Migraine Disorders: Nappi G

Anonymous00401, Olesen J, Bousser MG, Diener HC, Dodick D, First M, Goadsby PJ, Göbel H, Lainez MJ, Lance JW, Lipton RB, Nappi G, Sakai F, Schoenen J, Silberstein SD, Steiner TJ. · Department of Neurology, University of Copenhagen, Glostrup Hospital, Demark. · Cephalalgia. · Pubmed #16686915 No free full text.

Abstract: After the introduction of chronic migraine and medication overuse headache as diagnostic entities in The International Classification of Headache Disorders, Second Edition, ICHD-2, it has been shown that very few patients fit into the diagnostic criteria for chronic migraine (CM). The system of being able to use CM and the medication overuse headache (MOH) diagnosis only after discontinuation of overuse has proven highly unpractical and new data have suggested a much more liberal use of these diagnoses. The International Headache Classification Committee has, therefore, worked out the more inclusive criteria for CM and MOH presented in this paper. These criteria are included in the appendix of ICHD-2 and are meant primarily for further scientific evaluation but may be used already now for inclusion into drug trials, etc. It is now recommended that the MOH diagnosis should no longer request improvement after discontinuation of medication overuse but should be given to patients if they have a primary headache plus ongoing medication overuse. The latter is defined as previously, i.e. 10 days or more of intake of triptans, ergot alkaloids mixed analgesics or opioids and 15 days or more of analgesics/NSAIDs or the combined use of more than one substance. If these new criteria for CM and MOH prove useful in future testing, the plan is to include them in a future revised version of ICHD-2.

Nappi G, Termine C. · No affiliation provided · Funct Neurol. · Pubmed #19152729 No free full text.

This publication has no abstract.

Allena M, Katsarava Z, Nappi G, Anonymous00017. · IRCCS Neurological Institute C. Mondino Foundation, University Centre for Headache and Adaptive Disorders, Pavia Section, Via Mondino 2, 27100 Pavia, Italy. · J Headache Pain. · Pubmed #19238511 No free full text.

Abstract: Medication overuse headache (MOH) is a daily or almost-daily type of headache that results from the chronicization, usually migraine or tension-type headache, as a consequence of the progressive increase of intake of symptomatic drugs. MOH is now the third most frequent type of headache and affects a percentage of 1-1.4% of the general population. The currently available data on the impact of chronic headache associated with analgesic overuse in specialist headache centres confirm, beyond doubt, the existence of a serious health problem. Limited amount of data exists on the burden and impact of MOH in Latin American Countries. In this review, we summarise the reliable information from the literature on the epidemiological impact of MOH.

Antonaci F, Sances G, Guaschino E, De Cillis I, Bono G, Nappi G. · University Centre for Adaptive Disorders and Headache (UCADH), Section of Varese, Pavia, Italy. · J Headache Pain. · Pubmed #18607535 No free full text.

Abstract: Clinical outcomes of migraine treatment are generally based on two major endpoints: acute pain resolution and effects on quality of life (QOL). Resolution of acute pain can be evaluated in a number of ways, each increasingly challenging to achieve; pain relief, pain freedom at 2 h, sustained pain-freedom, and SPF plus no adverse events (SNAE, the most challenging). QOL questionnaires help assess the burden of migraine and identify optimal treatments. Pain resolution and improved QOL form the basis of the ultimate target-meeting patient expectations, to achieve patient satisfaction. To achieve this, it is crucial to choose appropriate endpoints that reflect realistic treatment goals for individual patients. Moreover, SNAE can help discriminate between triptans, with almotriptan having the highest SNAE score. Kaplan-Meier plots are also relevant when evaluating migraine treatments. The use of symptomatic medication may lead to the paradoxical development of medication-overuse headache. In general practice, patients should use simple tools for pain measurement (e.g. headache diary) and a QOL questionnaire. A composite endpoint of pain resolution and QOL restoration would constitute a step forward in migraine management.

Nappi G, Perrotta A, Rossi P, Sandrini G. · University Centre for Adaptive Disorders and Headache, IRCCS C. Mondino Institute of Neurology Foundation, University of Pavia, Italy. · Expert Rev Neurother. · Pubmed #18345968 No free full text.

