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Profissionais de saúde » Publicações

Nesta área do site estão disponíveis alguns dos estudos científicos apresentados em congressos e publicados pelo Dr. Abouch Krymchantowski em revistas especializadas em cefaleia do Brasil e do exterior.

*As publicações na íntegra estão disponíveis em alguns sites, mas, infelizmente, por exigência de algumas revistas médicas, outras não podem ter seu conteúdo acessado livremente.

 

1: Prog Orthod. 2011;12(1):2-7.

A double-blind, randomized clinical trial assessing the effects of a single dose of preemptive anti-inflammatory treatment in orthodontic pain.

Bruno MB, Bruno MA, Krymchantowski AV, da Motta AF, Mucha JN

OBJECTIVE: Strategies about how to mitigate or prevent the appearance of pain associated with orthodontic treatment are poorly defined. Herein we conduct a prospective, double-blind, randomized controlled clinical trial assessing the effects of a single dose of anti-inflammatory medication to preemptively treat pain following the placement of orthodontic separating elastics.

Conteúdo completo

 

2: Headache. 2011 Apr;51(4):604-8.

Cluster and other nonmigraine primary headaches with aura.

Evans RW, Krymchantowski AV.

Conteúdo completo

 

3: Headache. 2011 Apr;51(4):554-8.

Topiramate vs Divalproex Sodium in the Preventive Treatment of Migraine: A Prospective “Real-World” Study.

Krymchantowski AV, Jevoux CC.

BACKGROUND AND OBJECTIVES: Certain neuromodulators, most notably topiramate (TPM) and divalproex sodium (DVP), are effective preventive agents for migraine. Published data from head-to-head studies comparing TPM and DVP are not available. The purpose of this study was to compare TPM and DVP for the prophyaxis of migraine in a “real-world” setting.

Conteúdo completo

 

4: Curr Pain Headache Rep. 2010 Aug;14(4):321-4.

Headaches due to external compression.

Krymchantowski AV.

Abstract: Headache is one of the most common types of recurrent pain in medical practice. Although nearly everyone has occasional headaches, there are well-defined headache disorders that vary in incidence and prevalence. Among the unusual headache syndromes, headache due to external compression is a poorly studied headache considered to arise as a result of continued stimulation of cutaneous nerves by the application of pressure over the scalp or forehead. The wearing of bands around the head, specifically goggles (such as those worn for swimming), tight hats, or even professional helmets have been described as causative factors. The pain is often constant and more severe at the location where the object is pressing the head. In predisposed patients (ie, those with migraine), external compression may lead to a more severe migrainous headache if the stimulus is prolonged. The mechanism responsible is the compression of trigeminal or occipital nerves branches. The headache resolves after pressure is relieved, or is prevented by avoiding the precipitating cause. Drugs are rarely used.

Conteúdo completo

 

5: Headache. 2010 Sep;50(8):1306-12.

Chronic headache and comorbibities: a two-phase, population-based, cross-sectional study.

da Silva A Jr, Costa EC, Gomes JB, Leite FM, Gomez RS, Vasconcelos LP, Krymchantowski A, Moreira P, Teixeira AL.

OBJECTIVES: To estimate the 1-year prevalence of CDH, as well as the presence of associated psychiatric and temporomandibular disorders (TMD) comorbidities, on the entire population of a city representative of the rural area of Brazil.

Conteúdo completo

 

6: Pain Med. 2010 Jan;11(1):48-52.

An open pilot study assessing the benefits of quetiapine for the prevention of migraine refractory to the combination of atenolol, nortriptyline, and flunarizine.

Krymchantowski AV, Jevoux C, Moreira PF.

BACKGROUND: Migraine is a prevalent neurological disorder. Although prevention is the core of treatment for most, some patients are refractory to standard therapies. Accordingly, the aim of this study was to evaluate the use of Quetiapine (QTP) in the preventive treatment of refractory migraine, defined as previous unresponsiveness to the combination of atenolol, nortriptyline, and flunarizine.

Conteúdo completo

 

7: Arq Neuropsiquiatr. 2009 Jun;67(2B):559-69.

Migraine in the triptan era: progresses achieved, lessons learned and future developments.

Bigal ME, Krymchantowski AV, Ho T.

Abstract: Triptans, serotonin 5-HT1B/1D receptor agonists, more than revolutionizing the treatment of migraine, stimulated also ground breaking research that provided insights into the anatomy, physiology, and molecular pharmacology of migraine. This knowledge, in turn, is stimulating research on new mechanisms of action for the treatment of migraine. Accordingly, it is opportune to critically review the main advances in migraine science that happened in the triptan era. Herein we first review and conceptualize some of the progresses achieved in migraine science during the triptan era. We then review the class of the triptans–mechanism of action and clinical evidence. We close by briefly discus sing the class of CGRP receptor antagonists, which is currently being developed for the acute treatment of migraine.

Conteúdo completo

 

8: Expert Rev Neurother. 2009 May;9(5):649-59.

The triptans.

Bigal ME, Krymchantowski AV, Hargreaves R.

Abstract: The migraine-specific triptans have revolutionized the treatment of migraine and are currently the drugs of choice to treat a migraine attack in progress. Over the past 15 years, triptans were released in rapid succession, with each one demonstrating some specific pharmacokinetic properties that may be translated into clinical advantages. Triptans share many similarities, but also have important differences from one another. Accordingly, herein we discuss the class of the triptans. We first define the trigeminovascular system and its importance in migraine pain, then discuss the mechanism of action of the triptans and contrast the evidence supporting the use of different triptans. We close with our view of the future and hopes for the next generation of antimigraine therapies.

Conteúdo completo

 

9: Sociedade Brasileira de Cefaleia. 2009 Nov

O tratamento agudo da migrânea: evidências e estratégias – vídeo

Palestra em vídeo proferida pelo Dr. Abouch V. Krimchantowski no 1o Simpósio Merck-Sharp & Dohme.

Conteúdo completo

 

10: Arq Neuropsiquiatr. 2009 Jun;67(2B):559-69.

Migraine in the triptan era: progresses achieved, lessons learned and future developments.

Bigal ME, Krymchantowski AV, Ho T

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.

Triptans, serotonin 5-HT1B/1D receptor agonists, more than revolutionizing the treatment of migraine, stimulated also ground breaking research that provided insights into the anatomy, physiology, and molecular pharmacology of migraine. This knowledge, in turn, is stimulating research on new mechanisms of action for the treatment of migraine. Accordingly, it is opportune to critically review the main advances in migraine science that happened in the triptan era. Herein we first review and conceptualize some of the progresses achieved in migraine science during the triptan era. We then review the class of the triptans-mechanism of action and clinical evidence. We close by briefly discussing the class of CGRP receptor antagonists, which is currently being developed for the acute treatment of migraine.

Conteúdo completo

 

11: Headache. 2009 Jun;49(6):895-9. Epub 2009 Apr 27.

Prevalence of headache in the entire population of a small city in Brazil.

Junior AS, Krymchantowski A, Moreira P, Vasconcelos L, Gomez R e Teixeira A

University Hospital, Federal University of Minas Gerais-Headache Clinic, Neurology Division, Belo Horizonte, Brazil.

OBJECTIVE: To estimate the 1-year prevalence of headache, using face-to-face interviews of the entire population of a city in Brazil. METHODS: This was a cross-sectional, population-based study. We conducted face-to-face interviews of all individuals older than 10 years, in a town (Capela Nova) in Brazil. Prevalence of the headache was estimated using prevalence ratios, adjusted by gender, age, marital status, and level education. RESULTS: The estimated 1-year prevalence of any headache was 65.4%. Headache was 1.5 times more prevalent in women and individuals aged 20 and 29, but less prevalent in the elderly and divorced. There was not association with the level of education. CONCLUSIONS: From a public healthcare perspective, headache should be seen as hypertension and diabetes, and actively screened and treated.

Conteúdo completo

 

12: Expert Rev Neurother. 2009 May;9(5):649-59.

The triptans

Bigal ME, Krymchantowski AV e Hargreaves R

Merck Research Laboratories, Whitehouse Station, NJ 08889, USA. marcelo_bigal@merck.com

The migraine-specific triptans have revolutionized the treatment of migraine and are currently the drugs of choice to treat a migraine attack in progress. Over the past 15 years, triptans were released in rapid succession, with each one demonstrating some specific pharmacokinetic properties that may be translated into clinical advantages. Triptans share many similarities, but also have important differences from one another. Accordingly, herein we discuss the class of the triptans. We first define the trigeminovascular system and its importance in migraine pain, then discuss the mechanism of action of the triptans and contrast the evidence supporting the use of different triptans. We close with our view of the future and hopes for the next generation of antimigraine therapies.

Conteúdo completo

 

13: Headache. 2009 Jul;49(7):1028-41. Epub 2009 Apr 6.

