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

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 ANALYSIS: Forty 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 DISSEMINATION: The 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 NUMBERS: NCT02531893 and NCT00025935.