Introduction of a novel self-injector for sumatriptan. A controlled clinical trial in general practice

A novel self-injector for the administration of subcutaneous sumatriptan in the treatment of migraine attacks was tested in 138 patients recruited by family physicians in Denmark; 108 patients completed the initial double-blind, crossover part of the study. Sumatriptan 6 mg s.c. was significantly better than placebo at 30, 60, 90 and 120 min after injection in relieving moderate or severe headache to mild or none as well as relieving any headache to none. At 60 min after injection, the treatment response rate was 61% for sumatriptan and 6% for placebo. During the following open-phase trial of four attacks treated with sumatriptan, treatment response rates were 68–74%. During the total of 538 attacks treated, 12 attempts at using the self-injector failed. In the double-blind and open phases, 81% and 90% of patients respectively found the device easy or very easy to use. Adverse effects were benign and short-lasting, but led seven patients to discontinue the study. In conclusion, subcutaneous sumatriptan administered with a novel self-injector is an effective treatment for migraine compared to placebo in patients treated by their family physician.     

Treatment of migraine attacks with subcutaneous sumatriptan: first placebo-controlled study

The results of the very first large-scale placebo-controlled dose-response trial with the novel selective 5-hydroxytryptamine1-like (5HT1-like) receptor agonist sumatriptan are presented. We studied the efficacy and tolerability of subcutaneous injections of 1 mg, 2 mg and 3 mg of sumatriptan in alleviating migraine attacks in a double-blind, placebo-controlled, parallel-group, multicentre clinical trial. Six-hundred and ninety patients were randomized and 685 received study medication. At 30 min, reduction of headache severity to mild or none (primary efficacy endpoint) was achieved in 22% (95% CI: 15-28%) of placebo-treated patients and in 39% (CI: 31-46%) of patients treated with 1 mg sumatriptan, 44% (CI: 36-51%) treated with 2 mg sumatriptan and 55% (CI: 48-63%) treated with 3 mg sumatriptan. Differences from placebo were 17% (CI: 8-27%) for 1 mg sumatriptan, 22% (CI: 13-32%) for 2 mg sumatriptan and 34% (CI: 24-44%) for 3 mg sumatriptan (p < 0.001 for all three comparisons). Other migraine symptoms were also more effectively treated by sumatriptan than by placebo. Subsequently, an open-label 3 mg dose subcutaneous sumatriptan was given to partial or non-responders. Thirty minutes after this open dose the response rate to sumatriptan had improved to between 70 and 80%. Adverse events after sumatriptan were minor and short-lived. We conclude that subcutaneous sumatriptan is well tolerated in doses up to 3 + 3 mg and may rapidly abort migraine attacks.     

Sumatriptan-naproxen and butalbital: a double-blind, placebo-controlled crossover study