Abstract: The term chronic daily headache (CDH) identifies a heterogeneous group of headaches characterized by the presence of daily or near-daily headache, including forms associated with medication overuse. This group includes chronic (transformed) migraine, chronic tension-type headache, new daily-persistent headache and hemicrania continua. According to population studies, CDH affects 4-5% of the general population worldwide, making it a significant social problem. CDH evolves from an episodic form of headache or, more rarely, is daily from onset. The classification of CDH continues to be debated, even though the recent revision of the diagnostic criteria for several primary headache forms seems to have resolved some of the nosographical difficulties. To date, no specific therapies have been approved for CDH and there have been few large-scale controlled trials of treatments in this area. This article reviews various aspects of CDH: classification issues, pathophysiological hypotheses and therapeutic (pharmacological and nonpharmacological) approaches.

Sandrini G, Perrotta A, Nappi G. · University of Pavia, University Centre for Adaptive Disorders and Headache, IRCCS C. Mondino Institute of Neurology Foundation, Pavia, Italy. · Expert Rev Neurother. · Pubmed #17078782 No free full text.

Abstract: Eletriptan is a second-generation 5-hydroxytryptamine(1B/1D) receptor agonist, or triptan, indicated for the acute treatment of migraine. Eletriptan has a favorable pharmacokinetic and pharmacodynamic profile expressed by bioavailability, half-life and high selectivity for cranial arteries. It has been shown to be effective and well tolerated in a wide preapproval development program, which included over 11,000 patients and treated more than 74,000 migraine attacks. In clinical trials, eletriptan has been demonstrated to be one of the most effective oral therapies for the acute treatment of migraine and has shown a very high safety and tolerability profile across the studies performed. Eletriptan showed the most favorable cost-effectiveness profile when compared with other agents in its class.

Nappi G, Jensen R, Nappi RE, Sances G, Torelli P, Olesen J. · University Centre for Adaptive Disorders and Headache (UCADH), IRCCS C. Mondino Foundation Institute of Neurology, Pavia, Italy. · Cephalalgia. · Pubmed #16886925 No free full text.

Abstract: Headache is one of the most common types of pain and, in the absence of biological markers, headache diagnosis depends only on information obtained from clinical interviews and physical and neurological examinations. Headache diaries make it possible to record prospectively the characteristics of every attack and the use of headache calendars is indicated for evaluating the time pattern of headache, identifying aggravating factors and evaluating the efficacy of preventive treatment. This may reduce the recall bias and increase accuracy in the description. The use of diagnostic headache diaries does have some limitations because the patient's general acceptance is still limited and some subjects are not able to fill in a diary. In this review, we considered diaries and calendars especially designed for migraine and, in particular, we aimed at: (i) determining what instruments are available in clinical practice for diagnosis and follow-up of treatments; and (ii) describing the tools that have been developed for research and their main applications in the headache field. In addition to the literature review, we added two paragraphs concerning the authors' experience of the use of diaries and calendars in headache centres and their proposals for future areas of research.

Sandrini G, Dahlöf CG, Mathew N, Nappi G. · Department of Neurological Rehabilitation, University Centre for Adaptive Disorders and Headache, Pavia, Italy. · Int J Clin Pract. · Pubmed #16236092 No free full text.

Abstract: Almotriptan is a 5-HT(1B/1D) receptor agonist, or triptan, indicated for the acute treatment of migraine. It has been shown to be effective and well tolerated for the treatment of acute migraine in approximately 5000 patients enrolled in short-term placebo- and active-controlled trials and long-term open-label trials. A recent meta-analysis reported that almotriptan has the highest sustained pain-free (SPF) rate and lowest adverse-event (AE) rate of all oral triptans. Sustained pain free is a composite endpoint of pain freedom at 2 h, no recurrence of moderate-to-severe headache and no use of rescue medication from 2 to 24 h after dosing. Patient surveys have indicated that migraine sufferers consider complete pain relief, no recurrence, rapid onset and no side-effects to be the most important attributes of their acute treatment. Composite endpoints such as SPF and SPF with no AEs (SNAE) contain the attributes that migraine sufferers express as being the most important elements of an acute migraine therapy, and their use in future clinical trials should aid in the selection of agents that can offer patients the highest likelihood of consistent treatment success.

Buzzi MG, Tassorelli C, Nappi G. · IRCCS Neuromed, Pozzilli, Italy. · Cephalalgia. · Pubmed #12699454 No free full text.