Barriers to satisfactory migraine outcomes. What have we learned, where do we stand?

Bigal ME, Krymchantowski AV, Lipton RB

The Merck Research Laboratories, 1 Merck Drive, office WHS-3C26, Whitehouse Station, NJ 08889, USA. marcelo_bigal@merck.com

Barriers to optimal migraine care have traditionally been divided into a number of categories: under-recognition and underconsultation by migraine sufferers; underdiagnosis and undertreatment by health care professionals; lack of follow-up and treatment optimization. These “traditional” barriers have been recognized and addressed for at least 15 years. Epidemiologic studies suggest that consultation, diagnosis, and treatment rates for migraine have improved although many migraine sufferers still do not get optimal treatment. Herein, we revisit the problem, review areas of progress, and expand the discussion of barriers to migraine care. We hypothesize that the subjective nature of pain and difficulty in communicating it contributes to clinical and societal barriers to care. We then revisit some of the traditional barriers to care, contrasting rates of recognition, diagnosis, and treatment over the past 15 years. We follow by addressing new barriers to migraine care that have emerged as a function of the knowledge gained in this process.

Conteúdo completo

 

14: Headache. 2009 Mar;49(3):481-2.

Memantine in the preventive treatment for migraine and refractory migraine.

Krymchantowski A, Jevoux C.

Universidade Federal Fluminense – Neurology, Rio de Janeiro, Brazil.

 

15: Arq Neuropsiquiatr. 2008 Sep;66(3B):615-8.

Quetiapine for the prevention of migraine refractory to the combination of atenolol + nortriptyline + flunarizine: an open pilot study.

Krymchantowski AV, Jevoux C.

Headache Center of Rio, Rio de Janeiro, RJ, Brazil. abouchkrym@globo.com

BACKGROUND: Migraine is a prevalent neurological disorder. Although prevention is the mainstream treatment, some patients are refractory to standard therapies. AIM: To evaluate the use of quetiapine (QTP) in the preventive treatment of refractory migraine, defined as previous unresponsiveness to the combination atenolol + nortriptyline + flunarizine. METHOD: Thirty-four consecutive patients (30 women and 4 men) with migraine (ICHD-II) and headache attacks on less than 15 days per month not overusing symptomatic medications were studied. The main inclusion criterion was the lack of response (<50% reduction in attack frequency) after ten weeks to the combination of atenolol (60 mg/day) + nortriptyline (25 mg/day) + flunarizine (3 mg/day). The patients started on QTP as the sole treatment in a single daily dose of 25 mg, titrated to 75 mg. After ten weeks, headache frequency, consumption of rescue medications and adverse events were analyzed. RESULTS: Twenty nine patients completed the study. Among completers, 22 (75.9%; 64.7% of the intention-to-treat population) presented >50% headache reduction. The mean frequency of migraine days decreased from 10.2 to 6.2 and the average consumption of rescue medications decreased from 2.3 to 1.2 days/week. Adverse events were reported by 9 (31%) patients. CONCLUSION: Although limited by the open design, this study provides a pilot data to support the use of quetiapine in preventive treatment of refractory migraine.

Conteúdo completo

 

16: Curr Pain Headache Rep. 2008 Jun;12(3):220-3.

Migraine prevention trials and optimized acute therapy: translating lessons learned into clinical practice.

Krymchantowski AV, Jevoux Cda C.

Rua Siqueira Campos 43/1002 Copacabana, Rio de Janeiro, Brazil. abouchkrym@globo.com

Different classes of drugs, discovered by serendipity, have been used successfully for migraine prevention for more than 40 years. The progressive knowledge of migraine pathophysiology, brain hyperexcitability, and the specific neurotransmitter systems involved in pain perception has driven the attempts at targeting two crucial mechanisms: the restoration of nociceptive dysmodulation and the inhibition of cortical hyperexcitability. The success of modern research trials with preventive migraine agents (mainly neuromodulators) and optimized treatment of acute attacks with drug combinations aimed at low serotonergic function, neurogenic inflammation, and central sensitization has translated into better outcomes for patients and physicians. Trials combining preventive migraine agents with nonpharmacologic behavioral headache management have yielded additional benefits over either approach alone. With the clinical application of this updated information from clinical trials, migraine impact on productivity, quality of life, and suffering will certainly be diminished. We hope that these achievements will create a stable path of management to benefit our patients, without interruption, into the foreseeable future.

Conteúdo completo

 

17: Curr Pain Headache Rep. 2008 Oct;12(5):333-7.

Neuromodulators for the treatment of headache disorders and fibromyalgia.

Krymchantowski AV, Bryson J, Lipton RB, Bigal ME.

Merck Research Laboratories, 1 Merck Drive, Whitehouse Station, NJ 08889, USA.

Migraine and fibromyalgia are prevalent and disabling disorders with few preventive medications approved by the US Food and Drug Administration (FDA). Neuromodulators (or antiepileptic drugs; AEDs) are often effective in the treatment of these conditions. Divalproex sodium and topiramate are FDA-approved AEDs for migraine. For fibromyalgia, pregabalin has recently been approved in the United States. We review the use of AEDs in the preventive treatment of these highly prevalent disorders.

Conteúdo completo

 

18: Arq Neuropsiquiatr. 2008 Jun;66(2A):216-20.

Lysine clonixinate versus dipyrone (metamizole) for the acute treatment of severe migraine attacks: a single-blind, randomized study.

Krymchantowski AV, Carneiro H, Barbosa J, Jevoux C.

Headache Center of Rio, Rio de Janeiro, RJ, Brazil. abouchkrym@globo.com

BACKGROUND AND OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAID) are effective to treat migraine attacks. Lysine clonixinate (LC) and dipyrone (metamizol) have been proven effective to treat acute migraine. The aim of this study was to evaluate the efficacy and tolerability of the intravenous formulations of LC and dipyrone in the treatment of severe migraine attacks. METHOD: Thirty patients (28 women, 2 men), aged 18 to 48 years with migraine according the International Headache Society (IHS) (2004) were studied. The patients were randomized into 2 groups when presenting to an emergency department with a severe migraine attack. The study was single-blind. Headache intensity, nausea, photophobia and side effects were evaluated at 0, 30, 60 and 90 minutes after the drug administration. Rectal indomethacin as rescue medication (RM) was available after 2 hours and its use compared between groups. RESULTS: All patients completed the study. At 30 minutes, 0% of the dipyrone group 13% of the LC group were pain free (p=0.46). At 60 and 90 minutes, 2 (13%) and 5 (33%) patients from the dipyrone group and 11 (73%) and 13 (86.7%) patients from the LC group were pain free (p<0.001). At 60 minutes, significantly more patients from the LC group were nausea-free (p<0.001). Regarding photophobia, there were no differences between groups at 60 minutes (p=0.11). The use of RM at 2 hours did not differ among groups (p=0.50). Pain in the site of the injection was reported by more patients of the LC group compared to the dipyrone group (p<0.0001). CONCLUSION: LC is significantly superior to dipyrone in treating severe migraine attacks. LC promotes significantly more burning at the site of the injection.

Conteúdo completo

 

19: Recent Pat CNS Drug Discov. 2007 Jun;2(2):141-4.

The experience of combining agents, specially triptans and non steroidal anti-inflammatory drugs, for the acute treatment of migraine – a review.

Krymchantowski AV, Jevoux Cda C.

Headache Center of Rio. Rio de Janeiro, Brazil. abouchkrym@globo.com

BACKGROUND AND OBJECTIVES: Migraine is a highly prevalent neurological disorder with multiple mechanisms. Targeting a single mechanism has been found only partially effective for treating individual attacks. Recently, the role of combining agents for the acute migraine treatment has gained attention and the combination of a triptan plus a nonsteroidal anti-inflammatory drug (NSAID) has demonstrated better efficacy. This article focuses on the review of available literature for treating migraine attacks with two or more agents, related patents as well as analyzes the characteristics of the recently approved fixed combination sumatriptan-naproxen. METHODS: The following terms migraine, acute treatment, sumatriptan, naproxen and combination were searched on MEDLINE. In addition, abstracts presented in the major meetings carried out by the American Headache and the International Headache Societies along with the American Academy of Neurology were also evaluated. RESULTS: Although most of the few studies encountered were not controlled, there is a clear trend for the better efficacy in combining triptans with NSAID. Additionally, the results of two recent large and controlled studies using fixed combinations of sumatriptan (50mg and 85mg) with 500mg naproxen sodium confirm the initial observations of the clear superiority of this combination over the isolated use of each agent. The differences in the endpoints of 24-hour pain relief response as well as pain-free and pain-relief parameters at 2-hour time-points are the clearest efficacy measures. Tolerability was not different between the two studied drugs. CONCLUSIONS: Combining triptans with NSAID and other agents for the acute treatment of migraine suggests better outcome efficacy measures than the use of single agents. The fixed combination of sumatriptan and naproxen sodium offers improved 2-hour and 24-hour benefits over the monotherapy. Recently, issued FDA approval for marketing the combination (sumatriptan 50mg-naproxen 500mg) emphasizes the usefulness and safety of this new treatment for migraine attacks.

