Endogenous and exogenous serotonin, but not sumatriptan, ameliorate seizures and neuroinflammation in the pentylenetetrazole-induced seizure model in rats / A serotonina endógena e exógena, mas não o sumatriptano, melhora as convulsões e a neuroinflamação no modelo de convulsão induzida por pentilenotetrazol em ratos

ABSTRACT Background: Epilepsy has neuropsychiatric comorbidities such as depression, bipolar disorder, and anxiety. Drugs that target epilepsy may also be useful for its neuropsychiatric comorbidities. Objective: To investigate the effects of serotonergic modulation on pro-inflammatory cytokines and the seizures in pentylenetetrazole (PTZ)-induced seizure model in rats. Methods: Male Wistar rats were injected intraperitoneally with serotonin, selective serotonin reuptake inhibitor fluoxetine, 5-HT1B/D receptor agonist sumatriptan, or saline 30 min prior to PTZ treatment. Behavioral seizures were assessed by the Racine's scale. Concentrations of IL-1β, IL-6, and TNF-α in serum and brain tissue were determined by ELISA. Results: Serotonin and fluoxetine, but not sumatriptan, alleviated PTZ-induced seizures by prolonging onset times of myoclonic-jerk and generalized tonic-clonic seizures. The anti-seizure effect of fluoxetine was greater than that of serotonin. Likewise, serotonin and fluoxetine, but not sumatriptan, reduced PTZ-induced increases in the levels of IL-1β and IL-6 in both serum and brain tissue. None of the administered drugs including PTZ affected TNF-α concentrations. Conclusions: Our findings suggest that endogenous and exogenous serotonin exhibits anticonvulsant effects by suppressing the neuroinflammation. It seems that 5-HT1B/D receptors do not mediate anticonvulsant and anti-neuroinflammatory effects of serotonin.

RESUMO Antecedentes: A epilepsia apresenta comorbidades neuropsiquiátricas como depressão, transtorno bipolar e ansiedade. Os medicamentos que visam o tratamento da epilepsia podem ser úteis para a epilepsia e suas comorbidades neuropsiquiátricas. Objetivo: Investigar os efeitos da modulação serotonérgica em citocinas pró-inflamatórias e as convulsões no modelo de convulsão induzida por pentilenotetrazol (PTZ) em ratos. Métodos: Ratos Wistar machos foram injetados intraperitonealmente com serotonina, inibidor seletivo da recaptação da serotonina fluoxetina, sumatriptano agonista do receptor 5-HT1B / D ou solução salina 30 min antes do tratamento com PTZ. As crises comportamentais foram avaliadas pela escala de Racine. As concentrações de IL-1β, IL-6 e TNF-α no soro e tecido cerebral foram determinadas por ELISA. Resultados: A serotonina e a fluoxetina, mas não o sumatriptano, aliviaram as convulsões induzidas por PTZ ao prolongar os tempos de início das convulsões mioclônicas e tônico-clônicas generalizadas. O efeito anticonvulsivo da fluoxetina foi maior do que o da serotonina. Da mesma forma, a serotonina e a fluoxetina, mas não o sumatriptano, reduziram os aumentos induzidos por PTZ nos níveis de IL-1β e IL-6 no soro e no tecido cerebral. Nenhum dos medicamentos administrados, incluindo PTZ, alterou as concentrações de TNF-α. Conclusões: Nossos achados sugerem que a serotonina endógena e exógena exibe efeitos anticonvulsivantes por suprimir a neuroinflamação. Aparentemente, os receptores 5-HT1B / D não medeiam os efeitos anticonvulsivantes e anti-neuroinflamatórios da serotonina.