Abstract: Animal models for migraine have provided substantial advances on the mechanisms and mediators underlying migraine attacks. The neurogenic inflammation model has helped understanding the perivascular mechanisms underlying the pathophysiology of migraine attacks, the receptors involved and the effect of specific antimigraine drugs. The model based on probing the neuronal effects of nitroglycerin--an organic nitrate known to induce spontaneous-like migraine attacks in predisposed subjects--in the rat has provided interesting insights into the neuroanatomic circuits and neuropharmacological mechanisms involved in the initiation and repetition of migraine attacks [corrected].

Nappi G, Sandrini G, Sances G. · University Centre for Adaptive Disorders and Headache, IRCCS C. Mondino Foundation, University of Pavia, Italy. · Drug Saf. · Pubmed #12534326 No free full text.

Abstract: The triptans represent a relatively new class of compounds effective in the treatment of migraine. The safety and tolerability of these drugs have been extensively investigated since the first triptan (sumatriptan) became commercially available. A report on a very large population of patients tested during clinical trials and in postmarketing studies, confirms that these drugs are safe and well tolerated when correctly used. Adverse events are frequently reported, but are usually mild and only a few patients discontinue therapy because of them. These adverse events include, in particular, the so-called 'triptan symptoms' (tingling, sensation of warmth, etc.). The exact mechanism of chest symptoms reported by 20% of patients with migraine treated with triptans remains unclear, but are exceptionally related to a cardiac mechanism. CNS adverse events (i.e. somnolence) are also reported, but it is a matter of debate whether they are related to the pharmacological properties (i.e. lipophilicity) of the drug or are symptoms of the disease itself. The potential risk for drug overuse must be taken into account when the triptans are given to patients with a high frequency of migraine attacks. Clinical interaction of triptans with other drugs metabolised in the liver may theoretically influence the incidence of adverse events, but there is little evidence to support this assumption. There is no evidence of a teratogenic risk of triptans in pregnant women taking these drugs.

Tassorelli C, Greco R, Morocutti A, Costa A, Nappi G. · IRCCS C. Mondino Institute of Neurology, Laboratory of Neurophysiology of Integrative Autonomic Systems, Maugeri--Mondino--University of Pavia Research Center, Italy. · Funct Neurol. · Pubmed #11996533 No free full text.

This publication has no abstract.

Martini B, Grieco GS, Fortini D, Costa A, Nappi G, Santorelli FM. · IRCCS C. Mondino Institute of Neurology, Laboratory of Molecular Neurobiology, Mondino--Tor Vergata--S. Lucia Center of Experimental Neurobiology, Rome, Italy. · Funct Neurol. · Pubmed #11996532 No free full text.

This publication has no abstract.

Sandrini G, Cecchini AP, Tassorelli C, Nappi G. · University Center for Adaptive Disorders and Headache, C. Mondino Foundation, Via Palestro, Pavia 3-27100, Italy. · Curr Pain Headache Rep. · Pubmed #11676890 No free full text.

Abstract: A number of patients attending specialty headache centers complain of very frequent, almost continuous headaches, which are usually grouped together under the term chronic daily headache (CDH), a category which does not appear in the International Headache Society (IHS) classification published in 1988. More than 10 years later, this issue is still debated, also in light of the foreseen revised classification. Several terms have been used to define the clinical picture of CDH, and different criteria have been proposed for the diagnosis of these forms. In most cases, CDH appears to evolve from an episodic migraine, but the temporal limits between an episodic and a no-longer episodic form of migraine are questionable. Although some theoretic problems remain unresolved, it seems that the next revision of the IHS classification can no longer ignore the existence of CDH.

Tassorelli C, Costa A, Blandini F, Joseph SA, Nappi G. · Laboratory of Neurophysiopathology of Integrative Autonomic Systems, San Martino Research Center (University of Pavia, IRCCS C. Mondino Institute of Neurology, IRCCS S. Maugeri Rehabilitation Institute) Pavia, Italy. · Funct Neurol. · Pubmed #11200790 No free full text.

