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April 21, 2011 — When it comes to predicting who will respond to cognitive therapy (CT), the eyes may have it, new research suggests.

In a new study, researchers from the University of Pittsburgh in Pennsylvania report that measuring how much the pupil dilates when words that have an emotional connotation, such as death and guilt are spoken, is a good way to determine those depressed patients who will respond to CT and those who will not.

The findings are published in the April 15 issue of Biological Psychiatry.

"Personalized medicine is gaining traction," lead study author Greg J. Siegle, PhD, associate professor of psychiatry at the University of Pittsburgh School of Medicine, told Medscape Medical News.

"We realize that in psychiatry and psychology we often prescribe our treatments based on what works for most people and not on what might work best for 1 person in particular."

Eliminating Ineffective Treatment

The most effective treatments for depression, including CT, only work in about half of patients. Being able to predict those individuals who would be most likely to benefit from such treatment would save time, eliminate the use of ineffective treatments, and save money, Dr. Siegle said.


Dr. Greg J. Siegle

In previous work, Dr. Siegel and colleagues used brain scans with functional magnetic resonance imaging (fMRI) to show that depressed patients had large amounts of pupil dilation when confronted with emotional topics.

In the current study, the investigators sought to determine whether the pupillary responses to emotional stimuli could predict whether CT would be successful in obtaining a remission of depression.

The investigators measured the pupillary reaction to emotional words in 32 adults diagnosed as having unipolar depression. All patients received 16 to 20 sessions of CT. They then assessed 20 patients with fMRI.

The study showed that those patients who responded to CT had lower pupillary responses compared with those who did not respond. Those who got better had 0.1-mm less pupil dilation (SD, 0.8) than patients who did not.

"We need to replicate these results in a larger study. If they do replicate, I would like to see clinicians start to consider using a test before prescribing therapy," Dr. Siegel said.

Work is currently under way to make collection of the pupil data easy and inexpensive, he added.

"We would want to make this technology available to every clinician. Rather than having a research-grade pupilometer, with expensive presentation software, we are in the process of making it work on the kind of hardware and software that any psychiatrist would have in their office. That is what we are working toward."

Growing Problem of Treatment Resistance

In an interview with Medscape Medical News, Eric Plakun, MD, director of admissions and professional relations at the Austen Riggs Center, Stockbridge, Massachusetts, and past chair of the American Psychological Association Committee on Psychotherapy by Psychiatrists, said the study, although small, was a very interesting effort to seek out biological markers to help determine who are the people with the more severe depressions.


Dr. Eric Plakun

Importantly, the study also recognizes the growing problem of treatment resistance, he said.

Dr. Plakun noted that being able to form a therapeutic alliance with a patient is also an important predictor of response.

"When I'm trying to assess if the patient is worth investing the time, energy, and money in this kind of treatment, I do a nondigital, noncomputerized, old-fashioned analog investigation of the patient's face, response to emotion, how they look, how their face changes, how they relate to me and indicate their understanding and awareness of and ability to engage around issues in their therapy."

It would be great to have a solid and reliable test to tell who will respond to various treatments, he said. “To that end, this is important research.”

However, Dr. Plakun stressed that such a test would form only a small part of developing a specific patient’s treatment regimen.

"This is a very microscopic part of what skilled therapists tune into when they have an initial session with a patient and are trying to figure out if they’re treatable. The most robust predictor we know of for psychotherapy is the therapeutic alliance. If there is a good agreement between therapist and patient, that’s a very good predictor of good outcome."

Dr. Siegle and Dr. Plakun have disclosed no relevant financial relationships.

Biol Psychiatry. 2011;69:726-733. Abstract


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