Conteúdo completo

 

20: Curr Pain Headache Rep. 2007 Dec;11(6):449-53.

Migraine, tension-type headache, and transformed migraine.

Peres MF, Gonçalves AL, Krymchantowski A.

Al Joaquim Eugenio de Lima, 881 cj 708, 01403-001, São Paulo, SP, Brazil. marioperes@yahoo.com

Migraine and tension-type headache (TTH) are highly prevalent primary headaches that remain underdiagnosed and undertreated in clinical practice. The similarities and differences between migraine and TTH may impose diagnostic challenges as well as management difficulties. In addition, the possibility of migraine chronification or transformation in daily or near-daily headache raises the potential level of interaction between pathophysiologic mechanisms of TTH and migraine. The continuum concept is a possible key to the understanding of this association. Future studies are necessary to clarify epidemiology, pathophysiology, and management of these two most prevalent headaches.

Conteúdo completo

 

21: Expert Rev Neurother. 2007 Sep;7(9):1065-7.

Chronic (transformed) migraine and medication overuse: to withdraw or not?

Krymchantowski AV, Jevoux Cda C.

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22: MedGenMed. 2007 Apr 26;9(2):21.

Adherence to headache treatment and profile of previous health professional seeking among patients with chronic headache: a retrospective analysis.

Krymchantowski AV, Adriano MV, de Góes R, Moreira PF, da Cunha Jevoux C.

Outpatient Headache Unit, Instituto de Neurologia Deolindo Couto, Department of Neurology, Hospital Pasteur, Universidade Federal do Rio de Janeiro Rio de Janeiro, Brazil. abouchkrym@globo.com

BACKGROUND AND OBJECTIVES: Chronic headache is common among patients in neurology clinics. Patients may suffer important economic and social losses because of headaches, which may result in high expectations for treatment outcomes. When their treatment goals are not reached quickly, treatment may be difficult to maintain and patients may consult with numerous health professionals. This retrospective study evaluated the relationship between treatment and the profiles of previous health professionals consulted by patients in a tertiary headache center. PATIENTS AND METHODS: The records were reviewed of all patients from a headache center who were seen in initial consultation between January 2000 and June 2003. Data related to patient demographic characteristics (sex and age), headache diagnosis, and the profile (quality and quantity) of previous healthcare consultations exclusively related to headache, were collected. The headache diagnoses were confirmed according to the IHS criteria (1988) and to the Silberstein criteria (1994,1996). Although adherence includes taking the prescribed medicines, discontinuing overused symptomatic medications, and changing behavior, among other things, for this study, adherence was defined as when the patient returned at least 2 times within a 3- to 3.5-month period. Patients were separated into groups depending on the number of different healthcare professionals they had consulted, from none to more than 7. RESULTS: Data from 495 patients were analyzed; 357 were women and 138 were men (ages 6 to 90 years; mean, 41.1 +/- 15.05 years). The headache diagnoses included migraine without aura (43.2%), chronic (transformed) migraine (40%), cluster headache (6.5%), episodic tension-type headache (0.8%), and hemicrania continua (0.4%). The 24.2% of patients who sought care from no more than 1 health professional showed a 59.8% adherence rate; 29% of the total had consulted 7 or more health professionals and showed an adherence rate of 74.3% (P = .0004). COMMENTS: In Brazil, the belief is widespread that patients attending tertiary headache centers tend to be those who have consulted with numerous health professionals and are, therefore, refractory and/or have adherence problems. Despite the limitations imposed by the retrospective design and the fact that we excluded other important markers of real adherence, this study suggested the opposite. The patients who had seen the lowest number of health professionals presented the worse adherence profile. One of the possible reasons is that patients receive more comprehensive care in a specialized center. Further prospective studies to confirm these observations are warranted.

Conteúdo completo

 

23: Neurol Sci. 2007 May;28 Suppl 2:S166-78.

The future of acute care and prevention in headache.

Krymchantowski AV, Rapoport AM, Jevoux CC.

Rua Siqueira Campos 43/1002 Copacabana, Rio de Janeiro, Brazil. abouchkrym@globo.com

Migraine is a chronic neurological disease with heterogeneous characteristics resulting in a range of symptom profiles, burden and disability. It affects nearly 12% of the adult population in Western countries and up to 22% of the Brazilian population, imposing considerable suffering as well as personal, economic and social losses. The pharmacological treatment of migraine is divided into preventive and acute treatment. A better comprehension of migraine pathophysiology, as well as the finding of novel molecular targets, has led to a growing number of upcoming therapeutic opportunities. The same is true of cluster headache, which affects only about 0.07%-0.4% of most populations. This review focuses on current and emerging agents and procedures for the treatment of migraine and cluster headache.

Conteúdo completo

 

24: Arq Neuropsiquiatr. 2006 Sep;64(3B):802-6.

Prevalence and characteristics of headache in a population of regular physical exercise practitioners

Miranda F, Dantas B, Krymchantowski AV.

Cia Atlhética, Rua Siqueira Campos43/1002, 22031-070 Rio de Janeiro RJ, Brazil.

BACKGROUND: The burden of headache may impede sufferers from adhering to a routine of physical activity. OBJECTIVE: To evaluate the prevalence and characteristics of headache in a health club population. METHOD: One hundred attendees of a health club were interviewed. They all were regular attendees for the previous 12 months and practiced aerobic exercises no less than 3 times a week. A questionnaire with characteristics of headache was applied to all who had a headache attack during the previous 12 months. MIDAS questionnaire was used as well. RESULTS: 57 men and 43 women were included. Eighty subjects had a headache attack, which was pulsatile in 63% of the sufferers. MIDAS was lower than 5 days in 83% of the subjects. CONCLUSION: Although retrospective and based on recall, this study suggests that most of the regular exercise practitioners presented clinical characteristics of migraine. It is uncertain whether the regular practice of physical exercise has a role in reducing the impact life or those suffering less are the ones who practice exercise.

Conteúdo completo

 

25: Neuropsychiatr Dis Treat. 2006 Sep;2(3):293-7.

The use of combination therapies in the acute management of migraine.

Krymchantowski AV.

Headache Center of Rio, Rio de Janeiro, Brazil; Outpatient Headache Unit of the Instituto de Neurologia Deolindo Couto, Rio de Janeiro, Brazil.

BACKGROUND AND OBJECTIVES: Migraine is a highly prevalent neurological disorder with multiple peripheral and central mechanisms. Targeting a single mechanism for treating individual attacks as well as for performing the prophylaxis has been shown to be only partially effective. Recently, the role of combining agents for acute migraine treatment has gained attention and the combination of a triptan plus a non-steroidal anti-inflammatory drug (NSAID) has demonstrated better efficacy. This review focuses on the fundamentals of treating migraine attacks with two or more agents, and emphasizes the characteristics of the recently approved fixed combination sumatriptan-naproxen. METHODS: A PubMed search using the terms “migraine”, “treatment”, “acute”, “triptans”, “non-steroidal anti-inflammatory drugs”, “sumatriptan”, “naproxen”, and “combination” was used. In addition, abstracts presented in the major meetings of the American Headache and the International Headache Societies along with the American Academy of Neurology were also evaluated. RESULTS: Although most of the few studies encountered were not controlled, there is a clear trend for better efficacy in combining triptans with NSAID. Additionally, the results of two recent large and controlled studies using fixed combinations of sumatriptan (50 mg and 85 mg) with 500 mg naproxen sodium confirm the initial observations of the clear superiority of this combination over the use of each agent alone. The differences in the endpoints 24-hour pain-relief response as well as pain-free and pain-relief parameters at 2-hour time-point are the most noticeable efficacy measures. Tolerability was not different between studied drugs. CONCLUSIONS: Combining triptans with NSAID and other agents for the acute treatment of migraine suggests better outcome efficacy measures than the use of single agents. The fixed combination of sumatriptan and naproxen sodium offers improved 2-hour and 24-hour benefits over monotherapy with each one these options. Recently issued FDA approval for marketing the combination (sumatriptan 50 mg-naproxen 500 mg) emphasizes the usefulness and safety of this new treatment for migraine attacks.

Conteúdo completo

 

26: MedGenMed. 2006 May 4;8(2):31.

Emerging drugs for migraine prophylaxis and treatment.

Bigal ME, Krymchantowski AV.

The New England Center for Headache, P.C., Stamford, Connecticut, USA.

Migraine is a chronic neurologic disorder with heterogeneous characteristics resulting in a range of symptom profiles, burden, and disability. Migraine affects nearly 12% of the adult population in occidental countries, imposing considerable economic and social losses. The pharmacologic treatment of migraine includes preventive and acute strategies. A better understanding of the migraine pathophysiology along with the discovery of novel molecular targets has lead to a growing number of upcoming therapeutic proposals. This review focuses on new and emerging agents for the treatment of migraine.

