Brain Activity May Predict Vulnerability to Antidepressant Side Effects

Individuals susceptible to antidepressant side effects may show changes in brain activity prior to treatment, according to a study published in the April 2005 Neuropsychopharmacology. Use of a quantitative electroencephalography (QEEG) imaging technique developed by the UCLA Neuropsychiatric Institute may help physicians choose the best medication for patients, increasing chances for treatment success.

"The ability to identify individuals who are at greatest risk of side effects would greatly improve the success rate of antidepressant treatment," said Aimee M. Hunter, lead author and research fellow at the UCLA Neuropsychiatric Institute. "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."

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.

Study participants were 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.

Researchers compared brain function changes in healthy research subjects with no history of depression while taking an antidepressant vs. placebo. 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.

Antidepressant side effects may 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.

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.

"This finding shows the promise of new ways for assessing susceptibility to antidepressant side effects," Hunter said.