Abstract: The demonstration that nitrovasodilators act as nitric oxide (NO) donors has favored a resurgence of interest in this class of compounds. The demonstration of the different biological effects of NO in various districts, including the central nervous system, suggests a possible role for these substances besides their well-known cardiovascular activity. Among the various nitrovasodilators commercially available, nitroglycerin represents a well known substance to headache experts because of its capability to provoke spontaneous-like migraine attacks in headache-free migrainous subjects. Basic research has recently demonstrated that nitroglycerin activates a variegate set of brain nuclei following systemic administration via the intervention of selected neurotransmitters and neuromediators, with a specific time-pattern in different brain areas. Increasing evidence suggests that nitroglycerin-induced neuronal activation is mediated by multiple mechanisms that include direct neuronal and vascular action of nitroglycerin-derived and endogenously-synthesized NO, as well as indirect effects related to nitroglycerin-induced changes in cardiovascular and trigeminovascular systems. The study of the neurovascular effects of nitroglycerin in the rat provides relevant information for a better understanding of the pathophysiology of migraine attacks and of their triggers.

Nappi G, Costa A, Tassorelli C, Santorelli FM. · IRCCS C. Mondino Institute of Neurology, Pavia, Italy. · Funct Neurol. · Pubmed #10916720 No free full text.

Abstract: Migraine is a chronic illness interspersed with acute signs and symptoms which is currently defined, according to IHS criteria, in terms of "attacks". However, this should not lead us to ignore a critical point emerging from the simple observation of patients, i.e. the variability of the combinations in which the disease manifests itself in the same individual and especially in different individuals. This heterogeneity underpins both migraine "as attacks" (e.g. presence/absence of aura, different pain severity) and migraine "as a disease" (e.g. different onset, occurrence, association with other diseases, evolution, outcome). Genetic determinants are certainly at the basis of some migraine forms, and the role of genetics is now increasing due to the better phenotypical characterization rendered possible by the 1988 criteria. In most cases, however, migraine occurs as multifactorial inherited character. The level of complexity is further increased by the effect of "modifying" genes (such as those encoding for dopamine receptors), by comorbidity (the non coincidental association with other neurological diseases), and by the fact that the expression of comorbidity varies over time (phenotypical heterochronia). The clinical-descriptive approach allows only a partial understanding of migraine, the nature of which is more complex and heterogeneous than previously thought.

Bono G, Antonaci F, Ghirmai S, D'Angelo F, Berger M, Nappi G. · Department of Neuroscience, University of Insubria, Varese. · Clin Exp Rheumatol. · Pubmed #10824283 No free full text.

Abstract: The term "whiplash" commonly refers to symptoms and signs associated with a mechanical event such as a sudden acceleration and deceleration of the neck (due, in the majority of cases, to a road accident), instead of to the mechanism itself. The recent Quebec Classification of Whiplash Associated Disorders (WAD) contributed to define nosographically all the clinical manifestations usually grouped under the terms acute/post-traumatic and late "syndrome". In the late phase of WAD, neck pain and neck muscle contraction have been reported in all cases, together with headache in over 50%. "Headache stemming from the neck", despite numerous attempts to classify this entity (i.e. cervicogenic headache) according to the IASP classification (headache associated with neck disorders), is still a subject of debate. An adequate multiparametric procedure is required to study WAD, which takes into account: the patient's principal details; an exact reconstruction of the event; description and analysis of the signs and symptoms, with various complications and correlated dysfunctions; an objective neurological and neck-shoulder examination; and a battery of complementary instrumental tests which are described in this study. These investigations include evaluation of muscle tension (manual palpation, algometry, EMG recording), kinematic analysis of the cervical spine, neuropsychological and psychological evaluation, and evaluation of disability. In order to assess cervical spine mobility in WAD patients, a 3D kinematic analysis by means of the ELITE system and clinical evaluation were performed in our setting. Seventy patients with whiplash injury and 46 healthy volunteers were enrolled in the study. Patients were tested at the time of first consultation and again 6 months and 12 months later. Clinical evaluation of the range of motion was performed both in patients and in 41 healthy volunteers. Furthermore, patients diagnosed according to the WAD Classification as grade 2 (n = 68) or grade 3 (16) underwent a Quality of life (QoL) evaluation, measured using the short form (36-item) Health Survey (SF36) and the migraine-specific questionnaire (MSQ). According to our data, whiplash patients showed an impairment of cervical spine mobility, as well as a poor QoL, compared to a control group population, even though we observed a trend towards improvement over time in cervical ROM.

