A Pilot SMART for Developing an Adaptive Treatment Strategy for Adolescent Depression

In clinical practice, as well as in other areas where interventions are provided, a sequential individualized approach to treatment is often necessary, whereby each treatment is adapted based on the object's response. An adaptive intervention is a sequence of decision rules which formalizes the provision of treatment at critical decision points in the care of an individual. In order to inform the development of an adaptive intervention, scientists are increasingly interested in the use of sequential multiple assignment randomized trials (SMART), which is a type of multi-stage randomized trial where individuals are randomized repeatedly at critical decision points to a set treatment options. While there is great interest in the use of SMART and in the development of adaptive interventions, both are relatively new to the medical and behavioral sciences. As a result, many clinical researchers will first implement a SMART pilot study (i.e., a small-scale version of a SMART) to examine feasibility and acceptability considerations prior to conducting a full-scale SMART study. A primary aim of this paper is to introduce a new methodology to calculate minimal sample size necessary for conducting a SMART pilot.

The authors investigated the theoretical and clinical role of depression among cocaine abusers in treatment. Eighty-nine cocaine-abusing patients underwent 2 weeks of substance abuse treatment. Posttreatment major depressive disorder, depressive symptoms before and after substance abuse treatment, and alcohol diagnoses were assessed and their relation to pretreatment substance use, cravings in high-risk situations, and 3-month follow-up status was examined. High rates of major depressive disorder were found but were unrelated to pretreatment substance use. The decrease in depressive symptoms during treatment was independent of major depressive disorder or alcohol diagnoses and predicted treatment attrition. Higher levels of depressive symptoms during treatment were associated with greater urge to use cocaine, alcohol, and other drugs in high-risk situations. Concurrent major depressive disorder and depressive symptoms did not predict cocaine use at follow-up. However, patients who had an alcohol relapse episode experienced more depressive symptoms during treatment than did those who abstained. The results highlight the relationship of depression to alcohol use among cocaine abusers and suggest a need for further studies of the association between depression and substance use disorders.

This paper reviews the main principles of Interpersonal Psychotherapy and its adaptation for depressed adolescents (IPT-A). The work of IPT-A is put in the context of the significant problem of depression in adolescence and the other treatments and their efficacy in the treatment of adolescent depression. The paper also provides an overview of the approach and specific techniques to be used with adolescents. The efficacy and effectiveness data on IPT-A are presented briefly. IPT-A is an empirically supported psychotherapy for depressed, non-bipolar and non-psychotic adolescents. IPT-A is unique among evidence-based treatments in its demonstrated effectiveness when transported from a laboratory setting to a community setting (school-based health clinics) and delivered by community clinicians. Future studies are needed with other populations that include long-term follow-up of outcomes and are conducted by other investigator teams.

Suicidal ideation is increasing among university students. Despite growing demand for services, university counseling centers (UCCs) face limited resources to meet the complex needs of students who are suicidal. The Comprehensive Adaptive Multisite Prevention of University Student Suicide (CAMPUS) Trial evaluates 4 treatment sequences within UCCs to develop evidence-based treatment guidelines. The CAMPUS Trial consists of a feasibility study followed by a sequential multiple-assignment randomized trial (SMART). The original CAMPUS protocol was modified during the COVID-19 pandemic to accommodate new UCC tele-mental health services, including remote treatment, assessments, and monitoring. A smaller-scale feasibility study was conducted to (1) evaluate implementation of hybrid telehealth and in-person interventions and (2) fine-tune online procedures. Following the feasibility study, university students (aged 18-25 years) seeking UCC services with moderate to severe suicidal ideation will enroll in the CAMPUS Trial. Student participants are randomly assigned to 1 of 4 treatment sequences with 2 stages of intervention. In stage 1, students receive 4 to 6 weeks of either (1) a suicide-focused treatment-Collaborative Assessment and Management of Suicidality-or (2) enhanced treatment as usual. Treatment responders enter the maintenance phase. In stage 2, nonresponders are rerandomized for an additional 1 to 8 weeks of (1) Collaborative Assessment and Management of Suicidality or (2) an intensive skills-based treatment-dialectical behavior therapy for UCC settings. UCC counselors will enroll in the CAMPUS Trial to complete measures about their experience working with students who are suicidal. CAMPUS Trial administration includes representation from all sites to facilitate cross-site coordination and an advisory board of stakeholders from all UCCs to facilitate treatment implementation. Student participant recruitment began on October 25, 2022, and ended on May 16, 2024. As of November 2024, data collection for the SMART was ongoing with active study participants. Data collection was completed in November 2024, and as of April 2025, data analysis is underway. Full results will be available in 2025. The CAMPUS Trial offers a model for future SMARTs for the treatment of suicidal thoughts or behaviors (or both) across various settings. The results will inform treatment guidelines for students presenting with suicidality at UCCs. ClinicalTrials.gov NCT04707066; http://clinicaltrials.gov/ct2/show/NCT04707066. DERR1-10.2196/68441.

