Headache Response Research Articles

Early Responses in Randomized Clinical Trials of Triptans in Acute Migraine Treatment. Are They Clinically Relevant? A Comment

One can question the clinical relevance of early headache responses after oral and intranasal triptans. Thus, for pain-free the early responses were significant but in absolute values they were only a few percentages: the therapeutic gains (TGs) were 1.8% (95% CI = 0.3-3%) for oral almotriptan 12.5 after 30 minutes and 1.0% (95% CI = 0-2%) after intranasal zolmitriptan 5 mg after 15 minutes. These results are compared with subcutaneous sumatriptan 6 mg which has TGs of 11% (95% CI = 7-15%) to 14% (95% CI = 11-17%) for pain-free after 30 minutes. Subcutaneous sumatriptan has a 2 times higher response rate than intranasal zolmitriptan and is 5 times more effective than oral almotriptan at these early time points. It is concluded that if a very early and clinically relevant effect is desired then the migraine patient should use the subcutaneous administration form of sumatriptan.

Predictors of Migraine Headache Recurrence: A Pooled Analysis From the Eletriptan Database

To identify clinical variables associated with risk of headache recurrence within 22 hours of initial successful treatment of a migraine attack (2-hour headache response), and to analyze the effect of eletriptan in reducing the incidence of recurrence. Data were pooled from 10 randomized, double-blind, placebo-controlled trials evaluating eletriptan 40 mg (E40), eletriptan 80 mg (E80), and sumatriptan 100 mg (S100) for acute migraine treatment. Patients who achieved a headache response (improvement from moderate/severe pain at baseline to mild/no pain at 2 hours postdose) were evaluable. A multivariable logistic regression analysis identified significant predictors of headache recurrence (return to moderate/severe pain intensity within 22 hours of initial headache response). Treatment response was assessed in two high-risk subgroups, defined by the presence of significant recurrence predictors. Of 4312 patients responding to acute treatment within 2 hours postdose, 1232 (29%) experienced recurrence. Initial headache response within 2 hours was significantly higher for E40 (62.0%), E80 (67.4%), and S100 (57.9%) compared to placebo (25.1%; all P < .0001). Three clinical variables were significant predictors of recurrence: female gender, age > or = 35 years, and severe baseline headache pain. Among patients with all 3 risk factors (n = 742; 17% of total population), recurrence rates were lower with E40 (35.6%) and E80 (32.9%) than placebo (47.8% P < .01). The same result was observed in the subgroup of patients with 2 risk factors (female gender and age > or = 35 years; P < .0001 vs placebo). Sustained headache and pain-free response rates (a headache/pain-free response at 2 hours postdose with no headache recurrence and no rescue medication use in the subsequent 22 hours) were significantly higher with E40 and E80 than placebo in both high-risk subgroups (P < .05). Female gender, age > or = 35 years, and severe baseline headache pain are significant predictors of headache recurrence during a migraine attack. Eletriptan is effective at reducing the incidence of headache recurrence in high-risk subgroups.

Zolmitriptan nasal spray in the acute treatment of cluster headache

To evaluate the efficacy and tolerability of zolmitriptan 5 mg and 10 mg nasal spray (ZNS) vs placebo in the acute treatment of cluster headache. Design/ We conducted a multicenter, double-blind, randomized, three-period crossover study using ZNS 5 mg, ZNS 10 mg, and placebo. Headache intensity was rated by a 5-point scale: none, mild, moderate, severe, or very severe. The primary efficacy measure was headache response (pain reduced from moderate, severe, or very severe at baseline, to mild or none) at 30 minutes. Logistic regression was used to account for treatment period effect as well as for cluster headache subtype effect. A total of 52 adult patients treated 151 attacks. For the primary endpoint, both doses reached significance at 30 minutes (placebo = 30%, ZNS 5 mg = 50%, ZNS 10 mg = 63.3%). For headache relief, ZNS 10 mg separated from placebo at 10 minutes (24.5% vs 10%). Zolmitriptan 5 mg separated from placebo at 20 minutes (38.5% vs 20%). For pain-free status, ZNS 10 mg was superior to placebo at 15 minutes (22.0% vs 6%). Both doses had higher pain-free rates than placebo at 30 minutes (placebo = 20%, ZNS 5 mg = 38.5%, ZNS 10 mg = 46.9%). Side effects were mild and seen in 16% of those attacks treated with placebo, 25% of attacks treated with ZNS 5 mg, and 32.7% treated with ZNS 10 mg. Zolmitriptan nasal spray, at doses of 5 and 10 mg, is effective and tolerable for the acute treatment of cluster headache.