The effectiveness and tolerability of oral acetaminophen/aspirin/caffeine (AAC) combination regimen as an acute treatment for migraine in adults: A meta-analysis of randomized trials

BACKGROUND: Migraine is a highly common disorder that can cause significant disability on an individual, which collectively may lead to a substantial burden for the society. Various expert societies have recommended Acetaminophen/Aspirin/Caffeine (AAC) combination regimen as the first-line drug treatment for migraine attacks; however, there were no pooled evidences summarizing the effectiveness and tolerability of this regimen.OBJECTIVE: To determine the effectiveness and tolerability assessment of oral AAC combination regimen as an acute treatment for migraine in adults.METHODS: Relevant studies from inception to March 2014 were searched in Cochrane CENTRAL, MEDLINE, LILACS, Scopus and metaRegister of Controlled Trials. The Cochrane Collaboration's tool for the assessment of risk of bias was employed. Trials that were randomized, double-blind, parallel-group, placebo and active-controlled were included and the data were employed for meta-analysis. To evaluate the quality of evidence, the GRADE approach was utilized for outcomes with sufficient studies and data.RESULTS: From 225 records identified, 4 trials were included in this review, with a total of 3,608 participants with recorded baseline characteristics. Patient-reported migraine intensity was moderate-severe and the AAC dose used was at 500/500/130 mg. At 2 hours, AAC regimen was statistically different and found to be superior to placebo in terms of pain-free, headache relief, nausea-free, photophobia-free, phonophobia-free and functional disability reduction rates using intension-to-treat analysis. Missing data did not alter the outcome measures generating robust results. Sumatriptan 100 mg was found to be better than AAC in pain-free rate, and phonophobia-free rates at 2 hours. Statistically more patients in the AAC arm experienced "any adverse event" compared to placebo and complaints were commonly nausea and nervousness.CONCLUSION: For adult individuals with moderate-severe migraine, a fixed oral dose of Acetaminophen/Aspirin/Caffeine (AAC 500/500/130 mg) may be used as first-line therapy for the acute treatment of migraine and is only associated with mild, infrequent adverse events.

Determination of sumatriptan in human plasma using liquid chromatography-mass spectrometry for pharmacokinetic study in healthy Korean volunteers

This study describes the development of an analytical method to determine sumatriptan levels in human plasma using high performance liquid chromatography (HPLC) coupled with triple quadrupole tandem mass spectrometry (MS/MS) and its application to a pharmacokinetic study in healthy Korean volunteers. A single 50 mg dose of sumatriptan was orally administered to twelve healthy volunteers (nine women and three men). The HPLC-MS/MS analytical method was validated with respect to its specificity, linearity, sensitivity, accuracy, precision, recovery, and stability. The calibration curve was linear over a concentration range of 0.3–100 ng/mL (r > 0.999). The lower limit of quantitation for sumatriptan in plasma was 0.3 ng/mL. The accuracy and precision of the analytical method were acceptable within 15% at all quality control levels. We compared plasma concentration-time curves as well as pharmacokinetic parameters such as the area under the curve (AUC) and maximum plasma concentration (C(max)). Both the mean AUC and C(max) of sumatriptan were 1.56 times higher in women than in men. These differences could be largely explained by the difference in body weight (44%) between women and men. The outcomes may provide insights into developing appropriate individualized treatment strategies.

Population pharmacokinetic analysis of the multiple peaks phenomenon in sumatriptan

The objective of this study was to develop a population pharmacokinetic (PK) model for sumatriptan, which frequently shows an atypical absorption profile with multiple peaks. Sumatriptan, a selective agonist for the vascular serotonin (5-HT1) receptor that causes vasoconstriction of the cerebral arteries, is used for the acute treatment of migraine attack with or without aura. Despite its relatively high between-subject variability, few reports have addressed PK modeling of sumatriptan. Plasma data obtained after a single 50-mg oral dose of sumatriptan in 26 healthy Korean male subjects were used. Blood samples were collected 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 12 h after dosing. Plasma sumatriptan concentrations were analyzed using UPLC/MS/MS. Population PK analysis was performed using plasma concentration data for sumatriptan with NONMEM (ver. 7.2). A total of 364 concentrations of sumatriptan were captured by a one-compartment model with first-order elimination, and a combined transit compartment model and first-order absorption with lag time was successful in describing the PK with multiple peaks in the absorption phase of sumatriptan. The creatinine clearance as a covariate significantly (P < 0.01) influenced the absorption fraction (f ). The final model was validated through a visual predictive check and bootstrapping with no serious model misspecification.