This paper assesses acculturation and ethnic matching of therapist and patient as predictors and moderators of treatment outcome in a 12-week effectiveness study of Interpersonal Psychotherapy for depressed adolescents (IPT-A) versus treatment as usual (TAU). The treatment was delivered in school-based health clinics in which care was provided for a predominantly Latino patient population. Birthplace, length of residence in the United States (U.S.), and therapist-patient ethnic matching were examined as predictors and moderators of treatment outcomes for depression, social functioning, and global functioning scores. Birthplace significantly moderated treatment condition in predicting week 12 depression severity and improvement, and marginally significantly moderated treatment in predicting week 12 depression symptoms, with U.S.-born adolescents who received IPT-A having better outcomes. Birthplace predicted week 12 self-reports of depression, social (overall, school, and family) and global functioning, with U.S.-born adolescents faring worse across treatment conditions. Foreign-born adolescents treated with IPT-A as compared to TAU who lived for a longer period of time in the U.S. demonstrated better overall social functioning as compared to foreign-born adolescents who had lived for a shorter period of time in the U.S. Ethnic matching predicted significant reduction in depression severity and improved overall social functioning, and marginally significant improvement in week 12 depression scores, regardless of treatment condition. IPT-A may be a culturally responsive treatment for depressed Latino youth who are struggling with acculturation issues that affect their significant relationships. Ethnic matching appears beneficial for the general population in reducing depression and improving social functioning.

The aim of the present study was to examine the intervention effects of intensive interpersonal psychotherapy for depressed adolescents with suicidal risk (IPT-A-IN) by comparison with treatment as usual (TAU) at schools. A total of 347 students from one-fifth of the classes of a high school in southern Taiwan completed the Beck Depression Inventory-II, the Beck Scale for Suicide Ideation, the Beck Anxiety Inventory and the Beck Hopelessness Scale for screening for suicidal risk. Of them, 73 depressed students who had suicidal risk on screening were randomly assigned to the IPT-A-IN or TAU group. Analysis of covariance (ANCOVA) was performed to examine the effect of IPT-A-IN on reducing the severity of depression, suicidal ideation, anxiety and hopelessness. Using the pre-intervention scores as covariates, the IPT-A-IN group had lower post-intervention severity of depression, suicidal ideation, anxiety and hopelessness than the TAU group. Intensive school-based IPT-A-IN is effective in reducing the severity of depression, suicidal ideation, anxiety and hopelessness in depressed adolescents with suicidal risk.

MDD diagnosis based on EEG feature fusion and improved feature selection

BackgroundThe diagnosis of major depressive disorder (MDD) mainly depends on subjective clinical symptoms, without an acceptable objective biomarker for the clinical application of MDD. Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) showed a high specificity as biomarker for the diagnosis and treatment of MDD. The present study aimed to investigate differences in plasma ITIH4 in two different aged MDD patients and underlying pathological mechanisms of plasma ITIH4 in the occurrence and development of MDD.MethodsSixty-five adult MDD patients, 51 adolescent MDD patients, and 64 healthy controls (HCs) were included in the present study. A 14-days’ antidepressive treatment was conducted in all MDD patients. Psychological assessments were performed and plasma ITIH4 and astrocyte-related markers were detected for all participants.Results(1) Plasma levels of ITIH4 in adult MDD patients were significantly higher than adolescent MDD patients and HCs, and significantly increased plasma ITIH4 levels was observed in adolescent MDD patients compared with HCs (2). There were positive correlations between plasma ITIH4 levels and 24-item Hamilton Depression Scale (HAMD-24) scores and plasma glial fibrillary acidic protein (GFAP) levels in MDD patients, however, plasma ITIH4 levels were significantly correlated with age just in adult MDD patients (3). Plasma ITIH4 showed area under the curve values of 0.824 and 0.729 to differentiate adult MDD patients and adolescent MDD patients from HCs, respectively (4). There was significant decrease in plasma levels of ITIH4 between before and after antidepressive treatment in adult MDD patients, but not in adolescent MDD patients (5). Changed value of ITIH4 levels were correlated with the changed value of GFAP levels and changed rate of HAMD-24 scores in adult MDD patients following antidepressive treatment.ConclusionPlasma ITIH4 may be potential plasma biomarkers of MDD with age-related specificity, which was associated with depressive symptoms astrocyte-related pathologic changes, and antidepressive treatment efficacy.

A pilot study of depressed adolescents’ cortisol patterns during parent–adolescent conflict and response to interpersonal psychotherapy (IPT-A)

Diagnosis of major depressive disorder using a novel interpretable GCN model based on resting state fMRI.