Patient satisfaction with eletriptan in the acute treatment of migraine in primary care

SummaryObjective:The efficxacy of triptans for acute migraine has been well established in clinical trials but not in primary care, where they are most commonly prescribed. The aim of this open-label study was to evaluate the effectiveness of eletriptan 40 mg in primary care, using a patient-weighted satisfaction scale.Methods:Eligible patients met International Headache Society criteria for migraine, with 1–6 attacks per month. Patients completed questionnaires at screening and following a single eletriptan-treated attack. Treatment satisfaction was evaluated using a six-item Medication Satisfaction Questionnaire (MSQ). MSQ item scores were weighted, based on the important score ratings, to yield individualised satisfaction scores. The primary end-point was the difference in weighted satisfaction scores between the patient's previous treatment and eletriptan 40 mg. Secondary end-points assessed quality of life (QOL), functioning and efficacy of treatment.Results:Of 590 patients screened, 437 completed the study. Degree (95.2%), time (88.8%) and duration (83.8%) of headache pain relief were rated as most important by patients. The mean (±SD) total satisfaction score on the MSQ was higher for eletriptan than previous therapy (2.2 ± 3.0 vs. 0.6 ± 2.4; p < 0.001). The high level of satisfaction with eletriptan vs. previous treatment reflects the improvements in QOL and functioning observed, and the high headache and pain-free response rates.Conclusions:Patient-weighted satisfaction with eletriptan 40 mg was higher than with previous treatment for all items. The use of patient-weighted importance ratings of satisfaction is a promising approach for establishing effectiveness of treatment in primary care.

Efficacy of Zolmitriptan Nasal Spray in Adolescent Migraine

The goal was to evaluate the efficacy and tolerability of zolmitriptan nasal spray in the treatment of adolescent migraine. The "Double-Diamond" study used a novel, single-blind, "placebo challenge" in a multicenter, randomized, double-blind, placebo-controlled, 2-way, 2-attack, crossover design. A total of 248 US adolescent patients (12-17 years of age) with an established diagnosis of migraine, with or without aura, were enrolled. A single-blind placebo challenge was used for each migraine attack. No additional medications were taken if a headache response to the initial placebo treatment was achieved at 15 minutes; if migraine intensity remained moderate or severe, then patients treated the attack with zolmitriptan (5 mg) nasal spray or placebo according to a randomized, crossover schedule (double-blind). The primary efficacy variable was headache response at 1 hour after treatment. A comprehensive range of secondary end points included sustained headache response at 2 hours. A total of 171 patients (mean age: 14.2 years; 57.3% female) treated > or = 1 attack with study medication (intention-to-treat population). The onset of significant pain relief was apparent 15 minutes after treatment with zolmitriptan nasal spray. At 1 hour after the dose, zolmitriptan nasal spray produced a higher headache response rate than did placebo (58.1% vs 43.3%). Zolmitriptan nasal spray was also significantly superior to placebo in improvement in pain intensity, pain-free rates, sustained resolution of headache, and resolution of associated migraine symptoms. Return to normal activities was also consistently faster with zolmitriptan nasal spray than with placebo, with less use of any escape medication. Treatment with zolmitriptan nasal spray was well tolerated. This novel, placebo-challenge study demonstrated that zolmitriptan nasal spray was well tolerated and provided fast and significantly effective relief of migraine symptoms in the acute treatment of adolescent migraine.