Cyclic Vomiting Syndrome: A Functional Disorder / 대한소아소화기영양학회지

Cyclic vomiting syndrome (CVS) is a functional disorder characterized by stereotypical episodes of intense vomiting separated by weeks to months. Although it can occur at any age, the most common age at presentation is 3-7 years. There is no gender predominance. The precise pathophysiology of CVS is not known but a strong association with migraine headaches, in the patient as well as the mother indicates that it may represent a mitochondriopathy. Studies have also suggested the role of an underlying autonomic neuropathy involving the sympathetic nervous system in its pathogenesis. CVS has known triggers in many individuals and avoiding these triggers can help prevent the onset of the episodes. It typically presents in four phases: a prodrome, vomiting phase, recovery phase and an asymptomatic phase until the next episode. Complications such as dehydration and hematemesis from Mallory Wise tear of the esophageal mucosa may occur in more severe cases. Blood and urine tests and abdominal imaging may be indicated depending upon the severity of symptoms. Brain magnetic resonance imaging and upper gastrointestinal endoscopy may also be indicated in certain circumstances. Management of an episode after it has started ('abortive treatment') includes keeping the patient in a dark and quiet room, intravenous hydration, ondansetron, sumatriptan, clonidine, and benzodiazepines. Prophylactic treatment includes cyproheptadine, propranolol and amitriptyline. No mortality has been reported as a direct result of CVS and many children outgrow it over time. A subset may develop other functional disorders like irritable bowel syndrome and migraine headaches.

The pharmacological mechanism of gastrodin on calcitonin gene-related peptide of cultured rat trigeminal ganglion / 药学学报

The Chinese herbal medicine Tianma (Gastrodia elata) has been used for treating and preventing primary headache over thousands of years, but the exact pharmacological mechanism of the main bioactive ingredient gastrodin remains unclear. In present study, the effects of gastrodin on calcitonin gene-related peptide (CGRP) and phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) expression were observed in rat trigeminal ganglion (TG) after in vitro organ culture to explore the underlying intracellular mechanism of gastrodin on primary vascular-associated headache. CGRP-immunoreactivity (CGRP-ir) positive neurons count, positive area, mean optical density and integrated optical density by means of immunohistochemistry stain were compared at different concentrations of gastrodin, which was separately co-incubated with DMEM in SD rat TG for 24 hours. Only at 5 or 10 mmol L(-1) concentration, gastrodin demonstrated significantly concentration-dependent reduction of CGRP-ir (+) expression and its action closed to 1.2 mmol L(-1) sumatriptan succinate. While at 2.5, 20, and 40 mmol L(-1) concentration, gastrodin did not show remarkable effects on CGRP-ir (+) expression. The optimal concentration of gastrodin (5 and 10 mmol L(-1)) similarly inhibited CGRP-mRNA expression level separately compared with 1.2 mmol L(-1) sumatriptan succinate and 10 micromol L(-1) flunarizine hydrochloride, which was quantitatively analyzed by real-time PCR (RT-PCR). pERK1/2 level was examined by Western blotting after co-cultured with optimal concentration of gastrodin and effective specific ERK1/2 pathway inhibitors PD98059, U0126. The result indicated that gastrodin significantly reduced pERK1/2 protein actions similarly to ERK1/2 pathway specific blockade. It suggests ERK1/2 signaling transduction pathway may be involved in gastrodin intracellular mechanism. This study indicates gastrodin (5 and 10 mmol L(-1)) can remarkably reduce CGRP-ir (+) neuron, CGRP-mRNA and pERK1/2 expression level in cultured rat TG, with its actions similar to the effective concentration of sumatriptan succinate, flunarizine hydrochloride and specific ERK1/2 pathway blocker. The intracellular signaling transduction ERK1/2 pathway may be involved in the gastrodin reducing CGRP up-regulation in rat TG after organ culture.

