Brain activity prior to treatment flags vulnerability to antidepressant side effects

March 30, 2005

In a finding that opens new doors to determining susceptibility to antidepressant side effects, researchers at the UCLA Neuropsychiatric Institute report that changes in brain activity prior to treatment with antidepressants can flag patient vulnerability.

Published in the April 2005 edition of the peer-reviewed journal Neuropsychopharmacology, the study is the first to link brain function and medication side effects, and to show a relationship between brain function changes during brief placebo treatment and later side effects during treatment with medication.

The study's unique design compares brain function changes in healthy research subjects with no history of depression while taking an antidepressant vs. placebo, a pill with inactive ingredients. In addition, all participants took only placebo for one week prior to randomization to medication or placebo.

Using "cordance," a quantitative electroencephalography (QEEG) imaging technique developed at UCLA, the research team found changes in brain function in the prefrontal region during the one-week placebo lead-in were related to side effects in subjects who received an antidepressant.

"This finding shows the promise of new ways for assessing susceptibility to antidepressant side effects," said Aimee M. Hunter, lead author and research fellow at the UCLA Neuropsychiatric Institute.

"The ability to identify individuals who are at greatest risk of side effects would greatly improve the success rate of antidepressant treatment," Hunter said. "For example, physicians might select a medication with a lower side-effect profile, start medication at a lower dose or opt for psychotherapy alone when treating patients susceptible to antidepressant side effects."

Antidepressant side effects can be related to medication or to factors such as patient expectations derived from educational materials or consultations with a physician, but determining vulnerability or cause in a clinical setting is difficult.

To overcome this hurdle, the UCLA research team used healthy subjects so that brain function would not be affected by illness or changes in the illness. The team examined QEEG cordance during a placebo lead-in so brain function changes in the first phase of the trial could arise from only non-medication factors.

The study enrolled 32 healthy subjects who had never suffered from depression. All underwent a one-week, single-blind placebo lead-in before being randomized to four weeks of double-blind treatment with the antidepressant venlafaxine or placebo. Members of the research team met with subjects at seven time points over the course of the study -- at baseline, the end of the placebo lead-in, after randomization and weekly after randomization.

A research nurse obtained side effect reports during each visit, systematically asking subjects about specific complaints, including gastrointestinal upset, cardiovascular disturbance, sleep disturbance, anxiety and agitation. EEG readings were obtained at visits throughout the study. Changes in prefrontal brain function observed before start of medication signaled a greater number of adverse effects during antidepressant treatment.
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Grants from the National Institute of Mental Health, the National Alliance for Research in Schizophrenia and Depression, and Lilly Research Laboratories funded the project.

Other members of the research team included Dr. Andrew F. Leuchter, Melinda L. Morgan, Dr. Ian A. Cook, Michelle Abrams and Barbara Siegman at UCLA, and Drs. David J. DeBrota and William Z. Potter at Lilly Research Laboratories.

This study is part of a larger program headed by Leuchter in the UCLA Laboratory of Behavioral Pharmacology focusing on the use of QEEG cordance to predict and detect responses to antidepressant medications and placebo.

The UCLA Neuropsychiatric Institute is an interdisciplinary research and education institute devoted to the understanding of complex human behavior, including the genetic, biological, behavioral and sociocultural underpinnings of normal behavior, and the causes and consequences of neuropsychiatric disorders. In addition to conducting fundamental research, the institute faculty seeks to develop effective treatments for neurological and psychiatric disorders, improve access to mental health services, and shape national health policy regarding neuropsychiatric disorders. More information is available online at http://www.npi.ucla.edu/ and at http://www.placebo.ucla.edu/.

University of California - Los Angeles

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