Med Check

This is part 1 of a two-part, special edition of Med Check featuring new research posters presented at APA's 2008 annual meeting in Washington, D.C., in May.

New research poster presentations are usually preliminary in nature and often involve results that have not been peer reviewed for publication. In addition, reports may involve the use of medications for indications that the Food and Drug Administration has not approved, and they are largely funded by product manufacturers.

• Citalopram, a selective serotonin reuptake inhibitor (SSRI), and RU486, a glucocorticoid antagonist also known as mifepristone, may boost the resistance of macrophages to HIV infection. Researchers at the University of Pennsylvania Department of Psychiatry and Children's Hospital of Philadelphia, led by Tami Benton, M.D., recruited 36 HIV-positive women with and without depression, obtained their blood samples, and isolated mononuclear cells to generate macrophages. The macrophages were treated with citalopram or RU486 as test conditions and then exposed to a strain of HIV.

Macrophages treated wit h either citalopram or RU486 had a significantly lower rate of being infected by the virus than the control (untreated) macrophages, regardless of whether the person who donated the blood cells was depressed. “These findings lend support to the evidence suggesting that serotonergic and glucocorticoid systems are mediators in the relationship between depression and immune function,” the researchers concluded.

The study was funded by the National Institute of Mental Health.

• Patients with bipolar II depression who have incomplete response to lamotrigine did not benefit from the addition of bupropion, according to a double-blind, placebo-controlled study presented by Scott Aaronson, M.D., director of the Clinical Research Programs and associate medical director of the Retreat at Sheppard and Enoch Pratt Hospital, and colleagues. Thirty adult bipolar II patients with Montgomery-Åsberg Depression Rating Scale (MADRS) scores above 17 and Young Mania Rating Scale scores under 14 first underwent eight weeks of open-label treatment with lamotrigine alone. Among the 26 patients who completed the monotherapy phase, 20 did not reach a 50 percent improvement in their MADRS scores and were randomized to receive, in addition to lamotrigine, either bupropion 150 mg to 300 mg daily or placebo for 16 weeks.

Between the nine patients who took bupropion and 11 who received placebo, there was no difference in the scores on the depression and mania scales. In other words, bupropion did not alleviate symptoms or induce mania in these patients.

The study was funded by GlaxoSmith-Kline, which makes bupropion.

• SSRIs are inadequately prescribed for Medicaid-enrolled patients with newly diagnosed obsessive-compulsive disorder (OCD), a retrospective study by Cheryl Hankin, Ph.D., and colleagues demonstrates. Between 1997 and 2006, 1,346 adults in the Florida Medicaid database received a new diagnosis of OCD (that is, no OCD diagnosis in the previous two years), among whom 73.3 percent received the recommended SSRIs as first-line drug therapy consistent with APA's clinical practice guideline for OCD treatment. Among these patients, only 21.8 percent had an adequate course of pharmacotherapy for at least 12 consecutive weeks at the target dose recommended by the guidelines.

The study was funded by Jazz Pharmaceuticals Inc.

• An analysis of data from three randomized, double-blind, controlled trials has found that iloperidone, an investigational antipsychotic drug being developed by Vanda Pharmaceuticals, is not less effective than haloperidol in the efficacy of long-term treatment of schizophrenia or schizoaffective disorder. Nearly 500 patients received either iloperidone or haloperidol (n=359 and 114, respectively) in a double-blinded fashion for 46 weeks after they had completed a six-week, randomized, double-blind, acute treatment trial of the two drugs and had responded to the treatment. The relapse rate was 43.5 percent in the iloperidone group and 41.2 percent in the haloperidol groups during the 46-week, long-term phase; the mean time to relapse was 89.8 days and 101.8 days, respectively. Statistical noninferiorit y analyses confirmed that iloperidone was not significantly different from haloperidol in efficacy. The discontinuation rate during the long-term trials was the same in both groups at 36.4 percent.

In nine phase 2 and phase 3 clinical trials, pooled data indicated that patients taking iloperidone had similar degrees of weight gain to patients on risperidone and haloperidol. The mean change from baseline in iloperidone-treated patients was +5.4 mg/dL in blood glucose level, -3.9 mg/dL in total cholesterol level, -17.7 mg/dL in triglyceride level, and -1.8 ng/mL in prolactin levels. Overall, 3,210 subjects had received iloperidone for a mean duration of 230 days in these studies.

The trials were funded by Vanda Pharmaceuticals.

• A prospective, observational study of clozapine orally disintegrat ing tablets (ODTs) indicated that this formulation of clozapine may have favorable effects on salivation and weight in patients with schizophrenia who have failed other atypical antipsychotic drugs or who have been taking regular clozapine tablets. The preliminary results of this ongoing study were collected from 261 patients at baseline, among whom 174 took clozapine ODT for 12 weeks. The mean weight at week 12 was not statistically significantly different from baseline. The degree of salivation, assessed on a scale of 0 to 4, had a mean rating of 1.6 at baseline and 0.9 at week 12, and the decreasing trend was statistically significant.

The study was funded by the maker of clozapine ODT, Azur Pharma.

• The efficacy of asenapine, an antipsychotic drug being developed by Organon, now a subsidiary of Schering-Plough Corp., was found to be comparable to that of olanzapine in a one-year, randomized, double-blind study as maintenance treatment for patients with bipolar mania. After nine weeks of acute treatment, the mean score change on the YMRS from baseline was -24.4 in the asenapine group and -23.9 in the olanzapine group. After an additional 40 weeks, the response rates (50 percent reduction in YMRS score) were 93 percent in the asenapine group and 95 percent in the olanzapine group.

Treatment-related adverse events occurred in 65.7 percent of patients in the asenapine group and 61.7 percent in the olanzapine group. Weight gain, metabolic syndrome, and hyperprolactinemia were more commonly seen in the olanzapine group, while extrapyramidal symptoms were more frequent in the asenapine group.

Among the 504 patients who entered the initial nine-week study, 229 were randomized to the olanzapine group. Two hundred and eighteen patients entered the 40-week extension phase, including 68 who took olanzapine and 65 who took asenapine. Among the 133 (61 percent) patients who completed the extension phase, the two groups had similar dropout rates.

The study was funded by Organon and Pfizer.

• ABT-089, an investigational drug being developed by Abbott Laboratories, has shown efficacy in treating adults with attention-deficit/hyperactivity disorder (ADHD). ABT-089 is a neuronal nicotinic receptor partial agonist.

In a phase 2, double-blind, crossover clinical trial, 221 adults with ADHD were randomly assigned to receive both ABT-089 and placebo for four weeks each with a two-week washout period in between. The active drug, at doses of 40 mg four times daily and twice daily, was more effective than placebo in reducing symptoms as measured by the investigator-rated Conners' Adult ADHD Rating Scale. The drug was generally well tolerated, and the most common adverse events included headache, insomnia, and upper respiratory infection.

In two other studies in healthy adults, a single dose of ABT-089 up to 60 mg (n=72) or multiple doses up to 40 mg twice daily for seven days (n=43) did not result in elevations of systolic and diastolic blood pressure or heart rate. In a study of adult ADHD patients, the ABT-089 and placebo groups did not differ significantly in blood pressure and heart rate changes from baseline.

The study was funded by Abbott Laboratories. ▪