A Controlled Trial of Serotonin Reuptake Inhibitors Added to Stimulant Medication in Youth With Severe Mood Dysregulation
Condition: Mood Disorder; Mental Disorder Diagnosed in Childhood; Attention Deficit and Disruptive Behavior Disorder; Attention Deficit Hyperactivity Disorder
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity; Mental Disorders; Mood Disorders; Problem Behavior; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders
Intervention: Add-on citalopram following optimized methylphenidate; Add-on placebo following optimized methylphenidate
Intervention description: After optimized treatment with methylphenidate, those who meet threshold for chronic irritability are randomized to add-on citalopram or placebo; After optimized treatment with methylphenidate, those who meet threshold for chronic irritability are randomized to add-on citalopram or placebo
Intervention MeSH terms: Methylphenidate; Citalopram
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 103.0
Sex: All
Minimum age: 7 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Irritability; Attention Deficit Hyperactivity Disorder; Explosive; Tantrums; Bipolar Mood Disorder; Mood Disorder; Childhood Mood Disorder; ADHD

Summary:

      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 ) when combined (or not combined) with the antidepressant citalopram (Celexa ) 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.

      ...
    

Eligibility criteria:

        -  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 speech,
                  intrusiveness

               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 setting.

               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.

                  EXCLUSION CRITERIA:

               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
                  consequences)

               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
                  randomization.

               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
                  disorder.

              11. Medical contraindications to treatment with SSRI or stimulant (e.g. liver,
                  seizure, renal, platelet disorder).