Severe mood dysregulation (SMD) is a very common syndrome in children. Its symptoms include
very severe irritability, including persistent anger and frequent outbursts, as well as
distractibility, hyperactivity, and other symptoms of attention deficit hyperactivity
disorder (ADHD). Many children with SMD receive the diagnosis of bipolar disorder (BD) in
the community, although they do not have clear manic episodes (with symptoms such as extreme
happiness and decreased need for sleep). Because SMD has not been studied in depth, we do
not know which medications are most helpful to those with SMD. This study will evaluate the
effectiveness of the stimulant medication methylphenidate (MPH, more commonly known as
Ritalin(Registered Trademark)) when combined (or not combined) with the antidepressant
citalopram (Celexa(Registered Trademark)) in treating symptoms of SMD in children and
adolescents. This study will provide information about how to treat SMD in youth.
This study will include approximately 80 patients between 7 and 17 years of age with SMD.
The patient's symptoms must have started before age 12.
The study will consist of four phases carried out over 4 to 5 months. During Phase 1, the
patient will undergo blood and urine tests, and will gradually taper off his or her
medication. The duration of this phase depends on the patient's medication before starting
the study. In Phase 2, the patient remains off all medication for 1 week. In Phase 3, the
patient will be treated with MPH for 2 weeks, and then will be randomly assigned to receive
either MPH plus citalopram or MPH plus a placebo for a further 8 weeks. In Phase 4, the
researchers will evaluate the effectiveness of the medications taken, and begin an open
treatment phase using medications that they deem appropriate for that patient (this may
include MPH with citalopram and/or other medication combinations).
Most patients will be admitted to the Pediatric Behavioral Health Unit at the National
Institutes of Health Clinical Center during the medication withdrawal part of the study
(Phases 1 and 2). From Phase 3 on, a patient may participate as an inpatient, outpatient, or
in day treatment, depending on what is in his or her best interests.
||Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
|Ages Eligible for Study:||7 Years|
|Genders Eligible for Study:||Both|
|Accepts Healthy Volunteers:||No|
- INCLUSION CRITERIA:
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
4. Compared to his/her peers, the child exhibits markedly increased reactivity to
negative emotional stimuli that is manifest verbally and/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
5. Criteria 2, 3, and 4 are currently present and have been present for at least 12
months without any symptom-free periods exceeding two months.
6. The onset of symptoms must be prior to age 12 years.
7. The symptoms are severe in at least one setting (e.g. violent outbursts, extreme
verbal abuse, assaultiveness at home, school, or with peers). In addition,
there are at least mild symptoms (distractibility, intrusiveness) in a second
8. Currently in treatment with a psychiatrist for the symptoms.
9. The child is failing his/her treatment. To meet this criterion:
i.The child's current CGAS score must be less than or equal to 60.
ii.The child's psychiatrist/treater must agree that the child's response to
his/her current treatment is no more than minimal. According to this criterion,
it would be clinically appropriate to change the child's current treatment.
iii.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.
iv.The child has a score of greater than 12 on the irritability subscale of the
Aberrant Behavior Checklist.
1. As assessed in the mania section of the K-SADS-PL, the individual exhibits any
of these cardinal bipolar symptoms in distinct periods lasting more than 1 day,
and therefore meets criteria for bipolar disorder not otherwise specified:
i) Elevated or expansive mood
ii) Grandiosity or inflated self-esteem
iii) Decreased need for sleep
iv) Increase in goal-directed activity (this can result in the excessive
involvement in pleasurable activities that have a high potential for painful
2. Meets criteria for schizophrenia, schizophreniform disorder, schizoaffective
illness, more than mild PDD, or PTSD.
3. Meets criteria for substance use disorder in the three months prior to
4. IQ less than 70
5. The symptoms are due to the direct physiological effects of a drug of abuse, or
to a general medical or neurological condition.
6. Currently pregnant or lactating, or sexually active without using a barrier
method of contraception.
7. Failed an adequate trial (defined as four weeks of consecutive treatment at the
minimally effective) or severe ill effects while on citalopram (at least 20 mg)
or escitalopram (at least 10 mg).
8. Hypersensitivity or severe adverse reaction to methylphenidate
9. A history of serious adverse reactions (psychosis, severely increased activation
compared to baseline) to methylphenidate or amphetamines.
10. Any chronic medical condition that requires medications that are contraindicated
with SSRIs or methylphenidate, or any serious chronic or unstable medical
11. Medical contraindications to treatment with SSRI or stimulant (e.g. liver,
seizure, renal, platelet disorder).