Clinical Trial of Fluoxetine in Anxiety and Depression in Children, and Associated Brain Changes
| Status: | Recruiting |
|---|---|
| Conditions: | Anxiety, Depression, Healthy Studies, Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology, Other |
| Healthy: | No |
| Age Range: | 8 - 40 |
| Updated: | 3/16/2019 |
| Start Date: | June 27, 2001 |
| Contact: | Daniel S Pine, M.D. |
| Email: | pined@mail.nih.gov |
| Phone: | (301) 594-1318 |
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.
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.
Objective: This protocol uses functional magnetic resonance imaging (fMRI) to examine
neuro-cognitive 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.
Study Population: A total of 2530 children, adolescents, and adults will be recruited. Most
subjects will not be able to complete all procedures. We seek to comprehensively study 150
juveniles with only a current anxiety disorder, 60 juveniles with current major depression,
150 juveniles with no psychiatric disorder, 100 adults with major depression, 60 adults with
an anxiety disorder, and 150 adults with no psychiatric disorder. To achieve this, we are
recruiting 2530 individuals.
Design: 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. Treatment will comprise
open treatment with either fluoxetine or CBT, augmented with computer-based attention
retraining, delivered in a randomized-controlled design, with random assignment to either
active or placebo attentiontraining regimens. Adolescent subjects then will be re-tested
after eight-weeks using only the attention, memory, and conditioning paradigms.
Outcome Measures: 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.
Juvenile subjects also will be treated for eight-weeks, and a subset 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.
neuro-cognitive 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.
Study Population: A total of 2530 children, adolescents, and adults will be recruited. Most
subjects will not be able to complete all procedures. We seek to comprehensively study 150
juveniles with only a current anxiety disorder, 60 juveniles with current major depression,
150 juveniles with no psychiatric disorder, 100 adults with major depression, 60 adults with
an anxiety disorder, and 150 adults with no psychiatric disorder. To achieve this, we are
recruiting 2530 individuals.
Design: 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. Treatment will comprise
open treatment with either fluoxetine or CBT, augmented with computer-based attention
retraining, delivered in a randomized-controlled design, with random assignment to either
active or placebo attentiontraining regimens. Adolescent subjects then will be re-tested
after eight-weeks using only the attention, memory, and conditioning paradigms.
Outcome Measures: 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.
Juvenile subjects also will be treated for eight-weeks, and a subset 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.
- 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)
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 301-402-8225
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