Comparação entre o sumatriptano, a trimebutina, o meloxicam e a associação dos três fármacos no tratamento agudo de enxaqueca / Comparison among sumatriptane, trimebutine, meloxicam and the association of those drugs in the acute treatment of migraine

JUSTIFICATIVA E OBJETIVOS: A crise aguda de migrânea geralmente leva a grande incapacidade econômica e social para aqueles que sofrem deste transtorno. A fisiopatologia é complexa e envolve múltiplos mecanismos centrais e periféricos. O tratamento agudo tem como objetivo aliviar a dor e os fenômenos associados como a náusea e fotofobia, sem causar efeitos adversos importantes. Apesar do desenvolvimento de fármacos específicos como os triptanos, para o tratamento agudo, a sua eficácia ainda é baixa. O objetivo deste estudo foi comparar a eficácia e a tolerância da trimebutina, meloxicam, sumatriptano e a associação dos três fármacos no tratamento das crises agudas de migrânea de moderada a forte intensidade.MÉTODO: Após aprovação pelo Comitê de Ética das Instituições foram incluídos neste estudo prospectivo, duplamente encoberto e aleatório, 50 pacientes, sendo 43 mulheres e 7 homens, com idade entre 18 e 65 anos, portadores de migrânea com ou sem aura, que utilizavam medicação profilática, exceto anti-inflamatórios não esteroides (AINES). Foram tratadas quatro crises de migrânea de moderada a forte intensidade de cada paciente, com 200 mg de trimebutina, 50 mg de sumatriptano, 15 mg de meloxicam ou com a associação de 200 mg de trimebutina, 50 mg de sumatriptano e 15 mg de meloxicam. Os pacientes foram aleatorizados em 4 grupos de acordo com a ordem de chegada, de modo que o primeiro paciente incluído recebeu trimebutina para a primeira crise, sumatriptano para a segunda crise, meloxicam para a terceira crise e a associação entre os 3 fármacos para a quarta crise. O segundo paciente incluído recebeu sumatriptano para a primeira crise, meloxicam para a segunda superior a cada um desses fármacos isolados para controlar a dor, as náuseas e a fotofobia nas crises agudas de migrânea de moderada a forte intensidade. Além disso, a combinação dos fármacos apresentou maior incidência de efeitos adversos.crise, a associação para a terceira crise e a trimebutina para a quarta crise, e assim sucessivamente. A intensidade da crise de migrânea foi avaliada a partir da ingestão da cápsula com escala categorizada verbal na qual: 0 - sem dor, 1 - cefaleia leve, 2 - cefaleia moderada e 3 - cefaleia intensa. Cada paciente foi orientado para preencher o relatório de crise para cada crise tratada, na qual anotava a intensidade da cefaleia, a presença de náusea, fotofobia e dos efeitos adversos, e o uso da medicação de resgate, 100 mg de indometacina por via retal. RESULTADOS: Completaram o estudo 42 pacientes. Em uma hora 9,5% dos pacientes que utilizaram a associação dos fármacos estavam livres da dor, comparados com 14,2% com a trimebutina e sumatriptano e 2,4% com o meloxicam (p = 0,479). Em duas horas 21,4% dos pacientes que usaram a associação estavam livres da dor, comparados com 11,9% com a trimebutina, 26,1% com sumatriptano e 23,8% com o meloxicam (p = 0,555). Tanto a associação trimebutina, sumatriptano e meloxicam como os fármacos trimebutina, sumatriptano e meloxicam isolados foram efetivos para controlar a náusea e fotofobia após 1 e 2h para náusea (p = 0,157 e 0,587) e fotofobia (p = 0,671 e 0,929, embora sem diferença estatisticamente significativa entre eles. Dez pacientes em uso da associação dos fármacos, 6 em uso da trimebutina, 5 em uso do sumatriptano e 5 em uso do meloxicam relataram efeitos colaterais. CONCLUSÃO: Este estudo demonstrou que a associação sumatriptano, meloxicam e trimebutina não foi superior a cada um desses fármacos isolados para controlar a dor, as náuseas e a fotofobia nas crises agudas de migrânea de moderada a forte intensidade. Além disso, a combinação dos fármacos apresentou maior incidência de efeitos adversos.