Objectives.— The primary objective was to compare the efficacy of a sumatriptan and naproxen combination medication (SumaRT/Nap—85 mg sumatriptan and 500 mg naproxen sodium), a butalbital‐containing combination medication (BCM—50 mg butalbital, 325 mg acetaminophen, 40 mg caffeine), and placebo when used to treat moderate to severe migraine headache pain in subjects who used BCMs in the past. Background.— Despite the lack of Food and Drug Administration approval and the absence of placebo‐controlled trials to demonstrate efficacy, butalbital‐containing medications are among the most commonly prescribed acute migraine treatments in the United States. Butalbital‐containing medications are associated with serious and undesirable side effects, and have been linked to the chronification of migraine and development of medication‐overuse headaches. This study compares the relative efficacy, safety, and tolerability of a fixed dose SumaRT/Nap versus a BCM and placebo. Methods.— Enrolled subjects were required to have treated at least 1 migraine with a butalbital medication in the past. Enrolled subjects treated 3 moderate to severe migraines using each of the 3 study treatments once in a randomized sequence. The primary endpoint compared SumaRT/Nap versus BCM for sustained pain freedom at 2‐24 hours without the use of any rescue medication. This study combines data from 2 identical outpatient, randomized, multicenter, double‐blind, double‐dummy, 3 attack crossover studies in adult migraineurs (International Classification of Headache Disorders, 2nd edition). Results.— A total of 442 subjects treated at least 1 attack with study medication. The majority of the treated subjects were female (88%) with a mean age 43 years, who reported that their migraines had a severe impact on their lives (78% with Headache Impact Test‐6 of >59). At screening, 88% of subjects reported current butalbital use; 68% had used butalbital for more than 6 weeks; and 82% reported satisfaction with butalbital. Across treatment groups, 28‐29% of subjects took study medication within 15 minutes of migraine onset, 34‐37% of subjects took study medication >15 minutes to 2 hours after onset, and 32‐36% of subjects took study medication more than 2 hours after onset. This study did not detect a difference at the nominal 0.05 level in percent sustained pain‐free between SumaRT/Nap (8%), BCM (6%), and placebo (3%). SumaRT/Nap was superior to BCM for pain free at 2, 4, 6, 8, 24, 48 hours (P ≤ .044); pain relief (mild or no pain) at 2, 4, 6, 8, 24, 48 hours (P ≤ .01); sustained pain relief 2‐24 hours (P < .001); migraine free (pain free with no nausea, photophobia, or phonophobia) at 4, 6, 8, 24, 48 hours (P ≤ .046); and complete symptom free (migraine free with no neck/sinus pain) at 4, 6, 8, 48 hours (P ≤ .031). Adverse event incidence was similar for all treatments (10%, 12%, and 9% for placebo, SumaRT/Nap, and BCM, respectively). Nausea was the most frequent adverse event (2%, 2%, and <1% for placebo, SumaRT/Nap, and BCM, respectively). Five serious adverse events were reported by 3 subjects: viral meningitis and colon neoplasm (placebo); chest pain and hypertension 17 days postdose (SumaRT/Nap); and breast cancer (BCM). Investigators judged no serious adverse events related to study medication. Conclusions.— This study primarily included subjects whose migraines significantly impacted their lives. Before the study, these subjects used butalbital‐containing medications as part of their current migraine treatment regimen and were satisfied with it, suggesting they were butalbital responders who had found a workable treatment strategy for themselves. When treated with SumaRT/Nap versus BCM in this study, however, a significant proportion of subjects reported better treatment outcomes for themselves for both migraine pain and associated symptoms. Use of SumaRT/Nap was also associated with less rescue medication use and a longer time before use of rescue medication compared with both BCM and placebo.     

A double-blind, randomized, crossover assessment of blood pressure following administration of avitriptan, sumatriptan, or placebo to patients with mild to moderate hypertension

We examined the effects of avitriptan, a 5-hydroxytryptamine 1-like (5HT1) receptor agonist for the treatment of migraine, in patients with medicated, controlled, mild to moderate hypertension relative to placebo and sumatriptan. The study was randomized, double-blinded, placebo-controlled, and 4-way crossover in design. Twenty patients (12M, 8F) participated. As required by protocol, all were stable on medications for mild to moderate hypertension, with a supine diastolic blood pressure of < 95 mmHg. Qualified subjects were randomized to receive oral administration of either 75 or 150 mg of avitriptan, 100 mg sumatriptan or placebo during the four treatment visits. Supine blood pressure and pulse rates were recorded up to 24 h after drug administration. Avitriptan 150 mg significantly increased peak diastolic and systolic blood pressure, and mean arterial pressure compared to placebo and sumatriptan 100 mg (p < 0.05). Only those hypertensive patients receiving medication for hypertension should receive anti-migraine medications, such as avitriptan, which are 5HT1-like receptor agonists.     

Oral and subcutaneous sumatriptan in the acute treatment of migraine: an open randomized cress-over study

In an open, randomized cross-over study in 124 patients, we compared the efficacy, safety and patient preference of oral and subcutaneous sum triptan in the acute treatment of migraine. Patients were treated for 3 attacks or 3 months and then crossed over. Primary clinical efficacy was defined as a reduction in headache severity on a four-point self-rating scale from severe (3) or moderate (2) to mild (1) or none (0), or mild (1) to none (0). Efficacy was evaluated 2 h after the administration of subcutaneous and 4h after the administration of oral sumatriptan. Subcutaneous sumatriptan was significantly more effective than oral sumatriptan in relieving headache (over all three attacks 78% vs 61% improvement), improving clinical disability (55% vs 41 % improvement) and relieving nausea (69% vs 53%), vomiting (72% vs 32%) and phono- or photophobia (67% vs 49%). Median time to recurrence was shorter after subcutaneous (12.5 h) than after oral sumatriptan (18 h); the number of patients experiencing a recurrence was similar Patients reported more adverse events after subcutaneous sumatriptan (1.32 per attack) than after the oral form (0.85 per attack), but all adverse events were mild to moderate in intensity and of short duration. Patient opinion was more often positive after subcutaneous sumatriptan. These results may be useful in counselling patients to choose between the available marketed formulations of sumatriptan.     

