Diclofenac sodium in ureteral colic: a double-blind comparison trial with placebo

A randomized prospective double blind study of the analgesic effect of 75 mg intramuscular diclofenac sodium (Voltaren), a potent prostaglandin synthetase inhibitor, versus placebo (saline solution) was carried out in 131 consecutive patients with acute ureteral colic. Diclofenac provided complete relief of pain 25 minutes after the injection in 59% of the cases, while placebo provided relief in 29% (p less than 0.01). Forty patients in the placebo group and seventeen patients in the diclofenac group needed an open injection of 75 mg diclofenac intramuscularly after 25 minutes due to persistent pain. Fifty-four of the fifty-seven patients treated with an open injection of diclofenac achieved complete relief of pain after 30 minutes. There were no side-effects of the treatment.     

Ketoprofen Versus Paracetamol in the Treatment of Acute Migraine

The efficacy and safety of ketoprofen and paracetamol were compared for the treatment of acute migraine in a randomized, double-blind study of 64 patients. Thirty-four patients received ketoprofen 100 mg intramuscularly, and 30 patients received paracetamol 500 mg intramuscularly. Partial or complete relief of pain and other symptoms was achieved 15 to 20 minutes after administration in the ketoprofen group and within 35 minutes in the paracetamol group. Complete relief of pain was achieved within 30 to 40 minutes after ketoprofen in 28 patients (82.5%) compared to 5 patients (17.5%) in the paracetamol group. Six of the patients treated with ketoprofen needed a second dose for complete relief of pain during the 4-hour follow-up period. Side effects were rare and minimal. Our findings suggest that ketoprofen produced statistically significant benefit in the treatment of acute migraine.     

Efficacy of diclofenac sodium softgel 100 mg with or without caffeine 100 mg in migraine without aura: a randomized, double-blind, crossover study

OBJECTIVE: A phase II, randomized, double-blind, crossover study was designed to evaluate the efficacy of 100-mg diclofenac sodium softgel (formulated using ProSorb technology) with or without 100-mg caffeine versus placebo in migraineurs during migraine attacks. BACKGROUND: Diclofenac has been demonstrated to be an effective migraine treatment in several placebo-controlled studies. A rapidly absorbed softgel of diclofenac has been shown to be effective in the rapid relief of acute pain, and may have advantages in migraine treatment. In addition, caffeine has consistently been shown to increase both the efficacy and speed of onset of concurrently administered analgesics. The ability of caffeine to both enhance and accelerate analgesic effects has been documented with a variety of different medications (ie, aspirin, acetaminophen, ibuprofen, and ergotamine). METHODS: The 3-period crossover study was designed to compare diclofenac softgel 100 mg, diclofenac softgel 100 mg plus caffeine 100 mg, and placebo in the acute treatment of migraine. Subjects treated one moderate or severe attack with each study medication. The primary efficacy parameter was the percentage of subjects with headache relief at 60 minutes as defined by a reduction of headache severity from moderate or severe at baseline to absent or mild compared with placebo. Though the sample size estimate required that 72 subjects treat 3 separate attacks, 51 subjects treated 1 migraine attack, 44 treated 2 attacks, and 39 treated 3 attacks. Results.-In the placebo group, 6 (14%) of 43 subjects reported headache relief at 60 minutes versus 12 (27%) of 45 subjects in the diclofenac softgel group, and 19 (41%) of 46 subjects in the diclofenac softgel plus caffeine group. Differences were statistically significant for the diclofenac softgel plus caffeine group versus placebo (odds ratio, 4.2; 95% confidence interval, 1.3 to 13.7). Rescue medication was used by 27 (63%) of 43 subjects treated with placebo, 15 (33%) of 45 subjects treated with diclofenac softgel, and 14 (30%) of 46 subjects treated with diclofenac softgel plus caffeine. This result is highly statistically significant (chi22= 11.56, P=.003). Both the diclofenac plus caffeine (P <.03) and diclofenac only (P <.03) groups were significantly different from the placebo group in terms of the visual analog scale score at 60 minutes. CONCLUSIONS: The major finding of the present study is that diclofenac softgel plus caffeine produces statistically significant benefits relative to placebo at 60 minutes. Diclofenac softgel alone did not differ significantly from placebo, perhaps due to limits in sample size. Nonsignificant trends support the analgesic adjuvant benefit of caffeine when added to diclofenac softgels.     

