INCLUSION CRITERIA - CHILDREN WITH SEVERE MOOD AND BEHAVIORAL DYSREGULATION (all must be met):
1. Ages 7-17
2. Abnormal mood (specifically anger, sadness, and/or irritability), present at least half of the day most days, and of sufficient severity to be noticeable by people in the child's environment (e.g. parents, teachers, peers).
3. Hyperarousal, as defined by at least three of the following symptoms: insomnia, agitation, distractibility, racing thoughts or flight of ideas, pressured speech, intrusiveness.
4. Compared to his/her peers, the child exhibits markedly increased reactivity to negative emotional stimuli that is manifested verbally or behaviorally. For example, the child responds to frustration with extended temper tantrums (inappropriate for age and/or precipitating event), verbal rages, and/or aggression toward people or property. Such events occur, on average, at least three times a week for the past four weeks.
5. The symptoms in # 2, 3, and 4 above are currently present and have been present for at least 12 months without any symptom-free periods exceeding two months. The onset of symptoms must be prior to age 12 years.
6. The symptoms are severe in at least one setting (e.g. violent outbursts, assaultiveness at home, school, or with peers). In addition, there are at least mild symptoms (distractibility, intrusiveness) in a second setting.
7. For lithium treatment trial only, If the child meets DSM-IV criteria for major depressive disorder, he/she must have had an adequate trial of an SSRI antidepressant (defined as four weeks of consecutive treatment in minimally effective doses among adults: paroxetine 20 mg; fluoxetine 20 mg; citalopram 20 mg; fluvoxamine 150 mg; sertraline 50 mg). His/her response to the treatment must have been no more than minimal (i.e. CGI-I greater than 2).
8. For lithium treatment trial only, If the child meets DSM-IV criteria for attention deficit hyperactivity disorder, he/she must have had an adequate trial of methylphenidate (defined as two consecutive weeks of Ritalin, Metadate, Methylin, or Concerta, at least 30 mg/day if adverse effects present, and at least 60 mg/day if dose not limited by adverse effects), and an adequate trial of amphetamines (two consecutive weeks of Adderall 20 mg/day or dextroamphetamine 40 mg/day). His/her response to the treatment must have been no more than minimal (i.e. CGI-I greater than 2).
9. For lithium treatment trial only: Currently in treatment with a psychiatrist for the symptoms.
10. For medication taper or lithium treatment trial only: The child is failing his/her treatment. To meet this criterion:
a) The child's current CGAS score must be less than or equal to 60.
b) The child's psychiatrist/treater must agree that the child's response to his/her current treatment is no more than minimal (i.e. CGI-I greater than 2). According to this criterion, it would be clinically appropriate to change the child's current treatment.
c) On the basis of record review and interviews with child and parent, the research team agrees that the child's response to his/her current treatment is no more than minimal (i.e. CGI-I greater than 2).
INCLUSION CRITERIA - CONTROLS:
Control subjects will be age- and sex- matched to the patients. They will have normal physical and neurological examinations, and an identified primary care physician. Both control subjects and their first-degree relatives must be free of current or past psychopathology.
EXCLUSION CRITERIA - CHILDREN WITH SEVERE MOOD AND BEHAVIORAL DYSREGULATION:
1. The individual exhibits any of these cardinal bipolar symptoms:
- Elevated or expansive mood
- Grandiosity or inflated self-esteem
- Decreased need for sleep
- Increase in goal-directed activity (this can result in excessive involvement in pleasurable activities that have a high potential for painful consequences)
2. The symptoms occur in distinct periods lasting more than 4 days , and therefore meet criteria for hypomania or mania.
3. Meets criteria for schizophrenia, schizophreniform disorder, schizoaffective illness, PDD, or PTSD.
4. Meets criteria for substance use disorder in the three months prior to randomization.
5. IQ less than 70.
6. The symptoms are due to the direct physiological effects of a drug of abuse, or to a general medical or neurological condition.
7. Currently pregnant or lactating, or sexually active without using a barrier method of contraception.
8. For those entering the lithium treatment trial: Contraindications to treatment with lithium (e.g. renal, thyroid, cardiac disease, seizure disorder).
9. For those entering the treatment trial: previous adequate trial of treatment with lithium that did not have beneficial clinical effects. An adequate trial is defined as at least 6 weeks of treatment with a blood level of greater than or equal to 0.8 mEq/L.
EXCLUSION CRITERIA - CONTROLS:
I.Q. less than 80; ongoing medical illness; neurologic disorder (including seizures); pregnancy; meeting past or present criteria for any diagnosis on the K-SADS-PL(7); meeting the criteria for severe mood and behavioral dysregulation; meeting criterion of post-traumatic stress disorder (exposure to a traumatic event).
CHILDREN ENTERING MEDICATION DISCONTINUATION STUDY:
Children may be eligible to be admitted to the Pediatric Behavioral Health Unit at the Clinical Center in order to have their medication discontinued and to undergo research procedures (i.e., neuropsychological testing and neuroimaging) for up to two weeks medication-free without entering the Li/placebo trial. Individuals entering this arm of the study will meet the same inclusion/exclusion criteria as for the Li/placebo trial above (i.e. full diagnostic criteria and CGAS less than or equal to 60) with the following modifications:
a) On the basis of record review and interviews with child and parent, the research team concludes that the child's response to his/her current treatment is no more than minimal (i.e. CGI-S greater than 3).
b) If the child meets DSM-IV criteria for major depressive disorder, it is not necessary for him/her to have had an adequate trial of an SSRI antidepressant.
c) If the child meets DSM-IV criteria for attention deficit hyperactivity disorder, it is not necessary for him/her to have received an adequate trial of methylphenidate or dextroamphetamine.
d) A participant is not required to currently be in treatment with a psychiatrist for his/her symptoms.
e) If the child is in treatment, his/her psychiatrist/treater agrees that it is clinically appropriate to change the child's current treatment.
f) Contraindications to treatment with lithium (e.g.renal, thyroid, cardiac disease) don't apply to eligibility for this arm of the protocol.
g) Participants may have received a previous adequate trial of treatment with lithium that did not have sufficient beneficial clinical effects.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 09/17/2008