a number of active treatments, including other triptans, acetylsalicylic acid plus metoclopramide, and dihydroergotamine, but there were insufficient data for any pooled analyses.
AUTHORS' CONCLUSIONS
Subcutaneous sumatriptan is effective as an abortive treatment for acute migraine attacks, quickly relieving pain, nausea, photophobia, phonophobia, and functional disability, but is associated with increased adverse events.
Topics: Acute Disease; Adult; Humans; Injections, Subcutaneous; Migraine Disorders; Pain Management; Randomized Controlled Trials as Topic; Serotonin 5-HT1 Receptor Agonists; Sumatriptan; Time Factors
PubMed: 22336869
DOI: 10.1002/14651858.CD009665 -
The Journal of Headache and Pain Oct 2023Triptans are effective for many migraine patients, but some do not experience adequate efficacy and tolerability. The European Headache Federation (EHF) has proposed...
BACKGROUND
Triptans are effective for many migraine patients, but some do not experience adequate efficacy and tolerability. The European Headache Federation (EHF) has proposed that patients with lack of efficacy and/or tolerability of ≥ 2 triptans ('triptan resistance') could be considered eligible for treatment with the novel medications from the ditan and gepant groups. There is little data on the frequency of 'triptan resistance'.
METHODS
We used patient self-report data from the German Migraine and Headache Society (DMKG) Headache Registry to assess triptan response and triptan efficacy and/or tolerability failure.
RESULTS
A total of 2284 adult migraine patients (females: 85.4%, age: 39.4 ± 12.8 years) were included. 42.5% (n = 970) had failed ≥ 1 triptan, 13.1% (n = 300) had failed ≥ 2 triptans (meeting the EHF definition of 'triptan resistance'), and 3.9% (n = 88) had failed ≥ 3 triptans. Compared to triptan responders (current use, no failure, n = 597), triptan non-responders had significantly more severe migraine (higher frequency (p < 0.001), intensity (p < 0.05), and disability (p < 0.001)), that further increased with the level of triptan failure. Responders rates were highest for nasal and oral zolmitriptan, oral eletriptan and subcutaneous sumatriptan.
CONCLUSION
In the present setting (specialized headache care in Germany), 13.1% of the patients had failed ≥ 2 triptans. Triptan failure was associated with increased migraine severity and disability, emphasizing the importance of establishing an effective and tolerable acute migraine medication. Acute treatment optimization might include switching to one of the triptans with the highest responder rates and/or to a different acute medication class.
TRIAL REGISTRATION
The DMKG Headache Registry is registered with the German Clinical Trials Register (DRKS 00021081).
Topics: Adult; Female; Humans; Middle Aged; Cross-Sectional Studies; Headache; Migraine Disorders; Tryptamines; Serotonin 5-HT1 Receptor Agonists
PubMed: 37817093
DOI: 10.1186/s10194-023-01676-0