Bono G, Antonaci F, Dario A, Clerici AM, Ghirmai S, Nappi G. · Department of Neuroscience, University of Insubria, Varese. · Clin Exp Rheumatol. · Pubmed #10824280 No free full text.

Abstract: The concept of headache originating/starting in the neck is revised and considered in the light of previous descriptions of syndromes and entities and with reference to the current diagnostic systems for the classification of headache and other head pain. Cervicogenic headache (CEH), a clinical picture recently described by Sjaastad and coworkers and listed in the International Association for the Study of Pain (IASP) Classification, is analyzed, also taking into consideration its diagnostic criteria in terms of sensitivity and specificity. The problem of a differential diagnosis with migraine, tension headache and other well defined forms of unilateral headaches is discussed with reference to a case series of 114 patients who were selected based on their adherence to two fundamental criteria: (i) side-locked unilaterality of pain; and (ii) pain starting in the neck and spreading to the fronto-orbital area. Based on the results, these simple criteria can contribute to a preliminary identification of possible CEH cases that may then undergo a sequence of clinical and instrumental procedures in order to confirm the diagnosis and, possibly, to localize the level(s) of dysfunction in the cervical spine which may be the target for therapeutic investigations, whether invasive or non-invasive.

Tassorelli C, Sances G, Allena M, Ghiotto N, Bendtsen L, Olesen J, Nappi G, Jensen R. · University Centre for the Study of Adaptive Disorders and Headache (UCADH), IRCCS 'C. Mondino Institute of Neurology' Foundation, Pavia, Italy. · Cephalalgia. · Pubmed #18624804 No free full text.

Abstract: We tested the usefulness and applicability of a simplified headache diary in the diagnosis of migraine (M), tension-type headache (TTH) and medication overuse headache (MOH). The diary was given to headache patients before their first consultation at the headache centre. Seventy-six naive headache patients completed the study. Their understanding of the diary proved highly satisfactory. The patients' level of compliance was also good, with 71% returning the diary completely filled in. The data entered in the diary were deemed complete for the diagnostic purpose in 93% of cases. The level of agreement between headache information gathered through clinical interview and the headache diary was satisfactory. When comparing the diary with the clinical interview, sensitivity was 92% for M, 75% for TTH and MOH. Specificity was 58% for M and TTH, 87% for MOH. Combined use of a diagnostic diary and clinical interview is recommended from the first consultation for headache.

Velati D, Viana M, Cresta S, Mantegazza P, Testa L, Bettucci D, Rinaldi M, Sances G, Tassorelli C, Nappi G, Canonico PL, Martignoni E, Genazzani AA. · DiSCAFF and DFB Center, Via Bovio, 6, 28100 Novara, Italy. · Eur J Pharmacol. · Pubmed #18035351 No free full text.

Abstract: Triptans mediate vasoconstriction of meningeal vessels via stimulation of vascular 5-hydroxytryptamine (5-HT)(1B) receptors. These drugs are recommended for acute treatment in patients with moderate-to-severe migraine attacks and in those patients with mild-to-moderate headache that are not controlled adequately by other agents. Yet, approximately 25% of all migraine users and 40% of all attacks do not respond to triptan treatment. Among the hypothesis to explain this is the possibility that genetic single nucleotide polymorphisms that alter the receptor, for example changing the transcriptional rate and therefore the amount of target protein might change the clinical response to these drugs. In the present contribution, we therefore decided to evaluate whether single nucleotide polymorphisms on the 5-HT(1B) gene might contribute to inter-individual variability in clinical responses to triptans. Two polymorphisms in the promoter region of the 5-HT(1B) receptor (T-261G and A-161T) and the synonymous variation G861C in the coding region were genotyped by restriction fragment length polymorphism in 105 migraine patients. In our sample population, 71% of patients responded to triptans. Allelic and diplotype frequencies were not significantly different between responders and non-responders. On the other hand, extrapolation of in vitro data on promoter activity would suggest that patients with higher copy number of receptors respond slightly better. Our data therefore do not support the involvement of 5-HT(1B) single nucleotide polymorphisms in mediating the inter-individual variability to triptans.