RNA high-throughput sequencing and clinical outcome validation indicate that long non-coding RNAs are biomarkers in the peripheral blood of patients with major depressive disorder

Guideline-Consistent Antidepressant Treatment Patterns Among Veterans With Diabetes and Major Depressive Disorder

Evidence-based guidelines recommend regular depression screening among individuals with type 2 diabetes mellitus (T2DM). The purpose of this study is to examine depression screening patterns among a primary care population with T2DM, through use of the Patient Health Questionnaire-9 (PHQ-9). In total, 1817 patients with T2DM were analyzed through a retrospective observational study at 2 sites, a regional health center and a federally qualified health center (FQHC). The T2DM sample was divided into those with and without a major depressive disorder (MDD) diagnosis. Depression screening rates and depression severity were assessed through the PHQ-9. Both sites had higher rates of PHQ-9 screening among individuals with a history of MDD (64.82%) vs those without MDD (11.39%). Individuals from the FQHC without a history of depression had a higher mean PHQ-9 score (10.11) than those with a previous MDD diagnosis at both RHS and FQHC (7.16 and 9.85, respectively). Depression screening rates among individuals with diabetes and no history of MDD were remarkably low. Patients with diabetes but no MDD diagnosis who sought health care at a FQHC clinic had more depressive symptoms than those with a history of MDD at both sites. Individuals with diabetes and who have a MDD diagnosis are much more likely to receive regular depression screening than those without MDD, which leaves a substantial proportion of patients with undetected depression. Depression screening must be enhanced for all individuals with diabetes, particularly for low-income individuals and those without a previous diagnosis of MDD.

The authors' goal was to conduct an adult follow-up of subjects who had participated in a study of nortriptyline for childhood depression. The study group represented 100 (90. 9%) of the original 110 subjects and included 72 subjects who had a prepubertal diagnosis of major depressive disorder and 28 normal comparison subjects. Subjects were assessed with semistructured research interviews given by research nurses who were blind to the subjects' original diagnoses. In the original study, the mean age of the children with prepubertal major depressive disorder was 10.3 years (SD=1.5); at adult follow-up the mean age of these subjects was 20.7 years (SD=2.0). At follow-up, significantly more of the subjects who had prepubertal diagnoses of major depressive disorder (N=24 [33.3%]) than normal comparison subjects (none) had bipolar I disorder. Subjects who had prepubertal diagnoses of major depressive disorder also had significantly higher rates of any bipolar disorder than normal subjects (48.6% [N=35] versus 7.1% [N=2]), major depressive disorder (36.1% [N=26] versus 14.3% [N=4]), substance use disorders (30.6% [N=22] versus 10.7% [N=3]), and suicidality (22.2% [N=16] versus 3.6% [N=1]). Parental and grandparental mania predicted bipolar I disorder outcomes. High rates of switching to mania have implications for the treatment of depressed children. The authors discuss the reasons for their finding a higher rate of bipolar disorder in this outcome study than was found in the one other adult outcome study of prepubertal major depressive disorder.

Background: Sertraline is commonly prescribed to children for the treatment of anxiety and major depressive disorder and is metabolized in part by CYP2C19. While dosing recommendations based on CYP2C19 genotype exist, there is sparse data in children on the relationship between sertraline concentrations and CYP2C19 genotype. Additionally, although rarely utilized in the United States, therapeutic drug monitoring can also help to guide dosing. The primary objective of this pilot study was to compare sertraline concentrations with CYP2C19 genotype. Secondary objectives included exploring the feasibility of using pharmacogenetic testing and therapeutic drug monitoring in a residential treatment center for children and adolescents. Methods: This study was a prospective, open-label study of children prescribed sertraline being treated at a residential treatment center for children and adolescents. Individuals were included if they were < 18 years of age, taking sertraline for at least 2 weeks allowing them to reach steady-state concentrations, being treated through the residential treatment program, and able to understand and speak English. Results: A total of 20 participants (80% female) completed all study procedures, including pharmacogenetic testing and therapeutic drug monitoring, with an average age of 15.4 years (range: 9-17 years). Forty percent (n=8) of participants had a diagnosis of Generalized Anxiety Disorder, while 30% (n=6) had a diagnosis of Major Depressive Disorder. Overall, average sertraline and desmethylsertraline concentrations were 21.1 ng/ml (range: 1-78 ng/ml) and 52.4 ng/ml (range: 1-258 n/ml). Based on CYP2C19 genotypes, 60% (n=12) were normal metabolizers, 10% (n=2) were intermediate metabolizers, and 30% (n=6) were rapid metabolizers. Daily sertraline dose (mg/day) accounted for a significant amount of the observed variability in sertraline (p<0.0001; r2=0.62) and desmethylsertraline concentrations (p<0.001; r2=0.45). When comparing weight-based dosing by sertraline and desmethylsertraline concentrations, sertraline daily dose by weight (mg/kg/day) also accounted for a significant amount of the observed variability in sertraline (p<0.0001; r2=0.60) and desmethylsertraline (p<0.0001; r2=0.59) concentrations. Average daily and weight-based doses for CYP2C19 intermediate, normal, and rapid metabolizers were 75mg/day, 87.5mg/day, and 79.2mg/day and 1.5mg/kg/day, 1.3mg/kg/day, and 1.1mg/kg/day, though these were not significantly different. Conclusion: This small, pilot study showed sertraline dose to be significantly associated with sertraline and desmethylsertraline concentrations. No differences were noted between CYP2C19 metabolizer groups, likely due to the limited sample size. These results also suggest that ordering pharmacogenetic testing and therapeutic drug monitoring in the setting of a child and adolescent residential treatment center is feasible.