Diclofenac epolamine is effective in the treatment of acute migraine attacks. A randomized, crossover, double blind, placebo-controlled, clinical study

Hydrosoluble diclofenac epolamine (DHEP) represents an interesting approach to acute migraine attacks, where gastrointestinal motility and drug absorption are often reduced. Its efficacy was investigated in a randomized, crossover, double-blind trial on 155 patients who treated four consecutive mild-to-moderate migraine attacks, either with DHEP (65-mg sachet) or placebo. If pain was not relieved within 1 h, a second dose was given. The total number of treated attacks was 481. A pain-free condition was achieved within 2 h in 45.8% and 25.1% of attacks treated, respectively, with DHEP or placebo (P < 0.0001), with a therapeutic gain of 20.7%. Time to attack resolution, light and noise sensitivity and impact on working ability were significantly reduced by DHEP compared with placebo. Moreover, significantly fewer patients required a second drug dose or a rescue medication when treated with DHEP than with placebo. No adverse reaction was recorded. In conclusion, DHEP was effective and safe for pain relief in patients with an acute mild-to-moderate migraine attack.     

Evaluation of the efficacy of intravenous acetaminophen in the treatment of acute migraine attacks: a double-blind, placebo-controlled parallel group multicenter study

The efficacy of intravenous acetaminophen (1000mg) in the treatment of acute migraine attacks as an alternative to parenteral application of lysine acetylsalicylate or triptans was investigated, using a multi-center, randomized, double-blind, placebo controlled study design. Migraine diagnosis was made according to the International Headache Society Classification. Sixty patients were included in three headache outpatient centers (Neurology Departments of the Universities of Regensburg, Münster and München). In the acute migraine attack patients were treated intravenously with either 1000mg paracetamol (acetaminophen) or placebo. The primary end point was pain-free after 2h. Secondary efficacy criteria were pain-free after 24h or pain relief after 2hours and after 24hours. With regard to the efficacy criteria, 37% of patients reported pain relief or painfree after two hours, 12 patients after treatment with acetaminophen and 10 patients after treatment with placebo. Out of these, 3 patients in the acetaminophen and 4 patients in the placebo group were painfree. After 24hours 86% of the patients reported pain relief: 24 treated with acetaminophen and 27 treated with placebo. The results indicate, that 1000mg intravenous acetaminophen is not superior to placebo in treating severe acute migraine attacks.     

Intramuscular tramadol vs. diclofenac sodium for the treatment of acute migraine attacks in emergency department: a prospective, randomised, double–blind study

The aim of this prospective, randomised, double–blind study was to evaluate the efficacy of intramuscular (IM) tramadol 100 mg in emergency department treatment of acute migraine attack and to compare it with that of IM diclofenac sodium 75 mg. Forty patients who were admitted to our emergency department with acute migraine attack according to the International Headache Society criteria were included in the study. Patients were randomised to receive either tramadol 100 mg (n=20) or diclofenac sodium 75 mg (n=20) intramuscularly. Patients rated their pain on a four–point verbal scale (0=none, 1=mild, 2=moderate, 3=severe) at the beginning of the trial and at 30, 60, 90 and 120 min. At each time interval, severity of associated symptoms were also questioned and recorded. Global evaluation of the drugs by patients and doctors were also recorded. Patients were also asked if they would prefer the same injection in future visits. Any adverse events, whether related to the drug or not, were also recorded. Patients were followed up by telephone 48 h later to check for any headache recurrence. Two–hour pain response rate, which was the primary endpoint, was 80% for both tramadol and diclofenac groups. There were no statistically significant differences among groups in terms of 48–h pain response, rescue treatment, associated symptoms’ response, headache recurrence and adverse event rates. Fifteen (75%) patients in the tramadol group and 16 (80%) patients in the diclofenac group stated that they may prefer the same agent for future admissions. In selected patients, tramadol 100 mg IM may be an effective and reliable alternative treatment choice in acute migraine attacks.     