BACKGROUND AND OBJECTIVES: Acute migraine crisis often leads to major economic and social disability for those suffering from such syndrome. Pathophysiology is complex involving several central and peripheral mechanisms. The acute treatment aims at evaluating pain and associated phenomena, such as nausea and photophobia, without causing major adverse effects. Notwithstanding the development of specific drugs for the acute treatment, such as triptanes, their efficacy is still low. This study aimed at comparing efficacy and tolerance of trimebutine, meloxicam, sumatriptane and the association of such drugs to treat moderate to severe acute migraine crises.METHOD: After the Institutions? Ethics Committee approval, participated in this prospective, double-blind and randomized study 50 patients, being 43 females and 7 males, aged between 18 and 65 years, with migraine with or without aura, under prophylactic medication, except non-steroid anti-inflammatory drugs (NSAIDS). Patients were treated for 4 moderate to severe migraine crises with 200 mg trimebutine, 50 mg sumatriptane, 15 mg meloxicam, or with the association of 200 mg trimebutine, 50 mg sumatriptane and 15 mg meloxicam. Patients were randomized in 4 groups according to their arrival, so that the first patient included received trimebutine for the first crisis, sumatriptane for the second crisis, meloxicam for the third crisis and the association of the three drugs for the fourth crisis. The second patient included received sumatriptane for the first crisis, meloxicam for the second crisis, the association for the third crisis and trimebutine for the fourth crisis, and so on and so forth. Migraine crisis intensity was evaluated as from the ingestion of the first tablet with verbal categorized scale where: 0 = no pain, 1 = mild headache, 2 = moderate headache, 3 = severe headache. All patients were oriented to fill a crisis report for each treated crisis, where they would record headache intensity, presence of nausea, photophobia and adverse effects and the use of rescue medication, 100 mg of rectal indometacin.RESULTS: Forty-two patients completed the study. In one hour 9.5% of patients using the association of drugs were free of pain, as compared to 14.2% with trimebutine and sumatriptane and 2.4% with meloxicam (p = 0.479). In two hours 21.4% of patients using the association were free of pain, as compared to 11.9% with trimebutine, 26.1% with sumatriptane and 23.6% with meloxicam (p = 0.555). Both the association of trimebutine, sumatriptane and meloxicam and trimebutine, sumatriptane and meloxicam alone were effective to control nausea and photophobia after 1 and 2 h for nausea (p = 0.157 and 0.587) and photophobia (p = 0.671 and 0.929) although without statistically significant difference among them. Ten patients under the association of drugs, 6 under trimebutine, 5 under sumatriptane and 5 under meloxicam have reported side effects. CONCLUSION: This study has shown that the association of sumatriptane, meloxicam and trimebutine was not better than each of those drugs alone to control pain, nausea and photophobia during moderate to severe migraine crises. In addition, the combination of drugs has shown a higher incidence of adverse effects.

Seguridad en el tratamiento de la migraña aguda durante el embarazo: una revisión sistemática / Safety in the acute management of migraine during pregnancy: a systematic review

