A Double-Blind Randomized Placebo-Controlled Trial of Citalopram Adjunctive to Stimulant Medication in Youth With Chronic Severe Irritability

Towbin, Kenneth E.; Vidal‐Ribas, Pablo; Brotman, Melissa A.; Pickles, Andrew; Miller, Katherine V.; Kaiser, Ariela; Vitale, Aria; Engel, Chana; Overman, Gerald P.; Davis, Mollie; Lee, Beth; McNeil, Cheri; Wheeler, Wanda; Yokum, Catherine H.; Haring, Catherine T.; Roule, Alexandra; Wambach, Caroline G.; Sharif‐Askary, Banafsheh; Pine, Daniel S.; Leibenluft, Ellen; Stringaris, Argyris

doi:10.1016/j.jaac.2019.05.015

Cited by 51 publications

(37 citation statements)

References 64 publications

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“…65 The incorporation of these PMT strategies aims to counteract deficits in frustrative non-reward An open pilot trial of exposure-based CBT procedures for DMDD demonstrated initial feasibility. 32 Preliminary results indicated a pre-treatment to post-treatment reduction in DMDD symptom severity, as measured by the Clinical Global Impressions-Severity and Improvement (CGI-S, CGI-I) 67 68 scale and the Clinician-Rated Affective Reactivity Index (CL-ARI). 69 This CL-ARI is a paediatric, semistructured interview assessing temper outbursts and irritable mood.…”

Section: The Current Studymentioning

confidence: 99%

Across-subjects multiple baseline trial of exposure-based cognitive-behavioral therapy for severe irritability: a study protocol

et al. 2021

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IntroductionIrritability is defined as a tendency towards anger in response to frustration. Clinically, impairing irritability is a significant public health problem. There is a need for mechanism-based psychotherapies targeting severe irritability as it manifests in the context of disruptive mood dysregulation disorder (DMDD). This study protocol describes a randomised multiple baseline design testing the preliminary efficacy of a new treatment, exposure-based cognitive-behavioral therapy for severe irritability in youth, which also integrates components of parent management training. We will investigate associations of this intervention with primary clinical measures, as well as ecological momentary assessment measures.Methods and analysisForty youth will be enrolled. Participants, aged 8–17 years, must present at least one of two core symptoms of DMDD: abnormal mood or increased reactivity to negative emotional stimuli, with severe impairment in one domain (home, school, peers) and moderate in another, or moderate impairment in at least two domains. Each participant is randomised to a 2-week, 4-week or 6-week baseline observation period, followed by 12 active treatment sessions. Clinical ratings are conducted at baseline, biweekly (clinician), weekly (parent/child) throughout treatment, post-treatment, and 3-month and 6-month follow-up (clinician). Clinician ratings on the Affective Reactivity Index and Clinical Global Impressions-Improvement scale for DMDD are our primary outcome measures. Secondary outcome measures include parent and child reports of irritability. Post hoc additional symptom measures include clinician, parent and self-ratings of depression, anxiety and overall functional impairment. Prospective, digitally based event sampling of symptoms is acquired for a week pre-treatment, mid-treatment and post-treatment. Based on our pathophysiological model of irritability implicating frustrative non-reward, aberrant threat processing and instrumental learning, we probe these three brain-based targets using functional MRI paradigms to assess target engagement.Ethics and disseminationThe research project and all related materials were submitted and approved by the appropriate Institutional Review Board (IRB) of the National Institute of Mental Health (NIMH).Trial registration numbersNCT02531893 and NCT00025935.

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Section: The Current Studymentioning

confidence: 99%

Across-subjects multiple baseline trial of exposure-based cognitive-behavioral therapy for severe irritability: a study protocol

et al. 2021

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“…In irritable patients with other clear features of depression and the absence of a history of genuine mania (i.e., fulfilling all of the DSM‐5 criteria for a manic episode), we recommend treating patients as MDD until proven otherwise, which entails a trial of an SSRI, typically fluoxetine, for 8 weeks at a therapeutic dose. In fact, recent evidence demonstrates that severe irritability may be reduced using SSRIs (Towbin et al, ). While estimates vary (Offidani, Fava, Tomba, & Baldessarini, ), the risk of conversion to mania that meets full DSM‐5 criteria with SSRIs is a rare event that appears often coincidental rather than caused by changes in medications (Baldessarini et al, ).…”

