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NCT00794040

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

Completed Phase 2 Results posted Last updated 7 May 2019
What this trial tests

Phase 2 trial testing Add-on citalopram following optimized methylphenidate in Mood Disorder in 103 participants. Completed in 1 February 2018.

Timeline
17 November 2008
Primary endpoint
1 February 2018
1 February 2018

Quick facts

Lead sponsorNational Institute of Mental Health (NIMH)
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment103
Start date17 November 2008
Primary completion1 February 2018
Estimated completion1 February 2018
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Institute of Mental Health (NIMH)

Who can join

Adults 7 to 17, any sex, with Mood Disorder or Mental Disorder Diagnosed in Childhood. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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). Primary · 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.

GroupValue95% CI
Add-on Citalopram Following Optimized Methylphenidate35
Add-on Placebo Following Optimized Methylphenidate6
Irritability Severity at 8th Week of Trial. Secondary · Collected weekly during the 8th week trial. The 8th-week outcome is reported.

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).

GroupValue95% CI
Add-on Citalopram Following Optimized Methylphenidate3.1± 0.3
Add-on Placebo Following Optimized Methylphenidate3.9± 0.3
Functional Impairment at 8th Week of Trial Secondary · Collected weekly during the 8th week trial. The 8th-week outcome is reported.

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.

GroupValue95% CI
Add-on Citalopram Following Optimized Methylphenidate52.6± 2.3
Add-on Placebo Following Optimized Methylphenidate47.2± 2.1
Depressive Symptoms at 8th Week of Trial Secondary · Collected weekly during the 8th week trial. The 8th-week outcome is reported.

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.

GroupValue95% CI
Add-on Citalopram Following Optimized Methylphenidate28.6± 1.8
Add-on Placebo Following Optimized Methylphenidate30.1± 1.8
Anxiety Symptoms at 8th Week of Trial Secondary · Collected weekly during the 8th week trial. The 8th-week outcome is reported.

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.

GroupValue95% CI
Add-on Citalopram Following Optimized Methylphenidate12.0± 1.2
Add-on Placebo Following Optimized Methylphenidate13.4± 1.2

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event information was collected weekly during the study, including the 8th weeks of the trial.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Add-on Citalopram Following Optimized Methylphenidate
Serious: 0/23 (0%)
Deaths: 0/23
Add-on Placebo Following Optimized Methylphenidate
Serious: 0/26 (0%)
Deaths: 0/26
Other adverse events (47 terms — click to expand)

ReactionSystemAdd-on Citalopram Followin…Add-on Placebo Following O…
InsomniaGeneral disorders
Appetite changesGeneral disorders
AngerPsychiatric disorders
Restless/Inability to sit stillMusculoskeletal and connective tissue disorders
AgressionPsychiatric disorders
IntrusivenessPsychiatric disorders
Stomach painsGastrointestinal disorders
NervousnessPsychiatric disorders
Weight changesGeneral disorders
Clingy/separation anxietyPsychiatric disorders
Tiredness/fatigueGeneral disorders
HeadacheGeneral disorders
Motor ticsMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders
Poor concentrationPsychiatric disorders
Changes in stoolGastrointestinal disorders
Rash/itchSkin and subcutaneous tissue disorders
Drowsiness morning/afternoonNervous system disorders
Runny noseGeneral disorders
Loss of interest/apathyPsychiatric disorders
Speech changesPsychiatric disorders
VomitingGastrointestinal disorders
DizzinessNervous system disorders
Stiffness/Involuntary movementsMusculoskeletal and connective tissue disorders
Picking at skin or nailsSkin and subcutaneous tissue disorders
Dry mouthGastrointestinal disorders
AcneSkin and subcutaneous tissue disorders
Increased thirstGastrointestinal disorders
Trouble swallowingGastrointestinal disorders
Bloated abdomenGastrointestinal disorders
Early morning awakeningGeneral disorders
FeverGeneral disorders
Difficulty breathingRespiratory, thoracic and mediastinal disorders
DroolingGastrointestinal disorders
Change in heart rate fast/slowCardiac disorders
EnuresisRenal and urinary disorders
Eyes sensitive to lightEye disorders
Ringing or buzzing in earsEar and labyrinth disorders
Easy bruisingGeneral disorders
Disorganized thinkingPsychiatric disorders

Data from ClinicalTrials.gov NCT00794040 adverse events section.

Sponsor's own description

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. ...

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Emotion dysregulation in attention deficit hyperactivity disorder.
    Shaw P, Stringaris A, Nigg J, Leibenluft E. · · 2014 · cited 757× · PMID 24480998 · DOI 10.1176/appi.ajp.2013.13070966
  2. Severe mood dysregulation, irritability, and the diagnostic boundaries of bipolar disorder in youths.
    Leibenluft E. · · 2011 · cited 328× · PMID 21123313 · DOI 10.1176/appi.ajp.2010.10050766
  3. A Double-Blind Randomized Placebo-Controlled Trial of Citalopram Adjunctive to Stimulant Medication in Youth With Chronic Severe Irritability.
    Towbin K, Vidal-Ribas P, Brotman MA, Pickles A, et al · · 2020 · cited 56× · PMID 31128268 · DOI 10.1016/j.jaac.2019.05.015
  4. PhenoPredict: A disease phenome-wide drug repositioning approach towards schizophrenia drug discovery.
    Xu R, Wang Q. · · 2015 · cited 25× · PMID 26151312 · DOI 10.1016/j.jbi.2015.06.027
  5. Deficits in emotion recognition are associated with depressive symptoms in youth with disruptive mood dysregulation disorder.
    Vidal-Ribas P, Brotman MA, Salum GA, Kaiser A, et al · · 2018 · cited 15× · PMID 30004611 · DOI 10.1002/da.22810

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Other recruiting trials for Mood Disorder

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