The safety of acupuncture for migraine prevention during pregnancy.

Relief from migraine attacks may be obtained through non-pharmacological therapy during pregnancy when most drugs are contraindicated. There is accumulating evidence for the efficacy and safety of acupuncture for migraine in the general population but very little to no data on acupuncture during pregnancy. With this retrospective study, we wanted to determine whether an association exists between acupuncture treatment and preterm delivery and side effects of therapy. The initial study group was 68 women with migraine (29.78% with aura and 70.21% without aura), 47 of which responded to a questionnaire on acupuncture safety within 6 weeks of delivery. A so-called Formula Acupuncture was used for all these patients in order to permit comparison. Influence of acupuncture on gestational age at birth was carried out according to number of treatment sessions (more than and fewer than 10) and stratifying the study sample by age group (over and under 30 years) and risk pregnancy. Analysis showed no statistically significant difference in gestational duration between the two groups or an association between the number of acupuncture sessions and preterm delivery. Symptoms during treatment were generally transient or mild. The most common symptoms were relaxation, pain at the insertion sites, mild bleeding, and paresthesia. Our preliminary data indicate that acupuncture may be safe during pregnancy in women with migraine.

Effectiveness of ketogenic diet in treatment of patients with refractory chronic migraine.

BACKGROUND AND PURPOSE: Ketogenic diet (KD) is based on restriction of carbohydrate intake. Metabolism is forced to obtain energy starting from ß-oxidation of fatty acids which, turned into ketone bodies, can also be used by central nervous system (CNS). KD use in treatment of chronic migraine has recently been considered. We set out to verify modification of symptoms in patients with refractory chronic migraine in response to KD. METHODS: Fifty patients were enrolled of which 38 completed the procedures the study and 23 were considered in the statistics. All of the patients considered in our study were affected by medication overuse headache (MOH). They were on a KD for 3 months. The following parameters have been checked at t = 0 and every 30 days for 6 months: migraine episode length (n. hours/day), frequency (n. days/month), level of pain of every episode measured on a scale from 1 to 3 (1 = mild; 2 = moderate; 3 = severe), and n. analgesic drugs taken/month. RESULTS: Days with symptoms decreased from 30 (median value) to 7.5 with p < 0.0001. The duration of the migraine episodes decreased from 24 h (median value) to 5.5 h with p < 0.0016. The patients' pain level, initially at maximum value for 83% of the participants, improved for 55% of them (p < 0.0024). The number of drugs taken in a month decreased from 30 doses (median value) to 6 doses. CONCLUSIONS: It can be stated that a 3-month KD resulted in a reduction of painful symptoms of drug refractory chronic migraine. This result may suggest an improvement in quality of life of the patients, even without a tabulated data collection.

Narrative Medicine to integrate patients', caregivers' and clinicians' migraine experiences: the DRONE multicentre project.

BACKGROUND: Although migraine is widespread and disabling, stigmatisation and poor awareness of the condition still represent barriers to effective care; furthermore, research on migraine individual and social impact must be enhanced to unveil neglected issues, such as caregiving burden. The project investigated the migraine illness experience through Narrative Medicine (NM) to understand daily life, needs and personal resources of migraneurs, their caregivers and clinicians, and to provide insights for clinical practice. METHODS: The project involved 13 Italian headache centres and targeted migraneurs, their caregivers and migraine specialists at these centres. Written narratives, composed by a sociodemographic survey and illness plot or parallel chart, were collected through the project's webpage. Illness plots and parallel charts employed open words to encourage participants' expression. Narratives were analysed through Nvivo software, interpretive coding and NM classifications. RESULTS: One hundred and seven narratives were collected from patients and 26 from caregivers, as well as 45 parallel charts from clinicians. The analysis revealed migraine perception in social, domestic and work life within the care pathway evolution and a bond between chaos narratives and day loss due to migraine; furthermore, narratives suggested the extent of the caregiving burden and a risk of underestimation of migraine burden in patients' and caregivers' life. CONCLUSION: The project represents the first investigation on migraine illness experience through NM simultaneously considering migraneurs', caregivers' and clinicians' perspectives. Comparing narratives and parallel charts allowed to obtain suggestions for clinical practice, while NM emerged as able to foster the pursuing of migraine knowledge and awareness.