Intravenous valproate sodium (depacon) aborts migraine rapidly: a preliminary report

OBJECTIVE: This study was designed to investigate the efficacy and safety of intravenous valproate in the treatment of acute migraine attacks. BACKGROUND: Numerous studies have shown oral valproate therapy to be effective in preventing migraine. To date, no published studies have explored the use of valproate in the acute treatment of migraine. DESIGN/METHODS: After obtaining written informed consent, 61 patients presenting to a clinic with acute migraine were infused with 300 mg of intravenous valproate sodium. Sixty-six attacks were treated. The time at the beginning of infusion; the time at the end of infusion; the time to onset of relief of headache, nausea, and other associated symptoms; the time to meaningful relief; and the time to complete relief were recorded. Patient's pulse, blood pressure, and respiration were monitored. Adverse events were recorded. RESULTS: Mean time to onset of relief was 8 minutes, mean time to meaningful relief was 16 minutes, and mean time to complete relief was 25 minutes. A reduction in pain from severe or moderate to mild or no pain in 30 minutes was reported in 37 of 66 attacks; in 11 attacks, a reduction of more than 50% in headache severity in 30 minutes was reported. Thus, 48 (73%) of 66 attacks had significant improvement. After treatment with valproate, headache severity was significantly decreased (P<.0001); nausea, disability, and photophobia decreased; and patients became more alert. No serious adverse events were reported. CONCLUSION: Intravenous valproate appears to be safe and effective for the acute treatment of migraine. Double-blind, placebo-controlled studies to further investigate the use of this agent in acute treatment of migraine attacks are warranted.     

Dihydroergotamine for early and late treatment of migraine with cutaneous allodynia: an open-label pilot trial

OBJECTIVE: To explore whether dihydroergotamine (D.H.E. 45) is equally effective and safe for migraine with allodynia, when administered either early or late in an attack. BACKGROUND: Central sensitization may account for the extracranial tenderness and cutaneous allodynia that can occur with migraine. Once allodynia is established, triptans are less effective. Dihydroergotamine is often effective for patients whose refractory headaches have failed prior triptan therapy. METHODS: In this single-center, open-label pilot trial, patients with episodic migraine associated with cutaneous allodynia were treated on 2 occasions with dihydroergotamine 1.0 mg intramuscularly. One attack was treated within 2 hours (early) and a second attack at 4 hours (late) after the onset of throbbing pain. Headache pain and any associated symptoms, subjective cutaneous allodynia, and mechanical (brush) allodynia were assessed. All data were analyzed using the Fisher's exact test. RESULTS: Thirteen patients met the entry criteria; however, data from only 9 patients, those who completed treatment for 2 migraine attacks, were used to evaluate the efficacy and safety of dihydroergotamine. Whether they took dihydroergotamine early or late in the attack, most patients (>55%) had headache relief within 2 hours, and at least 44% of patients achieved headache-free status by 8 hours postdose. Subjective cutaneous allodynia started to decline after 30 minutes postdose in the early treated group and after 120 minutes postdose in the late-treated group. Brush allodynia began to decline after 15 minutes postdose in the early treated group and after 90 minutes postdose in the late-treated group. Six of 9 patients (67%) reported at least 1 adverse event. CONCLUSIONS: The results of this pilot trial provide proof of concept for the headache-relief benefit of dihydroergotamine in patients with migraine headache and allodynia. A large, placebo-controlled trial of dihydroergotamine in allodynic patients is warranted.     

A long-term open-label study of oral almotriptan 12.5 mg for the treatment of acute migraine

OBJECTIVE: Evaluate the long-term tolerability of almotriptan 12.5 mg for the treatment of acute migraine attacks occurring over a 6-month period. BACKGROUND: Almotriptan is a second-generation 5-HT(1B/1D) agonist that exhibits vascular selectivity for meningeal arteries and has demonstrated efficacy for the treatment of acute migraine in short-term controlled trials. METHODS: This was a 6-month open-label study. Adults (18 years of age or older) were required to have a diagnosis of acute migraine with or without aura (according to the diagnostic criteria of the International Headache Society), a history of at least 1 year of moderate-to-severe migraine pain with at least two and a maximum of six migraines per month, and at least 24 hours of freedom from head pain between attacks. Patients were instructed to take a single 12.5-mg dose of almotriptan at the onset of a migraine attack. If migraine pain did not disappear in 2 hours, escape medication could be taken; if relapse occurred in less than 24 hours, a second 12.5-mg dose could be taken. Tolerability was assessed from the nature and incidence of all adverse events, and efficacy was assessed according to the end point of pain relief 2 hours following almotriptan administration. RESULTS: Of 585 patients treated, 582 were included in the intent-to-treat population. The most frequent drug-related adverse events were nausea (3.1%) and dizziness (2.4%). No serious drug-related adverse events were reported, and no deaths occurred. Adverse events led to discontinuation of treatment in 36 patients (6.2%). Drug-related chest pain was reported in 9 patients (1.5%). Seventy-six percent of patients achieved pain relief at 2 hours for all attacks treated, and 49% were pain-free at 2 hours. After a second dose of almotriptan 12.5 mg, pain relief was achieved in 87% of attacks, and 59% were pain-free. Pain relief and pain-free rates were higher among those with moderate baseline pain. CONCLUSIONS: When taken at attack onset, almotriptan 12.5 mg is well tolerated, safe, and effective for the long-term treatment of acute migraine.     