Sumatriptan and corneal reflexes in headache-free migraine patients: a randomized and placebo-controlled crossover study

A temporary sensitization of central trigeminal neurones in migraine patients during acute attacks has been described in previous studies using the electrically evoked nociceptive blink reflex. The cornea is innervated by small myelinated A-delta and unmyelinated C-fibres only. Stimulation with air puffs activates peripheral nociceptors and allows the investigation of peripheral trigeminal nerve structures. Our objective was to investigate whether corneal reflex examinations with air puff stimulation detect abnormalities in migraineurs during their pain-free interval and if the corneal reflex may be modulated by the administration of an oral triptan. After validation of the nociceptive air puff technique by investigating the corneal reflexes before and after a local anaesthesia of the cornea, we recorded corneal reflexes in 25 migraineurs during their pain-free period and 25 healthy controls before and after the oral administration of 100 mg sumatriptan in a randomized, placebo-controlled, crossover study. Baseline response areas under the curve (AUCs) and latencies of the R2 components of the corneal reflexes did not show any significant differences between patients and controls. Patients did not show any significant differences regarding their headache and non-headache side. The use of an oral triptan had no significant influence on latencies or AUCs in both patients and controls. Our data suggest that there is no facilitation of the trigeminal system in the headache-free interval among patients with migraine. The stable corneal reflexes after the oral administration of 100 mg sumatriptan suggest that there was no inhibition of the trigeminal system, both in patients during their headache-free period and in healthy controls.     

Pilot study evaluating preference for 3-mg versus 6-mg subcutaneous sumatriptan

BACKGROUND: Subcutaneous sumatriptan (6 mg) is undeniably an excellent treatment of migraine. However, some patients have avoided using 6 mg sumatriptan because of unpleasant or unwanted side effects. OBJECTIVE: To evaluate the efficacy of subcutaneous sumatriptan (3 mg) during a moderate or severe migraine attack. METHODS: Thirty subcutaneous sumatriptan-naive patients with a history of migraine with and without aura treated their next two moderate or severe migraines with either 3-mg or 6-mg sumatriptan injection. The primary endpoint was whether patients preferred the low-dose (3 mg) or the high-dose (6 mg) subcutaneous sumatriptan. Other objectives included percentage of patients pain free at 15 and 30 minutes, 1 and 2 hours; a pain-free response lasting between 2 and 24 hours, patient satisfaction, and acceptability of formulation. A new combination endpoint (efficacy and lack of significant side effects) was also evaluated. RESULTS: Eighty percent of patients preferred 3-mg over 6-mg subcutaneous sumatriptan. At 1 hour postdose 57% of patients were pain free with 3 mg and 53% with 6 mg. At 2 hours postdose 87% were pain free with 3 mg and 80% with 6 mg. A sustained pain-free response was obtained by 70 to 80% of patients. When combining a pain-free response at 2 hours and a sustained pain-free response at 24 hours with no significant side effects, more patients met the endpoint with 3 mg (63 to 67%) than with 6 mg (33 to 50%). CONCLUSIONS: Combining efficacy and tolerability endpoints may be clinically meaningful and reflective of real-world expectations. In some patients, a lower dose of sumatriptan injection may be beneficial.     

