A Sequential Multiple Assignment Randomized Trial (SMART) study of medication and CBT sequencing in the treatment of pediatric anxiety disorders.

BACKGROUND: Treatment of a child who has an anxiety disorder usually begins with the question of which treatment to start first, medication or psychotherapy. Both have strong empirical support, but few studies have compared their effectiveness head-to-head, and none has investigated what to do if the treatment tried first isn't working well-whether to optimize the treatment already begun or to add the other treatment. METHODS: This is a single-blind Sequential Multiple Assignment Randomized Trial (SMART) of 24 weeks duration with two levels of randomization, one in each of two 12-week stages. In Stage 1, children will be randomized to fluoxetine or Coping Cat Cognitive Behavioral Therapy (CBT). In Stage 2, remitters will continue maintenance-level therapy with the single-modality treatment received in Stage 1. Non-remitters during the first 12 weeks of treatment will be randomized to either [1] optimization of their Stage 1 treatment, or [2] optimization of Stage 1 treatment and addition of the other intervention. After the 24-week trial, we will follow participants during open, naturalistic treatment to assess the durability of study treatment effects. Patients, 8-17 years of age who are diagnosed with an anxiety disorder, will be recruited and treated within 9 large clinical sites throughout greater Los Angeles. They will be predominantly underserved, ethnic minorities. The primary outcome measure will be the self-report score on the 41-item youth SCARED (Screen for Child Anxiety Related Disorders). An intent-to-treat analysis will compare youth randomized to fluoxetine first versus those randomized to CBT first ("Main Effect 1"). Then, among Stage 1 non-remitters, we will compare non-remitters randomized to optimization of their Stage 1 monotherapy versus non-remitters randomized to combination treatment ("Main Effect 2"). The interaction of these main effects will assess whether one of the 4 treatment sequences (CBT➔CBT; CBT➔med; med➔med; med➔CBT) in non-remitters is significantly better or worse than predicted from main effects alone. DISCUSSION: Findings from this SMART study will identify treatment sequences that optimize outcomes in ethnically diverse pediatric patients from underserved low- and middle-income households who have anxiety disorders. TRIAL REGISTRATION: This protocol, version 1.0, was registered in ClinicalTrials.gov on February 17, 2021 with Identifier: NCT04760275 .

The ReThink study: a 3-arm parallel randomized trial of cognitive bias modification, with and without adherence promotion, for adolescent anxiety disorder: trial design and protocol.

BACKGROUND: Anxiety disorders are the most common mental health problem among youth, contribute to reduced quality of daily life, and are associated with high rates of comorbidity. However, treatment rates for anxiety are very low, causing a sizeable treatment gap. There is an immediate need to identify treatment interventions that are effective, affordable, and can be delivered easily to the youth population. Cognitive Bias Modification (CBM) is one potentially effective intervention that could reach youth on a large scale, especially when self-administered at home. Thus, we aim to assess the benefit of CBM to treat youth anxiety. Further, we aim to test whether adding an adherence promotion (AP) component to the CBM intervention can improve outcomes, and whether CBM delivered both with and without the AP component is cost effective. METHODS: This is a 12-month randomized controlled trial (RCT) conducted within an existing healthcare system. Potentially eligible youth (ages 12 to 17) will be identified by reviewing the electronic health record (EHR) for clinical anxiety diagnoses, which are then confirmed via research interview. We aim to enroll 498 participants and randomize them 1:1:1 to one of three arms: Arm 1 is a Low-Ratio version of the CBM program (nearly identical to the other CBM versions, but minimally effective); Arm 2 is a High-Ratio "active" CBM program; and Arm 3 is the High-Ratio CBM program with an added AP component. Participants will complete assessments at baseline, 1-, 3-, 6- and 12-months post-baseline. Youth in all three arms will self-administer the CBM program at home and will be asked to complete twelve intervention sessions over a four-week period. Arm 3 participants (High-Ratio CBM + AP) will also receive up to four telephone calls from phone coaches during the intervention period to provide technical assistance, encouragement, and motivational enhancement to increase adherence. The primary clinical outcome will be anxiety remission at 6-month follow-up. DISCUSSION: This study protocol describes the method and design for an RCT to test whether self-administered CBM both with and without adherence promotion can be an effective at-home treatment for anxious youth. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02156531, First Posted June 5, 2014.