Eletriptan for the Acute Treatment of Migraine in Adolescents: Results of a Double‐Blind, Placebo‐Controlled Trial

Eletriptan is a potent 5-HT(1B/1D) agonist with proven efficacy in the acute treatment of migraine in adults. To evaluate the efficacy and tolerability of eletriptan 40 mg versus placebo in adolescent patients (aged 12-17). A multicenter, double-blind, parallel-group, placebo-controlled trial was conducted comparing 40 mg of oral eletriptan with placebo for the treatment of migraine in adolescent patients. The primary efficacy endpoint was 2-hour headache response, and a number of secondary endpoints were also evaluated. An exploratory analysis evaluated which clinical and demographic characteristics might be correlated with high placebo response. Of 274 patients who treated a migraine attack, 267 were evaluated for efficacy (n = 138 eletriptan; n = 129 placebo) at 2 hours post-dose. There was no significant difference in 2-hour headache response for eletriptan 40 mg versus placebo (57% vs 57%), and no significant improvements were observed for any of the outcomes at 1 or 2 hours post-dose. By contrast, there was a significant advantage for eletriptan 40 mg in reducing headache recurrence within 24 hours post-dose (11% vs 25%, P= .028), and post hoc analyses showed statistically significant differences for sustained headache response rates (52% vs 39%; P= .04) and sustained pain-free response rates (22% vs 10%; P= .013). The strongest clinical predictor of placebo response was triptan-naïve status (i.e., no previous use of any triptan). Eletriptan 40 mg was well tolerated in this population, and the profile of adverse events was similar to that observed in Phase III trials in adult patients. The high placebo response rates reported here for 1- and 2-hour outcomes are in accordance with other studies of triptans in adolescent patients. The evaluation of treatment effect in adolescent migraine might benefit from use of more stringent outcome measures, such as headache recurrence, sustained headache response, and sustained pain-free response at 24 hours post-dose.

Analysis of responses in migraine modelling using hidden Markov models

Markov-type models have been used in the analysis of disease progression. Although standard errors of model parameters are usually estimated, available software often does not permit the construction of confidence intervals around predictions of the dependent or response variable. A method is presented to calculate means and confidence intervals of model-predicted responses in time governed by a non-homogeneous hidden Markov model in continuous time. The Kolmogorov equations serve as the basis for the calculations. The method is realised in S-Plus and is applied to the prediction of headache responses in clinical studies of anti-migraine treatment. Means and confidence intervals are calculated by numerically solving differential equations that are non-linear in the explanatory variable. Results indicate that uncertainty on predicted drug responses is larger than that on predicted placebo responses and that pain-free responses are less precisely predicted than pain-relief responses. This is due to the uncertainty in the drug-specific parameters which is not present in predicted placebo responses.

Efficacy of Eletriptan in Triptan‐Naïve Patients: Results of a Combined Analysis

To compare the efficacy and tolerability of eletriptan 20 mg, 40 mg, and 80 mg in triptan-naïve patients (who have not previously used triptans) versus triptan-experienced patients (who have previously used triptans). Efficacy and tolerability data for eletriptan 20 mg, 40 mg, and 80 mg were pooled from 10 similarly designed, randomized, parallel-group studies, and triptan-naïve and triptan-experienced patients were compared with placebo across the 3 triptan doses. The primary efficacy endpoint was headache response at 2 hours postdose. Secondary efficacy endpoints were 2-hour pain-free response, 2-hour absence of associated symptoms, 2-hour functional response, 24-hour sustained headache response, and 24-hour sustained pain-free response. For eletriptan 20 mg, 40 mg, and 80 mg versus placebo, respectively, triptan-naïve patients showed significantly higher 2-hour headache response (54%, 61%, 66% vs. 31%; P < .0001), 2-hour pain-free response (20%, 28%, and 31% vs. 8%; P < .0001), and 24-hour sustained headache response (34%, 45%, and 51% vs. 20%; P < .0001). A similarly significant efficacy advantage was also observed in the triptan-experienced subgroup for 2-hour headache response (46%, 63%, 69% vs. 21%; P < .0001), 2-hour pain-free response (13%, 32%, and 38% vs. 4%; P < .0001), and 24-hour sustained headache response (29%, 41%, and 45% vs. 9%; P < .0001). Previous treatment status did not influence tolerability, and all 3 doses of eletriptan were well tolerated. These data suggest that eletriptan has comparable efficacy versus placebo among both triptan-naïve and triptan-experienced patients.

