Timolol Eyedrops in the Treatment of Acute Migraine Attacks: A Randomized Crossover Study.
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SUBMITTER: Cossack M
PROVIDER: S-EPMC6142935 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceOral β-blockers used for the prevention of migraine headache are not effective for the treatment of acute pain. Small case series have suggested that topically applied β-blockers may be useful in the management of acute migraine pain, warranting evaluation with randomized clinical trials.ObjectiveTo evaluate the short-term efficacy and safety of topically applied timolol maleate ophthalmic solution, 0.5%, compared with topically applied placebo eyedrops in the treatment of acute migraine attacks.Design, setting, and participantsIn this randomized, masked placebo-controlled crossover trial conducted from May 27, 2015, to August 28, 2017, 50 patients with migraine were randomized to receive either timolol eyedrops, 0.5%, or a placebo eyedrop (carboxymethyl cellulose, 0.5%). After a 3-month treatment period, patients completed a 1-month washout period and were crossed over to receive the opposite treatment for a final 3 months. Analysis was performed on a modified intent-to-treat basis.InterventionAfter random assignment, patients were instructed to use 1 drop of the assigned medication in each eye at the earliest onset of migraine.Main outcomes and measuresThe main outcome measure was reduction in pain score with treatment. The primary end point was reduction of pain score by 4 points, or to zero, 20 minutes after instillation of the eyedrop.ResultsOf the 50 patients, 42 (84%) were females and the mean (SD) age was 27.3 (11.3) years. Of a total of 619 migraine attacks, 284 (46%) were treated with timolol, 271 (44%) were treated with the placebo, and 64 (10%) occurred during the washout period when no study medications were used. Seven patients (14%) withdrew after randomization. A total of 233 of the timolol-treated migraine attacks (82%) were associated with a reduction in pain score by 4 points, or to zero, at 20 minutes compared with 38 of the placebo-treated attacks (14%), with a difference of 68 percentage points (95% CI, 62-74 percentage points). A generalized estimating equation analysis revealed that pain score reduction at 20 minutes was greater in the timolol group compared with the placebo group by a mean (SE) of 4.63 points (0.34) (P < .001).Conclusions and relevanceThis randomized crossover trial supports consideration of timolol eyedrops in the acute treatment of migraine. Further research is warranted to determine if the improvements observed are sustained for a longer follow-up and with larger groups.Trial registrationCTRI/2015/05/005829, UTN: U1111-1167-6439.
| S-EPMC7530820 | biostudies-literature
Project description:IntroductionDaily oral beta-adrenoreceptor antagonist has been shown to be effective in preventing migraine headaches. Timolol 0.5% ophthalmic solution is a non-selective beta-adrenoreceptor antagonist, where the primary use is for glaucoma. There have been case reports that timolol is effective in aborting or improving an acute migraine headache. The objective of this study was to assess the efficacy (decrease of ≥ 50% in pain scale at 120 minutes) of timolol 0.5% ophthalmic solution compared to placebo in acute treatment of migraine headache.MethodsWe performed a randomized, double-blind, crossover, placebo-controlled, study. Study entry criteria required subjects to have one to eight migraine episodes per month. The primary outcome was comparison of the change in a visual analog pain scale (VAS) at 120 minutes after taking the study medication. Study subjects were given a pain scale with a range of 1 (no pain) to 10 (most severe pain) to complete after onset of migraine but before administration of study drops and 120 minutes after administration of study drops. Improvement was defined as a ≥ 50% decrease in pain scale.ResultsNineteen subjects completed the study and were used for analysis. The primary outcome changes in pain scale, 120 minutes after dose, showed a similar decrease for placebo and drug with a slightly wider 95% CI for placebo. Six subjects in each arm experienced a ≥ 50% decrease in pain scale.ConclusionThese results support that timolol 0.5% ophthalmic solution is not an efficacious treatment for acute migraine headache.
