There is growing interest in how best to adapt and re-adapt treatments to individuals to maximize clinical benefit. In response, adaptive treatment strategies (ATS), which operationalize adaptive, sequential clinical decision making, have been developed. From a patient's perspective an ATS is a sequence of treatments, each individualized to the patient's evolving health status. From a clinician's perspective, an ATS is a sequence of decision rules that input the patient's current health status and output the next recommended treatment. Sequential multiple assignment randomized trials (SMART) have been developed to address the sequencing questions that arise in the development of ATSs, but SMARTs are relatively new in clinical research. This article provides an introduction to ATSs and SMART designs. This article also discusses the design of SMART pilot studies to address feasibility concerns, and to prepare investigators for a full-scale SMART. As an example, we consider an example SMART for the development of an ATS in the treatment of pediatric generalized anxiety disorders. Using the example SMART, we identify and discuss design issues unique to SMARTs that are best addressed in an external pilot study prior to the full-scale SMART. We also address the question of how many participants are needed in a SMART pilot study. A properly executed pilot study can be used to effectively address concerns about acceptability and feasibility in preparation for (that is, prior to) executing a full-scale SMART.

Objective This study examined aspects of depressed adolescents' perceived interpersonal functioning as moderators of response to treatment among adolescents treated with interpersonal psychotherapy for depressed adolescents (IPT-A) or treatment as usual (TAU) in school-based health clinics. Method Participants were 63 adolescents (ages 12-18) participating in a clinical trial examining the effectiveness of IPT-A (Mufson, Dorta, Wickramaratne, et al., 2004). The sample consisted of 53 (84.1%) female and 10 (15.9%) male adolescents (mean age = 14.67). Adolescents were 74.6% Latino, 14.3% African American, 1.6% Asian American, and 9.5% other, and they came primarily from low-income families. Adolescents were randomly assigned to receive IPT-A or TAU delivered by school-based mental health clinicians. Assessments were completed at baseline and weeks 4, 8, and 12 (or at early termination) and included the HRSD, CBQ-20, and SAS-SR. Results Multilevel modeling indicated that treatment condition interacted with adolescents' baseline reports of conflict with their mothers and social dysfunction with friends to predict the trajectory of adolescents' depressive symptoms over the course of treatment, controlling for baseline levels of depression. The benefits of IPT-A over TAU were particularly strong for the adolescents who reported high levels of conflict with their mothers and social dysfunction with friends. Conclusions Replication with larger samples would suggest that IPT-A may be particularly helpful for depressed adolescents who are reporting high levels of conflict with their mothers or interpersonal difficulties with friends.

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These results demonstrate the potential role for ketamine in treating adolescents with TRD. Limitations include the open-label design and small sample; future research addressing these issues are needed to confirm these results. Additionally, evidence suggested a dose-response relationship; future studies are needed to optimize dose. Finally, questions remain regarding the long-term safety of ketamine as a depression treatment; more information is needed before broader clinical use.