Conteúdo completo

 

27: Cephalalgia. 2006 Jul;26(7):871-4.

Rizatriptan vs. rizatriptan plus trimebutine for the acute treatment of migraine: a double-blind, randomized, cross-over, placebo-controlled study.

Krymchantowski AV, Filho PF, Bigal ME.

Instituto de Neurologia Deolindo Couto, Rio de Janeiro, Brazil. abouchkrym@globo.com

Gastroparesis frequently happens during migraine attacks, postponing the onset of action of orally administered drugs. Furthermore, triptans seem to work better in the earlier phases of the migraine attacks. Therefore, associating a gastrokinetic drug with a triptan may translate into better efficacy and higher consistency of response. Trimebutine is an opioid derivative with exclusive action on receptors of the Meissner and Auerbach plexus throughout the digestive tube. It has no absorption or central penetration. Herein we contrast the combination of rizatriptan plus trimebutine with rizatriptan alone in the acute treatment of migraine. Forty patients with migraine consecutively seen in our clinic were randomized to treat two consecutive moderate or severe attacks with one tablet of 10 mg rizatriptan plus one capsule of 200 mg trimebutine and two attacks with the same triptan and placebo, in counterbalanced order. We collected information on the severity of the attack, as well as presence of nausea and photophobia at the time of drug intake, and after 1, 2 and 4 h. Recurrence and adverse events were also contrasted. Sixty-four attacks were treated with each drug regimen. At 1 h postdose, 30 (46.8%) of 64 attacks treated with the combination resolved completely, vs. eight (12.5%) of the rizatriptan-treated attacks, a difference of 34% (P < 0.01). At 2 h postdose, 47 (73.4%) attacks treated with the combination vs. 20 (31.2%) of those treated with rizatriptan alone resolved completely, a difference of 42% (95% confidence interval 26, 58, P < 0.001). Regarding nausea and photophobia, the combination was also associated with significantly better response. Recurrence was similar among the two drug regimens, as well as adverse events. The combination rizatriptan and trimebutine is more effective than rizatriptan alone. The combination does not increase adverse events or recurrence of pain.

Conteúdo completo

 

28: Headache. 2006 Apr;46(4):683-6.

Side-locked headache as the chief complaint of inflammatory orbital pseudotumor (myositic form): a case report.

Krymchantowski AV, Oliveira T, Bigal ME.

Headache Center of Rio, Rio de Janeiro, Brazil.

The case of a 38-year-old woman with continuous unilateral side-locked headache is reported. She had continuous right-sided periorbital pain of mild to moderate intensity for the past 5 months. She also reported a few episodes of pain exacerbations every day. She had no autonomic features. Based on a normal CT scan ordered by her general physician, we started indomethacin (150 mg/day) as well as celecoxib (400 mg/day) for 2 weeks, without relief. Oral prednisone for 6 days provided important relief, and she stayed on daily use of steroids, refusing other forms of therapy. After 5 months she developed orbital and eyelid edema, with painful restrictions to eye movement. Orbital MRI and pathological exam demonstrated inflammatory orbital pseudotumor (myositic form).

 

29: Headache. 2006 Mar;46(3):515-7.

Migraine triggered by sucralose–a case report.

Bigal ME, Krymchantowski AV.

Department of Neurology, The Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Sucralose is the active compound of the most commonly sold sweetener in the United States. Different than aspartame, sucralose is not considered to be a migraine trigger. Herein we report a patient with attacks of migraine consistently triggered by sucralose. She also suffers from menstrually related migraine that had been well-controlled for several months since she switched her contraceptive from fixed estrogen to triphasic contraceptive pills. Some attacks triggered by sucralose were preceded by aura, and she had never experienced migraine with aura before. Withdrawal of the compound was associated with complete resolution of the attacks. Single-blind exposure (vs. sugar) triggered the attacks, after an attack-free period.

Conteúdo completo

 

30: MedGenMed. 2005 Dec 14;7(4):69.

Lysine clonixinate vs naproxen sodium for the acute treatment of migraine: a double-blind, randomized, crossover study.

Krymchantowski AV, Peixoto P, Higashi R, Silva A Jr, Schutz V.

Outpatient Headache Unit, Instituto de Neurologia Deolindo Couto, Department of Neurology, Hospital Pasteur, Universidade Federal do Rio de Janeiro Rio de Janeiro, Brazil.

BACKGROUND AND OBJECTIVES: The process of inflammation is crucial in migraine, and several nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in the treatment of migraine attacks. Despite their efficacy, the routine use of NSAIDs is limited by side effects as well as incomplete efficacy in some patients. Among the available options, lysine clonixinate (LC) and naproxen sodium (NS) have proved effective in migraine. The aim of this study was to compare the efficacy and tolerability of oral formulations of LC and NS in the treatment of moderate or severe migraine attacks, with a double-blind, crossover design. METHODS: Seventy subjects (62 women, 8 men) between ages 18 and 71 years (mean age, 41) with migraine according to the criteria of the International Headache Society were prospectively enrolled. The patients were randomized into 2 groups and each participant treated 2 migraine attacks. Group 1 treated the first attack with LC and the second attack with NS. Group 2 treated 2 attacks in a counterbalanced order. Doses were 250 mg of LC or 550 mg of NS, which were encapsulated for equal appearance. Headache intensity, nausea, photophobia, and side effects were evaluated at baseline, 1 hour, and 2 hours after drug administration. Rescue drugs were allowed after 2 hours for those who didn’t respond, and this was also compared between groups. RESULTS: Sixty patients (54 women, 6 men) completed the study. At 1 hour, 13.6% patients who used LC were pain-free compared with 11.9% who used NS (P = .78). At 2 hours, 35.6% patients who took LC and 32.2% who took NS were pain-free (P = .69). At baseline, 52.5% of the patients randomized to group 1 reported nausea, compared with 33.9% in group 2, and both drugs eliminated nausea: At both 1 hour and 2 hours, nausea diminished significantly for those taking LC, but only after 2 hours for those who took NS (P < .0001). Both drugs eliminated photophobia at 1 hour and 2 hours; however, LC was superior to NS in reducing photophobia at 2 hours (P = .027). Ten patients who took LC and 8 who took NS required rescue drugs after 2 hours. Twelve patients who used LC and 16 who took NS reported side effects. COMMENTS: Although this study did not include a placebo arm, which impairs any definitive efficacy claims, we found LC and NS to be similarly effective and well tolerated in patients presenting moderate or severe attacks of migraine.

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31: Expert Rev Neurother. 2006 Mar;6(3):283-9.

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

Krymchantowski AV, Bigal ME.

Headache Center of Rio, Rua Siqueira Campos 43/1002 Copacabana, Rio de Janeiro, 22031.070, Brazil. abouchkrym@globo.com

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.

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32: Headache. 2006 Feb;46(2):346-7.

Monitoring patients’ response to acute migraine treatment: a headache attack report form.

Krymchantowski AV.

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33: Expert Rev Neurother. 2005 Sep;5(5):597-603.

Rizatriptan in migraine.

Krymchantowski AV, Bigal ME.

Instituto de Neurologia Deolindo Couto, Av das Americas 1155/1608 Barra Rio de Janeiro, Brazil. abouchkrym@globo.com

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.

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34: Expert Rev Neurother. 2005 Sep;5(5):557-9.

Refractoriness in migraine treatment: what are we talking about?

Krymchantowski AV.

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35: Curr Pain Headache Rep. 2005 Aug;9(4):264-7.

Aura with non-migraine headache.

Krymchantowski AV.

Outpatient Headache Unit, Instituto de Neurologia Deolindo Couto, Headache Center of Rio, Rua Siqueira, Campos 43/1002, Copacabana Rio de Janeiro, 22031.070 Brazil. abouchkrym@globo.com

The typical aura associated with migraine is characterized by visual or sensory and speech symptoms, with a mix of positive and negative features and complete reversibility within 1 hour. However, auras are not an exclusive migraine-dependent phenomenon. There have been descriptions of aura occurring in association with cluster headache, hemicrania continua, and even with chronic paroxysmal hemicrania. In addition, the occurrence of aura without headache or followed by a headache resembling the criteria of tension-type headache is encountered in clinical practice. This paper reviews the literature about auras in non-migraine headaches and the features involving this uncommon presentation. The possibility of a specific genetic origin for the auras, not related to the primary headache type, also is raised.

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36: Expert Rev Neurother. 2005 Mar;5(2):145-7.

Combining therapies for the treatment of migraine: is there a role?

Krymchantowski AV.

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37: Expert Rev Neurother. 2005 Jan;5(1):55-61.

Rofecoxib in migraine.