| S-EPMC7106987 | biostudies-literature
Project description:In the field of headache disorders, the term "fear of attacks" refers to the fear of a headache attack occurring. Excessive fear of attacks may worsen the course of a migraine and lead to an increase in migraine activity. In the assessment of attack-related fear, a categorical (fear of attacks as a specific phobia) and a dimensional approach (measuring the extent of fear using a questionnaire) are available. The 29-item Fear of Attacks in Migraine Inventory (FAMI) is an economic self-report questionnaire for the assessment of attack-related fear, and it has good psychometric properties. The treatment of attack-related fear includes behavioral interventions as well as pharmacological therapy. Behavioral interventions have few side effects and are based on the treatment of common anxiety disorders (e.g., agoraphobia). Although the evidence of existing treatments is sparse, attack-related fear should be considered in routine care.
| S-EPMC10112828 | biostudies-literature
Project description:A 6-mg dose of SC sumatriptan is the most efficacious and fast-acting acute treatment for migraine, but a 3-mg dose of SC sumatriptan may improve tolerability while maintaining efficacy.This randomized, double-blind, crossover study compared the efficacy and tolerability of 3 mg subcutaneous (SC) sumatriptan (DFN-11) with 6 mg SC sumatriptan in 20 adults with rapidly-escalating migraine attacks. Eligible subjects were randomized (1:1) to treat 1 attack with DFN-11 and matching placebo autoinjector consecutively or 2 DFN-11 autoinjectors consecutively and a second attack similarly but with the alternative dose (3 mg or 6 mg).The proportions of subjects who were pain-free at 60 min postdose, the primary endpoint, were similar following treatment with 3 mg SC sumatriptan and 6 mg SC sumatriptan (50% vs 52.6%, P??=??.87). The proportions of subjects experiencing pain relief (P?????.48); reductions in migraine pain intensity (P?????.78); and relief from nausea, photophobia, or phonophobia (P?????.88) with 3 mg SC sumatriptan and 6 mg SC sumatriptan were similar, as were the mean scores for satisfaction with treatment (M??=??2.6 vs M??=??2.4, P??=??.81) and the mean number of rescue medications used (M??=??.11 vs M??=??.26, P??=??.32). The most common adverse events with the 3- and 6-mg doses were triptan sensations - paresthesia, neck pain, flushing, and involuntary muscle contractions of the neck - and the incidence of adverse events with both doses was similar (32 events total: 3 mg, n??=??14 [44%]; 6 mg, n??=??18 [56%], P??=??.60). Triptan sensations affected 4 subjects with the 6-mg dose only, 1 subject with the 3-mg dose only, and 7 subjects with both sumatriptan doses. Chest pain affected 2 subjects (10%) treated with the 6-mg dose and no subjects (0%) treated with the 3-mg dose of DFN-11. There were no serious adverse events.The 3-mg SC dose of sumatriptan in DFN-11 provided relief of migraine pain and associated symptoms comparable to a 6-mg SC dose of sumatriptan. Tolerability was similar with both study medications; DFN-11 treatment was associated with fewer triptan sensations than the 6-mg dose. DFN-11, with its 3-mg dose of sumatriptan, may be a clinically useful alternative to higher-dose autoinjectors.
| S-EPMC5296269 | biostudies-literature
Project description:BackgroundWe present findings from the multicenter, double-blind Phase 3 study, CENTURION. This study was designed to assess the efficacy of and consistency of response to lasmiditan in the acute treatment of migraine across four attacks.MethodsPatients were randomized 1:1:1 to one of three treatment groups - lasmiditan 200 mg; lasmiditan 100 mg; or a control group that received placebo for three attacks and lasmiditan 50 mg for either the third or fourth attack. The primary endpoints were pain freedom at 2 h (first attack) and pain freedom at 2 h in ≥2/3 attacks. Secondary endpoints included pain relief, sustained pain freedom and disability freedom. Statistical testing used a logistic regression model and graphical methodology to control for multiplicity.ResultsOverall, 1471 patients treated ≥1 migraine attack with the study drug. Both primary endpoints were met for lasmiditan 100 mg and 200 mg (p < 0.001). All gated secondary endpoints were met. The incidence of treatment-emergent adverse events (TEAEs) was highest during the first attack. The most common TEAEs with lasmiditan were dizziness, paresthesia, fatigue, and nausea; these were generally mild or moderate in severity.ConclusionsThese results confirm the early and sustained efficacy of lasmiditan 100 mg and 200 mg and demonstrate consistency of response across multiple attacks.Trial Registration Number: NCT03670810.