Gender-related differences in migraine.

Migraine is considered mostly a woman's complaint, even if it affects also men. Epidemiological data show a higher incidence of the disease in women, starting from puberty throughout life. The sex-related differences of migraine hold clinical relevance too. The frequency, duration, and disability of attacks tend to be higher in women. Because of this, probably, they also consult specialists more frequently and take more prescription drugs than men. Different mechanisms have been evaluated to explain these differences. Hormonal milieu and its modulation of neuronal and vascular reactivity is probably one of the most important aspects. Estrogens and progesterone regulate a host of biological functions through two mechanisms: nongenomic and genomic. They influence several neuromediators and neurotransmitters, and they may cause functional and structural differences in several brain regions, involved in migraine pathogenesis. In addition to their central action, sex hormones exert rapid modulation of vascular tone. The resulting specific sex phenotype should be considered during clinical management and experimental studies.

Migraine during pregnancy and in the puerperium.

Pregnancy can be seen as a positive time for women migraineurs because the elevated estrogen and endogenous opioid levels raise the pain threshold and the stable hormone levels, which no longer fluctuate, eliminate a major trigger factor for the attacks. In a great majority of cases, indeed, migraine symptoms spontaneously improve throughout pregnancy. Generally, migraine without aura (MO) improves better than migraine with aura (MA), which can occur ex novo in pregnancy more frequently than MO. After childbirth, the recurrence rate of migraine attacks increases, especially during the first month; breastfeeding exerts a protective effect against the reappearance of attacks. Migraine and pregnancy share a condition of hypercoagulability; therefore, attention must be paid to the risk of cardiovascular disorders, like venous thromboembolism and ischemic or hemorrhagic strokes. Some of these diseases can be linked to preeclampsia (PE), a serious complication of pregnancy, characterized by hypertension, proteinuria, or other findings of organ failure. This condition is more common in migraineurs compared with non-migraineurs; furthermore, women whose migraines worsen during pregnancy had a 13-fold higher risk of hypertensive disorders than those in which migraine remitted or improved. Pregnancy is generally recognized to exert a beneficial effect on migraine; nonetheless, clinicians should be on the alert for possible cardiovascular complications that appear to be more frequent in this patient population.

Prevention, education and counselling: the worldwide role of the community pharmacist as an epidemiological sentinel of headaches.

Headache disorders are the third among the worldwide causes of disability, measured in years of life lost to disability. Given the pharmacies' importance in general in headache patient and, in particular in migraine patient management, various studies have been carried out in recent years dealing with this issue. Indeed, in 2014, our research group first analysed publications on a number of studies conducted worldwide. As five years have passed since our first analysis of the literature and having carried out a number of specific studies in Italy since 2014, we wish to analyse once again the studies carried out globally on this topic to evaluate how the situation has evolved in the meantime. The key words used for the bibliographic search were "community pharmacy" and "headache"; we considered articles published between 2014 and 2018. The selected studies regarded Sweden USA, Belgium, Ireland, Jordan and Ethiopia. From the analysis of the international research papers, it is evident that, despite the time that has passed since the previous analyses and the general agreement that pharmacists find themselves in an ideal position to offer adequate levels of counselling to headache patients, the knowledge of pharmacists is not yet sufficient. Clearly, there is a strong need to develop training programmes specifically focused on this subject. Regarding Italy, a national study, commenced in 2016, was designed as a cross-sectional survey employing face-to-face interviews between pharmacist and patient using a questionnaire drawn up by experts in compliance with best practice from scientific literature. Six hundred ten pharmacists followed a specific training course; 4425 questionnaires were correctly completed. The use of pharmacies as epidemiological sentinels, given their capillarity and daily contact with the local population in Italy, enabled us to obtain an epidemiological snapshot closer to the real-life situation compared to specialist headache centres. Over the course of this study, data on headaches were gathered in Italian pharmacies with the highest levels of numerosity in the world.