Efficacy and tolerability of coadministration of rizatriptan and acetaminophen vs rizatriptan or acetaminophen alone for acute migraine treatment

Objective.— To evaluate the efficacy and tolerability of coadministration of rizatriptan and acetaminophen in the acute treatment of migraine.
Background.— Rizatriptan is a selective 5-HT_1B/1D agonist approved for the acute treatment of migraine. Acetaminophen has been studied for acute migraine treatment. In consideration of the prominent central and peripheral mechanisms in migraine, the use of "multi-mechanism therapy" is gaining momentum in the treatment of acute migraine attacks.
Study Design.— This was a randomized, double-blind, placebo-controlled trial conducted at 10 centers. Eligible patients with migraine according to International Headache Society criteria treated a single migraine attack of moderate or severe intensity within 4 h from pain onset. Patients were randomized into 1 of 4 groups (rizatriptan 10 mg + acetaminophen 1000 mg [RA], rizatriptan alone [R], acetaminophen alone [A], and placebo [P]). There were 3 co-primary hypotheses tested sequentially for 2-h pain relief: (1) RA would be superior to P; (2) if the first was fulfilled, RA would be superior to A; and (3) if the first 2 were fulfilled, RA would be superior to R.
Results.— Of 173 patients who treated a migraine, 123 patients (71.5%) achieved pain relief within 2 h. RA (90%) was significantly better than P (46%) and A (70%), but only numerically better than R (77%) for 2-h pain relief. No significant differences were seen between the active treatment groups in adverse events.
Conclusion.— Rizatriptan coadministered with acetaminophen achieved 2 of the 3 primary hypotheses, proving superior to both acetaminophen and placebo for 2-h pain relief, but failing to achieve superiority to rizatriptan alone. RA was as well tolerated as each of the individual agents.     

Aborting a Migraine Attack: Naproxen Sodium v Ergotamine plus Caffeine

SYNOPSIS
The tolerability and efficacy of naproxen sodium and of ergotamine tartrate plus caffeine (ergotamine) were compared in the treatment of acute migraine attacks and associated symptoms. In this multicenter, double-blind, parallel study of up to six headaches over a 3-month period, patients took naproxen sodium 825 mg, ergotamine 2 mg, or placebo at the time of the first symptom of an attack; 30 minutes later, if necessary, patients repeated naproxen sodium 275 mg, ergotamine 1 mg or placebo, as appropriate. Rescue medication was allowed 30 minutes following the second dose if needed. Active drugs provided notably better relief of head pain than did placebo; 1 hour following the first dose the difference between naproxen sodium and placebo was statistically significant. Naproxen sodium was as efficacious as ergotamine in the relief of migraine attacks and associated symptoms. Relief of vomiting, nausea, photophobia, and motor symptoms favored naproxen sodium over ergotamine; these differences were statistically significant for nausea and motor symptoms. Ergotamine-treated patients reported more complaints and had more severe and longer-lasting complaints than patients on the other two regimens. Overall tolerance ratings by both investigators and patients indicated that naproxen sodium and placebo were tolerated significantly better than ergotamine.     