Background. Migraine is three times more frequent in females than males and is modulated by changes in ovarian hormones throughout different stages of a female’s life; migraine thus begins with the onset of menstruation, improves during the second and third trimester of pregnancy and a remission may sometimes be brought about during menopause.Objetive.Evaluating the safety of acute management of migraine during pregnancy.Materials and methods. A systematic review was made of the literature concerning observational analytical studies. A systematic search and selection was made of all analytical studies (cohort studies and cases and controls studies) regarding the acute management of migraine during pregnancy published between January 1966 and September 2007. The search covered the COCHRANE, MEDLINE, EMBASE and LILACS databases. Data were extracted using the PECOT strategy bearing in mind the intervention strategy, methodological quality and presence of greater or lesser congenital malformations related to the different medicaments used for the acute management of migraine.Results. A total of 389 references were obtained of which 7 articles were selected by title and summary. Four articles complied with the inclusion criteria. No articles were found describing the risk of congenital malformations before being exposed to acetaminophen, anti-inflammatory agents non-steroidal, ergot alkaloids and/or opioids; just articles related to tryptans (specifically sumatryptan) were found.Conclusions. Only data concerning the risk of congenital malformations arising from sumatryptan use was found regarding all the medicaments used for acute migraine attack, this being insufficient as the information was really poor and the studies had limitations, thereby making it difficult to make statements concerning their safety during pregnancy.

Cefaléia em salvas durante a gravidez: um desafio a mais no tratamento / Cluster headache during pregnancy: an extra challenge for treatment

Cefaléia em salvas é uma cefaléia trigêmino-autonômica relativamente rara. Sua ocorrência na gravidez e as possíveis abordagens terapêuticas são apresentadas.

Sumatriptan and gabapentin for treatment of postdural puncture headache

Postdural puncture headache [PDPH] is one of frequent adverse complication of dural puncture. Although, it is a self limiting and non-fatal condition, its postural nature prevents the patient from performing routine activity and may make them anxious and depressed. In this study we evaluate a combination of sumatriptan and gabapentin for treatment of PDPH and compare it with sumatriptan or gabapentin as sole medication. ASA I and II 45 patients age between 20 and 40 years and non-parturient, who's developed PDPH after spinal or epidural neuraxial block was included in the study. Patients were randomized to receive either gabapentin 300 mg orally every 8 hours for one week group I, in group II patient was received sumatriptan 50 mg orally once daily for 3 successive days. In group III, patients received sumatriptan 50 mg orally every day for 3 days and gabapentin 300 mg every 8 hours for 7 days. PDPH was evaluated by using Visual Analog Scale [VAS], measured 20 min after patients assumed upright postures either sitting or standing. It was recorded before start the treatment as baseline and at 12, 24, 36, 48, 72 and 96 hours after. Satisfaction of patients with treatment was asked, after 4 days. Complications such as somnolence, dizziness, seizures, chest pain, nausea, vomiting and dry mouth were recorded. VAS was significantly low and patient satisfaction was high in group III when compared with the other two groups. Number of patients reported somnolence and dizziness were significantly high in group III compared to group I or II. Combination of sumatriptan and gabapentin could be beneficial for treatment of patients with PDPH, more than sumatriptan or gabapentin alone, as it relief the headache and decrease usage of epidural blood patch which is invasive and not safe procedure

Improvement of Migraine by Cervical Epidural Block: A case report / 대한통증학회지

Migraine is a disabling headache that can occur with or without aura. We present here a case of migraine that was effectively managed by a series of cervical epidural blocks. A 41-year-old woman who had suffered from severe headache on her left temporal area for 12 years visited our pain clinic. Her 11-point numeric pain rating scale was 10 out of 10 at the first visit and the symptoms were associated with homonymous visual disturbances, paresthesia on the left face, shoulder and arm, and general weakness. For the first 5 years after the headaches began, her headache was relatively well controlled by acetaminophen; after then, the acetaminophen wasn't effective. After wandering from this hospital to the next one in search of relief, she managed to visit our pain clinic. We tried several blocks including cervical epidural block, and she was continuously medicated with sumatriptan. Her headache was gradually relieved. Now, her 11-point numeric rating scale is 1-2 out of 10 at the most during her headache attacks.