Estrogen, migraine, and vascular risk.

Migraine has a predilection for female sex and the course of symptoms is influenced by life stage (presence of menstrual cycle, pregnancy, puerperium, menopause) and use of hormone therapy, such as hormonal contraception and hormone replacement therapy. Hormonal changes figure among common migraine triggers, especially sudden estrogen drop. Moreover, estrogens can modulate neuronal excitability, through serotonin, norepinephrine, dopamine, and endorphin regulation, and they interact with the vascular endothelium of the brain. The risk of vascular disease, and ischemic stroke in particular, is increased in women with migraine with aura (MA), but the link is unclear. One hypothesis posits for a causal association: migraine may cause clinical or subclinical brain lesions following repeated episodes of cortical spreading depression (CSD) and a second hypothesis that may explain the association between migraine and vascular diseases is the presence of common risk factors and comorbidities. Estrogens can play a differential role depending on their action on healthy or damaged endothelium, their endogenous or exogenous origin, and the duration of their treatment. Moreover, platelet activity is increased in migraineurs women, and it is further stimulated by estrogens.This review article describes the course of migraine during various life stages, with a special focus on its hormonal pathogenesis and the associated risk of vascular diseases.

Treating migraine with contraceptives.

At least 18% of women suffers from migraine. Clinically, there are two main forms of migraine: migraine with aura (MA) and migraine without aura (MO) and more than 50% of MO is strongly correlated to the menstrual cycle. The high prevalence of migraine in females, its correlation with the menstrual cycle and with the use of combined hormonal contraceptives (CHCs) suggest that the estrogen drop is implicated in the pathogenesis of the attacks. Although CHCs may trigger or worsen migraine, their correct use may even prevent or reduce some forms of migraine, like estrogen withdrawal headache. Evidence suggested that stable estrogen levels have a positive effect, minimising or eliminating the estrogenic drop. Several contraceptive strategies may act in this way: extended-cycle CHCs, CHCs with shortened hormone-free interval (HFI), progestogen-only contraceptives, CHCs containing new generation estrogens and estrogen supplementation during the HFI.

Community pharmacies as epidemiological sentinels of headache: first experience in Italy.

Migraine is a disabling neurovascular syndrome which affects 12-15% of the global population and it represents the third cause in years lived with disability in both males and females aged 15-49 years. Among migraineurs, the symptomatic drug abuse may be a risk factor in the development of medication overuse headache (MOH). Detecting cases of MOH is not straightforward; community pharmacists may, therefore, be in a strategic position to identify individuals who self-medicate, particularly with respect to prevent the development of MOH. In 2014, our group published the results of a survey conducted in Piedmont, Italy, on the patterns of use and dispensing of drugs in patients requesting assistance from pharmacists for relief of a migraine attack. We decided, now, to expand the scope of the model to a national level. The study is based on cross-sectional face-to-face interviews using questionnaires, presented in this paper, consisting of a first part regarding the socio-economic situation and a second part which aimed to classify the disease and any excessive use of drugs. Of the 610 pharmacists trained with an online course, 446 gathered a total of 4425 correctly compiled questionnaires. The participation of community pharmacies has highlighted various criticalities especially of an organisational nature; however, it also revealed the power of this method as a means of gathering epidemiological data with a capillarity which few other methods can match. The objective was also to identify each territory's requirements and facilitate the decision-making process in terms of understanding what patients/citizens actually require.

Acupuncture for the prevention of episodic migraine.

