ABSTRACT
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.
Subject(s)
Antipsychotic Agents/administration & dosage , Benzoxazoles/administration & dosage , Piperazines/administration & dosage , Schizophrenia/drug therapy , Acute Disease , Adult , Antipsychotic Agents/adverse effects , Benzoxazoles/adverse effects , Body Weight/drug effects , Cholesterol/blood , Dose-Response Relationship, Drug , Double-Blind Method , Dyskinesia, Drug-Induced/blood , Dyskinesia, Drug-Induced/diagnosis , Electrocardiography/drug effects , Female , Gastrointestinal Diseases/blood , Gastrointestinal Diseases/chemically induced , Humans , Male , Middle Aged , Neurologic Examination/drug effects , Piperazines/adverse effects , Prolactin/blood , Psychiatric Status Rating Scales , Risperidone/adverse effects , Risperidone/therapeutic use , Schizophrenia/blood , Schizophrenia/diagnosis , Treatment Outcome , Triglycerides/bloodABSTRACT
Postmenopausal osteoporosis is associated with significant morbidity, mortality, reduction in quality of life, and increasing health care costs. It is estimated that 1.5 million women in the United States have one or more osteoporosis-related fractures annually. Fractures may occur at any site, but vertebral fractures are the most common. Longitudinal studies have demonstrated a decreased life expectancy associated with both vertebral and nonvertebral fractures. Once an initial fracture occurs, there is a fivefold increased risk of a second fracture within 1 year. The management of osteoporosis today incorporates multiple modalities of therapy. In addition to early detection, patient education, exercise, and nutritional supplementation, multiple therapeutic agents should be implemented early in an attempt to prevent initial and subsequent fractures. This article reviews currently approved modalities of therapy for the prevention and treatment of postmenopausal osteoporosis.