News Release

PET predicts response to Paxil in study

Peer-Reviewed Publication

University of California - Los Angeles

UCLA neuroscientists using positron emission tomography (PET) brain imaging have discovered distinct patterns of brain activity that predict the effectiveness of paroxetine, or Paxil, in treating obsessive compulsive disorder (OCD) vs. major depression.

Published in the March 2003 edition of the peer-reviewed American Journal of Psychiatry, the study is the first to compare neurobiological predictors of response to the same treatment across different disorders. Since patient responses to treatment options vary widely, the findings demonstrate the potential for using brain scans prior to treatment to tailor psychiatric care.

"The study demonstrates the potential of functional brain imaging to predict how a patient will respond to treatment," said lead investigator Dr. Sanjaya Saxena, director of the UCLA Neuropsychiatric Institute's OCD Research Program and associate professor-in-residence of psychiatry and biobehavioral sciences at UCLA's David Geffen School of Medicine. "Pretreatment brain scans hold promise for accelerating the sometimes painstaking process of identifying the best treatment for an individual patient and speeding development of new interventions."

OCD affects up to 3 percent of the population, or 8 million people in the United States alone. Symptoms include recurrent fears, impulses or images that cause severe anxiety and drive people to do particular repetitive behaviors, such as washing, arranging, checking or hoarding.

Major depression is more common, affecting up to 15 percent of the population, or 35 million people in the United States, at some point in their life. Symptoms include depressed mood, loss of interest, fatigue, suicidal thoughts, and sleep and appetite problems.

Serotonim reuptake inhibitor (SRI) medications, such as paroxetine, are the first line of treatment for both OCD and major depression, but responses vary greatly among patients. SRIs fail to work in approximately one-half of all patients with OCD and one-third of patients with major depression.

In addition to SRIs, other effective treatments for OCD include cognitive-behavioral therapy and adjunctive (add-on) treatment with low-dose antipsychotic medication. For major depression, many other antidepressants are effective, including tricyclic antidepressants, bupropion, venlafaxine, nefazodone, mirtazapine, MAOIs and several others. Psychotherapies, including Cognitive Therapy and Interpersonal Therapy for Depression, are also effective for major depression.

The UCLA research team used PET to measure brain activity in 27 patients with OCD alone, 27 with major depression alone, and 17 with concurrent OCD and major depression. Patients were treated with 30 to 60 milligrams per day of paroxetine for eight to 12 weeks. The researchers analyzed the brain scans to determine pre- and post-treatment brain activity. They found that, although both OCD and depression symptoms improved with paroxetine treatment, the pattern of brain activity associated with improvement in OCD was different than that associated with improvement of depression.

The study showed a significant correlation of improved OCD symptoms with higher pre-treatment activity in the brain's right caudate nucleus. Among the depression patients, improvement correlated significantly with lower pretreatment activity in the brain's amygdala and thalamus, and with higher pretreatment activity in the brain's medial prefrontal cortex and rostral anterior cingulate gyrus.

Previous findings published in the March 2002 edition of Archives of General Psychiatry showed that paroxetine had different effects on brain activity in patients with OCD versus patients with major depression. OCD patients showed pre- to post-treatment decreases in activity in the orbitofrontal cortex, caudate nucleus and thalamus, while patients with depression showed decreased activity in the ventrolateral prefrontal cortex after treatment.

In addition to Saxena, other UCLA researchers involved in the study were Dr. Arthur L. Brody, Matthew L. Ho, Narineh Zohrabi, Karron M. Maidment and Dr. Lewis R. Baxter Jr.


Primary funding for the project was provided by the National Institute of Mental Health and the Charles A. Dana Foundation Consortium on Neuroimaging Leadership Training.

The OCD Research Program at the UCLA Neuropsychiatric Institute conducts research on functional brain imaging, medication treatment, cognitive-behavioral therapy, neuropsychological deficits, genetics and functional outcome of OCD, major depressive disorder, and OCD Spectrum Disorders such as body dysmorphic disorder and Tourette's syndrome.

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.

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