Prescribing of Drugs for the Treatment of Migraine with Specific Emphasis on Sumatriptan

Migraine affects between 5.15of males and 13;5-31of females in South Africa. Little is known about the prescribing patterns of anti-migraine drugs in South Africa. The aim of the study was to investigate the prescribing of drugs for the treatment of migraine (ATC Group NOZC); with specific emphasis on sumatriptan; in a primary care patient population in South Africa; making use of a computerised prescription database. A total of 3 01 1 products for the treatment of migraine at a cost of R451559 were prescribed to 578 patients in the study over a period of one year (1996) since sumatriptan was the onlytriptan available in South Africa in 1996. The average age of patients was 48;40 (SD = 14;19) years; with 74;57ofpatients between 20 and 59 years of age. Approximately 80of patients were females. Female patients were prescribed 81;53of the products. Most drugs (67;55) were for the prophylaxis of migraine; of which clonidine andflunarizine were the most frequentlyprescribed. Of the drugs prescribedspecifically for the management of migraine; sumatriptan (575prescriptions to 103 patients) was the most frequently prescribed; followed by 400 prescriptions for ergotamine. Tablets were the preferred dosage form. Since migraine affects primarily the economically active sector of the community and its treatment is relatively expensive; pharmacists have an important role to play in managing and counselling migraine sufferers

Dexamethasone decreases migraine recurrence observed after treatment with a triptan combined with a nonsteroidal anti-inflammatory drug

BACKGROUND AND OBJECTIVES: Triptans are effective drugs for the acute treatment of migraine. However, 30-40 percent of the patients commonly present recurrence before 24 hours therefore requiring another dose. Nonsteroidal anti-inflammatory drugs (NSAID) such as tolfenamic acid and naproxen sodium combined with sumatriptan have demonstrated efficacy in reducing recurrence observed with the single use of this drug. Steroids also have been suggested to treat refractory migraine and status migranosus. The aim of this study was to evaluate whether patients presenting frequent recurrence with the combination triptan plus NSAID, would decrease it with the association of dexamethasone. METHOD: Twenty three patients, 17 women and 6 men with migraine according to IHS criteria were prospectively studied. All patients presented frequent recurrence ( > or = 60 percent, mean recurrence rate 74,8 percent) with the single use of sumatritpan 100mg or zolmitriptan 2,5mg or rizatriptan 10mg in at least 5 consecutive attacks, and didn't present a reduction of the recurrence rate superior than 20 percent with the combination of tolfenamic acid 200mg or rofecoxib 25mg in at least 5 other consecutive attacks (mean recurrence rate 60 percent). The patients had to treat 6 consecutive moderate or severe migraine attacks with their usual combination plus 4mg of dexamathasone with a maximum of twice a week, and fill out a diary reporting headache parameters. RESULTS: Twenty patients, 16 women and 4 men completed the study. Of those who completed the study, 11 took rizatriptan plus rofecoxib, 4 rizatriptan plus tolfenamic acid, 3 zolmitriptan plus rofecoxib, 1 zolmitriptan plus tolfenamic acid and 1 patient took sumatriptan plus tolfenamic acid, having the 20 patients taken as a third medication, a single tablet of 4mg of dexamethasone. All patients took oral formulations and none presented vomiting after that. Among all 20 patients, one female and one male patient presented recurrence in 3 out of the 6 attacks (50 percent) while the remaining 18 patients revealed recurrence in 1 or 2 treated attacks (mean 23,4 percent) (p<0,001). CONCLUSION: We concluded that the judicious use of oral dexamethasone might be useful for a limited population of migraine patients still presenting recurrence with the combination of a triptan and a NSAID. Case-control studies and studies with a randomized double-blind design are necessary to confirm these observations

A Case of Vasospastic Angina Pectoris Occurring Following Administration of Oral Imigran(R) for Migraine

Imigran(R) (sumatriptan), a 5-hydroxytryptamine (HT) derivative, is highly effective in aborting attacks of migraine and cluster headache. The drug is generally well tolerated. However tolerated, although up to 8% of patients consistently have demonstrate chest symptoms, including chest pressure, tightness, and pain, often mimicking angina pectoris. It has been suggested that these chest symptoms are caused by coronary vasoconstriction, and that this effect may be mediated by endothelial dysfunction. This can be reversed by the administration of glyceryl trinitrate. We report a case of vasospastic angina pectoris occurring after the administration of oral sumatriptan in a patient with migraine.

