A Controlled Trial of Citalopram Added to Methylphenidate in Youth With Severe Mood Dysregulation
Overview
- Phase
- Phase 2
- Intervention
- Add-on citalopram following optimized methylphenidate
- Conditions
- Mood Disorder
- Sponsor
- National Institute of Mental Health (NIMH)
- Enrollment
- 103
- Locations
- 1
- Primary Endpoint
- Percentage of Participants That "Much Improved" (Score of 2) in, or "Completely Recovered" (Score of 1) From Their Irritability Severity, as Measured With the Clinical Global Impression-Improvement (CGI-I).
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief 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.
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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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Add-on citalopram following optimized methylphenidate
After optimized treatment with methylphenidate, those who meet threshold for chronic irritability are randomized to add-on citalopram or placebo
Intervention: Add-on citalopram following optimized methylphenidate
Add-on placebo after optimized methylphenidate
After optimized treatment with methylphenidate, those who meet threshold for chronic irritability are randomized to add-on citalopram or placebo
Intervention: Add-on placebo following optimized methylphenidate
Outcomes
Primary Outcomes
Percentage of Participants That "Much Improved" (Score of 2) in, or "Completely Recovered" (Score of 1) From Their Irritability Severity, as Measured With the Clinical Global Impression-Improvement (CGI-I).
Time Frame: Collected weekly during the 8-week trial. The 8th-week outcome is reported.
A measure of change of irritability severity taking the baseline before randomization as a reference. Scores range 1 to 8, in which 1=Completely recovered,... 5=Unchanged,... 8=Much worse. Percentage of participants who responded are based on an estimation and might not match exactly with discrete numbers of participants based on the denominator.
Secondary Outcomes
- Irritability Severity at 8th Week of Trial.(Collected weekly during the 8th week trial. The 8th-week outcome is reported.)
- Depressive Symptoms at 8th Week of Trial(Collected weekly during the 8th week trial. The 8th-week outcome is reported.)
- Anxiety Symptoms at 8th Week of Trial(Collected weekly during the 8th week trial. The 8th-week outcome is reported.)
- Functional Impairment at 8th Week of Trial(Collected weekly during the 8th week trial. The 8th-week outcome is reported.)