Almotriptan in migraine patients who respond poorly to oral sumatriptan: a double-blind, randomized trial

OBJECTIVE: To investigate the efficacy and tolerability of almotriptan 12.5 mg in migraine patients who respond poorly to sumatriptan 50 mg. BACKGROUND: Poor response to sumatriptan therapy for acute migraine attacks has been documented in the literature, but few controlled trials have investigated the efficacy of an alternative triptan in this subgroup of patients. METHODS: Patients with an International Headache Society diagnosis of migraine who self-described as experiencing at least two unsatisfactory responses to sumatriptan treated their first migraine attack with open-label sumatriptan 50 mg. Patients who did not achieve 2-hour pain relief (improvement of headache from moderate/severe to mild/no headache) were then randomized to treat their second attack with almotriptan 12.5 mg or placebo under double-blind conditions. RESULTS: In the first attack, 221 of 302 participants (73%) did not achieve 2-hour pain relief with sumatriptan and were randomized to treatment of their second attack with almotriptan 12.5 mg or placebo. Of the 198 sumatriptan nonresponders who treated their second attack (99 almotriptan; 99 placebo), 70% had severe headache pain at baseline. Two-hour pain-relief rates were significantly higher with almotriptan compared to placebo (47.5% vs 23.2%; P<.001). A significant treatment effect for almotriptan was also seen in pain-free rates at 2 hours (33.3% vs 14.1%; P<.005) and sustained freedom from pain (20.9% vs 9.0%; P<.05). In the second attack, 7.1% of patients in the almotriptan group experienced adverse events compared to 5.1% in the placebo group (P=.77). CONCLUSIONS: Almotriptan 12.5 mg is an effective and well-tolerated alternative for patients who respond poorly to sumatriptan 50 mg. A poor response to one triptan does not predict a poor response to other agents in that class.     

Sumatriptan nasal spray in adolescent migraineurs: a randomized, double-blind, placebo-controlled, acute study

OBJECTIVE: To compare the efficacy and tolerability of sumatriptan nasal spray (NS) (5, 20 mg) versus placebo in the acute treatment of migraine in adolescent subjects. BACKGROUND: Currently, no triptan is approved in the United States for the treatment of migraine in adolescent subjects (12 to 17 years). In a previous randomized, placebo-controlled study of 510 adolescent subjects, sumatriptan NS at 5, 10, and 20 mg doses was well tolerated. However, the primary efficacy analysis for headache relief with 20 mg at 2 hours did not demonstrate statistical significance (P = .059). A second study was initiated to evaluate the efficacy of sumatriptan NS in this population. METHODS: This was a randomized (1:1:1), placebo-controlled, double-blind, parallel-group study. Overall, 738 adolescent subjects (mean age: 14 years) with > or = 6-month history of migraine (with or without aura) self-treated a single attack of moderate or severe migraine. The primary endpoints were headache relief at 1 hour and sustained relief from 1 to 24 hours. Pain-free rates, presence/absence of associated symptoms, headache recurrence, and use of rescue medications were also assessed. Tolerability was based on adverse events (AEs) and vital signs. RESULTS: Sumatriptan NS 20 mg provided greater headache relief than placebo at 30 minutes (42% vs. 33%, respectively; P = .046) and 2 hours (68% vs. 58%; P = .025) postdose, but did not reach statistical significance at 1 hour (61% vs. 52%; P = .087) or for sustained headache relief from 1 to 24 hours (P = .061). Significant differences (P < .05) in favor of sumatriptan NS 20 mg over placebo were observed for several secondary efficacy endpoints including sustained relief from 2 to 24 hours. In general, sumatriptan NS 5 mg percentages were slightly higher than placebo but the differences did not reach statistical significance. Both doses of sumatriptan NS were well tolerated. No AEs were serious or led to study withdrawal. The most common event was taste disturbance (2%, placebo; 19%, sumatriptan NS 5 mg; 25%, sumatriptan NS 20 mg). CONCLUSIONS: This study suggests that sumatriptan may be beneficial to some adolescents and is generally well tolerated in the acute treatment of migraine in this population.     

A within-patient comparison of subcutaneous and oral sumatriptan in the acute treatment of migraine in general practice

This study compared, for the first time in the United Kingdom, the efficacy and safety of oral 100 mg and subcutaneous 6 mg sumatriptan within a patient for the acute treatment of migraine. The patient's preference for the two formulations of sumatriptan were also recorded. The study was a multicentre, randomized, open, crossover design with an optional open parallel group extension. Individual attacks were treated with one formulation only. Over 10% of patients who treated attack 1 in both treatment periods of the crossover phase reported headache relief with each formulation at 4 h. Only 3% of patients failed to respond to at least one of the formulations at this time point. At the end of the crossover phase patient preference for the injection more than doubled from the pretreatment level in those patients who were previously naive to sumatriptan. During the optional phase of the study, 38% of patients chose to treat some attacks with oral and some with subcutaneous sumatriptan. The main reason for choosing injection was speed of relief, whilst convenience was the major reason for the use of the tablet.     

