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Biomedical subjects

Marcelo Eduardo Bigal

Publications and source records attributed to Marcelo Eduardo Bigal.

7 recordsLinked to original sources

Polytherapy in the preventive and acute treatment of migraine: fundamentals for changing the approach.

The pathophysiology of migraine is complex and involves multiple neurophysiological pathways. Monotherapeutic approaches for migraine are the rule but many patients discontinue their medications owing to lack of efficacy. Polytherapy may provide a rational strategy for some of these individuals. Herein, we review the basis of polytherapy treatment for migraine. We suggest that refractory patients, with previous failure to single agents, may benefit from the use of a two- or three-drug regimen combining medications that target different neurotransmitter systems. In addition, those patients with high recurrence rates or not presenting pain free at 2 h and/or sustained pain free at 24 h may also respond better to combination therapy suited to their individual profile, which must include nonsteroidal anti-inflammatory agents plus a triptan or a gastrokinetic drug. The three-drug regimen may also be considered. Finally, changing the time medicine is taken (before the development of central sensitization and allodynia cutanea) and switching the choice of formulations to non-oral potentially achieves a better response and can be determined individually. Although highly speculative, these hypotheses could stimulate further controlled studies to support changing the current paradigm of monotherapeutic migraine treatment in some patients.

Analgesics↗

Rofecoxib in migraine.

Migraine is a highly prevalent primary headache. The disability of migraine attacks results in considerable economic and social losses. The acute treatment of migraine aims to rapidly and consistently alleviate the head pain and associated symptoms, therefore reducing the headache-related disability, ideally without side effects and recurrence of the attack within 24 h. Although several drug options and different formulations are available, the choice of a specific medication should depend on an individual patients characteristics. Among the available drugs, nonsteroidal anti-inflammatory drugs still represent effective options and a new class of nonsteroidal anti-inflammatory drugs known as selective cyclooxygenase-2 inhibitors may represent an even better-tolerated therapy with regard to gastrointestinal side effects. This article aims to discuss the role of rofecoxib in the acute treatment of migraine. Although this drug was recently withdrawn from the market, it provides a good model to understand the role of the cyclooxygenase-2 inhibitors in migraine therapy overall. The pharmacologic profile and therapeutic use in the acute treatment of migraine of rofecoxib is reviewed. In addition, the limitations of a monotherapeutic orally administered approach and possible ways of raising the efficacy of rofecoxib and other acute migraine treatments are reviewed.

Cyclooxygenase 2 Inhibitors↗

Rizatriptan in migraine.

The prevalence of migraine is high, affecting a significant proportion of the adult population during their most productive years of life and promoting impairment of their normal daily activities. Although guidelines for the acute treatment of migraine are available, outcome parameters are sometimes still below the expectations of both patients and physicians. Triptans represented an advance in clinical practice and have become the most well-studied class of medication for migraine. These agents present class I evidence for efficacy. However, they differ with regard to several of their clinical parameters, including onset of relief and consistency of response. Rizatriptan is a selective agonist of the 5-hydroxytryptophan(1B/1D )receptors, with proven superiority over placebo, ergotamine and selected oral triptans, demonstrating a good profile of safety and tolerability.

Dose-Response Relationship, Drug↗

Rizatriptan versus rizatriptan plus rofecoxib versus rizatriptan plus tolfenamic acid in the acute treatment of migraine.

