Kenneth Towbin1, Pablo Vidal-Ribas2, Melissa A Brotman3, Andrew Pickles4, Katherine V Miller1, Ariela Kaiser1, Aria D Vitale1, Chana Engel1, Gerald P Overman5, Mollie Davis6, Beth Lee7, Cheri McNeil6, Wanda Wheeler6, Catherine H Yokum6, Catherine T Haring8, Alexandra Roule9, Caroline G Wambach10, Banafsheh Sharif-Askary11, Daniel S Pine12, Ellen Leibenluft6, Argyris Stringaris13. 1. Mood Brain and Development Unit, Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD. 2. Mood Brain and Development Unit, Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD; Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK. 3. Neuroscience and Novel Therapeutics, Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD. 4. Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK. 5. National Institutes of Health, Bethesda, MD. 6. Section on Mood Dysregulation and Neuroscience, Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD. 7. College of Nursing, University of Arizona, Tuscon. 8. University of Michigan, Ann Arbor. 9. Penn State University, State College, PA. 10. Georgetown University School of Medicine, Washington, DC. 11. Duke University School of Medicine, Durham, NC. 12. Section on Development and Affective Neuroscience, Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD. 13. Mood Brain and Development Unit, Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD. Electronic address: argyris.stringaris@nih.gov.
Abstract
OBJECTIVE: Despite the clinical importance of chronic and severe irritability, there is a paucity of controlled trials for its pharmacological treatment. Here, we examine the effects of adding citalopram (CTP) to methylphenidate (MPH) in the treatment of chronic severe irritability in youth using a double-blind randomized placebo-controlled design. METHOD: After a lead-in phase of open treatment with stimulant, 53 youth meeting criteria for severe mood dysregulation (SMD) were randomly assigned to receive CTP or placebo (PBO) for 8 weeks. A total of 49 participants, 48 of them (98%) meeting disruptive mood dysregulation disorder (DMDD) criteria, were included in the intent-to-treat analysis. The primary outcome measure was the proportion of response based on improvements of irritability at the week 8 of the trial. RESULTS: At the end of the trial, a significantly higher proportion of response was seen in those participants randomly assigned to CTP+MPH compared to PBO+MPH (35% CTP+MPH versus 6% PBO+MPH; odds ratio = 11.70, 95% CI = 2.00-68.16, p = 0.006). However, there were no differences in functional impairment between groups at the end of the trial. No differences were found in any adverse effect between treatment groups, and no trial participant exhibited hypomanic or manic symptoms. CONCLUSION:Adjunctive CTP might be efficacious in the treatment of chronic severe irritability in youth resistant to stimulant treatment alone. CLINICAL TRIAL REGISTRATION INFORMATION: A Controlled Trial of Serotonin Reuptake Inhibitors Added to Stimulant Medication in Youth With Severe Mood Dysregulation; https://clinicaltrials.gov; NCT00794040. Published by Elsevier Inc.
RCT Entities:
OBJECTIVE: Despite the clinical importance of chronic and severe irritability, there is a paucity of controlled trials for its pharmacological treatment. Here, we examine the effects of adding citalopram (CTP) to methylphenidate (MPH) in the treatment of chronic severe irritability in youth using a double-blind randomized placebo-controlled design. METHOD: After a lead-in phase of open treatment with stimulant, 53 youth meeting criteria for severe mood dysregulation (SMD) were randomly assigned to receive CTP or placebo (PBO) for 8 weeks. A total of 49 participants, 48 of them (98%) meeting disruptive mood dysregulation disorder (DMDD) criteria, were included in the intent-to-treat analysis. The primary outcome measure was the proportion of response based on improvements of irritability at the week 8 of the trial. RESULTS: At the end of the trial, a significantly higher proportion of response was seen in those participants randomly assigned to CTP+MPH compared to PBO+MPH (35% CTP+MPH versus 6% PBO+MPH; odds ratio = 11.70, 95% CI = 2.00-68.16, p = 0.006). However, there were no differences in functional impairment between groups at the end of the trial. No differences were found in any adverse effect between treatment groups, and no trial participant exhibited hypomanic or manic symptoms. CONCLUSION: Adjunctive CTP might be efficacious in the treatment of chronic severe irritability in youth resistant to stimulant treatment alone. CLINICAL TRIAL REGISTRATION INFORMATION: A Controlled Trial of Serotonin Reuptake Inhibitors Added to Stimulant Medication in Youth With Severe Mood Dysregulation; https://clinicaltrials.gov; NCT00794040. Published by Elsevier Inc.
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