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.

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.

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.

Almotriptan 12.5 mg in menstrually related migraine: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Menstrually related migraine (MRM) affects more than half of female migraineurs. Because such migraines are often predictable, they provide a suitable target for treatment in the mild pain phase. The present study was designed to provide prospective data on the efficacy of almotriptan for treatment of MRM. METHODS: Premenopausal women with MRM were randomized to almotriptan (N = 74) or placebo (N = 73), taken at onset of the first perimenstrual migraine. Patients crossed over to the other treatment for the first perimenstrual migraine of their second cycle, followed by a two-month open-label almotriptan treatment period. RESULTS: Significantly more patients were pain-free at two hours (risk ratio [RR] = 1.81; p = .0008), pain-free from 2-24 hours with no rescue medication (RR = 1.99; p = .0022), and pain-free from 2-24 hours with no rescue medication or adverse events (RR = 1.94; p = .0061) with almotriptan versus placebo. Nausea (p = .0007) and photophobia (p = .0083) at two hours were significantly less frequent with almotriptan. Almotriptan efficacy was consistent between three attacks, with 56.2% of patients pain-free at two hours at least twice. Adverse events were similar with almotriptan and placebo. CONCLUSION: Almotriptan was significantly more effective than placebo in women with MRM attacks, with consistent efficacy in longer-term follow-up.

Evolution of migraine-associated symptoms in menstrually related migraine following symptomatic treatment with almotriptan.

In addition to headache, migraine is characterized by a series of symptoms that negatively affects the quality of life of patients. Generally, these are represented by nausea, vomiting, photophobia, phonophobia and osmophobia, with a cumulative percentage of the onset in about 90% of the patients. From this point of view, menstrually related migraine--a particularly difficult-to-treat form of primary headache--is no different from other forms of migraine. Symptomatic treatment should therefore be evaluated not only in terms of headache relief, but also by considering its effect on these migraine-associated symptoms (MAS). Starting from the data collected in a recently completed multicentre, randomized, double-blind, placebo-controlled, cross-over study with almotriptan in menstrually related migraine, an analysis of the effect of this drug on the evolution of MAS was performed. Data suggest that almotriptan shows excellent efficacy on MAS in comparison to the placebo, with a significant reduction in the percentages of suffering patients over a 2-h period of time.

The efficacy of withdrawal therapy in subjects with chronic daily headache and medication overuse following prophylaxis with topiramate and amitriptyline.

Management of patients affected by chronic daily headache (CDH) with medication overuse constitutes one of the most important unresolved problems. The uncertainty regarding the classification and the prophylaxis are a remarkable part of this problem. Objectives are to: (1) to evaluate the efficacy of withdrawal therapy following prophylaxis with topiramate and amitriptyline in a population affected by CDH and medication overuse with follow-up at 1 (T1), 3 (T2) and 6 (T3) months; (2) to identify which group of the Silberstein's CDH classification (1994) may benefit from this protocol. Inclusion criteria are patients with CDH (headache for more >15 days/month for at least 3 consecutive months) and medication overuse according with IHS second edition (8.2 group); exclusion criteria are patients with secondary headache. All patients included in the study were hospitalized for 1 week. Type of overuse: combination of medications, 38%; analgesics, 29%; triptans, 29%; opioids, 2%; ergotamines, 2%. During hospitalization the following protocol was applied: desametasone 4 mg i.v./day for 1 week, diazepam 6 mg/day for 10 days and prophylaxis with amitriptylin plus topiramate. This prophylaxis was protracted for at least 6 months. The dosages assumed ranged for amitriptylin from 10 to 20 mg/day and for topiramate from 50 to 100 mg/day. In the last 4 years 105 patients with CDH (age 24-89 years; f 96; m 9) were admitted to the hospital. The protocol was applied in 52 patients (age, 29-65 years; f 49; m 3). At T1, 89% of the patients did not fall again into medication overuse; at T2, 64%; and at T3,45% of the patients remained free from overuse. According to the Silberstein' proposal at T1, 93% of the subjects was affected by transformed migraine; and 7% by tension-type headache. At T3, all the patients free from overuse were affected by transformed migraine. Our data suggest that the patients affected by CDH and medication overuse benefit from withdrawal therapy performed during hospitalization plus prophylaxis with amitriptyline plus topiramate. This combination seems a good pharmacological solution to reduce the risk of relapse.