Prevalence of adult migraine in general practice

In 1988 the International Headache Society presented new criteria for the diagnosis of migraine. We used these criteria in a questionnaire to assist in the diagnosis of migraine. The questionnaire was answered by 230 patients in four general practices. We found a migraine prevalence of 11.7%. More than 70% of migraine patients had 12 or more attacks per year, and the length of attack varied between 4 and 24 h in 80% of them. The majority of migraineurs went to bed during the attack and 55% had stayed away from work due to migraine during the last year. The results of this study are in agreement with others. Migraine is an appreciable economic concern due to frequent short absenteeism from work.     

Resolution of concentration-response differences in onset of effect between subcutaneous and oral sumatriptan

OBJECTIVE: To investigate whether the concentration-response relationships for onset of effect of oral and subcutaneous (s.c.) sumatriptan differ, and if so, then to explore whether a single model for the onset of effect can nonetheless be found for multiple dose sizes and both routes of administration. METHODS: Active and placebo response rates and mean plasma concentrations were collected from the literature for 0 < or =t < or = 2 hours. Plasma concentration-response relationships were plotted. Logarithmic models for the onset of effect (ie, active response rates), characterized by convexity factor A and location parameter B were constructed from the same data. RESULTS: The concentration-response relationships for s.c. and oral sumatriptan are qualitatively different. A single logarithmic model for the onset of effect provides good estimates of observed response rates during the first 2 hours post-dose for multiple dose sizes after both oral and s.c. routes of administration. The precision of this model resides in both its variables. Location parameters for this model differ for similar absolute doses by the two routes of administration. However, curve convexity (representing rate of onset of effect) is related to absolute dose (and hence plasma concentration) in the same way for sumatriptan tablets and injections. CONCLUSIONS: No simple plasma concentration-response relationship exists that is sufficiently robust to apply to both s.c. and oral sumatriptan. There are separate pharmacokinetic-pharmacodynamic relationships for rate of onset and extent of effect. The design of exploratory clinical trials for new acute therapies for migraine may be more efficient when these factors are considered, and these factors may help to describe the gap between experimental and ordinary clinical environments.     

Self-treatment of acute migraine with subcutaneous sumatriptan using an auto-injector device: comparison with customary treatment in an open, longitudinal study

In a multicenter open longitudinal clinical trial where 479 patients suffering from migraine with or without aura were recruited, patients treated at home one to three migraine attacks with their customary treatment, and subsequently, over a 3-month period, one to three migraine attacks with (5 mg sumatriptan sc using an auto-injector. The headache response to customary treatment was 19% at 1 h and 30.5% at 2 h, and was not significantly different when only attacks treated "adequately" according to accepted treatment recommendations were considered: 16% at 1 h and 35% at 2 h. In contrast, 69% and 82% of patients treated with 6 mg sumatriptan sc had mild headache or no headache at 1 and 2 h respectively, regardless of migraine type or duration of symptoms prior to treatment. Other migraine symptoms (nausea, vomiting, photo- and phonophobia) were effectively treated with sumatriptan. Recurrence of migraine was observed in 31% of patients and was well controlled by a second injection of sumatriptan. It is concluded that 6 mg sumatriptan sc, self-administered using an auto-injector, is well tolerated and more effective than most currently used acute treatments for migraine in a population of severely affected patients consulting a neurologist.     