Krymchantowski AV, Bigal ME. abouchkrym@globo.com

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.

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38: MedGenMed. 2004 Jul 14;6(3):48.

Weight variations in patients receiving topiramate migraine prophylaxis in a tertiary care setting.

Krymchantowski A, Tavares C.

Headache Center of Rio, Department of Neurology, Universidade Federal Fluminense, Niteroi, Brazil.

BACKGROUND: Migraine is a highly prevalent chronic neurologic disorder. Frequent headache attacks require prophylactic treatment, and side effects are limiting prescribing factors among traditional agents for migraine prophylaxis. Beta-blockers, antidepressants, calcium channel blockers, and anticonvulsants have been used since the 1960s, and their efficacy has been demonstrated in several controlled studies. However, weight gain commonly occurs with most of these drugs and makes adherence to treatment a troublesome issue for many patients. Topiramate is a new anticonvulsant with proven efficacy in migraine and other conditions, which reportedly confers weight loss in patients receiving doses up to 300 mg/day. OBJECTIVE: The aim of this study was to evaluate adherence, weight loss, tolerability, and response to topiramate in adult migraineurs receiving treatment in a tertiary care center. METHODS: During a 2,5-year period, all patients receiving topiramate for migraine were evaluated after 3 months of treatment. The parameters evaluated were adherence to treatment, frequency in reduction of attacks > 50%, the presence and amount of weight loss, and adverse events. RESULTS: Among 175 patients included, 134 (76.6%) adhered to the regimen, whereas 4% interrupted before the 3-month evaluation and 19.4% did not return for follow-up. Among the 134 patients evaluated, 82 (61.2%) revealed headache-frequency reduction > 50%; 105 (78.4%) patients experienced weight loss (range 1-10 kg; average, 3.4 kg). The most frequent side effects were paresthesia (39.6%); emotional disturbances, including depression, irritability, and anxiety (17.9%); thinking impairment (12.7%); memory disturbances (12.7%); and altered taste (11.9%). CONCLUSION: Despite methodologic limitations, we conclude that good adherence to topiramate in a “real-world” headache clinic occurred in most of the study participants. The majority of patients also experienced weight loss and reductions in headache frequency, with an acceptable side-effect profile.
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39: MedGenMed. 2004 May 14;6(2):45.

Helmet-related, external compression headache among police officers in Rio de Janeiro.

Krymchantowski A, Barbosa JS, Cvaigman M, Lorenzatto W, Silva MT.

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40: BMC Neurol. 2004 Jun 28;4:10.

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

Krymchantowski AV, Bigal ME.

Department of Neurology, Universidade Federal Fluminense, Niterói, Brazil. abouchkrym@globo.com

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.

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41: Arq Neuropsiquiatr. 2004 Mar;62(1):91-5. Epub 2004 Apr 28.

Topiramate in the preventive treatment of migraine: experience in a tertiary center

Krymchantowski AV, Tavares C, Penteado Jd Jde C, Adriano M.

Departamento de Neurologia, Universidade Federal Fluminense, Niteroi, RJ, Brazil. abouchkrym@globo.com

Frequent migraine attacks require prophylactic treatment. Anticonvulsants have been suggested due to the progressive knowledge that cortical hyperexcitability is involved in migraine pathophysiology. Topiramate is one of these drugs and its efficacy has been demonstrated in several studies. The aim of this study is to evaluate the adherence and response to topiramate in migraineurs under treatment in a tertiary center. During a 2-year period, all of the patients receiving topiramate for migraine were evaluated after 3 months. The parameters evaluated were adherence to treatment, frequency reduction of attacks >50% and adverse events. Among 175 patients included, 134 (76.6%) returned. Among the 134 patients evaluated, 82 (61.2%) revealed frequency reduction >50% and 105 (78.4%) patients presented weight loss (average 3.4Kg). The most frequent side effects were paresthesias (39.6%); emotional disturbances (including depression, irritability and anxiety) in 17,9%; thinking impairment (12.7%); memory disturbances (12.7%) and altered taste (11.9%). Despite methodological limitations we concluded that adherence to its use and efficacy occurred in most of the patients. In addition, the side effect profile was acceptable. Further controlled studies are necessary to confirm these observations.

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42: Curr Pain Headache Rep. 2004 Jun;8(3):178-84


Prophylactic migraine therapy: emerging treatment options.

Bigal ME, Krymchantowski AV, Rapoport AM.

Department of Neurology, Albert Einstein College of Medicine, 1165 Morris Park Avenue, Bronx, NY 10461, USA. mbigal@aecom.yu.edu

In this paper, new treatment options for migraine prevention are reviewed. An overview about migraine pathophysiology is provided and current indications for migraine prevention and new and upcoming preventive medications are discussed briefly. Data are presented on topiramate, levetiracetam, zonisamide, botulinim toxin, tizanidine, nefazodone, lisinopril, candesartan, carabersat, petasites, and coenzyme Q.

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43: BMC Neurol. 2004 Jan 28;4:4.

Acute treatment of migraine. Breaking the paradigm of monotherapy.

Krymchantowski AV.

Department of Neurology, Universidade Federal Fluminense, Rio de Janeiro, Brazil. abouchkrym@globo.com

BACKGROUND: Migraine is a highly prevalent disorder. The disability provoked by its attacks results in suffering as well as considerable economic and social losses. The objective of migraine acute treatment is to restore the patient to normal function as quickly and consistently as possible. There are numerous drugs available for this purpose and despite recent advances in the understanding of the mechanisms and different biological systems involved in migraine attacks, with the development of specific 5-HT agonists known as triptans, current options for acute migraine still stand below the ideal. DISCUSSION: Monotherapeutic approaches are the rule but up to one third of all patients discontinue their medications due to lack of efficacy, headache recurrence, cost and/or side effects. In addition, a rationale has been suggested for the development of polytherapeutic approaches, simultaneously aiming at some of the biological systems involved. This paper reviews the fundamentals for this changing approach as well as the evidence of its better efficacy. CONCLUSION: As a conclusion, most of the patients with a past history of not responding (no pain-free at 2 hours and/or no sustained pain-free at 24 hours) in at least 5 previous attacks should undergo a combination therapy suiting to their individual profile, which must include analgesics or non-steroidal anti-inflammatory agents plus a triptan or a gastro kinetic drug. The three-drug regimen may also be considered. In addition, changing the right moment to take it and the choice for formulations other than oral has also to be determined individually and clearly posted to the patient.

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44: Am J Ther. 2004 Mar-Apr;11(2):130-40.

The medical management of migraine.

Bigal ME, Lipton RB, Krymchantowski AV.

Department of Neurology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. mbigal@aecom.yu.edu

Migraine is a common, chronic neurologic disorder that affects 11% of the adult population in Western countries. In this article, we review the current approaches to the pharmacologic treatment of migraine. Once migraine is diagnosed, and illness severity has been assessed, clinicians and patients should work together to develop a treatment plan based on the patient needs and preferences. The goals of the treatment plan usually include reducing attack frequency, intensity, and duration; minimizing headache-related disability; improving health-related quality of life; and avoiding headache escalation and medication misuse. Medical treatments for migraine can be divided into preventive drugs, which are taken on a daily basis regardless of whether headache is present, and acute drugs taken to treat individual attacks as they arise. Acute treatments are further divided into nonspecific and migraine-specific treatments. The US Headache Consortium Guidelines recommend stratified care based on the level of disability to help physicians individualize treatment. Simple analgesics are appropriate as first-line acute treatments for less disabled patients; if simple analgesics are unsuccessful, treatment is escalated. For those with high disability levels, migraine-specific acute therapies, such as the triptans, are recommended as the initial treatment, with preventive drugs in selected patients. A variety of behavioral interventions are helpful. The clinicians have in their armamentariums an ever-expanding variety of medications. With experience, clinicians can match individual patient needs with the specific characteristics of a drug to optimize therapeutic benefit.
45: Cephalalgia. 2003 Dec;23(10):982-93.

Out-patient detoxification in chronic migraine: comparison of strategies.

Krymchantowski AV, Moreira PF.

