This study seeks to learn about brain function in adolescents with depression and to
determine whether adding lithium carbonate to antidepressant medication can reduce
depression in children and adolescents. Functional magnetic resonance imaging (fMRI) and
magnetic resonance spectroscopy (MRS) will examine brain chemistry and function.
The participants may or may not have taken a selective serotonin reuptake inhibitor (SSRI)
(such as paroxetine (Paxil), sertraline (Zoloft) or fluoxetine (Prozac)) to treat their
The participants and their parents are interviewed both individually and together with
questions about the child's general mood, degree of nervousness, and behavior and how family
members are doing. Children and adolescents will have a physical examination, blood tests,
and intelligence and memory evaluations. Tests include standardized questions and tasks that
involve looking at pictures, remembering things, testing reaction times, and making simple
choices. Participants spend time in a, mock MRI scanner, to become comfortable with the
procedure. Participants and their parents meet weekly for 2 weeks with a psychologist or
psychiatrist for sessions. Those who remain depressed after these two sessions will begin
Those who are not currently taking an SSRI will be offered paroxetine. Those already taking
an SSRI will be randomly assigned to receive either lithium or a placebo (non-active pill)
in addition to the SSRI. Treatment continues for 8 weeks. During this time, the participant
and parent meet with the doctor once a week and complete written and oral evaluations. Blood
will be drawn before medication begins and at the end of the 8-week treatment. Participants
will have additional blood taken after 1 week on medication to help in deciding whether dose
adjustment is needed. Additional blood tests might be needed later on to ensure that the
dose is correct. Those who improve after 8 weeks will continue treatment at NIH until
responsibility for their care can be assume by an outside physician. Program staff will
help in facilitating referrals to physicians who will monitor the medication after the child
leaves the study.
Age: 9 to 17.
Consent: can give consent/assent.
IQ: All subjects will have IQ greater than 70.
Severity Criterion: CDRS greater than 39.
Impairment: All subjects will have a CGAS less than 60.
SUBJECTS WITH A RESISTANT MDD:
Diagnosis: Current Diagnosis of Major Depression.
Treatment Resistant:At least six-weeks continual use of an SSRI, the last two of which are
at high dose by the research team; CGI-S greater than 2 confirmed by observation during an
additional two weeks (at least 8-weeks total duration).
MEDICATION-FREE MDD SUBJECTS:
Diagnosis: Current Diagnosis of Major Depression
Clinical Impairment: CGAS less than 60.
Medication-Free: No psychotropic medications for two month period; depressed for less than
Any medical condition that increases risk for SSRI or lithium treatment or for MRI exam.
This will include screening for standard MRI scanning contraindications such as metallic
implants or pacemakers.
Current use of any psychoactive substance beyond ab SSRI; 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 stress disorder, conduct
Past or current history of mania, psychosis, or pervasive developmental disorder.
Long-Term SSRI Treatment: Subjects who have been receiving an SSRI medication for 12 wks
or longer upon entry into the observational phase of the study will not be eligible for