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A Controlled Trial of Serotonin Reuptake Inhibitors Added to Stimulant Medication in Youth With Severe Mood Dysregulation
This study is currently recruiting participants.
Verified by National Institutes of Health Clinical Center (CC), November 2008
Sponsored by: National Institute of Mental Health (NIMH)
Information provided by: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00794040
  Purpose

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 2-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.


Condition Intervention Phase
Mood Disorder
Mental Disorder Diagnosed in Childhood
Attention Deficit and Disruptive Behavior Disorder
Attention Deficit Hyperactivity Disorder
Drug: Citalopram
Drug: Methylphenidate
Phase II

MedlinePlus related topics: Attention Deficit Hyperactivity Disorder Bipolar Disorder Child Mental Health Mental Health
Drug Information available for: Escitalopram Benzetimide Citalopram Citalopram hydrobromide Dexetimide Escitalopram oxalate Methylphenidate hydrochloride Methylphenidate Serotonin
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title: A Controlled Trial of Serotonin Reuptake Inhibitors Added to Stimulant Medication in Youth With Severe Mood Dysregulation

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Clinical Global Impression -- Improvement; Aberrant Behavior Checklist irritability subscale [ Time Frame: Treatment trial is 10 weeks and the study will run for 4 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: November 2008
Intervention Details:
    Drug: Citalopram
    N/A
    Drug: Methylphenidate
    N/A
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 2-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.

  Eligibility

Ages Eligible for Study:   7 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00794040

Contacts
Contact: Patient Recruitment and Public Liaison Office (800) 411-1222 prpl@mail.cc.nih.gov
Contact: TTY 1-866-411-1010

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

NIH Clinical Center Detailed Web Page  This link exits the ClinicalTrials.gov site

Publications:
Responsible Party: National Institutes of Health ( Ellen Leibenluft, M.D./National Institute of Mental Health )
Study ID Numbers: 090034, 09-M-0034
Study First Received: November 18, 2008
Last Updated: January 27, 2009
ClinicalTrials.gov Identifier: NCT00794040  
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Irritability
Attention Deficit Hyperactivity Disorder
Explosive
Tantrums
Bipolar Mood Disorder
Mood Disorder
Childhood Mood Disorder
Attention Deficit Hyperactivity Disorder
ADHD

Study placed in the following topic categories:
Bipolar Disorder
Attention Deficit and Disruptive Behavior Disorders
Methylphenidate
Dyskinesias
Citalopram
Serotonin
Signs and Symptoms
Dopamine
Attention Deficit Disorder with Hyperactivity
Mental Disorders
Mental Disorders Diagnosed in Childhood
Mood Disorders
Hyperkinesis
Neurologic Manifestations
Dexetimide

Additional relevant MeSH terms:
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Disease
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Nervous System Diseases
Psychotropic Drugs
Central Nervous System Stimulants
Serotonin Uptake Inhibitors
Pharmacologic Actions
Serotonin Agents
Pathologic Processes
Therapeutic Uses
Dopamine Agents
Antidepressive Agents, Second-Generation
Central Nervous System Agents
Antidepressive Agents

ClinicalTrials.gov processed this record on January 30, 2009