| S-EPMC7961651 | biostudies-literature
Project description:Use of auriculotherapy to prevent episodic migraine pain has seldom been reported. The aim of this open study was to show that three sessions of auriculotherapy, 1 month apart, using semi-permanent needles decrease frequency and intensity of an attack in patients presenting episodic migraine. A total of 90 patients were randomized to the treatment group (AUR group, n = 58) or the control group (C group, n = 32). Four patients dropped out during the study (three in the AUR group and one in the C group). The number of days with migraine and non-migraine headache was similar when the analysis focused on the 3 months of the study or on the difference in each group of this number between the 3 months preceding the inclusion and the 3 months of the study (p = 0.123). AUR group patients had fewer days with non-migraine headache (p = 0.011) and took less Triptans (p = 0.045) than group C. Number of days with migraine, sum of the pain intensities of all migraines and non-migraine headaches, and total number of analgesics taken, other than triptan, were similar between groups. MIDAS score decreased with time in the AUR group while it increased in the C group whether in absolute values (p = 0.035) or as categories (p = 0.037). These contrasted results should lead to further study of the effectiveness of auriculotherapy for the prevention of migraine. Clinical trail registration: Protocol registered on the Clinicaltrials.gov, website (January 30, 2017, NCT03036761).
| S-EPMC10241207 | biostudies-literature
Project description:ObjectiveTo assess the relief of migraine pain, especially in the acute phase, by comparing active treatment, ie, kinetic oscillation stimulation (KOS) in the nasal cavity, with placebo.BackgroundExploratory trials testing the efficacy of KOS on migraine patients indicated that this treatment could be a fast-acting remedy for acute migraine pain.MethodThirty-six patients were randomized 1:1 using a placebo module to active or placebo treatment in this double-blinded parallel design study. Treatment was administered with a minimally invasive inflatable tip oscillating catheter. Symptom scores (0-10 visual analog scale) were obtained before treatment, every 5 minutes during treatment, at 15 minutes, 2, and 24 hours post-treatment, as well as daily (0-3 migraine pain scale) from 30 days pretreatment until Day 60 post. Thirty-five patients were evaluated (active n=18, placebo n=17). The primary end-point was the change in average pain score from before treatment to 15 minutes after treatment.ResultsPatients who received active treatment reported reduced pain, eg, average visual analog scale pain scores fell from 5.5 before treatment to 1.2 15 minutes after, while the corresponding scores for recipients of placebo fell from 4.9 to 3.9. The changes in pain scores differed between the 2 treatments by 3.3 points (95% confidence interval: 2.3, 4.4), P<.001. Already 5 minutes into the treatment, the difference (1.9 points) was significant (P=.007). The difference was likewise significant at 2 hours post-treatment (3.7 points, P<.001). One patient experienced an adverse event (a vasovagal reaction with full spontaneous recovery) during placebo treatment.ConclusionKOS is an effective and safe treatment for acute migraine pain.