Efficacy and Safety of 400 and 800 mg Etodolac vs. 1,000 mg Paracetamol in Acute Treatment of Migraine: A Randomized,Double‐blind,Crossover, Multicenter,Phase III Clinical Trial

Aim: We aimed to determine the efficacy and safety of etodolac, in acute migraine attacks in comparison with paracetamol (acetaminophen). Methods: We designed a randomized, double‐blind, crossover phase III clinical trial for patients diagnosed with migraine for at least 1 year, according to ICHD‐II criteria. Two hundred and twenty‐nine adult patients having 2 to 8 attacks monthly from 17 centers were included. The patients were instructed to use 3 attack treatment packages consisting of 1,000 mg paracetamol, 400 mg etodolac, and 800 mg etodolac on 3 migraine attacks of moderate–severe intensity each in a 3‐month treatment period, interchangeably. Results: Any pain medication was used in 1,570 migraine attacks while study treatments were used in 1,047 attacks. The results for 1,000 mg paracetamol, 400 mg etodolac, and 800 mg etodolac were as follows: response of headache at 2 hours 44.9%, 48.3% and 46.1%; pain‐free at 2 hours 19.2%, 19.3% and 24.1%; sustained pain‐free from 2 to 24 hours 34.3%, 38.3% and 41.1%; relapse rates in 2 to 24 hours 7.3%, 14.3% and 9.7%. There were no statistically significant differences between the groups regarding the headache response, pain‐free, sustained pain‐free, and relapse rates. Nausea, vomiting, phonophobia, or photophobia decreased similarly in all groups within 24 hours of treatment administration. Drug‐related adverse events were noted in 8 patients with 1,000 mg paracetamol, in 9 patients with 400 mg etodolac and in 9 patients for 800 mg etodolac during the study. Comment: Our study showed that etodolac is a safe and effective alternative in acute migraine treatment and showed comparable efficacy to paracetamol 1,000 mg. Etodolac may be considered as an alternative option for acute treatment of migraine.     

Sumatriptan/Naproxen sodium for migraine: efficacy, health related quality of life, and satisfaction outcomes

OBJECTIVE: To describe the pain relief, satisfaction, and health-related quality of life results of moderate or severe migraines treated with a sumatriptan/naproxen sodium combination tablet. METHODS: Sumatriptan and naproxen sodium as a single-dose formulation tablet was used to treat moderate to severe migraines over a 12-month period in a phase 3, open-label, multicenter study (n = 565) in patients with at least 6 months' history of migraine headaches. RESULTS: Seventy percent of all attacks were treated with 1 dose of sumatriptan/naproxen sodium. Overall subjects treated 24,485 attacks; of these, 81% attacks achieved pain relief and 60% pain-free by 2 hours. At 3 months, the percentage of patients satisfied or very satisfied increased from baseline on all 8 Patient Perception of Migraine Questionnaire (PPMQ) items and remained high throughout the study. Mean Migraine-Specific Quality of Life Questionnaire (MSQ) domain scores also increased by 13-15 points from baseline during this time and remained high. CONCLUSIONS: Sumatriptan/naproxen sodium provides consistent relief of migraine attacks over 12 months, resulting in improved patient satisfaction and migraine specific quality of life.     

Meta‐Analysis of the Efficacy and Safety of Naproxen Sodium in the Acute Treatment of Migraine

(Headache 2010;50:808‐818) Objective.— To assess the efficacy and safety of naproxen sodium in the treatment of acute migraine attacks. Background.— Non‐steroidal anti‐inflammatory drugs including naproxen sodium have been used in treating migraine attack. A number of clinical trials of naproxen sodium in migraine have been reported. However, it remains to be established whether naproxen sodium unequivocally offers clinical benefits taken into account the desired outcomes in acute migraine therapy as recommended by the International Headache Society. Methods.— Clinical trials were identified through electronic searches (MEDLINE, EMBASE, EBM review, and the Cochrane Library) up to June 2009 and historical searches of relevant articles. Studies were included in the meta‐analysis if they were (1) double‐blind, randomized, placebo‐controlled trials that evaluated naproxen sodium tablet in moderate or severe migraine attacks in adult patients, and (2) reporting the efficacy in terms of headache relief, pain‐free, relief of migraine‐associated symptoms, sustained headache relief, sustained pain‐free, or headache recurrence. Data extraction and study quality assessment were performed independently by 2 investigators. Disagreements were resolved by a third investigator. Treatment effects and adverse effects were expressed as risk ratio. A random effects model was used when significant heterogeneity existed, otherwise the fixed effects model was performed. Results.— We identified 16 published randomized controlled trials of naproxen in the treatment of migraine. Four trials met the inclusion criteria and were included in the meta‐analysis. Naproxen sodium was more effective than placebo in reducing pain intensity and providing pain‐free within 2 hours in adults with moderate or severe migraine attacks. The pooled risk ratios were 1.58 (95% confidence interval [CI] 1.41‐1.77, P < .00001), and 2.22 (95% CI 1.46‐3.37, P = .0002), respectively, for headache relief at 2 hours and pain‐free at 2 hours. It was also effective in achieving headache relief at 4 hours, relief of migraine‐associated symptoms, sustained headache relief, and sustained pain‐free responses. There was no significant difference in headache recurrence rate between naproxen sodium and placebo. The risk of any adverse event was greater with naproxen sodium than with placebo (pooled risk ratio 1.29, 95% CI 1.04‐1.60, P = .02). The adverse events commonly associated with naproxen sodium were nausea, dizziness, dyspepsia, and abdominal pain. Conclusions.— The available evidence suggests that naproxen sodium is more effective but may cause more adverse events than placebo in the acute treatment of moderate to severe migraine. It is effective in reducing headache intensity, rendering pain‐free at 2 hours and improving migraine‐associated symptoms. However, its effectiveness relative to other active comparators needs to be better defined by appropriate head‐to‐head clinical trials.     