Palatal myoclonus: report of two cases

We describe two cases of palatal myoclonus (PM), one essential and another secondary to a stroke. Case 1: a 64 years old female who developed clicking sounds in both ears after a stroke and three years later on noticed a progressive involuntary movement of the throat associated with rhythmic contractions of the soft palate, muscles of tongue and throat. MRI showed an ischemic area in brainstem. The patient had a partial response to the use of sumatriptan 6 mg subcutaneously. Case 2: a 66 years old female who began with ear clicking at left ear that worsed slowly associated with tinnitus and arrhythmic movements of soft palate and an audible click at left ear. Brain MRI was normal; audiometry showed bilateral neurosensory loss. She was prescribed clonazepan 1 mg daily with complete recovery. Primary and secondary palatal myoclonus share the same clinical features but probably have different pathophysiological underlying mechanisms

Naproxen sodium decreases migraine recurrence when administered with sumatriptan

Forty to 78 per cent of the patients using sumatriptan for the acute treatment of migraine may present recurrence at least occasionally. The concomitant use of a NSAID (nonsteroidal anti-inflammatory drug) has been recommended to decrease the recurrence rate. Sixty seven patients that treated successfully 8 migraine attacks with 100 mg of sumatritpan PO and presented recurrence in at least 5 attacks were studied prospectively. The patients received 100 mg of sumatriptan and 550 mg of naproxen sodium PO to treat 4 consecutive moderate or severe migraine attacks. The recurrence rate, once at least 62.5 per cent (5 out of 8 attacks), decreased to 14.2 per cent (38 out of 268 attacks) with the combination of compounds (p<0.0001). We then studied two groups of 13 patients made randomicaly from the 67 initially evaluated, that were given sumatriptan 100 mg plus naproxen sodium 550 mg or placebo, in a double-blind design, to treat 3 other consecutive migraine attacks. Each group of patients treated 39 attacks. The recurrence among the patients taking sumatriptan plus placebo was 59 per cent (23 out of 39 attacks) and the recurrence presented by the group taking sumatriptan plus naproxen was 25.5 per cent (10 out of 39 attacks) (p<0.0003). We concluded that the combination of sumatriptan plus naproxen sodium decreases significantly migraine recurrence presented by patients taking sumatriptan alone.

Respuesta clínica de metoclopramida en comparación con sumatriptán en el tratamiento de ataques agudos de migraña / Clinical response to metoclopramide in comparison to sumatriptan for treatment of acute migraine

Se realizó un estudio prospectivo, clínico y ciego único con 40 pacientes (37 mujeres y 3 hombres) con diagnóstico de ataques agudos de migraña. El 50 por ciento de los pacientes estuvo en el grupo de 18 a 30 años de edad. En forma aleatoria se les aplicó ya fuere una ampolleta de metoclopramida vía intravenosa o una ampolleta de 6 mg de sumatriptán vía subcutánea. Se valoraron los signos vitales, la intensidad de la cefalea y los síntomas asociados durante una hora. La cefalea disminuyó o tuvo alivio en el 100 por ciento de los pacientes tratados con metoclopramida por vía intravenosa; siendo mejor que la respuesta con sumatriptán (70 por ciento), con diferencia estadística de p< 0.01. En cuanto a los síntomas asociados ambos medicamentos aliviaron la mayoría de los síntomas, pero la metoclopramida tuvo mejor respuesta para aliviar la náusea, siendo estadísticamente significativo con p< 0.01. Los signos vitales permanecieron en márgenes normales desde la aplicación del medicamento y la valoración del paciente hasta el término de ésta. Nosotros concluimos que la metoclopramida intravenosa es eficaz en el tratamiento de ataques agudos de migraña y de los síntomas asociados