Department of Neurology, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil. abouchkrym@globo.com

Chronic migraine (CM) patients frequently overuse symptomatic medications (SM). These medications may create a cycle of rebound, worsening of headache and withdrawal symptoms that perpetuate the headache itself. In addition, the overuse of such substances is believed to counteract the efficacy of preventive treatments. We conducted a prospective randomized open-label trial comparing approaches to out-patient management in 150 CM patients (125 women, 25 men; ages 18-80 years, mean 40.3 +/- 13.8) with overuse of SM. In each group, 50 patients received education and orientation and were then abruptly withdrawn from all SM. Immediately following withdrawal, the first group took prednisone (60 mg/ day 2 days, 40 mg/day 2 days and 20 mg/day 2 days) for 6 days, the second group did not have any regular medications to take and the third group took naratriptan (2.5 mg twice a day) during this initial period. All patients had similar profiles of headache characteristics and consumption (quality and quantity) of SM before initiation of the treatment, but most were not severe headache sufferers, heavy SM overusers or were overusing opioids. After 5 weeks the headache frequency and intensity, the prevalence and frequency of withdrawal symptoms and consumption of rescue medications during the first 6 days were compared between groups. In addition, adherence to treatment (who returned or not and for which reasons, between groups) and headache frequency, week by week, among the groups of patients were also compared. Forty-four (88%) patients from the prednisone group, 41 (82%) from the ‘nothing’ group and 35 (70%) from the naratriptan group adhered to the treatment and returned. The were no differences between groups with regard to treatment adherence (P = 0.072), headache frequency as well as intensity (P = 0.311) and decreasing of days with headache after 5 weeks and weekly (P = 0.275). However, the incidence of withdrawal symptoms and consumption of rescue drugs was higher among the patients who did not take regular medications during the first 6 days (P = 0.0001 and P = 0.006). We concluded that CM patients with moderate overuse of SM other than opioids may be detoxified on an out-patient basis regardless of the strategy adopted with regard to the use of regular drugs during the initial days of withdrawal, but prednisone and naratriptan may be useful for reducing withdrawal symptoms and rescue medication consumption. Further controlled studies are necessary to confirm these observations.

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46: Arq Neuropsiquiatr. 2003 Jun;61(2B):364-7. Epub 2003 Jul 28.

Primary headache diagnosis among chronic daily headache patients.

Krymchantowski AV.

Department of Neurology, Universidade Federal Fluminense, Rio de Janeiro, RJ Brasil. abouchkrym@globo.com

Chronic daily headache (CDH) refers to a group of non-paroxysmal daily or near-daily headaches with peculiar characteristics that are highly prevalent in populations of neurological clinics and not uncommon among non-patient populations. Most of the patients with CDH had, as primary diagnosis, episodic migraine, which, with the time, presented a progressive frequency, pattern modification and loss of specific migraine characteristics. Other CDH patients had chronic tension-type headache, new daily persistent headache and hemicrania continua, which evolved thru the time to the daily or near-daily presentation. The objective of this study was to determine the primary headache diagnosis among a population of chronic daily headache patients attending a tertiary center for headache treatment. During a 5-year period 651 consecutive chronic daily headache patients attending a private subspecialty center were studied prospectively. The criteria adopted were those proposed by Silberstein et al (1994, revised 1996). Five hundred seventy four patients (88.1%) had episodic migraine as primary headache before turning into daily presentation, 52 (8%) had chronic tension-type headache, 14 (2.2%) had hemicrania continua and 11 patients (1.7%) had new daily persistent headache. CDH is quite frequent in patients from clinic-based studies suggesting a high degree of disability. Emphasis on education of patients suffering from frequent primary headaches with regard to measures that are able to decrease suffering and disability as well as better medical education directed to more efficient ways to handle these patients are necessary to improve outcome of such a prevalent condition.

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47: Arq Neuropsiquiatr. 2003 Mar;61(1):43-7. Epub 2003 Apr 16.

Overuse of symptomatic medications among chronic (transformed) migraine patients: profile of drug consumption.

Krymchantowski AV.

Centro de Avalia o e Tratamento da Dor de Cabe a do Rio de Janeiro, Departamento de Neurologia, Universidade Federal Fluminense, Rio de Janeiro, RJ, Brazil. abouchkrym@globo.com

Chronic daily headache and chronic (transformed) migraine (TM) patients represent more than one third of the subjects seen in specialized headache centers. Most of these patients may overuse symptomatic medications (SM) taken on a daily basis to relieve headache and associated symptoms. The conversion to the daily or near-daily pattern of headache presentation is thought to be related to the medication overuse. The aim of this study was to evaluate the profile of SM consumption among transformed migraine patients attending a tertiary center. One hundred thirty three consecutive patients (22 men and 111 women, ages 17 to 80) with TM and overuse of SM according to the proposed criteria of Silberstein et al (1994, 1996) were prospectively studied. None of the patients were under treatment for other conditions. Among them, 73 (54.9%) were using one category of SM, while 55 (41.3%) and 5 (3.8%) patients were taking simultaneously two and three categories of SM respectively. The categories of overused symptomatic medications varied from simple analgesics to narcotics, triptans and combinations of ergot derivatives and caffeine and of analgesics and caffeine. The average intake per patient per day was of 3 to 4 tablets and mostly of the patients overused simple analgesics (isolated or in combination with other substances) (75.2%), caffeine containing drugs (71.4%), drugs containing ergotamine derivatives (26.1%), triptans (alone or combined) (15.5%), drugs with narcotics or ansiolitics (13%) and anti-inflammatory drugs (3.7%). The mechanisms by which the overuse of symptomatic medications may play a role in this transformation are uncertain but despite of the necessity of controlled trials to demonstrate the real role of such compounds in the development of transformed migraine, this study emphasizes the necessity for more rigorous prescribing guidelines for patients with frequent headaches.

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48: Expert Opin Pharmacother. 2003 Apr;4(4):433-43.

New developments in migraine prophylaxis.

Bigal ME, Krymchantowski AV, Rapoport AM.

Department of Neurology, Albert Einstein College of Medicine, New York, USA. mbigal@aecom.yu.edu

Migraine is a common neurological disorder that afflicts > or = 12% of the adult US population. Severe, frequent and disabling attacks require effective prophylaxis. Traditional preventive drugs such as beta-blockers, antidepressants and calcium antagonists, despite their documented efficacy, fail to offer relief for a significant proportion of migraine sufferers. Multiple threads of research over the last 15 years have led to the concept that migraine is generated from a hyperexcitable brain. This opens new perspectives in terms of preventive options, especially regarding the anticonvulsants agents. Additionally, different groups of substances, some of which nominated as non-orthodox agents, have been recently subjected to clinical trials and found to be effective. The aim of this review is to present and discuss the new options for migraine prevention.

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49: Headache. 2002 Jun;42(6):510-4.

Amitriptyline versus amitriptyline combined with fluoxetine in the preventative treatment of transformed migraine: a double-blind study.

Krymchantowski AV, Silva MT, Barbosa JS, Alves LA.

Headache Center of Rio and Instituto de Neurologia Deolindo Couto/UFRJ, Rio de Janeiro, Brazil.

BACKGROUND AND OBJECTIVES: Antidepressants are often used to treat chronic daily headache disorders such as transformed migraine, in part because of the high prevalence of associated mood disorder. We conducted this study to evaluate the efficacy and tolerability of combined treatment with amitriptyline and fluoxetine compared with amitriptyline alone for chronic daily headache due to transformed migraine. PATIENTS AND METHODS: Thirty-nine patients, 26 women and 13 men, aged 20 to 69 years (mean, 36.4; SD, 2.5) who fulfilled criteria for transformed migraine proposed by Silberstein et al were studied prospectively. Amitriptyline was dosed as follows: 8 mg/day for 6 days, 8 mg twice a day for 6 days, 20 mg/day for 6 days, and 20 mg twice a day for 45 days. In the group receiving combination therapy, fluoxetine was dosed and administered identically. The initial and end of the study (9 weeks) headache indices (frequency x intensity) were compared between groups. RESULTS: Twenty-seven patients completed the study, 13 in the amitriptyline-alone group (group 1) and 14 in the combination-therapy group (group 2). The most frequent adverse event in both groups was dry mouth, and there was no significant difference in the occurrence of this or other adverse events between the two groups. Initial headache indices were similar for groups 1 and 2. The mean difference between the initial and final headache index for group 1 was 513.5 (P<.0005) and 893 (P<.0017) for group 2. The difference between the final headache index for the two groups was not significant (P>.207). CONCLUSIONS: We were unable to demonstrate any significant benefit from amitriptyline plus fluoxetine over amitriptyline alone in the treatment of chronic daily headache/transformed migraine. Because of the small number of subjects involved and the short duration of our study, a type II error cannot be excluded.

50: CNS Drugs. 2002;16(9):611-34.

New and emerging prophylactic agents for migraine.

Krymchantowski AV, Bigal ME, Moreira PF.