Diagnosis of menstrual headache and an open-label study among those with previously undiagnosed menstrually related migraine to evaluate the efficacy of sumatriptan 100 mg

Background: Headache associated with menses is often not formally diagnosed. Objectives: The goal of this study was to evaluate patients with menstrual headache who had never previously been diagnosed with migraine and assign 1988 International Headache Society (IHS) diagnoses to their menstrual headaches. Secondary objectives included evaluation of the treatment efficacy of newly diagnosed menstrually related migraine (MRM) with sumatriptan 100 mg and patient satisfaction with sumatriptan versus satisfaction with previous therapy. Methods: Patients were recruited via advertisement in a local daily newspaper, and headache diagnosis and eligibility criteria of respondents were assessed by telephone. During telephone screening, IHS criteria for headache were applied to symptoms described by patients as menstrual headache. Those with previously undiagnosed headaches who fulfilled criteria for migraine without or with aura (IHS 1.1 or 1.2) and all inclusion/exclusion criteria at visit 1 were provided with sumatriptan 100 mg to treat 1 MRM. Patients were instructed to treat their next MRM as early as possible after the onset of headache. A treatment diary was provided with study medication for documentation of headache pain severity and associated symptoms; time of treatment and response at 30, 60, and 90 minutes and at 2, 4, 24, and 48 hours posttreatment; medication for persistence or recurrence; adverse effects; and onset of menstrual cycle. In analysis, headache response was defined as a reduction in pretreatment head pain from moderate or severe to mild or no pain. Results: A total of 153 patients responded to an advertisement seeking menstrual headache sufferers. After the preliminary screening by telephone, 105 patients were assigned IHS diagnoses based on reported symptoms associated with their menstrual headache. Overall, 63% (66/105) fulfilled criteria for IHS 1.1 (migraine without aura), 12% (13/105) met criteria for IHS 1.2 (migraine with aura), and 5% (5/105) met criteria for IHS 1.7 (migrainous disorder). Of the 79 patients meeting the criteria for IHS 1.1 or 1.2, 45 patients were enrolled. Thirty-nine (mean age, 34.8 years; mean duration of experiencing menstrual headaches, 11.1 years) of the 45 patients treated 1 MRM with sumatriptan 100 mg per protocol (6 patients were lost to follow-up or withdrew consent). Headache response was reported by 70% of patients at 2 hours and 86% at 4 hours. The pain-flee response after treatment at the moderate or severe phase occurred in 41% of patients at 2 hours and in 61% at 4 hours. All 39 patients reported previous use of nonsteroidal anti-inflammatory medications for acute treatment of headache; in addition, 1 of the 39 also took acetylsalicylic acid/caffeine/butalbital, 1 took acetaminophen/caffeine/butalbital, 1 took ketorolac, and 1 took acetaminophen plus codeine. In terms of patient satisfaction, 69% of patients were satisfied with sumatriptan versus 15% of patients who were satisfied with their previous therapy. Conclusions: Seventy-five percent of women with previously undiagnosed menstrual headaches met diagnostic criteria for migraine in this small sample. Two hours after treatment with sumatriptan 100 rag, 70% of patients with headaches treated at moderate to severe pain had a pain relief response (reduction to mild or no pain).

Efficacy of sumatriptan tablets in migraineurs self-described or physician-diagnosed as having sinus headache: A randomized, double-blind, placebo-controlled study

