This study will determine if fluoxetine (Prozac® (Registered Trademark)) is effective for treating anxiety or depression in children and adolescents. The study will also use functional magnetic resonance imaging (fMRI) to learn more about how the brain functions in children/adolescents taking this medication for anxiety or depression.

Condition
Depression Mood Disorder Anxiety Disorder Healthy

Further Study Details: 

Expected Total Enrollment:  748

This protocol uses functional magnetic resonance imaging (fMRI) to examine the effects of pharmacologic treatment on neurocognitive correlates of pediatric mood and anxiety disorders. The first goal of the project is to document deficits in brain systems mediating attention bias and emotional memory in pediatric mood and anxiety disorders. The second goal of the project is to examine the effects of treatment with fluoxetine, a specific serotonin reuptake inhibitor (SSRI), on these deficits. A total of 215 children, adolescents, and adults will be recruited, including 75 juveniles with a current anxiety disorder, 60 juveniles with current major depression, 40 juveniles with no psychiatric disorder, and 40 adults with no psychiatric disorder. Before the initiation of treatment, these subjects will be tested using fMRI paradigms designed to examine brain regions engaged by attending to and encoding emotionally salient stimuli. After this initial fMRI test, 105 of the subjects with depression or an anxiety disorder will be randomized to receive eight weeks of double-blind treatment with fluoxetine or placebo. An additional 30 will receive cognitive behavioral therapy at the University of Maryland, Maryland Center for Anxiety Disorders. All subjects will be re-tested after eight-weeks using the same fMRI paradigms.

Prior neuropsychological studies in children, as well as in adults, note that mood and anxiety disorders are associated with deficits in attention modulation and emotional memory. Prior imaging studies in healthy adults note that tasks requiring attention modulation or emotional memory engage cortico-limbic brain regions previously implicated in adult mood and anxiety disorders. These regions include the amygdala, ventro-medial prefrontal cortex, cingulate gyrus, and hippocampus. As a result, we hypothesize that fMRI attention modulation and emotional memory paradigms will engage these cortico-limbic brain regions in both psychiatrically healthy and impaired subjects. However, these groups will differ in the degree of cortico-limbic engagement.

Prior psychopharmacologic studies in children and adolescents suggest that SSRIs might effectively treat both mood and anxiety disorders. As a result, we hypothesize that mood and anxiety symptoms will show significantly greater decreases among children and adolescents randomized to receive fluoxetine versus placebo. Prior studies in adults suggest that effective treatments also ameliorate abnormalities in attention bias and emotional memory. In the current protocol, subjects will be re-tested after eight-weeks using fMRI. We hypothesize that effective fluoxetine treatment will normalize neuropsychological abnormalities in attention and emotional memory. These effects on behavioral performance will be paralleled by effects on brain activation patterns. Specifically, subjects who respond to fluoxetine, relative to those who do not respond to placebo, will differ in fMRI activations within cortico-limbic brain regions.

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA:
ALL JUVENILE SUBJECTS:
Age: 9 - 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: 20-50
Consent: can give consent/assent
IQ: all subjects will have IQ greater than 70. Assessment relies on WASI.
EXCLUSION CRITERIA:
ALL SUBJECTS:
Any medical condition that increases risk for SSRI treatment. All subjects will have complete physical examination and 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

Maryland
      National Institute of Mental Health (NIMH), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  010192; 01-M-0192
Record last reviewed:  June 9, 2004
Last Updated:  November 23, 2004
Record first received:  June 29, 2001
ClinicalTrials.gov Identifier:  NCT00018057
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08