FDA Issues Go-Ahead for Trial of Deep Brain Stimulation Device for Depression

Marlene Busko

Medscape Medical News 2008. © 2008 Medscape

February 8, 2008 — The US Food and Drug Administration (FDA) has issued an Investigational Device Exemption (IDE) allowing enrollment to begin for a study of a device for deep brain stimulation for major depressive disorder, according to a statement issued by St. Jude Medical Inc (St. Paul, Minnesota), which holds intellectual property rights for the device.

The Brodmann Area 25 Deep Brain Neuromodulation (BROADEN) study will evaluate the safety and effectiveness of deep brain stimulation in patients with depression for whom currently available treatments are not effective.

This 12-month clinical trial will evaluate the Libra deep brain stimulation system, which is designed to deliver mild electrical pulses to the Brodmann Area 25 region of the brain in the prefrontal cortex, which appears to be overactive when people are profoundly depressed.

The deep brain stimulation system consists of a neurostimulator that is surgically implanted near the collarbone and connected to implanted leads and extension wires in the brain. The system also has an external controller and programmer.

The first study of deep brain stimulation in depression was done at the University of Toronto, in Ontario, by Helen S. Mayberg, MD (now with Emory University, in Atlanta, Georgia) and Andres Lozano, MD, and was published in Neuron in 2005.

"Major depressive disorder is severely disabling," said Dr. Lozano in a statement. "Currently, there are no widely accepted treatment options for patients with this condition once multiple medications, psychotherapy, and electroconvulsive therapy have failed."

The press release notes that in the United States, more than 21 million adults suffer from a depressive disorder, according to the National Institute of Mental Health, and of these, only about 80% can be effectively treated with currently available therapies, according to the National Advisory Mental Health Council.

"We are hopeful that this trial will lead to the successful development of a sustainable therapy for those patients who have exhausted other treatment options," said Chris Chavez, president of St. Jude Medical’s Advanced Neuromodulation Systems division.

To be eligible for the study, participants must:

• Be currently diagnosed with major depressive disorder.


• Be aged 21 to 70 years old, with onset of the first depression episode before age 45 years.


• Have tried at least 4 treatments in their current depression episode, such as different medications, various combinations of medications, or electroconvulsive therapy.


• Have been depressed for at least 1 year.

Study information is available at www.BROADENstudy.com or toll-free at 866-787-4332.

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Varenicline Tablets May Be Linked to Risk for Serious Neuropsychiatric Symptoms

Yael Waknine

Medscape Medical News 2008. © 2008 Medscape

February 2, 2008 — The prescribing information for varenicline tablets (Chantix, Pfizer, Inc) has been updated to include warnings about the risk for serious neuropsychiatric symptoms, the US Food and Drug Administration (FDA) announced yesterday in a public health advisory.

The changes follow an early communication from the agency in November 2007 that advised healthcare professionals and the public regarding postmarketing cases of new-onset depressed mood, suicidal ideation, and behavioral/emotional changes within days to weeks of starting varenicline therapy. At that time, the causal role of varenicline remained unclear.

However, new information from an ongoing FDA analysis increasingly suggests that a link exists between varenicline and reports of behavioral changes, agitation, depressed mood, suicidal ideation, and attempted and completed suicide.

Although some of these events may have occurred in association with nicotine withdrawal, other patients had not yet discontinued smoking, according to an alert issued by MedWatch, the FDA's safety information and adverse event reporting program. Most cases occurred during treatment, but some also were reported following withdrawal of varenicline therapy.

"Chantix has proven to be effective in smokers motivated to quit, but patients and healthcare professionals need the latest safety information to make an informed decision regarding whether or not to use this product," says Bob Rappaport, MD, director of the FDA's Division of Anesthesia, Analgesia and Rheumatology Products, in an FDA news release.

"While Chantix has demonstrated clear evidence of efficacy, it is important to consider these safety concerns and alert the public about these risks. Patients should talk with their doctors about this new information and [about] whether Chantix is the right drug for them, and healthcare professionals should closely monitor patients for behavior and mood changes if they are taking this drug," Dr. Rappaport adds.

Because varenicline may cause worsening of current psychiatric illness (even if it is under control) and cause recurrence of prior illness, patients should inform their healthcare provider of any such illness before initiating varenicline therapy.

Patients and their families/caregivers should be alert to changes in mood or behavior during treatment with varenicline; these should be immediately reported to a healthcare provider. The FDA also warns that vivid, unusual, or strange dreams may occur during therapy and that patients may experience impairment of their ability to drive or operate heavy machinery.

At present, the FDA is working with the manufacturer to finalize a medication guide for patients. Further safety labeling changes may be warranted as the FDA continues its review of data and of new information regarding varenicline and the risk for severe changes in mood and behavior.

Varenicline is indicated as an aid to smoking cessation treatment. Adverse events related to its use should be reported to the FDA's MedWatch reporting program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787

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