Background: Many patients and physicians interpret episodic headache in the presence or absence of nasal symptoms as “sinus’ headache, while ignoring the possible diagnosis of migraine. Objective: The purpose of this study was to assess the efficacy and tolerability of sumatriptan succinate 50-mg tablets in patients with migraine presenting with “sinus” headache. Methods: A randomized, double-blind, placebo-controlled, multicenter study was conducted in adult (aged 18–65 years) migraine patients presenting with self-described or physician-diagnosed “sinus” headache. From November 2001 to March 2002, patients meeting International Headache Society criteria for migraine (with ≥2 of the following: unilateral location, pulsating quality, moderate or severe intensity, aggravation by moderate physical activity; and ≥1 of: phonophobia and phonophobia, nausea and/or vomiting) and with no evidence of bacterial rhinosinusitis were enrolled and randomized in a 1:1 ratio via computer-generated randomization schedule to receive either 1 sumatriptan 50-mg tablet or matching placebo tablet. The primary efficacy end point was headache response (moderate or severe headache pain reduced to mild or no headache pain) at 2 hours after administration. The presence or absence of migraine-associated symptoms and sinus and nasal symptoms was also measured. Tolerability was assessed through patient-reported adverse events (AEs). Results: Two hundred sixteen patients with self-described or physician-diagnosed “sinus” headache received a migraine diagnosis and treated 1 migraine attack with sumatriptan 50 mg. The efficacy (intentto-treat) analysis included 215 patients treated with sumatriptan 50 mg (n = 108; mean [SD] age, 39.6 [12.3] years; mean [SD] weight, 77.7 [17.7] kg; sex, 71% female; race, 69% white) or placebo (n = 107; mean [SD] age, 41.0 [11.3] years; mean [SD] weight 80.7 [20.9] kg; sex, 69% female; race, 64% white). Significantly more patients treated with sumatriptan 50 mg achieved a positive headache response at 2 and 4 hours after administration compared with those treated with placebo (69% vs 43% at 2 hours and 76% vs 49% at 4 hours, respectively; both, P < 0.001). Significantly more sumatriptan-treated patients were free from sinus pain compared with placebo recipients at 2 hours (63% vs 49% placebo, P = 0.049) and 4 hours (77% vs 55%, P = 0.001). All treatments were generally well tolerated. The most common drug-related AEs reported in the sumatriptan and placebo groups, respectively, were dizziness (5% vs < 1%), nausea (3% vs 2%), other pressure/tightness (defined as sense of heaviness; heaviness of upper body, upper extremities; jaw tension; neck tension) (4% vs 0%), and temperature sensations (defined as warm feeling of back of neck, or flushing) (2% vs 0%). No patients experienced any serious AEs. Conclusions: Sumatriptan 50-mg tablets were effective and generally well tolerated in the treatment of these patients presenting with migraine headaches that were self-described or physician-diagnosed as sinus headaches.

Comparative sensitivity of stopwatch methodology and conventional pain assessment measures for detecting early response to triptans in migraine: Results of a randomized, open-label pilot study

Background:The standard measure of efficacy used in migraine trials is a 4-point patient-rated headache pain intensity (HPI) scale. However, it has been suggested that using a stopwatch to measure the time to meaningful pain relief can provide a more precise measurement of treatment response. Objective:This study evaluated the sensitivity of a stopwatch method for detecting meaningful relief of headache pain and the correlation of this method with the HPI scale and a 5-point pain relief scale. Methods:In this open-label, parallel-group pilot study, patients were randomized to receive oral eletriptan 40 mg, eletriptan 80 mg, or rizatriptan 10 mg for the treatment of a single acute migraine attack. The effect of study treatment on migraine pain was assessed immediately before dosing and at 0.5, 1, 1.5, 2, 3, and 4 hours after dosing. At each time point, patients recorded the 3 types of pain assessment in a patient diary. HPI was rated using the standard 4-point International Headache Society pain intensity scale (from 0 = no pain to 3 = severe pain). Pain relief was rated on a 5-point pain relief scale (from 4 = no relief to 0 = complete relief). The time to the onset of meaningful pain relief was measured using a stopwatch. At 4 hours after dosing, patients provided a global rating of the overall efficacy of study medication on a 5-point scale (from 0 = poor to 4 = excellent). Results:Seventy-nine patients participated in the trial (78.5% female; mean [SD] age, 37.7 [9.8] years; 58.2% white). The median times to meaningful pain relief measured by stopwatch were 84, 72, and 93 minutes for eletriptan 40 mg, eletriptan 80 mg, and rizatriptan 10 mg, respectively (log-rank P = 0.029, eletriptan 80 mg vs rizatriptan 10 mg). At 90 minutes (approximating the median time to meaningful pain relief on the stopwatch), headache response rates using HPI scoring (mild to no pain) were 65%, 68%, and 52% in the respective treatment groups, with no significant difference between groups. On the pain relief scale, the corresponding mean (SD) scores at 90 minutes were 1.6 (1.2), 1.4 (1.3), and 2.0 (1.4) (P = NS). The pain relief-defined response (≥ 75% pain relief) at 90 minutes did not differ significantly between the 3 treatment groups (62%, 56%, and 48%). Detection of early improvement (0.5 and 1 hour) was similar with the HPI and pain relief scales. Conclusion:The results of this open-label pilot study suggest the convergent validity of 3 pain-assessment methods in migraine, but indicate that the use of a stopwatch may be a more sensitive method for detecting between-group differences.