Nappi RE, Sances G, Brundu B, De Taddei S, Sommacal A, Ghiotto N, Polatti F, Nappi G. · Research Centre for Reproductive Medicine, University of Pavia, Italy. · Hum Reprod. · Pubmed #16123089 links to  free full text

Abstract: BACKGROUND: Migraine triggered by oral contraception (OC)-free interval is very common and may be extremely severe, long-lasting and poorly responsive to analgesics (status migrainosus). The serotoninergic (5-HT) system is crucially involved in pain threshold and it is sensitive to estradiol (E2). Therefore, we aimed to assess neuroendocrine correlates of OC status migrainosus in response to the direct central 5-HT agonist meta-chlorophenylpiperazine (m-CPP) and to test the effect of transdermal E2 supplementation of the OC-free interval. METHODS: Clinical investigative protocol, single-blinded placebo-controlled treatment. Oral m-CPP (0.5 mg/kg body weight) challenge test was performed in 10 patients with status migrainosus occurring within 48 h of the discontinuation of a monophasic pill (30 microg of ethinyl estradiol and 150 microg of desogestrel) and in six healthy women assuming the same OC as controls. In a consecutive menstrual cycle, patients with OC status migrainosus underwent to the same test after they were blindly treated with 2.0 g of percutaneous E2 gel or placebo daily during the pill-free interval. Plasma prolactin and cortisol levels and clinical characteristics of migraine attacks were evaluated. RESULTS: Women with OC-status migrainosus showed a derangement of prolactin release (F = 4.8; P < 0.01) and a lack of cortisol response (F = 5.8; P < 0.001) after m-CPP in comparison with controls. Transdermal E2 during the pill-free interval significantly restored prolactin (F = 2.8; P < 0.01) and cortisol responses (F = 18.9; P < 0.001) against placebo and positively affected the duration (P < 0.001), the number of hours in which pain intensity prohibits daily activity (P < 0.001), the episodes of vomiting (P < 0.001) and the consumption of analgesics (P < 0.001). CONCLUSIONS: Status migrainosus triggered by OC-free interval is associated with impaired prolactin and cortisol responses following m-CPP challenge. Transdermal E2 supplementation is able to restore neuroendocrine response to this specific 5-HT agent, exerting a positive clinical effect on the course of menstrually related migraine.

Rossi P, Di Lorenzo G, Malpezzi MG, Faroni J, Cesarino F, Di Lorenzo C, Nappi G. · Headache Clinic, INI Grottaferrata, University Centre for Adaptive Disorders and Headache, IRCCS C. Mondino Institute of Neurology and University of Pavia, Pavia, Italy. · Cephalalgia. · Pubmed #15955036 No free full text.

Abstract: The use of complementary and alternative medicine (CAM) in migraine is a growing phenomenon about which little is known. This study was undertaken to evaluate the rates, pattern and presence of predictors of CAM use in a clinical population of patients with different migraine subtypes. Four hundred and eighty-one migraineurs attending a headache clinic were asked to undergo a physician-administered structured interview designed to gather information on CAM use. Past use of CAM therapies was reported by 31.4% of the patients surveyed, with 17.1% having used CAM in the previous year. CAM therapies were perceived as beneficial by 39.5% of the patients who had used them. A significantly higher proportion of transformed migraine patients reported CAM treatments as ineffective compared with patients suffering from episodic migraine (73.1% vs. 50.7%, P < 0.001). The most common source of a recommendation of CAM was a friend or relative (52.7%). In most cases, migraineurs' recourse to CAM treatments was specifically for their headache (89.3%). Approximately 61% of CAM users had not informed their medical doctors of their CAM use. The most common reason for deciding to try a CAM therapy was that it offered a 'potential improvement of headache' (47.7%). The greatest users of CAM treatments were: patients with a diagnosis of transformed migraine; those who had consulted a high number of specialists and reported a higher lifetime number of conventional medical visits; those with a comorbid psychiatric disorder; those with a high income; and those whose headache had been either misdiagnosed or not diagnosed at all. Our findings suggest that headache clinic migraine patients, in their need of and quest for care, seek and explore both conventional and CAM approaches. Physicians should be made aware of this patient-driven change in the medical climate in order to prevent misuse of healthcare resources and to be better equipped to meet patients' needs.