Decision making in migraine patients taking sumatriptan: an exploratory study

Until recently, much of the medical and psychological literature has examined and conceptualized the taking of medication from the viewpoint of adherence to or compliance with recommendations from health professionals. However, some authors have argued that medication taking is mostly determined by patient decision making. In order to investigate the factors and processes influencing the patient's decision to take or not take abortive therapy for migraines, 20 migraineurs (according to International Headache Society criteria) were asked, using a semistandardized interview, what factors influenced their decision to take or not take sumatriptan when they had a migraine. Qualitative analysis revealed a 2-stage decision-making process. First, the patient collects information from interoceptive and environmental cues (symptom monitoring) to predict whether the headache that is beginning will become a migraine. Then, if the patient decides it is a migraine, he or she weighs various factors to decide whether to take sumatriptan. These results are consistent with the current cognitive psychology literature on decision-making processes and could lead to significant improvements in understanding the process by which patients make decisions about taking sumatriptan and, ultimately, could lead to better patient education and more effective headache control. They also open a whole new field in the empirical investigation of medication-taking behavior.     

Oral sumatriptan for the acute treatment of probable migraine: first randomized, controlled study

OBJECTIVE: To evaluate the efficacy and tolerability of sumatriptan tablets in adults who meet International Headache Society (IHS) criteria for probable migraine but who do not meet IHS criteria for migraine with or without aura. BACKGROUND: Headaches with some but not all of the features of migraine meet criteria for probable migraine, a form of migraine recognized by the IHS. Probable migraine attacks are also prevalent and frequently underdiagnosed. METHODS: This was a randomized, multicenter, double-blind, placebo-controlled, parallel-group study. Adults (18 to 65 years) with a 1-year history of headaches that met 2004 IHS criteria for probable migraine without aura (same operational definition as 1988 IHS migrainous disorder) were eligible for enrollment. All patients were triptan- and ergot-na?ve and had never been diagnosed with migraine. Patients were randomized in a 1:1:1:1 fashion to receive sumatriptan 25, 50, or 100 mg conventional tablets or matching placebo and were instructed to treat a single moderate or severe probable migraine attack. A post hoc analysis was conducted to evaluate the population of patients who achieved headache relief sustained throughout the immediate posttreatment period. Patients who reported relief within 2 hours and subsequently lost headache relief within 4 hours were considered nonresponders. RESULTS: At 2 hours, more patients treated with sumatriptan achieved headache relief, the primary efficacy measure, compared with placebo, but differences only approached statistical significance for 100 mg (P= .053). The 2-hour headache relief rate in the sumatriptan 25 or 50 mg groups was not significantly different than placebo. The time to use of rescue was significantly shorter in the placebo group compared with the sumatriptan 100 mg group (P= .002). The time to use of rescue in the sumatriptan 25 or 50 mg groups was not significantly different than placebo. More patients treated with placebo (22%) lost headache relief within 4 hours compared with patients treated with sumatriptan 25 mg (17%), 50 mg (14%), or 100 mg (7%). A post hoc analysis demonstrated that at 2 hours, headache relief sustained through 4 hours (S 0-4 hours) was achieved in 44%, 49%, and 57% of patients treated with sumatriptan 25, 50, and 100 mg, respectively, compared with 34% of patients treated with placebo (P < .05 for sumatriptan 50 and 100 mg vs. placebo). All doses of sumatriptan were well tolerated and no serious adverse events were reported. CONCLUSION: These results suggest that oral sumatriptan may be effective and is well tolerated for the acute treatment of probable migraine without aura, however, the difference between sumatriptan and placebo was not statistically significant for the a priori defined primary endpoint.     

Impact of antimigraine compounds on cognitive processing: a placebo-controlled crossover study

OBJECTIVE: To evaluate potential cognitive impairment caused by acute antimigraine drugs. METHODS: We conducted a placebo-controlled, double-blind, crossover study to detect the short-term impact of sumatriptan, zolmitriptan, and ergotamine tartrate on cognitive processing as measured by event-related potentials and a d2 test. Sixteen healthy subjects were enrolled in the study and given placebo, sumatriptan 100 mg, zolmitriptan 2.5 mg, and ergotamine tartrate 2 mg on different days and in random order. Before and 2 hours after drug administration, visually evoked event-related potentials and a d2 test were measured. RESULTS: The N2 latency was significantly increased after ergotamine intake. No other significant differences could be observed in all other event-related potential parameters. In the d2 test, the GZ value was unchanged after ingestion of zolmitriptan and ergotamine, but improved significantly after taking placebo and sumatriptan. The number of relative errors and the concentration value did not change significantly. All results fell within the reference values for the d2 test in all examinations. CONCLUSION: Our data suggest that there may be a slight cognitive decline 2 hours after ingestion of ergotamine tartrate and, to an even lesser extent, zolmitriptan, but not after ingestion of sumatriptan or placebo. All changes recorded were very mild and unlikely to be clinically relevant.     

