Med Check

This is Part 2 of a special edition of Med Check featuring summaries of new research posters presented in May at APA's 2008 annual meeting in Washington, D.C.

These presentations are usually preliminary in nature and often involve results that have not been peer reviewed for publication.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 frontal-quantitative electroencephalogram (fqEEG) index may prove a useful early predictor for an individual patient's response to antidepressant treatment and his or her remission, according to interim results from the multicenter Biomarkers for Rapid Identification of Treatment Effectiveness in Major Depression (BRITE-MD) trial.

This poster was presented by Andrew Leuchter, M.D., from Semel Institute at UCLA, and colleagues. They used a composite EEG index known as ATR (Antidepressant Treatment Response) to try to predict whether patients would respond to antidepressant treatment. Adults with major depressive disorder were started on escitalopram 10 mg/day for one week, assessed with fqEEG, and then randomized to continue on escitalopram (n=73), switch to bupropion extended-release 300 mg/day (n=73), or take both medications (n=74) for seven weeks. All patients were regularly evaluated with fqEEG and the Hamilton Rating Scale for Depression (HAM-D).

Sixty-eight percent of patients who were predicted by the ATR index to be responders at week 1 and remained on esciptalopram alone achieved response at week 7, compared with 28 percent of those who were predicted as nonresponders (p=0.001).

Statistical analyses revealed that after one week of escitalopram treatment, the ATR index findings significantly predicted patient response and remission rates at week 7. ATR index correlated with clinical assessment measured by HAM-D at every visit.

Among patients predicted by ATR as nonresponders to escitalopram after one week of treatment on this medication, those who were randomized to switching to bupropion had a higher response rate at week 7 (53 percent) than those who were kept on further escitalopram treatment (28 percent).

The BRITE-MD trial is ongoing and funded by Aspect Medical Systems Inc., which owns the EEG-based ATR index for depression.

• Genetic variations may be associated with the increased rate of certain medication-related adverse events, according to analyses of DNA samples from 243 Caucasian participants in a randomized, double-blind, clinical trial of duloxetine for major depression. Researchers analyzed the incidence rates of the seven most commonly reported adverse events considered related to taking the drug and 145 single nucleotide polymorphisms (SNPs) in 14 genes potentially relevant to the antidepressant and side effects. Decreased appetite was statistically significantly associated with SNP rs5569 in the norepinephrine transporter gene NET1. Gastric discomfort was significantly associated with SNP rs8071667 in the serotonin transporter gene SLC6A4.

The researchers cautioned that the findings must be confirmed with further replication and placebo-controlled data. The study was funded by Eli Lilly and Co.

• Pooled data from five randomized, double-blind, placebo-controlled, eight-week clinical trials of desvenlafaxine in patients with major depressive disorder showed that the drug is associated with small but statistically significant increases in systolic and diastolic blood pressure, compared with placebo. The analyses included 1,365 adult patients who received at least one dose of desvenlafaxine at dosages ranging from 50 mg/day to 400 mg/day and 636 who received placebo. The mean change in supine systolic blood pressure from baseline to the final treatment was -1.4 for the placebo group and +1.2, +2.0, +2.5, and +2.1 mmHg for the desvenlafaxine 50 mg, 100 mg, 200 mg, and 400 mg groups, respectively. The mean change in supine diastolic blood pressure was -0.6 for the placebo group and +0.7, +0.8, +1.8, and +2.3 mmHg for the other groups, respectively.

The study was led by Michael Thase, M.D., of the University of Pennsylvania School of Medicine and funded by Wyeth Research Inc.

• Escitalopram has been shown to be more effective than placebo in improving depression symptoms in a randomized, placebo-controlled, double-blind clinical trial in adolescents. In this phase 3 clinical trial conducted by Forest Laboratories, 316 patients from ages 12 to 17 with major depressive disorder received either 10 mg to 20 mg escitalopram (n=155) or placebo (n=157) for eight weeks. At the end of the trial, patients' scores on the Children's Depression Rating Scale–Revised, decreased on average by 22.1 points in the escitalopram group and 18.8 points in the placebo group. The difference was statistically significant. Adverse events led to 2.6 percent of patients in the escitalopram group and 0.6 percent of patients in the placebo group discontinuing the trial.

This poster was presented by Graham Emslie, M.D., from the University of Texas Southwestern Medical Center, and colleagues. Forest Laboratories plans to file an application with the Food and Drug Administration (FDA) to seek approval for escitalopram as a treatment for adolescent depression, according to the online newsletter FDANews.com in May. Fluoxetine is the only antidepressant approved by the FDA to treat depression in children and adolescents.

• The first randomized, controlled, single-blind study of implanting a cortical stimulation device in the left dorsal, lateral prefrontal cortex (DLPFC) in 12 patients with refractory depression suggests that cortical stimulation may be a treatment option that deserves further research. Robert Howland, M.D., at the University of Pittsburgh Medical Center, and colleagues from other institutions performed a feasibility study in 12 patients with severe, treatment-resistant depression who had been ill for 11 to 42 years and had failed seven to 13 courses of treatments, including 10 patients who had failed electroconvulsive therapy. An epidural electrode was implanted in the left DLPFC in each patient. The patients were randomly assigned to single-blind active or sham stimulation for eight weeks; after that all received active stimulation.

At the end of eight weeks, patients who received active stimulation (n=6) had a mean decrease of 22 percent in the HAM-D score, compared with an 8 percent decrease in HAM-D score in the sham group (n=5). “Preliminary results indicate that... cortical stimulation may have a treatment effect that... increases over time” beyond eight weeks, when all patients received active stimulation, the researchers noted. No serious adverse event related to the device was reported. The study was funded by Northstar Neuroscience, which developed the stimulation device.

• An open-label clinical trial of deep brain stimulation (DBS) conducted at three sites in Canada provides further support for the efficacy of DBS against treatment-resistant, severe depression. The results of this trial in 20 patients duplicate the findings from a previous pilot study by Helen Mayberg, M.D., and colleagues (Psychiatric News, June 23) that used the same method. Electrodes were surgically implanted in the subgenual cingulated cortex Brodmann area 25 (Scg25) on both sides of the brain, so that the white matter in this region received constant electrical currents. Study participants had all failed at least four treatments including cognitive-behavioral therapy and had a mean baseline HAM-D score of 28.

Sixteen patients had completed six months of continuous DBS at the time results were reported. Nine (56 percent) of the 16 patients achieved response, defined as a 40 percent reduction in HAM-D score. Three patients had so far achieved remission, defined as a HAM-D score of 7 or less. Two serious adverse events due to broken wires (which connect the stimulator in the brain and the battery in the chest) were reported. One completed suicide and one suicide attempt were judged by the clinicians as not related to the device. The majority of reported adverse events were mild; headache was the most common. The researchers, led by Sidney Kennedy, M.D., at the University Health Network (affiliated with the University of Toronto) and Mayberg, concluded that there were “no unexpected device-related adverse events” and “no acute stimulation-related adverse events.”

The trial was supported by the St. Jude Medical ANS Division. ▪