Randomized, controlled, double-blind trial of taranabant for smoking cessation.

RATIONALE: It has been proposed that cannabinoid-1 receptor inverse agonists might be effective for smoking cessation. We evaluated this hypothesis with the cannabinoid-1 receptor inverse agonist taranabant. METHODS: Adults who smoked > or =10 cigarettes a day for >1 year and had an expired CO level of > or =10 ppm participated in a randomized, double-blind, 8-week, study of taranabant (N = 159) or placebo (N = 158). Taranabant was titrated from 2 mg once daily to 8 mg once daily. Patients received smoking cessation counseling. The primary efficacy endpoint was continuous abstinence, defined as no cigarettes assessed by daily patient self-report and verified by breath CO level (<10 ppm) and plasma cotinine test (<10 ng/ml), during the last 4 weeks of the 8-week treatment period. RESULTS: The percentage of patients achieving continuous abstinence was 7.5% for taranabant 2-8 mg and 6.3% for placebo (odds ratio = 1.2 [90% confidence interval (CI), 0.6, 2.5], P = 0.678). Change from baseline in body weight in the taranabant 2-8-mg group was -1.5 (90% CI, -1.8, -1.3) versus 0.6 kg (90% CI, 0.4, 0.9) in the placebo group. Compared to placebo, taranabant 2-8 mg was associated with an increased incidence of psychiatric-related adverse events (e.g., depression, 8.2% versus 2.5%, P = 0.048), gastrointestinal-related adverse events (e.g., nausea, 49.7% versus 19.0%, P < 0.001), and flushing/hot flash adverse events (10.7% versus 1.9%, P = 0.002). CONCLUSIONS: Taranabant 2-8 mg did not improve smoking cessation and was associated with increased incidences of psychiatric-related, gastrointestinal-related, and flushing adverse events (ClinicalTrials.gov NCT00109135).

Montelukast for migraine prophylaxis: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and tolerability of montelukast 20 mg in the prophylactic treatment of migraine. BACKGROUND: A previous small open-label study in migraine patients suggested prophylactic efficacy for montelukast, an antagonist of the cysteinyl leukotriene receptor that is used in the treatment of asthma. We sought to confirm these findings in a randomized controlled trial. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-groups study enrolled adult migraine outpatients who experienced > or =3 and < or =8 migraine attacks per month for the last 6 months. Patients were entered into a 2-month, single-blind, placebo run-in phase. Only patients who experienced > or =3 migraine attacks in the second month were eligible to enter the subsequent 3-month, double-blind treatment phase of the study. The primary efficacy endpoint was the percentage of patients reporting at least a 50% decrease in migraine attack frequency per month during the double-blind treatment period (months 3-5) compared to baseline (run-in month 2). RESULTS: A total of 93 patients were randomized to montelukast 20 mg and 84 patients to placebo at the end of the placebo run-in month 2; 76 patients on montelukast and 72 patients on placebo completed the double-blind treatment period. Over 3 months of treatment, there was no significant difference between the two groups in the percentage of patients who reported at least a 50% decrease in migraine attack frequency per month: 15.4% for montelukast versus 10.3% for placebo (P= .304). In addition, montelukast 20 mg was not significantly superior to placebo on any of the secondary endpoints. There were no differences between treatment groups for adverse events. CONCLUSION: Montelukast 20 mg was well tolerated in migraine patients but was not an effective prophylactic for prevention of migraine.

Telephone screening for amnestic mild cognitive impairment.

OBJECTIVES: To evaluate the utility of telephone screening for identifying subjects with amnestic mild cognitive impairment (aMCI) for enrollment in a clinical trial and to identify which elements of the modified Telephone Interview for Cognitive Status (TICS-m) best predicted the in-clinic determination of aMCI. METHODS: Subjects aged >/=65 years with memory complaints responded to an advertisement for a clinical trial by calling a central telephone recruiting agency. To determine eligibility, subjects went through a stepwise selection procedure involving a review of major protocol inclusion and exclusion criteria, followed by administration of the Category Fluency Test (CFT) and then the TICS-m. Subjects meeting entry criteria, who obtained a score of /=24 on the Mini-Mental State Examination and a score of