Mary Almas

Eletriptan for the acute treatment of migraine in adolescents: Results of a double-blind, placebo-controlled trial

Background.—Eletriptan is a potent 5‐HT1B/1D agonist with proven efficacy in the acute treatment of migraine in adults.

Identification of negative predictors of pain-free response to triptans: Analysis of the eletriptan database

Thirty to forty percent of migraineurs do not respond to any given triptan treatment. We identified clinical variables that significantly predict therapeutic non-response and evaluated the efficacy of eletriptan (20, 40 and 80 mg) and sumatriptan (100 mg) vs. placebo in a subgroup of patients with all predictor variables. First-attack data were pooled from 10 randomized, double-blind, placebo-controlled migraine trials (n = 8473). Multivariate regression analyses identified three significant baseline predictors of failure to achieve 2-h pain-free response: severe headache pain, presence of photophobia/phonophobia and presence of nausea. Time of dosing following headache onset did not influence 2-h pain-free response. Among patients with all three risk factors (n = 2010; 24± of total sample), 2-h pain-free response was significantly higher in patients receiving all three doses of eletriptan or sumatriptan vs. placebo (all P< 0.01). Thus, eletriptan and sumatriptan are efficacious in difficult-to-treat patients at high risk for non-response to triptans.

Treatment-emergent CNS symptoms following triptan therapy are part of the attack

If treatment-emergent central nervous system (CNS) symptoms following triptan therapy represent direct pharmacological effects of the drug, they should occur independent of response to active drug. However, if they represent unmasking of neurological symptoms of the migraine attack after pain is relieved, they should be more common in responders both to active drug and to placebo. To explore this issue, we evaluated the relationship between the CNS adverse events and treatment response following triptan or placebo treatment. We used pooled data from seven double-blind, placebo-controlled trials involving eletriptan 20 mg (E20, n = 402), eletriptan 40 mg (E40, n = 1870), eletriptan 80 mg (E80, n = 1393), sumatriptan 100 mg (S100, n = 275) and placebo (Pbo, n = 1024). Somnolence was more prevalent among 2 h headache responders than non-responders for all treatments, including E80 (8.8% vs. 5.0%; P < 0.05), E40 (6.4% vs. 5.0%; NS), E20 (4.0% vs. 2.0%; NS), S100 (4.7% vs. 3.2%; NS) and Pbo (7.6% vs. 3.0%; P < 0.05). Similarly, the incidence of asthenia was higher among patients who responded to treatment compared with those who did not respond to E80 (15.2% vs. 7.8%; P < 0.05), E40 (6.5% vs. 3.6%; P < 0.05), E20 (6.5% vs. 1.0%; P < 0.05), S100 (10.1% vs. 4.7%; NS) and Pbo (4.4% vs. 2.7%; NS). The generally higher rates of somnolence and asthenia in patients who respond to treatment suggests that these treatment-emergent neurological symptoms may represent the unmasking of CNS symptoms associated with the natural resolution of a migraine attack, rather than simply representing drug-related side-effects. The rate of somnolence in placebo responders is comparable to that in responders to E40 and E80, indicating that somnolence is related, at least in some important part, to headache relief and not treatment.

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

Objective.—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).

Predictors of migraine headache recurrence: A pooled analysis from the eletriptan database

Objective.— 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.

Efficacy and safety of pregabalin versus levetiracetam as adjunctive therapy in patients with partial seizures: A randomized, double‐blind, noninferiority trial

To assess the comparative efficacy and safety of pregabalin and levetiracetam for the reduction of seizure frequency in patients with partial seizures.

Quantifying the return of headache in triptan-treated migraineurs: An observational study

To improve understanding of secondary treatment failure in migraine patients, we evaluated ‘headache return’ as a novel endpoint to assess returning headaches according to their severity, expanding on current standard assessments of overall recurrence or relapse rates, in a six-month observational study of triptan-treated migraineurs. A total of 359 patients (91% female; mean age, 42.5 years) recorded data for 2168 headaches in electronic diaries. Two-thirds of headaches responded to triptan treatment (improved-to-mild or no pain two hours post-dose); 34% of headaches had a pain-free response. By 48 hours post-dose, 19% of all responding headaches returned; 24% of headaches achieving a pain-free response returned, predominantly to mild pain. More severe baseline headache, short duration since diagnosis of migraine, and female gender were associated with increased likelihood of headache return. Treatment satisfaction declined with increasing severity of headache return, demonstrating the value of assessing headache return by severity to fully evaluate its impact.

Efficacy of Eletriptan in Migraine-Related Functional Impairment: Functional and Work Productivity Outcomes

Objective.—To provide a multidimensional assessment of the extent of functional impairment during an acute migraine attack, and of the improvement in functioning in response to treatment, using 4 concurrently administered scales: the 7‐item work productivity questionnaire (PQ‐7), the functional assessment in migraine (FAIM) activities and participation (FAIM‐A&P) subscale, the FAIM‐impact of migraine on mental functioning (FAIM‐IMMF) subscale, and the traditional 4‐point global functional impairment scale (FIS).

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 (> or = 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.

Pregabalin Does Not Affect Sperm Production in Healthy Volunteers: A Randomized, Double-blind, Placebo-controlled, Noninferiority Study

The primary objective of this study was to compare the effects of pregabalin and placebo on sperm concentration in healthy male subjects. Changes in follicle‐stimulating hormone (FSH), testosterone, sperm motility, semen volume, and sperm morphology were also examined.