Clinical Trial of Fluoxetine in Anxiety and Depression in Children, and Associated Brain Changes

Condition(s) targeted: Depression; Mood Disorder; Anxiety Disorder; Healthy

Phase: N/A

Status: Recruiting

Sponsored by: National Institute of Mental Health (NIMH)

Overall contact:
Allison M. Detloff, Phone: (301) 451-6817, Email: detloffa@mail.nih.gov

This study uses functional magnetic resonance imaging (fMRI) to learn how the brain functions in adolescents receiving fluoxetine (Prozac) cognitive behavioral therapy (CBT) or interpersonal therapy (IPT) for anxiety or depression in children/adolescents.

All participants will receive interviews to assess how they are doing in general, including general mood, degree of nervousness and behavior. Each participant and one of his or her parents will be interviewed separately and together. Those electing the medication study will also receive a physical examination. Participants are asked to complete tasks involving problem-solving and memory that involve looking at pictures, remembering things, testing reaction times, and making simple choices.

Participants with anxiety or depression will first meet with a psychiatrist or psychologist for two weekly sessions of talk therapy. Those who remain anxious or depressed after these 2 weeks will have the 3 options based on their choice: 1) treatment with fluoxetine daily for 8 weeks 2) cognitive-behavioral therapy or interpersonal therapy (two kinds of talk therapy) once a week for 8 weeks 3) a random assignment (50% chance) to either placebo or fluoxetine for 8 weeks. During and after the 8 weeks of treatment, each participant will complete verbal and written symptom ratings. Blood samples will be drawn for laboratory tests before drug treatment and after it ends.

Those who have not improved by the end of the study will be offered other treatment for 1 to 3 months, and the clinicians will help with finding subsequent aftercare. Those who improve with treatment will continue therapy at NIH until an outside physician is able to assume responsibility for monitoring medication.

FOR MORE INFORMATION REGARDING THIS STUDY CALL THE CORE PHONE NUMBER: 301-496-5645

Official title: Fluoxetine's Effects on Attention and Emotional Memory in Anxious and Depressed Youth and Adults

Study design: N/A

Detailed description: This protocol uses functional magnetic resonance imaging (fMRI) to examine neurocognitive correlates of pediatric and adult mood and anxiety disorders. The primary goal of the project is to document in pediatric anxiety disorders and major depression perturbations in brain systems mediating attention biases, fear conditioning, emotional memory, and response to various forms of motivational stimuli. As one secondary goal, the project measures the relationship between these factors and treatment response to either fluoxetine, a specific serotonin reuptake inhibitor (SSRI), cognitive behavioral therapy (CBT), or interpersonal psychotherapy (IPT). Another secondary goal examines similar associations in adults.

A total of 630 children, adolescents, and adults will be recruited and comprehensively studied. This will include 150 juveniles with only a current anxiety disorder, 60 juveniles with current major depression, 150 juveniles with no psychiatric disorder, 60 adults with major depression, 60 adults with an anxiety disorder, and 150 adults with no psychiatric disorder. Subjects will be tested using fMRI paradigms designed to examine brain regions engaged when processing motivationally salient stimuli, as assessed during attention, memory, social interaction, reward, and fear-conditioning paradigms. After these initial fMRI tests, subjects with depression or an anxiety disorder receive treatment. Adolescent subjects then will be re-tested after eight-weeks using only the attention, memory, and conditioning paradigms.

Prior studies note that mood and anxiety disorders are associated with deficits in attention and emotional memory. Prior imaging studies note that tasks requiring attention modulation, emotional memory, social interchange, and fear conditioning engage brain regions previously implicated in adult mood and anxiety disorders. These regions include most consistently the amygdala and ventral prefrontal cortex. Moreover, imaging studies of reward function implicate the striatum and prefrontal cortex in adult mood disorders. As a result, we hypothesize that attention, memory, social interaction, reward, and conditioning paradigms will engage the amygdala, ventral prefrontal cortex and striatum in both psychiatrically healthy and impaired subjects. Moreover, we hypothesize that these healthy and psychiatrically impaired groups will differ in the degree of engagement.