BACKGROUND: Rizatriptan is an effective and fast acting drug for the acute treatment of migraine. Some nonsteroidal anti-inflammatory drugs (NSAID) have also demonstrated efficacy in treating migraine attacks. There is evidence that the combination of a triptan and a NSAID decreases migraine recurrence in clinical practice. The primary aim of this randomized open label study was to assess the recurrence rates in migraine sufferers acutely treated with rizatriptan (RI) alone vs. rizatriptan plus a COX-2 enzyme inhibitor (rofecoxib, RO) vs. rizatriptan plus a traditional NSAID (tolfenamic acid, TO). We were also interested in comparing the efficacy rates within these three groups. METHODS: We assessed 45 patients from a headache clinic in Rio de Janeiro (35 women and 10 men, ages 18 to 65 years, mean 37 years). Patients with IHS migraine were randomized to one out of 3 groups, where they had to treat 6 consecutive moderate or severe attacks in counterbalanced order. In group 1, patients treated the first two attacks with 10 mg RI, the third and fourth attacks with RI + 50 mg RO and the last attacks with RI + 200 mg of TA. In group 2, we began with RI + TA, followed by RI, and RI + RO. Group 3 treated in the following order: RI + RO, RI + TA, RI alone. The presence of headache, nausea and photophobia at 1, 2 and 4 hours, as well as recurrence and side effects were compared. RESULTS: A total of 33 patients finished the study, treating 184 attacks. The pain-free rates at 1 hour were: RI: 15.5%; RI + RO: 22.6%; RI + TA: 20.3%(NS). Pain-free rates at 2 h were: RI: 37.9%; RI + RO: 62.9%, and RI + TA: 40.6% (p = 0.008 for RI vs. RI + RO; p = 0.007 for RI + RO vs. RI + TA, NS for RI vs RI + TA). At 4 h, pain-free rates were: RI: 69%; RI + RO: 82.3%; RI + TA: 78.1% (NS for all comparisons). The combination of RI + RO was superior to RI and to RI + TA in regard of the absence of nausea and photophobia at 4 hours. Recurrence (after being pain-free at 2 h) was observed in 50% of patients treated with RI, in 15,4% of those treated with RI + RO, and in 7,7% of those treated with RI + TA. CONCLUSIONS: Despite the methodological limitations of this study, the combination of RI and RO revealed a higher response rate at 2 hours. Recurrence was also clearly decreased with both combinations in relation to the use of RI alone. Controlled studies are necessary to provide additional evidence.

Acute Disease↗

Intravenous chlorpromazine in the emergency department treatment of migraines: a randomized controlled trial.

The aim of this study is to assess, in a double blind randomized clinical trial, the effect of chlorpromazine (CPZ) on the pain and associated symptoms in patients with migraine. Sixty patients with migraine with aura and 68 patients with migraine without aura were assigned at random to receive IV 0.1 mg/Kg CPZ or placebo. We assessed pain intensity, nausea, photophobia, and phonophobia at baseline, 30 min, and 60 min post-IV administration. End-point efficacy at 60 min was used to calculate the number needed to treat (NNT). We also recorded adverse effects, need for rescue medication at 24 h, and recurrence of headache at 24 h. We found clinically and statistically significant (p < 0.01) improvement associated with CPZ in pain scores, nausea, photophobia, phonophobia, and need for rescue medication, all at 60 min, and in rate of recurrence at 24 h, both in patients with and without aura. NNT = 2. Those allocated to CPZ had less nausea and dyspepsia, but more drowsiness and postural hypotension than those receiving placebo. CPZ is an excellent option for the treatment of migraines, with and without aura, in the Emergency Department.

Chlorpromazine↗

Intravenous chlorpromazine in the acute treatment of episodic tension-type headache: a randomized, placebo controlled, double-blind study.

Acute headache is a very frequent symptom, responsible for a significant percentage of caseload at primary care units and emergency rooms. Chlorpromazine is easily available in such settings. The aim of this study is to conduct a randomized, placebo-controlled, double-blind study to assess the efficacy of chlorpromazine on the acute treatment of episodic tension-type headache. We randomized 30 patients to receive placebo (10 ml of saline intravenous injections) and 30 patients to receive 0.1 mg/Kg chlorpromazine intravenously. We used 7 parameters of analgesic evaluation. Patients receiving chlorpromazine showed a statistically significant improvement (p < 0.05 and p < 0.01) of pain compared to placebo, far up to 30 minutes after the drug administration. The therapeutic gain was 36.7% in 30 minutes and 56.6 % in 60 minutes. The number needed to treat (NNT, the reciprocal or the therapeutic gain) was 2.7 in 30 minutes and 1.8 in 60 minutes. There were reductions in the recurrence and in the use of rescue medication in the chlorpromazine group. We can conclude that intravenous chlorpromazine is an effective drug to relief the pain in tension-type headache.

Acute Disease↗