Department of Neurology, Universidade Federal Fluminense and Institute of Neurology Deolindo Couto, Rio de Janeiro, Brazil. abouchkrym@globo.com

Frequent, severe and long-lasting migraine attacks require prophylaxis. Established drugs used for the prevention of migraine such as beta-adrenoceptor antagonists (beta-blockers), calcium channel antagonists, antidepressants and others have an unknown mode of action in migraine. Their prophylactic effect in migraine was discovered by chance in clinical practice when these drugs were used for other purposes. Recently, research into the mechanisms of migraine and the progressive recognition that cortical hyperexcitability and an imbalance between neuronal inhibition [mediated by gamma-aminobutyric acid (GABA)] and excitation (mediated by excitatory amino acids) may play an important role in migraine pathophysiology have lead to the identification of potential new agents for the prevention of migraine attacks. This paper reviews the recent literature on these new agents. A search was conducted using MEDLINE from 1998 to November 2001 with the following search terms: migraine, preventive, prophylactic and treatment. Headache textbooks edited in 2000 and 2001 were also used. After analysing the available controlled and uncontrolled clinical studies as well as abstracts, divalproex sodium (valproate semisodium) can be recommended for the prevention of migraine. Lamotrigine may be useful for preventing aura associated with migraine, and topiramate seems a promising option pending trials with more patients, which are currently underway. Riboflavin (which is possibly involved in improving neuronal energy production) appears to be a promising agent, although comparisons with established prophylactic medications are needed. Gabapentin, magnesium, lisinopril and botulinum toxin A have recently been suggested to be effective; however, at present, there are insufficient rigorous and reliable controlled data on these drugs for them to be indicated for such use. Emerging options such as tiagabine, levetiracetam, zonisamide and petasites may all be useful, but controlled data are required to confirm their efficacy. The anti-asthma medication montelukast was found to be effective in an open trial, but ineffective in a recently completed controlled trial. There is an expectation that modern neuroscience will soon provide more efficacious and better tolerated prophylactic medications for migraine.

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51: Cephalalgia. 2002 May;22(4):309-12.

Rizatriptan combined with rofecoxib vs. rizatriptan for the acute treatment of migraine: an open label pilot study.

Krymchantowski AV, Barbosa JS.

Rio Military Police, Department of Neurology, Universidade Federal Fluminense, Headache Center of Rio, Rio de Janeiro, Brazil. abouchkrym@globo.com

Rizatriptan is an effective and fast acting drug for the acute treatment of migraine. As with any other acute treatment for migraine, headache recurrence may occur in up to one-third of responders. Combination with non-steroidal anti-inflammatory drugs (NSAIDs) seems to reduce the incidence of headache recurrence in clinical practice. Rofecoxib is a member of a new class of NSAIDs, which selectively inhibits the COX-2 enzyme and therefore is associated with a lower risk of gastrointestinal side-effects; the drug has a long plasma half-life (17 h). This open label study compared rizatriptan with rizatriptan plus rofecoxib in the acute treatment of migraine. Fifty-six triptan naive patients from a tertiary centre (37 women and 19 men, ages 16-55 years, mean 35 years) with International Headache Society migraine were randomized into two groups. They were instructed to treat three consecutive moderate or severe attacks with either 10 mg rizatriptan (group 1: 18 women and 10 men) or with 10 mg rizatriptan plus 25 mg rofecoxib (group 2: 19 women and 9 men). The presence of headache and nausea at 1, 2 and 4 h, and of side-effects, use of rescue medication and recurrence were compared. Fifty-four patients completed the study. Group 1 treated 76 attacks and group 2 treated 81 attacks. Absence of headache at 1 h was seen in 19 attacks (25%) in group 1 and in 34 attacks (42%) in group 2 (P=0.082); at 2 h absence of headache was seen in 60% of group 1 attacks and in 76% of group 2 attacks (P=0.115). At 4 h, 75% of group 1 attacks and 88% of group 2 attacks were pain free (P=0.122). With regard to nausea, of those who had nausea at baseline, 31% and 49% of attacks in groups 1 and 2, respectively, were nausea free at 1 h (P=0.091), 75% and 79% at 2 h (P=0.736) and 82% and 91% (P=0.479) at 4 h. Recurrence, based on all attacks of those patients who achieved pain free at 4 h, was observed in 53% of group 1 and 20% of group 2 attacks (P<0.001). Sustained pain-free rates (for the 4-h time point) were 45.6% of group 1 and 78.9% of group 2 attacks. There were no significant differences with regard to rescue medication consumption after 4 h and side-effects in both groups. There was a non-significant trend for the combination group to have a higher response rate. The group treated with rizatriptan and rofecoxib had a lower recurrence rate than the group treated with rizatriptan. This study demonstrated that combining a fast acting triptan such as rizatriptan with rofecoxib reduced headache recurrence rates, was well tolerated and may be more effective than the use of rizatriptan alone. Double-blind, placebo-controlled studies are necessary to confirm these observations.

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52: Arq Neuropsiquiatr. 2001 Sep;59(3-B):708-11.

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

Krymchantowski AV, Barbosa JS.

Headache Center of Rio and Institute of Neurology Deolindo Couto/UFRJ, Rio de Janeiro, Brasil. abouchkrym@globo.com

BACKGROUND AND OBJECTIVES: Triptans are effective drugs for the acute treatment of migraine. However, 30-40% 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%, mean recurrence rate 74,8%) with the single use of sumatritpan 100 mg or zolmitriptan 2,5 mg or rizatriptan 10mg in at least 5 consecutive attacks, and didn’t present a reduction of the recurrence rate superior than 20% with the combination of tolfenamic acid 200 mg or rofecoxib 25 mg in at least 5 other consecutive attacks (mean recurrence rate 60%). The patients had to treat 6 consecutive moderate or severe migraine attacks with their usual combination plus 4 mg 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 4 mg 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%) while the remaining 18 patients revealed recurrence in 1 or 2 treated attacks (mean 23,4%) (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.

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53: Cephalalgia. 2001 Jun;21(5):558-66.

Clinical presentation of transformed migraine: possible differences among male and female patients.

Krymchantowski AV, Moreira PF.

Headache Center of Rio and Institute of Neurology Deolindo Couto, Rio de Janeiro, Brazil. abouchkrym@openlink.com.br

Chronic daily headache (CDH) represents a group of non-paroxysmal headache disorders that occur on a daily or near-daily basis, for longer than 6 months. Even though it is a common problem, affecting 30-70% of the patients attending specialized headache clinics, it is not a well-defined and classified disorder, resulting in controversies regarding its description and approach. The aim of this study was to evaluate the clinical presentation of CDH due to transformed migraine and possibly compare the differences among male and female patients. Two hundred and seventy-one patients, 217 women and 54 men, ages 16-83 (mean 37.5 years for women and 41.4 for men), fulfilling the proposed criteria for transformed migraine and selected from a group of 300 consecutive CDH patients attending a subspecialty headache centre, were studied retrospectively. The most observed clinical presentation was pressure or tightening, bilateral fronto-temporal, moderate non-continuous headache, with a progressive onset. The association with nausea and phonophobia was demonstrated in 60% and 32% of the patients, respectively. The association with photophobia (29.6% male, 44.2% female, P = 0.05) sleep (77.7% male, 49.8% female, P = 0.0002) and emotional (87% male, 64.1% female, P = 0.001) disturbances, as well as the occurrence of intermittent full-blown migraine attacks (81.5% male, 95.4% female, P = 0.001) was significantly different among male and female patients. Overuse of symptomatic medications (SM) was observed in 87% of the male and in 83.8% of the female patients, with a significant difference concerning the use of more than one type of SM (male 68% compared with female 91.7%; P = 0.006). We concluded that TM patients have a clinical presentation compatible with previous descriptions but suggesting, even though limited by the restricted number of male patients, different aspects among male and female patients.

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54: Arq Neuropsiquiatr. 2001 Mar;59(1):46-9.

Oral lysine clonixinate in the acute treatment of migraine: a double-blind placebo-controlled study.

Krymchantowski AV, Barbosa JS, Cheim C, Alves LA.

Headache Center of Rio, Rio de Janeiro, Brazil.

Several oral nonsteroidal anti-inflammatory drugs (NSAIDs) are effective to treat migraine attacks. Lysine clonixinate (LC) is a NSAID derived from nicotinic acid that has proven to be effective in various pain syndromes such as renal colic and muscular pain. The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of oral LC compared to placebo in the acute treatment of migraine. Sixty four patients with the diagnosis of migraine, according to the IHS criteria, were studied prospectively. Patients received LC or placebo once the headache reached moderate or severe intensity for 6 consecutive attacks. With regard to the moderate attacks, LC was superior than placebo after 1, 2 and 4 hours. The consumption of other rescue medications after 4 hours was significantly higher in the placebo group. With regard to the severe attacks, there was no difference between the active drug group and the placebo group concerning headache intensity and consumption of other rescue medications. We conclude that the NSAID lysine clonixinate is effective in treating moderately severe migraine attacks. It is not superior than placebo in treating severe migraine attacks.

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55: Cephalalgia. 2000 Mar;20(2):107-13.

Prednisone as initial treatment of analgesic-induced daily headache.

Krymchantowski AV, Barbosa JS.