Efficacy of a fixed combination of indomethacin,prochlorperazine, and caffeine versus sumatriptan in acute treatment of multiple migraine attacks: a multicenter,randomized, crossover trial

OBJECTIVE: To compare the efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine suppositories with sumatriptan suppositories in the treatment of 2 consecutive migraine attacks of moderate or severe intensity in a multicenter, randomized, crossover study. BACKGROUND: A fixed combination of indomethacin, prochlorperazine, and caffeine is the most commonly used drug for the acute treatment of migraine in Italy. No studies have been published comparing the efficacy of this combination with sumatriptan, the most widely prescribed of the triptans. METHODS: One hundred twelve patients with migraine with or without aura according to the diagnostic criteria of the International Headache Society were randomized to treat 2 migraine attacks with a fixed combination of indomethacin, prochlorperazine, and caffeine and 2 migraine attacks with sumatriptan. Both drugs were rectally administered in a single dose for each attack. Patients were asked to take study medication as soon as possible at the onset of a headache. RESULTS: Of the 112 patients, 88 were compliant to the protocol. More attacks became pain-free at 2 hours postdose (primary end point) on the combination than on sumatriptan (49% versus 34%; P<.01), while there was no difference in the relief of headache at 2 hours postdose (71% versus 65%). The combination was statistically superior to sumatriptan in the time to a pain-free response (a higher percentage of attacks became pain-free from 0.5 hours postdose to 5 hours postdose), in alleviation of nausea, and in a sustained pain-free response (pain-free at 2 hours postdose with no use of rescue medication or relapses within 48 hours). Moreover, a significant consistent response was achieved for the combination compared with sumatriptan across (higher percentage of patients pain-free at 2 hours postdose in the first, second, third, and fourth treated attack) and within patients (pain-free in 2 of 2 treated attacks in 35% of patients taking the combination and 20% of patients on sumatriptan). Both drugs were well-tolerated. CONCLUSIONS: This study, analyzed according to the more recent guidelines for controlled trials in migraine, showed that a fixed combination of indomethacin, prochlorperazine, and caffeine is significantly more effective than sumatriptan in the acute treatment of migraine attacks. It is notable that the combination is less expensive than sumatriptan per unit dose.     

Satisfaction with and confidence in needle-free subcutaneous sumatriptan in patients currently treated with triptans

(Headache 2011;51:1202‐1211) Objective.— To evaluate patient satisfaction with and confidence in Sumavel^® DosePro^® (needle‐free subcutaneous sumatriptan) among current triptan users administering Sumavel DosePro for up to 4 migraine attacks. Background.— Sumavel DosePro is a needle‐free, single‐use device that facilitates subcutaneous injection of sumatriptan 6 mg and confers relief as early as 10 minutes after dosing. Design/Methods.— In this open‐label, multicenter study, Sumavel DosePro was self‐administered for ≤4 migraine attacks (over a ≤60‐day period) involving moderate or severe baseline pain by adult migraineurs who currently were using triptans (any form, any dosage) and reported being less than very satisfied with their current therapy (ie, baseline satisfaction ranging from satisfied to very dissatisfied). Treatment satisfaction was measured via the Patient Perception of Migraine Questionnaire, revised (PPMQ‐R). Results.— Among the 212 patients using Sumavel DosePro to treat ≥1 migraine attack, PPMQ‐R Overall Satisfaction (primary endpoint) increased significantly from baseline to the end of treatment (mean ± SD 65.7 ± 19.8 vs 73.7 ± 29.1, P = .0007), an improvement that met the criterion for clinical significance. From baseline to the end of treatment, PPMQ‐R scores also improved significantly for Efficacy (62.2 ± 17.6 vs 76.2 ± 23.7, P < .0001), Functionality (59.0 ± 22.3 vs 73.8 ± 25.3, P < .0001), and Tolerability (83.9 ± 13.1 vs 86.4 ± 15.0, P = .02), but declined for Ease of Use (82.6 ± 15.3 vs 67.8 ± 27.6, P < .0001). For all global satisfaction domains, the percentage of patients satisfied or very satisfied increased from baseline to the end of treatment (Overall Satisfaction 36.3% vs 64.0%, Satisfaction with Medication Effectiveness 40.1% vs 68.2%, Satisfaction with Side Effects 48.6% vs 67.3%). The percentage of patients who were confident or very confident in treating repeated migraine attacks also increased (baseline: 41.0%, 90% confidence interval [CI] 35.4, 46.9 vs end of treatment: 66.5%, 90% CI 58.9, 70.1). The efficacy results (pain relief, pain‐free response, sustained 24‐hour pain relief and pain‐free response) were consistent with those previously observed with needle‐based sumatriptan. Conclusion.— Patients currently treated with triptans and less than very satisfied with their acute migraine therapy experienced a statistically significant and clinically relevant increase in satisfaction with therapy and enhanced confidence in treatment after use of Sumavel DosePro for up to 4 migraine attacks.     

