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
Study type: Interventional
Phase: Phase 2

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.

      ...
    

Detailed description: 
      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.
    

Intervention name(s): Add-on citalopram following optimized methylphenidate; Add-on placebo following optimized methylphenidate
Intervention type(s): Drug; Drug
Intervention description(s): 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
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Irritability; Attention Deficit Hyperactivity Disorder; Explosive; Tantrums; Bipolar Mood Disorder; Mood Disorder; Childhood Mood Disorder; ADHD