BACKGROUND: Acupuncture is often used for migraine prevention but its effectiveness is still controversial. We present an update of our Cochrane review from 2009. OBJECTIVES: To investigate whether acupuncture is a) more effective than no prophylactic treatment/routine care only; b) more effective than sham (placebo) acupuncture; and c) as effective as prophylactic treatment with drugs in reducing headache frequency in adults with episodic migraine. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL: 2016, issue 1); MEDLINE (via Ovid, 2008 to January 2016); Ovid EMBASE (2008 to January 2016); and Ovid AMED (1985 to January 2016). We checked PubMed for recent publications to April 2016. We searched the World Health Organization (WHO) Clinical Trials Registry Platform to February 2016 for ongoing and unpublished trials. SELECTION CRITERIA: We included randomized trials at least eight weeks in duration that compared an acupuncture intervention with a no-acupuncture control (no prophylactic treatment or routine care only), a sham-acupuncture intervention, or prophylactic drug in participants with episodic migraine. DATA COLLECTION AND ANALYSIS: Two reviewers checked eligibility; extracted information on participants, interventions, methods and results, and assessed risk of bias and quality of the acupuncture intervention. The primary outcome was migraine frequency (preferably migraine days, attacks or headache days if migraine days not measured/reported) after treatment and at follow-up. The secondary outcome was response (at least 50% frequency reduction). Safety outcomes were number of participants dropping out due to adverse effects and number of participants reporting at least one adverse effect. We calculated pooled effect size estimates using a fixed-effect model. We assessed the evidence using GRADE and created 'Summary of findings' tables. MAIN RESULTS: Twenty-two trials including 4985 participants in total (median 71, range 30 to 1715) met our updated selection criteria. We excluded five previously included trials from this update because they included people who had had migraine for less than 12 months, and included five new trials. Five trials had a no-acupuncture control group (either treatment of attacks only or non-regulated routine care), 15 a sham-acupuncture control group, and five a comparator group receiving prophylactic drug treatment. In comparisons with no-acupuncture control groups and groups receiving prophylactic drug treatment, there was risk of performance and detection bias as blinding was not possible. Overall the quality of the evidence was moderate. Comparison with no acupunctureAcupuncture was associated with a moderate reduction of headache frequency over no acupuncture after treatment (four trials, 2199 participants; standardised mean difference (SMD) -0.56; 95% CI -0.65 to -0.48); findings were statistically heterogeneous (I² = 57%; moderate quality evidence). After treatment headache frequency at least halved in 41% of participants receiving acupuncture and 17% receiving no acupuncture (pooled risk ratio (RR) 2.40; 95% CI 2.08 to 2.76; 4 studies, 2519 participants) with a corresponding number needed to treat for an additional beneficial outcome (NNTB) of 4 (95% CI 3 to 6); there was no indication of statistical heterogeneity (I² = 7%; moderate quality evidence). The only trial with post-treatment follow-up found a small but significant benefit 12 months after randomisation (RR 2.16; 95% CI 1.35 to 3.45; NNT 7; 95% 4 to 25; 377 participants, low quality evidence). Comparison with sham acupunctureBoth after treatment (12 trials, 1646 participants) and at follow-up (10 trials, 1534 participants), acupuncture was associated with a small but statistically significant frequency reduction over sham (moderate quality evidence). The SMD was -0.18 (95% CI -0.28 to -0.08; I² = 47%) after treatment and -0.19 (95% CI -0.30 to -0.09; I² = 59%) at follow-up. After treatment headache frequency at least halved in 50% of participants receiving true acupuncture and 41% receiving sham acupuncture (pooled RR 1.23, 95% CI 1.11 to 1.36; I² = 48%; 14 trials, 1825 participants) and at follow-up in 53% and 42%, respectively (pooled RR 1.25, 95% CI 1.13 to 1.39; I² = 61%; 11 trials, 1683 participants; moderate quality evidence). The corresponding NNTBs are 11 (95% CI 7.00 to 20.00) and 10 (95% CI 6.00 to 18.00), respectively. The number of participants dropping out due to adverse effects (odds ratio (OR) 2.84; 95% CI 0.43 to 18.71; 7 trials, 931 participants; low quality evidence) and the number of participants reporting adverse effects (OR 1.15; 95% CI 0.85 to 1.56; 4 trials, 1414 participants; moderate quality evidence) did not differ significantly between acupuncture and sham groups. Comparison with prophylactic drug treatmentAcupuncture reduced migraine frequency significantly more than drug prophylaxis after treatment ( SMD -0.25; 95% CI -0.39 to -0.10; 3 trials, 739 participants), but the significance was not maintained at follow-up (SMD -0.13; 95% CI -0.28 to 0.01; 3 trials, 744 participants; moderate quality evidence). After three months headache frequency at least halved in 57% of participants receiving acupuncture and 46% receiving prophylactic drugs (pooled RR 1.24; 95% CI 1.08 to 1.44) and after six months in 59% and 54%, respectively (pooled RR 1.11; 95% CI 0.97 to 1.26; moderate quality evidence). Findings were consistent among trials with I² being 0% in all analyses. Trial participants receiving acupuncture were less likely to drop out due to adverse effects (OR 0.27; 95% CI 0.08 to 0.86; 4 trials, 451 participants) and to report adverse effects (OR 0.25; 95% CI 0.10 to 0.62; 5 trials 931 participants) than participants receiving prophylactic drugs (moderate quality evidence). AUTHORS' CONCLUSIONS: The available evidence suggests that adding acupuncture to symptomatic treatment of attacks reduces the frequency of headaches. Contrary to the previous findings, the updated evidence also suggests that there is an effect over sham, but this effect is small. The available trials also suggest that acupuncture may be at least similarly effective as treatment with prophylactic drugs. Acupuncture can be considered a treatment option for patients willing to undergo this treatment. As for other migraine treatments, long-term studies, more than one year in duration, are lacking.