Risk factors for headache recurrence after sumatriptan: a study in 366 migraine patients

Headache recurrence (HR) is the major limitation of sumatriptan in the acute treatment of migraine attacks. The risk of HR is mainly patient dependent. We analyzed, in 366 migraine patients, clinical differences between patients who always have HR and patients who never have HR. We found remarkably few differences. HR more frequently occurred in patients with more severe attacks and longer untreated attack duration; in patients who experienced a sensation of a subclinically ongoing attack, despite headache relief after sumatriptan; and in females, mainly with menstruation-related migraine, most probably due to the more severe and longer lasting attacks these patients suffer, rather than due to hormonal factors. The incidence of HR was, among other factors, not related to the (other) clinical effects of sumatriptan, the timing of administration within the attack, the duration of use of sumatriptan, pharmacokinetic factors, or whether patients were experiencing HR after use of ergot alkaloids.     

Long-term tolerability of sumatriptan nasal spray in adolescent patients with migraine

OBJECTIVE: This 1-year, open-label, multicenter study was designed to assess the long-term tolerability and efficacy of sumatriptan nasal spray 20 mg in adolescent patients with migraine. METHODS: A prospective, multicenter, open-label study was conducted in patients aged 12 to 17 years who were allowed to treat an unlimited number of migraines at severe, moderate, or mild pain intensity with sumatriptan nasal spray for up to 1 year. All patients started the study at the 20-mg dose of sumatriptan nasal spray. Dose could be adjusted downward to 5 mg at the discretion of the investigator to optimize therapy. RESULTS: A total of 484 adolescent migraineurs treated 4676 migraines with sumatriptan nasal spray 20 mg (3593 during the first 6 months and 1083 during the second 6 months). A total of 3940 migraines and 699 migraines were treated with one and two 20-mg doses of sumatriptan nasal spray, respectively. Only 10 patients (treating 42 migraines) took the 5-mg dose of sumatriptan nasal spray. The overall percentage of migraines treated with either one 20-mg dose or one, two, or three 20-mg doses with at least 1 drug-related adverse event was 19%. The most common specific drug-related adverse event was unpleasant taste, reported in 17% of migraines. No other single drug-related adverse event was reported in more than 1% of migraines over the 1-year treatment period. When unpleasant taste was excluded from the adverse-event tabulations, the percentages of migraines with at least 1 drug-related adverse event after one or one, two, or three 20-mg doses declined to 4% and 3%, respectively. No patient experienced any drug-related changes in 12-lead ECGs, vital signs, or nasal assessments; and no clinically meaningful changes in clinical laboratory values were observed. Across all migraines with evaluable efficacy data (n=4334), headache relief was reported in 43% of migraines at 1 hour and in 59% at 2 hours after dosing with sumatriptan nasal spray 20 mg. Of the 2561 migraines with headache relief 2 hours postdose, headache recurrence was reported within 24 hours of initial dosing in 7% of migraines. None of the efficacy or tolerability results varied as a function of time in the study (ie, first 6 months vs. second 6 months). CONCLUSION: Sumatriptan nasal spray 20 mg is generally well tolerated and may be beneficial during long-term use by adolescent migraineurs ages 12 to 17 years.