Sumatriptan in Acute Migraine Using a Novel Cartridge System Self-Injector

SYNOPSIS
This double-blind. randomized, placebo-controlled, parallel-group, multicenter study assessed the efficacy, acceptability, safety, and tolerability of subcutaneous sumatriptan 6 mg administered using a novel cartridge system self-injector for the acute treatment of migraine.
Eighty-six patients treated one migraine attack at home with sumatriptan or placebo. A second identical injection was available after 1 hour for inadequate relief or if the headache recurred. Rescue medication was available I hour later. The primary end point was headache relief (improvement in headache from moderate or severe to mild or no pain) within 60 minutes of the first injection. Secondary end points included the acceptability of the self-injector, requirement for and efficacy of a second dose, relief of nonheadache symptoms, use of rescue medication, and adverse events.
Significantly more patients taking sumatriptan than placebo reported headache relief I hour after the first injection (88% vs 11%, P <0.001). The device was well accepted by patients; about 90% found it easy to use and wanted to take further medication using it. Significantly fewer patients taking sumatriptan than placebo required a second injection (33% vs 92%, P <0.001) or rescue medication after the second injection (35% vs 67% P <0.05). Significantly more patients taking sumatriptan than placebo reported headache relief after the second injection (83% vs 32%, P <0.01), and resolution of non-headache migraine symptoms (54% vs 23%, P <0.01). Sumatriptan was generally well tolerated.
Subcutaneous sumatriptan 6 mg self-administered using the novel self-injector is an effective, well accepted, and well tolerated acute treatment of migraine.     

Paracetamol vs piroxicam to relieve pain in renal colic. Results of a randomized controlled trial

Purpose

We tested whether paracetamol could improve pain relief in patients visiting the emergency department with acute renal colic as compared to piroxicam, a nonsteroidal anti-inflammatory drug (NSAID).

Materials and Methods

Patients with a diagnosis of acute renal colic were prospectively randomized to receive either intravenous paracetamol (1 g) or intramuscular piroxicam (20 mg). We monitored patients for visual analog scale (VAS), heart rate, arterial blood pressure, need for rescue therapy, and adverse events at different time points for 90 minutes. We recorded admission requirement and new visit for renal colic at 72 hours. The primary end point was pain relief at 90 minutes, defined as a decrease of 50% or more as compared to the initial VAS. The secondary objectives were comparison of the 2 groups for VAS at any time points and the occurrence of adverse events.

Results

Of the 226 eligible patients, 100 entered the study. Fifty patients received paracetamol and 50 received NSAID. Pain relief at 90 minutes was obtained in 40 patients receiving paracetamol (80%) and 24 (48%) receiving NSAID (P = .002). Visual analog scale was lower in the paracetamol group since 45 minutes. Only 2 adverse events were observed.

Conclusion

A single therapy with intravenous paracetamol more efficiently relieved pain in acute renal colic than did intramuscular piroxicam.     

