AzTrials
AzTrials

Mood DisorderPhase 2NCT00794040

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

A Phase 2 study testing Add-on citalopram following optimized methylphenidate in people with Mood Disorder and Mental Disorder Diagnosed in Childhood, run by National Institute of Mental Health (NIMH) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 7 to 17 years
What is being tested?
Add-on citalopram following optimized methylphenidate
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
103 participants
Where
1 siteUnited States
Study dates
17 Nov 2008to 1 Feb 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 7 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.
Show all 13Show fewer
  • 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.

Who cannot join

  • <!-- -->
  • 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:
  • Elevated or expansive mood
  • Grandiosity or inflated self-esteem
  • Decreased need for sleep
  • Increase in goal-directed activity (this can result in the excessive involvement in pleasurable activities that have a high potential for painful consequences)
Show all 16Show fewer
  • 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).

Trial locations and contacts

1 site in 1 country.

United States1 site
  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Controlled Trial of Citalopram Added to Methylphenidate in Youth With Severe Mood Dysregulation

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.

Read more

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.

...

Read the 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.

Being tested
Add-on citalopram following optimized methylphenidate, Add-on placebo following optimized methylphenidate
Keywords
Irritability, Attention Deficit Hyperactivity Disorder, Explosive, Tantrums, Bipolar Mood Disorder, Mood Disorder, Childhood Mood Disorder, ADHD
Medical subject headings
Mood Disorders, Attention Deficit Disorder with Hyperactivity, Attention Deficit and Disruptive Behavior Disorders, Bipolar Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Add-on citalopram following optimized methylphenidateDrug

    After optimized treatment with methylphenidate, those who meet threshold for chronic irritability are randomized to add-on citalopram or placebo

  • Add-on placebo following optimized methylphenidateDrug

    After optimized treatment with methylphenidate, those who meet threshold for chronic irritability are randomized to add-on citalopram or placebo

Study groups in NCT00794040
Study groupRoleWhat they receive
Add-on citalopram following optimized methylphenidateActive comparatorAfter optimized treatment with methylphenidate, those who meet threshold for chronic irritability are randomized to add-on citalopram or placebo
Receives: Drug: Add-on citalopram following optimized methylphenidate
Add-on placebo after optimized methylphenidatePlacebo comparatorAfter optimized treatment with methylphenidate, those who meet threshold for chronic irritability are randomized to add-on citalopram or placebo
Receives: Drug: Add-on placebo following optimized methylphenidate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    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.

    Measured: Collected weekly during the 8-week trial. The 8th-week outcome is reported.

Secondary outcomes (4)
  1. Irritability Severity at 8th Week of Trial.

    Clinical Global Impression-Severity (CGI-S): A measure of severity of irritability scale (from 1=Normal, not at all ill to 7=Among the most extremely ill patients).

    Measured: Collected weekly during the 8th week trial. The 8th-week outcome is reported.

  2. Functional Impairment at 8th Week of Trial

    Difference in functional impairment at 8th week of trial as measured with Children's Global Impression Scale (CGAS) with scores ranging from 1=Most impaired to 100=Not impaired at all.

    Measured: Collected weekly during the 8th week trial. The 8th-week outcome is reported.

  3. Depressive Symptoms at 8th Week of Trial

    Difference in depressive symptoms at 8th week of trial as measured with Children's Depression Rating Scale (CDRS) with scores ranging 17-113, where scores >40 are considered over the clinical threshold, and scores <28 are considered within the healthy range.

    Measured: Collected weekly during the 8th week trial. The 8th-week outcome is reported.

  4. Anxiety Symptoms at 8th Week of Trial

    Difference in anxiety symptoms at 8th week of trial as measured with the Pediatric Anxiety Rating Scale (PARS) with scores ranging 0-25. Higher values represent a worse outcome.

    Measured: Collected weekly during the 8th week trial. The 8th-week outcome is reported.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Nov 2008 (estimated)
  2. Study start17 Nov 2008
  3. Primary completion1 Feb 2018
  4. Study completion1 Feb 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
103 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00794040
Sponsor's protocol ID
090034
Other IDs
09-M-0034
Status last verified
1 Feb 2018
First submitted
18 Nov 2008
Last updated
7 May 2019

Publications

  • Amsterdam JD, Shults J. Comparison of fluoxetine, olanzapine, and combined fluoxetine plus olanzapine initial therapy of bipolar type I and type II major depression--lack of manic induction. J Affect Disord. 2005 Jul;87(1):121-30. doi: 10.1016/j.jad.2005.02.018.

    PubMed 15923042
  • Baumer FM, Howe M, Gallelli K, Simeonova DI, Hallmayer J, Chang KD. A pilot study of antidepressant-induced mania in pediatric bipolar disorder: Characteristics, risk factors, and the serotonin transporter gene. Biol Psychiatry. 2006 Nov 1;60(9):1005-12. doi: 10.1016/j.biopsych.2006.06.010. Epub 2006 Aug 30.

    PubMed 16945343
  • Binks CA, Fenton M, McCarthy L, Lee T, Adams CE, Duggan C. Pharmacological interventions for people with borderline personality disorder. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005653. doi: 10.1002/14651858.CD005653.

    PubMed 16437535
  • Towbin K, Vidal-Ribas P, Brotman MA, Pickles A, Miller KV, Kaiser A, Vitale AD, Engel C, Overman GP, Davis M, Lee B, McNeil C, Wheeler W, Yokum CH, Haring CT, Roule A, Wambach CG, Sharif-Askary B, Pine DS, Leibenluft E, Stringaris A. A Double-Blind Randomized Placebo-Controlled Trial of Citalopram Adjunctive to Stimulant Medication in Youth With Chronic Severe Irritability. J Am Acad Child Adolesc Psychiatry. 2020 Mar;59(3):350-361. doi: 10.1016/j.jaac.2019.05.015. Epub 2019 May 23.

    PubMed 31128268

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Add-on citalopram following optimized methylphenidate in people with Mood Disorder and Mental Disorder Diagnosed in Childhood, run by National Institute of Mental Health (NIMH) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00794040, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2019.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in