Eletriptan in Migraine Patients Reporting Unsatisfactory Response to Rizatriptan

The objective of this open-label study was to evaluate the efficacy of switching patients who had a previous unsatisfactory response to rizatriptan to eletriptan 40 mg. Background.-The characteristics of individual migraine patients can vary tremendously and can have a significant impact on treatment outcomes. In addition, clinical experience has demonstrated that the triptans are not identical or interchangeable and that patients who respond poorly or who are dissatisfied with one agent can derive benefit by being switched to another agent within the triptan class. Patients were eligible if they met International Headache Society criteria for migraine, with a frequency of 1 to 6 migraine attacks per month, and had documented "unsatisfactory treatment response" to rizatriptan within the past year (54% on the melt formulation; 46% on tablets). Reasons for dissatisfaction with rizatriptan (>1 could be cited) included inadequate (84%) or slow onset (50%) of pain relief, high recurrence rate (69%), and lack of improvement in associated symptoms (60%). One hundred twenty-three patients were eligible for treatment. Patients were instructed to take eletriptan 40 mg as soon as they were certain that their headache was a migraine, regardless of level of pain severity (8% treated headaches that were mild). Headache response at 2 hours (first-attack data) was 64%. Absence of nausea (from baseline to 2 hours) increased from 50% to 78%, absence of photophobia from 30% to 72%, and absence of phonophobia from 39% to 77%. Functional response at 2 hours was 63%, with 41% of patients reporting normal functioning. Treatment with eletriptan 40 mg was associated with a 27% to 40% reduction in migraine attack-related functional impairment, as measured by the PQ-7. Recurrence rates were 36.6%. Overall, 72% of patients rated eletriptan as a "good-to-excellent" treatment, and 78% reported overall satisfaction with the degree of headache relief. The results of this study suggest that eletriptan is an efficacious treatment option for patients who are dissatisfied with their response to rizatriptan.

Response of cluster headache to psilocybin and LSD

The authors interviewed 53 cluster headache patients who had used psilocybin or lysergic acid diethylamide (LSD) to treat their condition. Twenty-two of 26 psilocybin users reported that psilocybin aborted attacks; 25 of 48 psilocybin users and 7 of 8 LSD users reported cluster period termination; 18 of 19 psilocybin users and 4 of 5 LSD users reported remission period extension. Research on the effects of psilocybin and LSD on cluster headache may be warranted.

The effect of epidural needle type on postdural puncture headache: a randomized trial