Acupuncture for the prevention of tension-type headache.

BACKGROUND: Acupuncture is often used for prevention of tension-type headache but its effectiveness is still controversial. This is an update of our Cochrane review originally published in Issue 1, 2009 of The Cochrane Library. OBJECTIVES: To investigate whether acupuncture is a) more effective than no prophylactic treatment/routine care only; b) more effective than 'sham' (placebo) acupuncture; and c) as effective as other interventions in reducing headache frequency in adults with episodic or chronic tension-type headache. SEARCH METHODS: We searched CENTRAL, MEDLINE, EMBASE and AMED to 19 January 2016. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform to 10 February 2016 for ongoing and unpublished trials. SELECTION CRITERIA: We included randomised trials with a post-randomisation observation period of at least eight weeks, which compared the clinical effects of an acupuncture intervention with a control (treatment of acute headaches only or routine care), a sham acupuncture intervention or another prophylactic intervention in adults with episodic or chronic tension-type headache. DATA COLLECTION AND ANALYSIS: Two review authors checked eligibility; extracted information on participants, interventions, methods and results; and assessed study risk of bias and the quality of the acupuncture intervention. The main efficacy outcome measure was response (at least 50% reduction of headache frequency) after completion of treatment (three to four months after randomisation). To assess safety/acceptability we extracted the number of participants dropping out due to adverse effects and the number of participants reporting adverse effects. We assessed the quality of the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). MAIN RESULTS: Twelve trials (11 included in the previous version and one newly identified) with 2349 participants (median 56, range 10 to 1265) met the inclusion criteria.Acupuncture was compared with routine care or treatment of acute headaches only in two large trials (1265 and 207 participants), but they had quite different baseline headache frequency and management in the control groups. Neither trial was blinded but trial quality was otherwise high (low risk of bias). While effect size estimates of the two trials differed considerably, the proportion of participants experiencing at least 50% reduction of headache frequency was much higher in groups receiving acupuncture than in control groups (moderate quality evidence; trial 1: 302/629 (48%) versus 121/636 (19%); risk ratio (RR) 2.5; 95% confidence interval (CI) 2.1 to 3.0; trial 2: 60/132 (45%) versus 3/75 (4%); RR 11; 95% CI 3.7 to 35). Long-term effects (beyond four months) were not investigated.Acupuncture was compared with sham acupuncture in seven trials of moderate to high quality (low risk of bias); five large studies provided data for one or more meta-analyses. Among participants receiving acupuncture, 205 of 391 (51%) had at least 50% reduction of headache frequency compared to 133 of 312 (43%) in the sham group after treatment (RR 1.3; 95% CI 1.09 to 1.5; four trials; moderate quality evidence). Results six months after randomisation were similar. Withdrawals were low: 1 of 420 participants receiving acupuncture dropped out due to adverse effects and 0 of 343 receiving sham (six trials; low quality evidence). Three trials reported the number of participants reporting adverse effects: 29 of 174 (17%) with acupuncture versus 12 of 103 with sham (12%; odds ratio (OR) 1.3; 95% CI 0.60 to 2.7; low quality evidence).Acupuncture was compared with physiotherapy, massage or exercise in four trials of low to moderate quality (high risk of bias); study findings were inadequately reported. No trial found a significant superiority of acupuncture and for some outcomes the results slightly favoured the comparison therapy. None of these trials reported the number of participants dropping out due to adverse effects or the number of participants reporting adverse effects.Overall, the quality of the evidence assessed using GRADE was moderate or low, downgraded mainly due to a lack of blinding and variable effect sizes. AUTHORS' CONCLUSIONS: The available results suggest that acupuncture is effective for treating frequent episodic or chronic tension-type headaches, but further trials - particularly comparing acupuncture with other treatment options - are needed.