Diener HC, Bussone G, de Liano H, Eikermann A, Englert R, Floeter T, Gallai V, Göbel H, Hartung E, Jimenez MD, Lange R, Manzoni GC, Mueller-Schwefe G, Nappi G, Pinessi L, Prat J, Puca FM, Titus F, Voelker M, Anonymous00008. · Department of Neurology, University Essen, Germany. · Cephalalgia. · Pubmed #15482357 No free full text.

Abstract: Acetylsalicylic acid (ASA) in combination with metoclopramide has been frequently used in clinical trials in the acute treatment of migraine attacks. Recently the efficacy of a new high buffered formulation of 1000 mg effervescent ASA without metoclopramide compared to placebo has been shown. To further confirm the efficacy of this new formulation in comparison with a triptan and a nonsteroidal anti-inflammatory drug (ibuprofen) a three-fold crossover, double-blind, randomized trial with 312 patients was conducted in Germany, Italy and Spain. Effervescent ASA (1000 mg) was compared to encapsulated sumatriptan (50 mg), ibuprofen (400 mg) and placebo. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (primary endpoint) was 52.5% for ASA, 60.2% for ibuprofen, 55.8% for sumatriptan and 30.6% for placebo. All active treatments were superior to placebo (P < 0.0001), whereas active treatments were not statistically different. The number of patients who were pain-free at 2 h was 27.1%, 33.2%, 37.1% and 12.6% for those treated with ASA, ibuprofen, sumatriptan or placebo, respectively. The difference between ASA and sumatriptan was statistically significant (P = 0.025). With respect to other secondary efficacy criteria and accompanying symptoms no statistically significant differences between ASA and ibuprofen or sumatriptan were found. Drug-related adverse events were reported in 4.1%, 5.7%, 6.6% and 4.5% of patients treated with ASA, ibuprofen sumatriptan or placebo. This study showed that 1000 mg effervescent ASA is as effective as 50 mg sumatriptan and 400 mg ibuprofen in the treatment of migraine attacks regarding headache relief from moderate/severe to mild/no pain at 2 h. Regarding pain-free at 2 h sumatriptan was most effective.

Nappi RE, Sances G, Brundu B, Ghiotto N, Detaddei S, Biancardi C, Polatti F, Nappi G. · Department of Obstetric and Gynecology, IRCCS San Matteo, Pavia, Italy. · Neuroendocrinology. · Pubmed #12869800 No free full text.

Abstract: To assess the neuroendocrine correlates of menstrual status migrainosus (MSM) and menstrual migraine (MM), we evaluated the prolactin (PRL) and cortisol responses to the direct central serotoninergic (5-HT) agonist meta-chlorophenylpiperazine (m-CPP) administered orally (0.5 mg/kg) during the follicular (FP: +6, +8) and luteal phases (LP: -4, -6) of the same menstrual cycle. Ten women with MSM (migraine attacks occurring within 2 days of the onset of menstrual bleeding but lasting more than 72 h) and 9 women with MM (migraine occurring within 2 days of the onset of menstrual bleeding with a typical duration of attacks) were studied. Six healthy women served as controls. Blood samples were taken at times -30, 0 and every 30 min over 4 h. Statistical analysis was performed using MANOVA followed by Duncan's post hoc comparisons. We found that the PRL response to the m-CPP test was significantly blunted in MSM compared with MM and controls in both phases of the menstrual cycle (F = 4.6; p < 0.001). Indeed, the PRL area under the curve (AUC) after m-CPP was higher in both MM and controls compared with MSM (F = 12.7; p < 0.001). The m-CPP-induced cortisol response was absent in MSM compared with MM and controls in both FP and LP (F = 4.1; p < 0.001). On the other hand, the pattern of the plasma cortisol response to m-CPP was similar in MM and controls throughout the menstrual cycle. In addition, the basal plasma cortisol levels were significantly higher in MSM compared with controls (p < 0.001) and MM (p < 0.001) during FP, but not in LP, and progressively decreased over time. Thus, no significant effect of the menstrual cycle phase and diagnosis on the cortisol AUC was found, while a significant diagnosis effect (F = 25.6; p < 0.001) on %delta(max) plasma cortisol levels was evident and consistent with the lack of cortisol response to m-CPP in MSM during the FP and LP compared with MM and controls. A derangement in central 5-HT control of pituitary PRL, and even more so in cortisol release, is present in women with MSM, but not with MM, regardless of the phase of the menstrual cycle, suggesting the involvement of some 5-HT(1) and 5-HT(2) receptor subtypes in the occurrence of extremely severe migraine attacks triggered by menstruation.

