Efficacy and safety of bifeprunox in patients with an acute exacerbation of schizophrenia: results from a randomized, double-blind, placebo-controlled, multicenter, dose-finding study.

RATIONALE: Bifeprunox is a partial dopamine agonist with a unique receptor-binding profile and potential antipsychotic properties. OBJECTIVES: The current study evaluated the efficacy and safety of bifeprunox in patients with an acute exacerbation of schizophrenia. MATERIALS AND METHODS: In this 6-week, double-blind, placebo-controlled study, 589 patients were randomly assigned to once-daily treatment with bifeprunox 5, 10, or 20 mg, placebo, or risperidone 6 mg. Efficacy was assessed by changes in symptom rating scales [Positive and Negative Syndrome Scale (PANSS) total and subscale scores; PANSS-derived BPRS scores; Clinical Global Impression--Severity (CGI--S) and Clinical Global Impression--Improvement (CGI--I) scores]. Safety and tolerability were assessed by monitoring adverse events, extrapyramidal symptoms (EPS), laboratory values, electrocardiograms, prolactin levels, and weight. RESULTS: Compared with placebo, bifeprunox 20 mg produced a statistically significantly greater reduction from baseline to last assessment in the primary efficacy variable (PANSS total score; effect size = -0.339), as well as most secondary efficacy measures. No statistically significant differences in efficacy were seen with lower doses of bifeprunox. The most common treatment-emergent adverse events (TEAEs) noted with bifeprunox were gastrointestinal; no clear dose-related trend in the incidence of any TEAE was observed in the bifeprunox groups. Compared to placebo, treatment with bifeprunox led to small but statistically significant decreases in weight and prolactin levels. EPS were comparable between bifeprunox and placebo. The active reference in this study, risperidone 6 mg, showed statistically significant differences from placebo for the primary efficacy parameter (effect size = -0.628) and all secondary efficacy parameters. CONCLUSIONS: These data suggest that 20 mg of bifeprunox may be efficacious in improving symptoms in patients with an acute exacerbation of schizophrenia. Bifeprunox appeared to be safe and well tolerated by patients in this 6-week study.

Comparative effects of oral esterified estrogens with and without methyltestosterone on endocrine profiles and dimensions of sexual function in postmenopausal women with hypoactive sexual desire.

OBJECTIVE: In some women, a decline in sexual interest accompanies a relative androgen insufficiency after menopause. We sought to characterize the hormonal effects of the combination of oral esterified estrogens and methyltestosterone and to investigate whether this regimen improves hypoactive sexual desire. DESIGN: Double-blind randomized trial. SETTING: Healthy volunteers in a multicenter research environment. PATIENT(S): Postmenopausal women taking estrogen therapy who were experiencing hypoactive sexual desire. INTERVENTION(S): 4 months of treatment with 0.625 mg of esterified estrogens (n = 111) or the combination of 0.625 mg of esterified estrogens and 1.25 mg of methyltestosterone (n = 107). MAIN OUTCOME MEASURES: Baseline and end-of-study measurements of total and bioavailable testosterone and sex hormone-binding globulin (SHBG), and mean change in level of sexual interest or desire as rated on the Sexual Interest Questionnaire. RESULT(S): Treatment with the combination of esterified estrogens and methyltestosterone significantly increased the concentration of bioavailable testosterone and suppressed SHBG. Scores measuring sexual interest or desire and frequency of desire increased from baseline with combination treatment and were significantly greater than those achieved with esterified estrogens alone. Treatment with the combination was well tolerated. CONCLUSION(S): Increased circulating levels of unbound testosterone and suppression of SHBG provide a plausible hormonal explanation for the significantly improved sexual functioning in women receiving the combination of esterified estrogen and methyltestosterone.

Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting.

OBJECTIVE: To compare the efficacy and tolerability of dronabinol, ondansetron, or the combination for delayed chemotherapy-induced nausea and vomiting (CINV) in a 5-day, double-blind, placebo-controlled study. RESEARCH DESIGN AND METHODS: Patients receiving moderately to highly emetogenic chemotherapy received dexamethasone (20 mg PO), ondansetron (16 mg IV) and either placebo or dronabinol (2.5 mg) prechemotherapy on day 1. Patients randomized to active treatment (dronabinol and/or ondansetron) also received dronabinol (2.5 mg) after chemotherapy on day 1. On day 2, fixed doses of placebo, dronabinol (10 mg), ondansetron (16 mg), or combination therapy were administered. On days 3-5, patients received placebo, flexible doses of dronabinol (10-20 mg), ondansetron (8-16 mg), or dronabinol and ondansetron (10-20 mg dronabinol, 8-16 mg ondansetron). MAIN OUTCOME MEASURES: Total response (TR = nausea intensity <5 mm on visual analog scale, no vomiting/retching, no rescue antiemetic), nausea (occurrence and intensity) and vomiting/retching episodes. RESULTS: Sixty-four patients were randomized; 61 analyzed for efficacy. TR was similar with dronabinol (54%), ondansetron (58%), and combination therapy (47%) versus placebo (20%). Nausea absence was significantly greater in active treatment groups (dronabinol, 71%; ondansetron, 64%; combination therapy, 53%) versus placebo (15%; p < 0.05 vs. placebo for all). Nausea intensity and vomiting/retching were lowest in patients treated with dronabinol. Active treatments were well tolerated. The low number of patients due to slow enrollment limits the interpretation of these data. CONCLUSIONS: Dronabinol or ondansetron was similarly effective for the treatment of CINV. Combination therapy with dronabinol and ondansetron was not more effective than either agent alone. Active treatments were well tolerated.

Menopausal Sexual Interest Questionnaire (MSIQ): a unidimensional scale for the assessment of sexual interest in postmenopausal women.

A panel of experts formulated relevant domains of sexual function with a focus on sexual interest and desire. The resulting 10-item scale, the Menopausal Sexual Interest Questionnaire (MSIQ), was examined for reliability (internal consistency and test-retest repeatability), construct validity (concurrent, convergent, and discriminant), sensitivity, and specificity in a clinical trial. A principal components analysis identified three factors (desire, responsiveness, and satisfaction) with eigenvalues > 1. A high degree of internal consistency was observed for each of the three domains. Test-retest repeatability correlation coefficients for domain scores were all highly significant. The MSIQ demonstrated adequate construct validity, with all three domains showing a high degree of sensitivity and with two of the three exhibiting specificity to the effects of treatment.