Early (≤ 1-h) vs. late (>1-h) administration of frovatriptan plus dexketoprofen combination vs. frovatriptan monotherapy in the acute treatment of migraine attacks with or without aura: a post hoc analysis of a double-blind, randomized, parallel group study.

The early use of triptan in combination with a nonsteroidal anti-inflammatory drug after headache onset may improve the efficacy of acute migraine treatment. In this retrospective analysis of a randomized, double-blind, parallel group study, we assessed the efficacy of early or late intake of frovatriptan 2.5 mg + dexketoprofen 25 or 37.5 mg (FroDex 25 and FroDex 37.5) vs. frovatriptan 2.5 mg alone (Frova) in the acute treatment of migraine attacks. In this double-blind, randomized parallel group study 314 subjects with acute migraine with or without aura were randomly assigned to Frova, FroDex 25, or FroDex 37.5. Pain free (PF) at 2-h (primary endpoint), PF at 4-h and pain relief (PR) at 2 and 4-h, speed of onset at 60, 90, 120 and 240-min, and sustained pain free (SPF) at 24-h were compared across study groups according to early (≤1-h; n = 220) or late (>1-h; n = 59) intake. PF rates at 2 and 4-h were significantly larger with FroDex 37.5 vs. Frova (early intake, n = 71 FroDex 37.5 and n = 75 Frova: 49 vs. 32 % and 68 vs. 52 %, p < 0.05; late intake, n = 20 Frodex 37.5, and n = 18 Frova: 55 vs. 17 %, p < 0.05 and 85 vs. 28 %, p < 0.01). Also with FroDex 25, in the early intake group (n = 74) PF episodes were significantly higher than Frova. PR at 2 and 4-h was significantly better under FroDex 37.5 than Frova (95 % vs. 50 %, p < 0.001, 100 % vs. 72 %, p < 0.05) in the late intake group (n = 21). SPF episodes at 24-h after early dosing were 25 % (Frova), 45 % (FroDex 25) and 41 % (FroDex 37.5, p < 0.05 combinations vs. monotherapy), whereas they were not significantly different with late intake. All treatments were equally well tolerated. FroDex was similarly effective regardless of intake timing from headache onset.

Comparison of frovatriptan plus dexketoprofen (25 mg or 37.5 mg) with frovatriptan alone in the treatment of migraine attacks with or without aura: a randomized study.

