A Controlled Trial of Serotonin Reuptake Inhibitors Added to Stimulant Medication in Youth With Severe Mood Dysregulation

Objective: To test the efficacy of citalopram plus methylphenidate vs. placebo plus methylphenidate in decreasing irritability in youth with severe mood dysregulation.

Study population: Youth ages 7-17 with severe mood dysregulation (SMD). SMD is characterized by nonepisodic, impairing irritability (defined as increased reactivity to negative emotional stimuli at least 3 times/week and angry or sad mood, most days, most of the time, noticeable to others) and hyperarousal (three of: distractibility, intrusiveness, pressured speech, racing thoughts, agitation, insomnia), with onset before age 12. Many of these children receive the diagnosis of bipolar disorder (BD) in the community, although they do not meet DSM-IV criteria for BD because of the lack of distinct manic episodes.

Design: Medication withdrawal, followed by a 5-week dose stabilization phase of methylphenidate and an 8-week double-blind, placebo-controlled treatment trial of citalopram plus methylphenidate vs. placebo plus methylphenidate. There will also be optional open treatment at the end, so that all patients have the opportunity to have a total of up to 10 weeks of citalopram plus methylphenidate. The target dose of citalopram will be 20-40 mg/day.

Outcome measures: The primary outcome measures will be the Aberrant Behavior Checklist Irritability subscale and the CGI-I.

• INCLUSION CRITERIA:

• Ages 7-17
• 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).
• Hyperarousal, as defined by at least three of the following symptoms: insomnia, agitation, distractibility, racing thoughts or flight of ideas, pressured speech, intrusiveness
• 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
• 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.
• The onset of symptoms must be prior to age 12 years.
• 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 setting.
• Currently in treatment with a psychiatrist for the symptoms.
• 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.

Exclusion criteria

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• 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 consequences)

• Meets criteria for schizophrenia, schizophreniform disorder, schizoaffective illness, more than mild PDD, or PTSD.
• Meets criteria for substance use disorder in the three months prior to randomization.
• IQ less than 70
• The symptoms are due to the direct physiological effects of a drug of abuse, or to a general medical or neurological condition.
• Currently pregnant or lactating, or sexually active without using a barrier method of contraception.
• 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).
• Hypersensitivity or severe adverse reaction to methylphenidate
• A history of serious adverse reactions (psychosis, severely increased activation compared to baseline) to methylphenidate or amphetamines.
• Any chronic medical condition that requires medications that are contraindicated with SSRIs or methylphenidate, or any serious chronic or unstable medical disorder.
• Medical contraindications to treatment with SSRI or stimulant (e.g. liver, seizure, renal, platelet disorder).