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

Depression research study

What is the primary objective of this study?

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. In addition, subjects also will be randomly and blindly assigned to receive either an active computer-based training task or an inactive computer-based training task, administered as part of the other,along with their medication or talk -therapy treatment. The active training is thought to help anxiety whereas the inactive training is thought to have no effect. The purpose of this part of the study is to understand the best way to help children and adolescents who are having problems with anxiety. However, more research is needed to find the best way to help such children and adolescents. 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.

Who is eligible to participate?

- INCLUSION CRITERIA: - ALL JUVENILE SUBJECTS: - Age: 8 - 17 (subjects who consent as 17- year-olds but turn 18 during the course of the study will be eligible to complete all procedures completed by other subjects who consent as 17- year- olds but do not turn 18). - Consent: can give consent/assent (Parents will provide consent; minors will provide assent) - IQ: all subjects will have IQ > 70 (Assessment relies on WASI) - Language: all subjects will speak English - ALL ADULT SUBJECTS - Age: 18-50 - Consent: can give consent - IQ: all subjects will have IQ>70 (Assessment relies on WASI) - Language: all subjects will speak English - ALL SUBJECTS WITH AN ANXIETY DISORDER - Diagnosis: Current Diagnosis of Social Phobia, Separation Anxiety, Generalized Anxiety Disorder, or Panic Disorder (Based on K-SADS (juveniles) or SCID (adults)) - Symptom Severity: Clinically significant, ongoing anxiety symptoms - Clinical Impairment: Clinically significant, ongoing distress or impairment from anxiety - ALL SUBJECTS WITH A MOOD DISORDER - Diagnosis: Current Diagnosis of Major Depression (Based on K-SADS (juveniles) or SCID (adults)) - Clinical Impairment: Clinically significant, ongoing distress or impairment from depressive symptoms - Symptom Severity: Clinically significant, ongoing depressive symptoms 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 and history. 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. - Current diagnoses Tourette s Disorder, OCD, post-traumatic distress disorder, conduct disorder - Past or current history of mania, psychosis, or severe pervasive developmental disorder - 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. - NIMH employees and staff and their immediate family members will be excluded from the study per NIMH policy - HEALTHY ADULT SUBJECTS - Any current psychiatric diagnosis (Assessment relis on SCID)

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?


Mood Disorder

Anxiety Disorder


Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Study Status


Start Date: June 27, 2001

Completed Date:


Type: Observational


Primary Outcome: The Pediatric Anxiety Rating Scale (PARS)

Secondary Outcome:

Study sponsors, principal investigator, and references

Principal Investigator: Daniel S Pine, M.D.

Lead Sponsor: National Institute of Mental Health (NIMH)

Collaborator: University of Minnesota - Clinical and Translational Science Institute

More information:

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.

Discuss Prozac