Med Check
This is Part 1 of a special edition of Med Check featuring summaries of new research posters presented in May at APA's 2009 annual meeting in San Francisco.
These presentations usually report preliminary data and often involve results that have not been peer reviewed for publication. In addition, the reports, which may involve the use of medications for indications that the FDA has not approved, are largely funded by product manufacturers.
• A panel of biological assays developed by Ridge Diagnostic Inc., based in North Carolina, may offer a blood test for diagnosing major depressive disorder. The proprietary test uses immunoassays to quantify the levels of nine biomarkers in blood samples. Among the biomarkers are four inflammatory markers, two stress hormones, one neuroendocrine protein, and one metabolic protein that are known to be altered in patients with depression and reflect physiological changes associated with the disorder. When these assays are analyzed in combination using mathematical algorithms, the score yielded from the analytical model has been shown to have 87 percent sensitivity and 95 percent specificity in a study of 50 patients and 20 controls. Sensitivity measures the percentage of test-positives among people who actually have the disease, while specificity measures the percentage of test-negatives among people who actually do not have the disease. The company is conducting a longitudinal study to evaluate whether the test can monitor patients' response to antidepressant treatments.
• Lurasidone, an investigational antipsychotic drug with high affinity for dopamine D2 and serotonin 5HT2A receptors, is being studied in phase 3 clinical trials by Dainippon Sumitomo Pharma America Inc. For the treatment of schizophrenia in one trial conducted by the company, 180 patients with schizophrenia were randomly assigned to either lurasidone 80 mg fixed dose (n=90) or placebo (n=90) in a double-blinded manner for six weeks. Based on intent-to-treat analyses, patients who received lurasidone had statistically significantly greater reduction in psychotic symptoms, as measured by the Brief Psychiatric Rating Scale and the Positive and Negative Syndrome Scale total scores, compared with the patients who received placebo. The lurasidone group also showed significant improvement on the Clinical Global Impression–Severity Scale, and the Montgomery-Asberg Depression Rating Scale. Thirty-eight patients in the lurasidone group and 43 in the placebo group discontinued the study treatment without completing the full six weeks of treatment, including six patients in the lurasidone group and one in the placebo group who withdrew because of adverse events (AEs).
The changes in metabolic indicators—including blood glucose; total, high-density lipoprotein, and low-density lipoprotein cholesterol; and triglyceride levels—did not differ significantly between the lurasidone and placebo groups after six weeks. The lurasidone and placebo groups had increased weight of 0.9 kg and 0.5 kg, respectively, which was not significantly different. The median change in prolactin level was an increase of 2.4 ng/mL in the lurasidone group, significantly higher than the change in the placebo group (reduced by 0.3 ng/mL). The changes in QTc interval did not differ significantly between the groups. The most frequent treatment-emergent AEs that occurred in at least 10 percent of patients were nausea, headache, constipation, vomiting not otherwise specified, dyspepsia, somnolence, insomnia, and sedation.
• Tasimelteon is a melatonin MT1/MT2 receptor agonist being investigated by Vanda Pharmaceuticals Inc. for the potential treatment of insomnia related to circadian rhythm disruptions such as jet lag and shift work. In a company-sponsored clinical trial, 411 healthy adults with artificially induced transient insomnia (on the first night at a sleep laboratory) and circadian rhythm disruption (moving bedtime earlier) were randomly assigned to placebo (n=103) or tasimelteon 20 mg (n=100), 50 mg (n=102), and 100 mg (N=106) taken before bedtime. The primary outcome measure, latency to persistent sleep, was shortened in the tasimelteon groups by 21.5 to 26.3 minutes compared with the placebo group, a statistically significant difference. The tasimelteon 20 mg and 50 mg groups, but not the 100 mg group, had significantly shorter duration of wake after sleep onset during the night. The amounts of rapid eye movement sleep and slow wave sleep were comparable between the placebo and tasimelteon groups. The AEs seen in the study were generally mild and similar in the groups. No significant next-day effects on cognitive and mood assessments were observed.
• A randomized, double-blind, placebo-controlled clinical trial of guanfacine extended-release tablets was conducted by Shire Inc. in 214 children aged 6 to 12 years with diagnosed attention-deficit/hyperactivity disorder (ADHD). After eight weeks on the treatment and one week of tapering off, the guanfacine group (n=136) had a statistically significantly larger reduction from baseline in both the Conduct Problem Scale score, rated by parents, and the Clinical Global Impressions–Severity scores, rated by clinicians. Treatment-emergent AEs were reported by 84 percent of the guanfacine-treated patients and 58 percent of the placebo patients. Severe treatment-emergent AEs occurred in 14 (10 percent) patients in the guanfacine group and none in the placebo group. The most common AEs reported by more than 5 percent of patients in the guanfacine group were somnolence, headache, sedation, upper abdominal pain, fatigue, irritability, vomiting, decreased diastolic blood pressure, and dizziness.
• An investigational product that combines naltrexone and bupropion may provide a smoking-cessation treatment for overweight and obese smokers with little risk for the weight gain commonly seen after stopping smoking. In an open-label study funded by Orexigen Therapeutics Inc., 27 volunteers with body mass index between 27 kg/m2 and 46 kg/m2 and who smoked an average of 10 or more cigarettes a day were given the combination treatment of naltrexone sustained-release (SR) and bupropion SR, titrated to a daily total dose of 32 mg and 360 mg, respectively. They also received instructions on healthy eating and exercise and participated in the Mayo Clinic's smoking-cessation program. Through 24 weeks of treatment, the self-reported continuous abstinence was 41 percent in the intent-to-treat analysis and nearly 60 percent in the 17 patients who completed the 24-week study. The mean serum cotinine level, a biochemical assessment of nicotine intake, at week 24 also decreased significantly from baseline. The authors concluded that the nicotine abstinence rates were comparable to currently available smoking-cessation treatments with no significant weight change from baseline.
• Ondansetron was tested in 14 patients with a DSM-IV diagnosis of treatment-resistant obsessive-compulsive disorder as an augmentation to serotonin-reuptake inhibitors and antipsychotics in a single-blind, prospective study. At a low dose of 0.5 mg/day for six weeks and 1 mg/day for an additional six weeks, nine patients met the criterion for response—at least a 25 percent reduction in the Yale-Brown Obsessive Compulsive Scale (YBOCS) score, and five did not. Currently approved for the prevention of chemotherapy-related and postoperative nausea and vomiting, ondansetron is a serotonin 5HT3 receptor antagonist that is hypothesized to down-regulate the dopaminergic system in the brain. The study was funded by Transcept Pharmaceuticals Inc.
• Gabapentin enacarbil, a once-daily extended-release tablet form of gabapentin being studied by XenoPort Inc., was tested in a randomized, double-blind, placebo-controlled clinical trial for the treatment of restless legs syndrome. After 12 weeks of treatment, patients who received gabapentin enancarbil 1200 mg daily (n=114) had a statistically significantly greater reduction from baseline in the International Restless Legs Scale total score than the placebo group. The proportion of patients who were classified as responders by clinicians, as assessed on the Clinical Global Impression–Improvement Scale, was 76 percent in the gabapentin group and 39 percent in the placebo group at week 12, and the difference was statistically significant. Somnolence and dizziness were the most commonly reported treatment-emergent AEs, occurring in 27 percent and 19 percent of patients in the gabapentin group, which led to five patients' withdrawing from the treatment. None withdrew because of these AEs in the placebo group.▪