Prior studies suggest that SSRIs, CBT, and IPT effectively treat symptoms of mood and anxiety disorders. Moreover, prior studies in adults also suggest that fMRI response patterns predict response to these treatments. In the current protocol, juvenile subjects will be treated for eight-weeks using either SSRIs, CBT, or IPT. Subjects also may elect to receive attention-retraining as part of their treatment with one of these agents. A subset of subjects will be re-tested with fMRI. We predict that pre-treatment abnormalities in neural circuitry will predict response to treatment, such that increased amygdala and prefrontal activation will occur in individuals who show the strongest response to treatment. Moreover, we hypothesize that effective treatment will normalize abnormalities in attention and emotional memory, as manifest in fMRI.

Minimum age: 8 Years. Maximum age: 40 Years. Gender(s): Both.

Criteria:

- INCLUSION CRITERIA:

ALL JUVENILE SUBJECTS:

Age: 8 - 17

Consent: can give consent/assent (Parents will provide consent; minors will provide assent)

IQ: all subjects will have IQ greater than 70 (Assessment relies on WASI)

SUBJECTS WITH AN ANXIETY DISORDER:

Diagnosis: Current Diagnosis of Social Phobia, Separation Anxiety, or Generalized Anxiety Disorder (Based on K-SADS)

Symptom Severity: Score greater than 9 on PARS (This score was used to enroll subjects in previous trial demonstrating efficacy of an SSRI in pediatric anxiety)

Clinical Impairment: CGAS less than 60

SUBJECTS WITH A MOOD DISORDER:

Diagnosis: Current Diagnosis of Major Depression (Based on K-SADS (juveniles) or SCID (adults))

Clinical Impairment: CGAS less than 60 (juveniles) GAS less than 70 (adults)

Symptom Severity: CDRS Score greater than 39 (juveniles) (This score was used to enroll subjects in previous trials demonstrating efficacy of an SSRI in pediatric depression)

ALL ADULT SUBJECTS:

Age: 20-40

Consent: can give consent/assent

IQ: all subjects will have IQ greater than 70. Assessment relies on WASI.

EXCLUSION CRITERIA:

ALL SUBJECTS:

Any serious medical condition or condition that interferes with fMRI scanning, and for patients electing medication, any condition that increases risk of SSRI treatment. All patients will have complete physical examination. Healthy volunteer participants will be medication-free and have no current serious medical conditions, based on a review of their medical history.

Pregnancy

Current use of any psychoactive substance; current suicidal ideation; current diagnosis of attention deficit hyperactivity disorder (ADHD) of sufficient severity to require pharmacotherapy. These factors could complicate treatment with an SSRI. No subject on medication will be accepted into the trial. Subjects will not be taken off of medications to enter the trial.

Current diagnoses Tourette's Disorder, OCD, post-traumatic distress disorder, conduct disorder. These factors may be effected by SSRI treatment, influencing ability to detect effects on anxiety/depression

Past or current history of mania, psychosis, or pervasive developmental disorder. These factors may be effected by SSRI treatment, influencing ability to detect effects on anxiety/depression

Recent use of an SSRI; all subjects must have been free of any SSRI-use for at least one month (fluoxetine six months) and must not have been treated with an SSRI for their current depressive episode. This is designed to exclude subjects who have failed a trial of an SSRI for their current episode of major depression.

ALL ADULT SUBJECTS:

Any current psychiatric diagnosis. Assessment relies on SCID.

SUBJECTS WITH AN ANXIETY DISORDER:

Current Major Depressive Disorder

Allison M. Detloff, Phone: (301) 451-6817, Email: detloffa@mail.nih.gov

National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States; Recruiting

New York University Child Study Center, New York, New York 10016, United States; Recruiting

NIH Clinical Center Detailed Web Page

Related publications:

Merikangas KR, Avenevoli S, Dierker L, Grillon C. Vulnerability factors among children at risk for anxiety disorders. Biol Psychiatry. 1999 Dec 1;46(11):1523-35.

Rosenbaum JF, Biederman J, Bolduc-Murphy EA, Faraone SV, Chaloff J, Hirshfeld DR, Kagan J. Behavioral inhibition in childhood: a risk factor for anxiety disorders. Harv Rev Psychiatry. 1993 May-Jun;1(1):2-16. Review.

Pine DS, Cohen P, Gurley D, Brook J, Ma Y. The risk for early-adulthood anxiety and depressive disorders in adolescents with anxiety and depressive disorders. Arch Gen Psychiatry. 1998 Jan;55(1):56-64.

Starting date: June 2001
Last updated: October 16, 2008