Protocol for a randomized controlled trial examining multilevel prediction of response to behavioral activation and exposure-based therapy for generalized anxiety disorder

• Published in: Current controlled trials in cardiovascular medicine 2020-01, Vol.21 (1), p.17-17, Article 17
• Main Authors: Santiago, J, Akeman, E, Kirlic, N, Clausen, A N, Cosgrove, K T, McDermott, T J, Mathis, B, Paulus, M, Craske, M G, Abelson, J, Martell, C, Wolitzky-Taylor, K, Bodurka, J, Thompson, W K, Aupperle, Robin L
• Format: Article
• Language: English
• Subjects: Adult; Anxiety; Anxiety Disorders - diagnosis; Anxiety Disorders - physiopathology; Anxiety Disorders - psychology; Anxiety Disorders - therapy; Avoidance behavior; Avoidance Learning - physiology; Behavior therapy; Behavioral activation; Behavioral medicine; Brain - diagnostic imaging; Brain - physiopathology; Care and treatment; Clinical outcomes; Clinical trials; Cognitive Behavioral Therapy; Cognitive therapy; Comorbidity; Decision making; Decision Making - physiology; Depression; Electroencephalography; Evidence-based medicine; Exposure therapy; Female; Forecasting - methods; Functional magnetic resonance imaging; Generalized anxiety disorder; Humans; Implosive Therapy; Information systems; Machine learning; Magnetic Resonance Imaging; Male; Medical imaging; Mental depression; Mental disorders; Mental health; Middle Aged; Neuroimaging; Neurosciences; Precision medicine; Prognosis; Questionnaires; Randomized Controlled Trials as Topic; Retrospective Studies; Self Report; Study Protocol; Suicidal behavior; Treatment Outcome; Young Adult
• ISSN: 1745-6215; 1745-6215
• DOI: 10.1186/s13063-019-3802-9

Only 40-60% of patients with generalized anxiety disorder experience long-lasting improvement with gold standard psychosocial interventions. Identifying neurobehavioral factors that predict treatment success might provide specific targets for more individualized interventions, fostering more optimal outcomes and bringing us closer to the goal of "personalized medicine." Research suggests that reward and threat processing (approach/avoidance behavior) and cognitive control may be important for understanding anxiety and comorbid depressive disorders and may have relevance to treatment outcomes. This study was designed to determine whether approach-avoidance behaviors and associated neural responses moderate treatment response to exposure-based versus behavioral activation therapy for generalized anxiety disorder. We are conducting a randomized controlled trial involving two 10-week group-based interventions: exposure-based therapy or behavioral activation therapy. These interventions focus on specific and unique aspects of threat and reward processing, respectively. Prior to and after treatment, participants are interviewed and undergo behavioral, biomarker, and neuroimaging assessments, with a focus on approach and avoidance processing and decision-making. Primary analyses will use mixed models to examine whether hypothesized approach, avoidance, and conflict arbitration behaviors and associated neural responses at baseline moderate symptom change with treatment, as assessed using the Generalized Anxiety Disorder-7 item scale. Exploratory analyses will examine additional potential treatment moderators and use data reduction and machine learning methods. This protocol provides a framework for how studies may be designed to move the field toward neuroscience-informed and personalized psychosocial treatments. The results of this trial will have implications for approach-avoidance processing in generalized anxiety disorder, relationships between levels of analysis (i.e., behavioral, neural), and predictors of behavioral therapy outcome. The study was retrospectively registered within 21 days of first participant enrollment in accordance with FDAAA 801 with ClinicalTrials.gov, NCT02807480. Registered on June 21, 2016, before results.