BACKGROUND: Drugs for migraine attacks include triptans and NSAIDs; their combination could provide greater symptom relief. METHODS: A total of 314 subjects with history of migraine, with or without aura, were randomized to frovatriptan 2.5 mg alone (Frova), frovatriptan 2.5 mg + dexketoprofen 25 mg (FroDex25) or frovatriptan 2.5 mg + dexketoprofen 37.5 mg (FroDex37.5) and treated at least one migraine attack. This was a multicenter, randomized, double-blind, parallel-group study. The primary end point was the proportion of pain free (PF) at two hours. Secondary end points were PF at one and four hours, pain relief (PR) at one, two, four hours, sustained PF (SPF) at 24 and 48 hours, recurrence at 48 hours, resolution of nausea, photophobia and phonophobia at two and four hours, the use of rescue medication and the judgment of the treatment. RESULTS: The results were assessed in the full analysis set (FAS) population, which included all subjects randomized and treated for whom at least one post-dose intensity of headache was recorded. The proportions of subjects PF at two hours (primary end point) were 29% (27/93) with Frova compared with 51% (48/95 FroDex25 and 46/91 FroDex37.5) with each combination therapies ( P < 0.05). Proportions of SPF at 24 hours were 24% (22/93) for Frova, 43% (41/95) for FroDex25 ( P < 0.001) and 42% (38/91) for FroDex37.5 ( P < 0.05). SPF at 48 hours was 23% (21/93) with Frova, 36% (34/95) with FroDex25 and 33% (30/91) with FroDex37.5 ( P = NS). Recurrence was similar for Frova (22%, 6/27), FroDex25 (29%, 14/48) and FroDex37.5 (28%, 13/46) ( P = NS), meaning a lack of improvement with the combination therapy. Statistical adjustment for multiple comparisons was not performed. No statistically significant differences were reported in the occurrence of total and drug-related adverse events. FroDex25 and FroDex37.5 showed a similar efficacy both for primary and secondary end points. There did not seem to be a dose response curve for the addition of dexketoprofen. CONCLUSION: FroDex improved initial efficacy at two hours compared to Frova whilst maintaining efficacy at 48 hours in this study. Tolerability profiles were comparable. Intrinsic pharmacokinetic properties of the two single drugs contribute to this improved efficacy profile.

Gender and triptan efficacy: a pooled analysis of three double-blind, randomized, crossover, multicenter, Italian studies comparing frovatriptan vs. other triptans.

Migraine is three times as common in females as in males, and attacks may be more severe and difficult to treat in women. However, no study specifically addressed possible gender differences in response to antimigraine therapy. The objective of this study was to review the efficacy of frovatriptan vs. other triptans, in the acute treatment of migraine in subgroups of subjects classified according to gender (men vs. women) through a pooled analysis of three individual randomized Italian studies. 414 patients suffering from migraine with or without aura were randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan 2.5 mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5 mg (study 3). All studies had a multicenter, randomized, double-blind, crossover design. After treating 1-3 episodes of migraine in no more than 3 months with the first treatment, patients switched to the other treatment for the next 3 months. In this analysis, traditional migraine endpoints were compared between the 66 men and 280 women of the intent-to-treat population. At baseline, long-term and debilitating migraine attacks were more frequently reported by women than men. During the observation period, the proportion of pain-free attacks at 2 h did not significantly differ between frovatriptan and the comparators in either men (32 vs. 38 %, p = NS) or women (30 vs. 33 %, p = NS). Pain relief was also similar between treatments for both genders (men: 56 % frovatriptan vs. 57 % comparators; women: 55 vs. 57 %; p = NS for both). The rate of relapse was significantly lower with frovatriptan than with the comparators in men (24 h: 10 vs. 30 %; 48 h: 21 vs. 39 %; p < 0.05) as well as in women (24 h: 14 vs. 23 %; 48 h: 28 vs. 40 %; p < 0.05). The rate of adverse drug reactions was significantly larger with comparators, irrespectively of gender. Although migraine presents in a more severe form in women, frovatriptan seems to retain its good efficacy and favorable sustained antimigraine effect regardless of the gender.

Efficacy of frovatriptan and other triptans in the treatment of acute migraine of normal weight and obese subjects: a review of randomized studies.