Headache Center of Rio/Institute of Neurology Deolindo Couto, Rio de Janeiro, Brazil. abouchkrym@openlink.com.br

The majority of the patients who seek medical care in tertiary headache centres present with transformed migraine, and convert to daily headache, as a result of excessive intake of symptomatic medications (SM). This study aimed to analyse the possibility of using a short course of oral prednisone for detoxifying patients with chronic daily headache due to medication overuse in an out-patient setting. Four hundred patients with headache occurring more than 28 days per month for longer than 6 months were studied (mean baseline frequency of 0.96). Symptomatic medications were stopped suddenly and prednisone was initiated in tapering doses during 6 days, followed by the introduction of preventive treatment. Withdrawal symptoms and the frequency, intensity and duration of the headache, as well as the consumption of rescue medications, were analysed during the first 16 and 30 days of withdrawal. Eighty-five percent of the patients experienced a reduction in headache frequency and no patients presented severe attacks during the first 6 days. With regard to the following 10 days, 46% of the patients experienced at least 2 days without headache and 58% less intense attacks. Most of the patients noticed attacks with longer duration. After the 30-day period there was a significant decrease in headache frequency (mean 0.83, P<0.001), and no patients returned to overuse of SM. This study demonstrates that it is possible to detoxify patients suffering from rebound headaches, using oral prednisone during the first days of withdrawal, in an out-patient setting.

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56: Arq Neuropsiquiatr. 2000 Jun;58(2B):437-51.

Chronic daily headache: clinical presentation

Krymchantowski AV, Moreira Filho PF.

Centro de Avaliação e Tratamento da Dor de Cabeça do Rio de Janeiro, Brazil. abouchkrym@openlink.com.br

Chronic daily headache (CDH) represents a group of any headache disorder that occurs on a daily or near daily basis, for longer than 6 months. Even though it is a common problem, it is not a well defined disorder, resulting in controversies regarding its identification, description and approach. Three hundred patients, 232 women and 68 men, ages 16 to 86 (mean 38 years old for the women and 42 for the men), attending a headache center and fulfilling the proposed criteria for CDH (Silberstein et al.) and presenting headache 28 days per month were retrospectively studied. The clinical features allowed the primary headache diagnosis, before the transformation into daily presentation as: transformed migraine (TM ) in 271 patients (90,3%), chronic tension-type headache (CTTH) in 26 patients (8,7%) and new daily persistent headache (NDPH) in 3 patients (1%). Among the TM patients, the most observed presentation was pressure or tightening, bilateral fronto-temporal, moderate non-continuous headache, with a progressive onset. The association with nausea and phonophobia was demonstrated in 60% and 32% of the patients respectively. The association with photophobia and sleep disturbances, as well as the occurrence of intermittent headache attacks, was different among male and female patients. With regard to the CTTH patients, pressure or tightening, bilateral fronto-temporal, moderate non-continuous headache, with sleep disturbances and no associated symptoms, was the predominant presentation.

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57: Arq Neuropsiquiatr. 2000 Jun;58(2B):428-30.

Naproxen sodium decreases migraine recurrence when administered with sumatriptan.

Krymchantowski AV.

Headache Center of Rio de Janeiro, Brasil. abouchkrym@openlink.com.br

Forty to 78% 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% (5 out of 8 attacks), decreased to 14.2% (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% (23 out of 39 attacks) and the recurrence presented by the group taking sumatriptan plus naproxen was 25.5% (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.

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58:
Arq Neuropsiquiatr. 1999 Dec;57(4):990-3.

Clinical features of transformed migraine.

Krymchantowski AV, Barbosa JS, Lorenzatto W, Cheim C, Adriano M.

Centro de Avaliação e Tratamento da Dor de Cabeça do Rio de Janeiro, Universidade Federal do Rio de Janeiro (UFRJ), Brasil. abouchkrym@openlink.com.br

Most daily headache patients seen in specialized clinics present a past history of migraine. Some authors refer to it as transformed migraine and emphasize its milder intensity and clinical characteristics different from migraine. The aim of this study was to evaluate the clinical presentation of the daily headache in patients with prior history of migraine. We studied retrospectively 215 patients. We observed that a significant percentage of the patients presenting the so-called transformed migraine, reported frontal and/or temporal bilateral pain and had pressure or tightening pain, which is a characteristic of chronic tension-type headache. It emphasizes the loss or changing of the standard migraine features. The pulsatile pain quality remained as an important feature, specially for those with intermittent typical migraine attacks.

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59: Arq Neuropsiquiatr. 1999 Sep;57(3A):606-9.

Intravenous lysine clonixinate for the treatment of migraine: an open pilot study

Krymchantowski AV, Barbosa J.

Serviço de Neurologia, Universidade Federal Fluminense (UFF), Brasil. abouchkrym@openlink.com.br

Several oral nonsteroidal anti-inflammatory drugs (NSAID) are effective to treat migraine attacks. Despite its efficacy to treat migraine and other pain, there are a few commercial NSAIDs available for intravenous (i.v.) administration. Lysine clonixinate (LC) is a NSAID derived from nicotinic acid that has been proven effective in various algic syndromes such as renal colic, nerve compression, muscular pain and odontalgias. The aim of this study was to evaluate the efficacy of the i.v. LC in the treatment of severe attacks of migraine. We studied prospectively 19 patients, 17 women and 2 men, ages from 18 to 57 years, with the diagnosis of migraine according to the International Headache Society criteria. The patients were oriented to proceed to the clinic once the headache has started, and were placed under an i.v. infusion of LC and saline in a superficial vein of the forearm, once the intensity reached severe. Evaluating the headache intensity after 30, 60 and 90 minutes, as well as the presence of side effects, we observed that all of the 19 patients were headache free after 90 minutes. Some patients presented mild adverse effects and the vital signs were not significantly affected. We then concluded that the i.v. infusion of the NSAID LC (2-3-chloro-o-toluidin)piridin-3-lysine carboxilate), a derived from the nicotinic acid with a chemical structure that resembles the flufenamic acid, was efficient abolishing a severe migraine attack after 90 minutes in 19 patients. Controlled studies with a double-blind and randomized design, and treating a greater number of patients and attacks are necessary to confirm these initial observations.

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60: Arq Neuropsiquiatr. 1999 Jun;57(2B):513-9.

Update on migraine prophylactic treatment

Krymchantowski AV, Moreira Filho PF.

Centro de Avaliação e Tratamento da Dor de Cabeça do Rio de Janeiro, Brasil. abouchkrym@openlink.com.br

Among the primary headaches, patients with migraine are those that seek for medical help the most. Its prevalence is estimated in 12% of the population being more common in women with a prevalence of 18 to 20%, 6% of the men and 4 to 8% of the children. Its economic impact in the productivity and leisure is significant, and the headache attacks may incapacitate the patients for the usual activities. With a complex and still unknown pathophysiology, migraine may present with intermittent and peculiar episodes of intense headache. The most efficient approach for the treatment includes the avoidance of the trigger factors, preventive treatment, rescue treatment for the moments of pain and the accessory or non drug treatment. For the preventive treatment, scope of this update, various classes of substances are used and include the beta blockers, tricyclic antidepressants (and recently the selective serotonin reuptake inhibitors), calcium antagonists, serotonin antagonists, anticonvulsants and others. Even though its mechanisms of action in the treatment of migraine are unknown, it seems that all of the drugs influence the central serotonergic, noradrenergic and gabaergic functions. New proposals for the mechanisms of action of some of these drugs, also include the inhibition of the synthesis of nitric oxide and the modulation of the neuronal cationic channels. When individualized and correctly used, these preventive medications have been held responsible for important reductions in the frequency and intensity of migraine episodes, decreasing this way, the marathon of suffering and doubtful approaches, that these patients are usually submitted.

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61:
Cephalalgia. 1999 Apr;19(3):186-7.

Tolfenamic acid decreases migraine recurrence when used with sumatriptan.

Krymchantowski AV, Adriano M, Fernandes D.

Centro de Avaliação e Tratamento da dor de Cabeça do Rio de Janeiro, Brazil.

Although sumatriptan is an effective drug for the treatment of acute migraine attacks, recurrence has been cited as an important limitation for its use. Tolfenamic acid is also effective in the acute treatment of migraine attacks. We studied the recurrence rate of migraine attacks with the use of sumatriptan plus tolfenamic acid among patients who presented frequent recurrence with sumatriptan. Fifty migraineurs were retrospectively studied, all having treated at least 10 attacks with 100 mg P.O.; sumatriptan was effective in at least eight of them. The patients also presented recurrence in less than 24 h in at least five of the treated attacks. We then used sumatriptan 100 mg plus tolfenamic acid 200 mg P.O. during the first 60 min of the attack; 240 attacks were treated and there was recurrence in 57 (23.8%). With sumatriptan alone, 5 out of 8 attacks (62.5%) presented recurrence. We therefore conclude that the combination sumatritpan plus tolfenamic acid is effective in reducing the recurrence rate from 5 of 8 (62.5%) to 1.19 of 5 (23.8%). Further prospective studies with a double-blind design and a higher number of treated attacks are necessary to confirm these initial observations.

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