A prospective, randomized trial in labouring parturients was undertaken to assess whether the 18G Special Sprotte epidural needle is associated with a lower incidence of accidental dural puncture (ADP) in comparison with the 17G Tuohy needle. A secondary purpose was to determine if the incidence of postdural puncture headache (PDPH ) differed between groups when ADP occurred. Following Institutional Review Board approval 1,077 parturients requesting epidural analgesia at three tertiary obstetrical units were randomized to epidural catheter insertion with a 17G Tuohy or 18G Special Sprotte needle. Patients were followed for seven days by a blinded assessor to determine the occurrence of PDPH using standardized criteria. If postural headache or neck ache presented, an ADP was diagnosed even if cerebrospinal fluid (CSF) was not observed at insertion. This subgroup was followed daily to assess headache characteristics and response to blood patch. Six Tuohy group patients, and two patients in the Sprotte group were excluded. One of the six excluded in the Tuohy group had an ADP. Twenty-eight ADPs occurred, nine unrecognized by CSF visualization (1.8% Tuohy, 3.4% Sprotte, P = 0.12). The incidence of unrecognized ADPs was higher in the Sprotte group (40% Sprotte vs 20% Tuohy, P < 0.05). If ADP occurred, the incidence of PDPH was lower in the Sprotte group (100% Tuohy vs 55% Sprotte, P = 0.025). The ease of use, and user satisfaction were higher in the Tuohy group (84 +/- 17.3% Tuohy vs 68.2 +/- 25.3% Sprotte, P < 0.001). The incidence of ADP was not reduced with the Special Sprotte epidural needle in comparison with the Tuohy needle, but PDPH after ADP occurred less frequently in the Sprotte group.

Efficacy and Tolerability of Diclofenac Potassium Sachets in Migraine

A randomized, controlled, cross-over trial compared single doses of 50 mg diclofenac potassium sachets and tablets with placebo in 328 patients with migraine pain, treating 888 attacks. For the primary endpoint 24.7% of the patients were pain free at 2 h postdose with sachets, 18.5% for tablets and 11.7% for placebo. Treatment differences were significant for sachets vs. placebo (P<0.0001), tablets vs. placebo (P=0.0040) and for sachets vs. tablets (P=0.0035). The numbers needed to treat compared with placebo to achieve pain free at 2 h were 7.75 [95% confidence interval (CI) 5.46, 13.35] for sachets and 15.83 (95% CI 8.63, 96.20) for tablets. Sachets were also statistically superior to tablets for sustained headache response, sustained pain free and reduction in headache intensity within the first 2 h postdose measured on a visual analogue scale (P<0.05). Onset of analgesic effect was 15 min for sachets and 60 min for tablets. Fewer patients needed rescue medication, and there were marked improvements in accompanying symptoms and working ability with both sachets and tablets vs. placebo. No safety issues were identified. This study demonstrates that sachets offer patients suffering from migraine pain a more effective treatment with a faster onset of analgesia when compared with tablets.

Does Earlier Headache Response Equate to Earlier Return to Functioning in Patients Suffering from Migraine?

This study explored the association between headache response and return to functioning, and identified migraine-associated symptoms related to functional status and acceptability of migraine treatment as reported by patients. Data from migraineurs enrolled in the active arms of a randomized, double-blind, parallel group, placebo-controlled, clinical trial were analysed. The relationships between headache response and functional response, and clinical factors and treatment acceptability were assessed using chi(2) tests of proportions and logistic regressions. A greater proportion of patients with headache response at 0.5 h were functioning at 0.5, 1 and 2 h compared with patients who did not attain a headache response at 0.5 h (P < 0.0001). These patients also were more likely to find their treatment acceptable (P < 0.05). The results suggest a direct temporal relationship among the key determinants of migraine resolution. Rapid headache response is associated with faster return to functioning; rapid headache and functional responses are significant attributes of treatment acceptability.

Headache Improvement Through TMD Stabilization Appliance and Self-management Therapies

The purpose of this study was to assess headache response of unselected neurology clinic chronic headache patients to TMD stabilization appliance and self-management therapies, and to identify features of patients whose headaches are more likely to improve from these therapies. Twenty chronic headache patients in a nontreatment control period were provided appliance and self-management therapies, evaluated five weeks after therapy, and those who chose to continue using their appliances were evaluated three months later. The mean pretreatment Headache Disability Inventory (HDI) score of 64.5 suggested the headaches were severe. After five weeks, the mean HDI score decreased by 17 percent (p<0.003), headache medication consumption dropped by 18 percent (p<0.0001), and headache symptoms decreased by 19 percent (p<0.002). Comparing the three months with pretreatment follow-up, the fourteen participants who chose to continue using their appliances had a mean HDI score decrease of 23 percent (p<0.003), headache medication consumption drop of 46 percent (p<0.001), and headache symptom decrease of 39 percent (p<0.001). There was no correlation between response and headache type (p=0.722). These results suggest appliance and self-management therapies can be beneficial for many severe headache patients, irrespective of the headache type (tension-type, migraine without aura, and migraine with aura).

