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.

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 In each group, 50 patients received education and orientation and were then abruptly withdrawn from all SM.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.

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.

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.

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.