| S-EPMC4312979 | biostudies-literature
Project description:ObjectiveTo assess the efficacy and safety of lasmiditan in the acute treatment of migraine.MethodsAdult patients with migraine were randomized (1:1:1) to a double-blind dose of oral lasmiditan 200 mg, lasmiditan 100 mg, or placebo and were asked to treat their next migraine attack within 4 hours of onset. Over 48 hours after dosing, patients used an electronic diary to record headache pain and the presence of nausea, phonophobia, and photophobia, one of which was designated their most bothersome symptom (MBS).ResultsOf the 1,856 patients who treated an attack, 77.9% had ≥1 cardiovascular risk factors in addition to migraine. Compared with placebo, more patients dosed with lasmiditan 200 mg were free of headache pain at 2 hours after dosing (32.2% vs 15.3%; odds ratio [OR] 2.6, 95% confidence interval [CI] 2.0-3.6, p< 0.001), similar to those dosed with lasmiditan 100 mg (28.2%; OR 2.2, 95% CI 1.6-3.0, p< 0.001). Furthermore, compared with those dosed with placebo, more patients dosed with lasmiditan 200 mg (40.7% vs 29.5%; OR 1.6, 95% CI 1.3-2.1, p< 0.001) and lasmiditan 100 mg (40.9%; OR 1.7, 95% CI, 1.3-2.2, p< 0.001) were free of their MBS at 2 hours after dosing. Adverse events were mostly mild or moderate in intensity.ConclusionsLasmiditan dosed at 200 and 100 mg was efficacious and well tolerated in the treatment of acute migraine among patients with a high level of cardiovascular risk factors.Clinicaltrialsgov identifierNCT02439320.Classification of evidenceThis study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack.
| S-EPMC6329326 | biostudies-literature
Project description:Limited evidence suggests that dietary interventions may offer a promising approach for migraine. The purpose of this study was to determine the effects of a low-fat plant-based diet intervention on migraine severity and frequency.Forty-two adult migraine sufferers were recruited from the general community in Washington, DC, and divided randomly into two groups. This 36-week crossover study included two treatments: dietary instruction and placebo supplement. Each treatment period was 16 weeks, with a 4-week washout between. During the diet period, a low-fat vegan diet was prescribed for 4 weeks, after which an elimination diet was used. Participants were assessed at the beginning, midpoint, and end of each period. Significance was determined using student's t-tests.Worst headache pain in last 2 weeks, as measured by visual analog scale, was initially 6.4/10 cm (SD 2.1 cm), and declined 2.1 cm during the diet period and 0.7 cm during the supplement period (p=0.03). Average headache intensity (0-10 scale) was initially 4.2 (SD 1.4) per week, and this declined by 1.0 during the diet period and by 0.5 during the supplement period (p=0.20). Average headache frequency was initially 2.3 (SD 1.8) per week, and this declined by 0.3 during the diet period and by 0.4 during the supplement period (p=0.61). The Patient's Global Impression of Change showed greater improvement in pain during the diet period (p<0.001).These results suggest that a nutritional approach may be a useful part of migraine treatment, but that methodologic issues necessitate further research.Clinicaltrials.gov, NCT01699009 and NCT01547494.
| S-EPMC4227630 | biostudies-literature
Project description:Background Impaired brain oxygen delivery can trigger and exacerbate migraine attacks. Normoxic hypercapnia increases brain oxygen delivery markedly by vasodilation of the cerebral vasculature, and hypercapnia has been shown to abort migraine attacks. Stable normoxic hypercapnia can be induced by a compact partial rebreathing device. This pilot study aimed to provide initial data on the device's efficacy and safety. Methods Using a double-blinded, randomized, cross-over study design, adult migraine-with-aura patients self-administered the partial rebreathing device or a sham device for 20 minutes at the onset of aura symptoms. Results Eleven participants (mean age 35.5, three men) self-treated 41 migraine attacks (20 with the partial rebreathing device, 21 with sham). The partial rebreathing device increased mean End Tidal CO2 by 24%, while retaining mean oxygen saturation above 97%. The primary end point (headache intensity difference between first aura symptoms and two hours after treatment (0-3 scale) - active/sham difference) did not reach statistical significance (-0.55 (95% CI: -1.13-0.04), p?=?0.096), whereas the difference in percentage of attacks with pain relief at two hours was significant ( p?=?0.043), as was user satisfaction ( p?=?0.022). A marked efficacy increase was seen from first to second time use of the partial rebreathing device. No adverse events occurred, and side effects were absent or mild. Conclusion Normoxic hypercapnia shows promise as an adjunctive/alternative migraine treatment, meriting further investigation in a larger population. Clinical study registered at ClinicalTrials.gov with identifier NCT03472417.
| S-EPMC6158684 | biostudies-literature