Section: Risk Factors and Diagnostic Challengesmentioning

confidence: 99%

Annual Research Review: Defining and treating pediatric treatment‐resistant depression

Dwyer

Stringaris

Brent

et al. 2020

Child Psychology Psychiatry

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Background Adolescent major depressive disorder (MDD) is a significant health problem, associated with substantial morbidity, cost, and mortality. Depression is a significant risk factor for suicide, which is now the second leading cause of death in young people. Up to twenty per cent of adolescents will experience MDD before adulthood, and while a substantial proportion will improve with standard‐of‐care treatments (psychotherapy and medication), roughly one third will not. Methods Here, we have reviewed the literature in order to discuss the concept of treatment‐resistant depression (TRD) in adolescence, examine risk factors, diagnostic difficulties, and challenges in evaluating symptom improvement, and providing guidance on how to define adequate medication and psychotherapy treatment trials. Results We propose a staging model for adolescent TRD and review the treatment literature. The evidence base for first‐ and second‐line treatments primarily derives from four large pediatric clinical trials (TADS, TORDIA, ADAPT, and IMPACT). After two medications and a trial of evidence‐based psychotherapy have failed to alleviate depressive symptoms, the evidence becomes quite thin for subsequent treatments. Here, we review the evidence for the effectiveness of medication switches, medication augmentation, psychotherapy augmentation, and interventional treatments (i.e., transcranial magnetic stimulation, electroconvulsive therapy, and ketamine) for adolescent TRD. Comparisons are drawn to the adult TRD literature, and areas for future pediatric depression research are highlighted. Conclusions As evidence is limited for treatments in this population, a careful consideration of the known risks and side effects of escalated treatments (e.g., mood stabilizers and atypical antipsychotics) is warranted and weighed against potential, but often untested, benefits.

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“…Towbin and Vidal-Ribas, and a team led by Dr. Argyris Stringaris, examined the effects of adding citalopram (CTP) to methylphenidate (MPH) in the treatment of chronic severe irritability in youths. 3 Despite the clinical importance of chronic and severe irritability, only 1 pharmacological randomized controlled trial had been conducted, and it yielded negative results. The test of serotonin reuptake inhibitors (SRIs) with MPH to specifically target severe irritability in this trial was motivated by the efficacy of MPH in treating irritability in children with attention-deficit/ hyperactivity disorder (ADHD) and the phenotypic and genetic links between irritability and depression/anxiety, for which SRIs have shown efficacy.…”

Section: The 2020 Aacap Klingenstein Third Generation Foundation Awarmentioning

confidence: 99%

Hats Off: Journal Awards 2020

Novins¹,

Ng²,

Findling³

et al. 2020

Journal of the American Academy of Child & Adolescent Psych

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Journal award winners were challenged with selecting 3 new award-winning JAACAP articles. a To be eligible, articles must epitomize scholarly excellence in a key area of our discipline and have been published in the Journal between July of the previous year and June of the current year by a lead or senior author who is a child and adolescent psychiatrist and an AACAP member. Each of the Academy's prestigious Journal awards acknowledges the need for more and better mental health research and funding, and for improving mental health in children and adolescents. By supporting and collaborating with other organizations to provide these awards, the Academy encourages innovative research that contributes to improving the care and treatment of young people. We invited this year's award winners to share brief descriptions of their studies and contribution to the literature (included below). The Journal's excellence reflects the hard work of authors and peer reviewers, a commitment to advancing pediatric mental health through scientific originality and rigor, and adherence to the highest ethical standards. We salute the authors of all articles published during this time period, and celebrate this year's recipients for their remarkable accomplishments.

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A Double-Blind Randomized Placebo-Controlled Trial of Citalopram Adjunctive to Stimulant Medication in Youth With Chronic Severe Irritability

Cited by 51 publications

References 64 publications

Across-subjects multiple baseline trial of exposure-based cognitive-behavioral therapy for severe irritability: a study protocol

Across-subjects multiple baseline trial of exposure-based cognitive-behavioral therapy for severe irritability: a study protocol

Annual Research Review: Defining and treating pediatric treatment‐resistant depression

Hats Off: Journal Awards 2020

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