An association between obesity and migraine has been observed in recent studies and it is supported by plausible biological mechanisms. The objective of this study is to evaluate the efficacy of frovatriptan and other triptans in the acute treatment of migraine, in patients enrolled in three randomized, double-blind, crossover, Italian studies and classified according to body mass index (BMI) levels, as normal weight or non-obese (NO, BMI 18.5-24.9 kg/m(2)) and overweight or obese subjects (O, BMI ≥ 25 kg/m(2)). 414 migraineurs with or without aura were randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan 2.5 mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5 mg (study 3). After treating up to three episodes of migraine in 3 months with the first treatment, patients switched to the alternate treatment for the next 3 months. The present analysis assessed triptan efficacy in 220 N and in 109 O subjects of the 346 individuals of the intention-to-treat population. The proportion of pain free at 2 h did not significantly differ between frovatriptan and the comparators in either NO (30 vs. 34 %) or O (24 vs. 27 %). However, the rate of pain free at 2 h was significantly (p < 0.05) larger in NO than in O, irrespective of the type of triptan. Pain relief at 2 h was also similar between drug treatments for either subgroup. Pain relapse occurred at 48 h in significantly (p < 0.05) fewer episodes treated with frovatriptan in both NO (26 vs. 36 %) and O (27 vs. 49 %). The rate of 48-h relapse was similar in NO and O with frovatriptan, while it was significantly (p < 0.05) higher in O with the comparators. Frovatriptan, in contrast to other triptans, retains a sustained antimigraine effect in NO and even more so in O subjects.

Efficacy of early vs. late use of frovatriptan combined with dexketoprofen vs. frovatriptan alone in the acute treatment of migraine attacks with or without aura.

Early triptan use after headache onset may help improve the efficacy of acute migraine treatment. This may be particularly the case when triptan therapy is combined with a nonsteroidal anti-inflammatory drug (NSAID). The objective of this is to assess whether the combination of frovatriptan 2.5 mg + dexketoprofen 25 or 37.5 mg (FroDex25 and FroDex37.5) is superior to frovatriptan 2.5 mg alone (Frova) in the acute treatment of migraine attacks in patients who took the drug within 30 min from the onset of pain (early use) or after (late use). A total of 314 subjects with a history of migraine with or without aura were randomized into a double-blind, multicenter, parallel group, pilot study to Frova, FroDex25 or FroDex37.5 and were required to treat at least one migraine attack. In the present post hoc analysis, traditional migraine endpoints were compared across study drugs for subgroups of the 279 patients of the full analysis set according to early (n = 172) or late (n = 107) drug use. The proportion of patients pain free at 2 h in the early drug use subgroup was 33 % with Frova, 50 % with FroDex25 and 51 % with FroDex37.5 mg (p = NS combinations vs. monotherapy), while in the late drug use subgroup was 22, 51 and 50 % (p < 0.05 FroDex25 and FroDex37.5 vs. Frova), respectively. Pain-free episodes at 4 h were 54 % for early and 34 % for late use of Frova, 71 and 57 % with FroDex25 and 74 and 68 % with FroDex37.5 (p < 0.05 for early and p < 0.01 for late use vs. Frova). The proportion of sustained pain free at 24 h was 26 % under Frova, 43 % under FroDex25 mg and 40 % under FroDex37.5 mg (p = NS FroDex25 or 37.5 vs. Frova) in the early drug intake subgroup, while it was 19 % under Frova, 43 % under FroDex25 mg and 45 % under FroDex37.5 mg (p < 0.05 FroDex25 and FroDex37.5 vs. Frova) in the late drug intake subgroup. Risk of relapse at 48 h was similar (p = NS) among study drug groups (Frova: 25 %, FroDex25: 21 %, and FroDex37.5: 37 %) for the early as well as for the late drug use subgroup (14, 42 and 32 %). FroDex was found to be more effective than Frova taken either early or late. The intrinsic pharmacokinetic properties of the two single drug components made FroDex combination particularly effective within the 2-48-h window from the onset of the acute migraine attack. The efficacy does not seem to be influenced by the time of drug use relative to the onset of headache.