Early migraine intervention with sumatriptan 100 mg in patients with a history of nonresponse to sumatriptan 50 mg: an open-label, prospective study of multiple attacks

Background

Early treatment with sumatriptan tablets (50 and 100 mg) has been shown to be effective in retrospective and prospective study designs. Despite the efficacy of sumatriptan 50 mg and early intervention, however, some patients continue not to respond completely to this dose. New evidence with a scientific basis for early intervention suggests that some patients may need to treat early to prevent the establishment of central sensitization. Also, patients cite complete pain relief as the most important attribute of a migraine medication.

Objective

The primary objective of this study was to determine the 2-hour efficacy of sumatriptan 100 mg in achieving complete pain relief in patients with a history of nonresponse to sumatriptan 50 mg in an early-intervention treatment paradigm. Secondary end points included complete pain relief at 4 hours, consistency of complete relief in at least 2 of 3 attacks, sustained complete relief over 24 hours, satisfaction with the 100-mg dose, and relief of associated symptoms.

Methods

This open-label, prospective study was conducted at the Wesley Headache Clinic (Memphis, Tennessee). Male and female patients between the ages of 18 and 65 years who fulfilled International Headache Society classification criteria for migraine, and who had a documented history of nonresponse to sumatriptan 50 mg at 2 hours after dosing when treating in the early, mild-pain phase in at least 2 of 3 migraine attacks were eligible for the study. Patients were instructed to receive one 100-mg sumatriptan tablet at the earliest sign of pain, while still mild, in 3 subsequent migraine attacks. After each treated attack, patients were to record a detailed diary entry.

Results

Twenty patients (17 women, 3 men; mean age, 44 years) treated all 3 migraines during the early, mild-pain phase and completed the study. Of the 60 attacks treated, 48 (80%) were pain free at 2 hours, 56 (93%) were pain free at 4 hours, and 45 (75%) were pain free at 2 hours and continued to be pain free at 24 hours (sustained pain-free response). Sumatriptan 100 mg was well tolerated; none of the patients reported any adverse events.

Conclusions

In this study of migraineurs with a history of nonresponse to sumatriptan 50 mg at 2 hours after dosing in the early, mild-pain phase of migraine, increasing the dose of sumatriptan from 50 mg to 100 mg in the early-intervention paradigm, in most attacks complete pain relief was achieved for up to 24 hours. Because patients have indicated that becoming pain free was their therapeutic goal, based on the results of this study, physicians may want to consider increasing the dose of sumatriptan to 100 mg at the first sign of pain if the patient has consistently not responded to sumatriptan 50 mg in the early-intervention model.     

Sumatriptan is effective in the treatment of menstrual migraine: a review of prospective studies and retrospective analyses

Menstrual migraine may be debilitating, long-lasting, and refractory to treatment. Because the efficacy and tolerability of abortive and prophylactic treatment options for menstrual migraine have generally not been evaluated in controlled clinical trials, treatment choices are often made on the basis of personal experience and anecdotal reports. This article reviews evidence from retrospective analyses and prospective studies showing that sumatriptan injection and tablets are effective and well tolerated in menstrual migraine. (1) Sumatriptan injection 6 mg was as effective in the treatment of menstrual migraine attacks as it was for nonmenstrual attacks in a retrospective analysis of data from two randomized, double-blind, placebo-controlled, parallel-group trials (n = 1104). In the menstrual migraine group, 80% of women treated with sumatriptan injection 6 mg compared with 19% of placebo-treated patients reported headache relief 1 h postdose (p < 0.001). (2) Sumatriptan injection 6 mg was effective in the acute treatment of menstrual migraine attacks in a prospective, double-blind, placebo-controlled, parallel-group, two-attack study (n = 226). Across the two attacks, 70-71% of patients treating menstrual migraine attacks with sumatriptan injection 6 mg compared with 22-24% of placebo-treated patients reported headache relief 1 h postdose (p < 0.001). (3) Sumatriptan tablets 100 mg were effective in the acute treatment of menstrual migraine attacks in a prospective, double-blind, placebo-controlled, crossover study in women diagnosed with menstrual migraine (n = 115). For menstrual migraine attacks, headache relief 4 h postdose was reported by 67% of sumatriptan-treated patients compared with 33% of placebo-treated patients. Sumatriptan injection and tablets were generally well tolerated in these studies, in which adverse events were characteristic of those typically observed in sumatriptan acute migraine clinical trials. These data demonstrate that sumatriptan injection and tablets are effective and well tolerated in the treatment of menstrual migraine.     

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.