Prediction of Headache Response in Migraine Treatment

Triptans are efficacious for the acute treatment of migraine attacks. Yet, defining a concentration-effect relation for these compounds is difficult as the dynamics of the migraine attack are not thoroughly understood. The objective of this investigation was to develop a disease model to predict measures of headache in randomized placebo-controlled clinical trials investigating oral sumatriptan as a paradigm compound. A hidden Markov model based on the states of response (no relief, relief, and pain free) and headache scores (observed variable) was used in conjunction with population pharmacokinetics. Model parameters were capable of predicting the course of headache relief, pain-free status and headache recurrence. It was shown that sumatriptan shortens mean transit times between states by up to 5 h. The potency of sumatriptan (EC(50)) was 9 ng/ml. These findings demonstrate the value of combining pharmacokinetic and efficacy information to model disease and characterize time-independent drug properties in a population of migraineurs.

Acetaminophen, Aspirin, and Caffeine in Combination Versus Ibuprofen for Acute Migraine: Results From a Multicenter, Double‐Blind, Randomized, Parallel‐Group, Single‐Dose, Placebo‐Controlled Study

Compare the effectiveness of a combination analgesic containing acetaminophen, aspirin, and caffeine to that of ibuprofen in the treatment of migraine. Multicenter, double-blind, randomized, parallel-group, placebo-controlled, single-dose study. A total of 1555 migraineurs were included in the analysis. No patients were excluded solely because of severity of symptoms or degree of disability. A single 2-tablet dose for each of the 3 treatment groups: a combination product containing acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg per tablet (AAC); ibuprofen 200 mg per tablet (IB); or matching placebo. The primary efficacy endpoint was the weighted sum of pain relief (PAR) scores at 2 hours postdose (TOTPAR2) and an important secondary endpoint was the time to onset of meaningful relief. There were 669 patients in the AAC group, 666 patients in the IB group, and 220 patients in the placebo group. The 3 treatment groups had similar demographic profiles, migraine histories, and baseline symptom profiles. While both active treatments were significantly better than placebo in relieving the pain and associated symptoms of migraine, AAC was superior to IB for TOTPAR2, as well as for PAR, time to onset of meaningful PAR, pain intensity reduction, headache response, and pain free. The mean TOTPAR2 scores for AAC, IB, and placebo were 2.7, 2.4, and 2.0, respectively (AAC vs. IB, P < .03). The median time to meaningful PAR for AAC was 20 minutes earlier than that of IB (P < .036). AAC and IB are safe, cost-effective treatments for migraine; AAC provides significantly superior efficacy and speed of onset compared with IB.

Bias from industry trial funding? A framework, a suggested approach, and a negative result

Bias from funding sources of trials would threaten their validity. Meta-analyses of high quality acute pain and migraine trials were used to explore the hypothesis that industry funding of clinical trials produced more favourable results than non-profit sponsorship. Analyses were planned to evaluate whether industry-sponsored trials had different results from trials funded by academic or other non-profit sources, but of 176 trials, only two were supported by non-profit sources, while 31 provided no statement of support. An alternative method is proposed within industry-sponsored trials, looking at conflicting industry interests for the same drug, used either as test or comparator treatment. Fifty-three trials used an analgesic as test and 90 as comparator, allowing comparisons to be made for aspirin 600/650 mg, ibuprofen 400 mg, paracetamol (acetaminophen) 1000 mg, rofecoxib 50 mg and sumatriptan 50 and 100 mg. Only for sumatriptan 50 and 100 mg, with the outcome of headache response at 2 h, was there any significant difference between the drug used as a test or as a comparator. The direction was for higher (worse) NNTs with sumatriptan as comparator. Investigating potential industry bias through the funding source of trials is unlikely to be adequate because of a dearth of trials funded by non-profit organisations. We propose a method based on potential conflict of interest within industry-sponsored trials. Using this method, established clinical trial results in acute pain and migraine appear to be unbiased.