Diener HC, Matias-Guiu J, Hartung E, Pfaffenrath V, Ludin HP, Nappi G, De Beukelaar F. · Department of Neurology, University Essen, Germany. · Cephalalgia. · Pubmed #12047461 No free full text.

Abstract: This was a phase-IV double-blind equivalence trial designed to assess the efficacy and tolerability of two doses of flunarizine (10 mg o.d.=FLU 10 mg and 5 mg o.d.=FLU 5 mg) in the prophylaxis of migraine, in comparison with slow-release propranolol (160 mg o.d.). A total of 808 subjects were treated in a treatment period of 16 weeks. 142 subjects discontinued the trial prematurely, mainly because of adverse events (n=58). The mean attack frequency in the double-blind period was 2.0 for the FLU 5 mg group, 1.9 for the FLU 10 mg group, and 1.9 for the propranolol group. The mean attack frequency in the last 28 days of the double-blind period was 1.8 for FLU 5 mg, 1.6 for FLU 10 mg, and 1.7 for propranolol. Both flunarizine groups were at least as effective as propranolol (P<0.001 in one-sided test). The percentage of responders (defined as subjects for whom attack frequency decreased by at least 50% compared to run-in) in the last 28 days of the double-blind period was 46% (118/259) for FLU 5 mg, 53% (141/264) for FLU 10 mg, and 48% (125/258) for propranolol. Statistical analysis showed that FLU 10 mg is at least as effective as propranolol (P<0.001) and showed a trend for noninferiority of FLU5 and propranolol (P=0.053). No statistically significant differences between the treatment groups were found for any of the secondary parameters. Overall, 190 subjects reported one or more adverse events during the run-in phase: 54 (20.5%) in the FLU 5 mg group, 76 (27.7%) in the FLU 10 mg group and 60 (22.3%) in the propranolol group. The results of this equivalence trial show that 10 mg flunarizine daily with a drug-free weekend is at least as effective as 160 mg propranolol in the prophylaxis of migraine for all evaluated parameters (one-sided equivalence tests) after 16 weeks of treatment. In addition, 5 mg flunarizine proves to be at least as effective as 160 mg propranolol when looking at the mean attack frequency for both the whole double-blind period and the last 28 days of treatment. However, in the analysis of responders, 160 mg propranolol seems to be slightly better than 5 mg flunarizine. In addition, no significant differences between the three treatments were found with regard to safety: all three treatments were generally well-tolerated and safe.

Micieli G, Cavallini A, Marcheselli S, Mailland F, Ambrosoli L, Nappi G. · Headache Center, Department of Neurology, C. Mondino Institute, University of Pavia, Italy. · Int J Clin Pharmacol Ther. · Pubmed #11332869 No free full text.

Abstract: OBJECTIVE: A double-blind, crossover study was carried out to compare the efficacy of alpha-dihydroergocryptine mesylate (10 mg twice daily) vs propranolol (40 mg twice daily) in the prophylaxis of migraine without aura, and to identify possible predictors of therapeutic response by evaluating the symptomatological profile of individual migraine attacks and the autonomic cardiovascular response to noradrenergic and dopaminergic (cold pressor, bromocriptine) tests. PATIENTS AND METHODS: Forty migraineurs (10 males, 30 females) were randomized according to a two-period (3-month), two-treatment, crossover design. Efficacy was assessed using quantitative data recorded in the patient's headache diary. Data were evaluated using the Wallenstein's method. RESULTS: Both drugs showed a significant reduction in all the efficacy variables (headache attacks, days with headache, analgesic consumption) with no difference between treatments. Neither a bromocriptine test, nor a cold pressor test nor the symptomatological profile of individual migraine attacks differed between the two groups of migraine patients. Ten patients experienced at least one adverse drug reaction during the first period of the crossover design, 5 being treated with alpha-dihydroergocryptine and 5 with propranolol. CONCLUSIONS: It is concluded that alpha-dihydroergocryptine is an effective medication for migraine prophylaxis. The biochemical tests and the type of psychological profile cannot be used to predict drug response.