Cognitive-behavioral psychotherapy for anxiety and depressive disorders in children and adolescents: an evidence-based medicine review.

OBJECTIVE: To review the literature on the cognitive-behavioral treatment of children and adolescents with anxiety and depressive disorders within the conceptual framework of evidence-based medicine. METHOD: The psychiatric and psychological literature was systematically searched for controlled trials applying cognitive-behavioral treatment to pediatric anxiety and depressive disorders. RESULTS: For both anxiety and depression, substantial evidence supports the efficacy of problem-specific cognitive-behavioral interventions. Comparisons with wait-list, inactive control, and active control conditions suggest medium to large effects for symptom reduction in primary outcome domains. CONCLUSIONS: From an evidence-based perspective, cognitive-behavioral therapy is currently the treatment of choice for anxiety and depressive disorders in children and adolescents. Future research in this area will need to focus on comparing cognitive-behavioral psychotherapy with other treatments, component analyses, and the application of exportable protocol-driven treatments to divergent settings and patient populations.

What is the evidence for evidence-based treatments? A hard look at our soft underbelly.

In the rising quest for evidence-based interventions, recent research often does not give adequate attention to "nonspecific therapeutic factors," including the effects of attention, positive regard, and therapeutic alliance, as well as the effects of treatment dose, intensity and actual processes mediating therapeutic change. To determine the extent to which recent clinical trial designs fully this problem, the authors conducted a systematic review of Psych-Lit/Medline of all controlled child psychotherapy treatment studies from 1995 to 2004. A total of 52 studies were identified that met review criteria: two or more therapy conditions and random assignment of participants to intervention groups. Of the 52 studies, one group (n = 29) compared a presumably active treatment with 1 or more similarly intensive treatments (often an attention control group) presumably not containing the active therapeutic ingredients. Of these, 14 studies found evidence of consistent differences between the two groups, whereas 15 did not. An additional group of studies (n = 27) compared therapy groups with different levels of intensity and "dose" of the putatively active treatment; 13 of these found evidence of the effects of different levels of treatment dose/intensity on outcomes and 14 did not. Four studies met criteria for inclusion in both groups. Across both groups of studies, when positive effects were found, few studies systematically explored whether the presumed active therapeutic ingredients actually accounted for the degree of change, nor did they often address plausible alternative explanations, such as nonspecific therapeutic factors of positive expectancies, therapeutic alliance, or attention. Findings suggest that many child psychotherapy treatment studies have not inadequately controlled for nonspecific factors such as attention and treatment intensity and have failed to assess specific mediators of change. Specific recommendations for future studies are offered, specifically: 1. Initial specification in study design how investigators will test if the intervention is efficacious over and above the effects of positive expectancies, positive regard, or attention; 2. Planned (rather than post hoc) analyses to explore whether and how a given treatment's specific ingredients or the overall intensity of its "dose" are related to treatment outcomes; 3. More studies conducting head-to-head tests of different types but equally credible forms of treatment, with planned analyses testing different mechanisms of change 4. When positive effects of a treatment vs. a control are found, systematic elimination of specific, competing hypotheses of reasons for treatment efficacy (e.g., attention, therapeutic alliance, face validity of treatment and client's treatment expectations, changes in self-efficacy), and 5. When negative effects are reported, appropriate analyses to address alternative explanations (lack of power, floor or ceiling effects, mediator analyses to address possible fidelity or adherence problems, therapist effects, absence of main effects but possible subgroup/moderator effects, etc.).