Problem statement. Major Depressive Disorder (MDD) is a significant concern among adolescents, characterized by episodes of mood changes, cognitive symptoms, and neurovegetative dysfunction, often lasting months or even years, with a high recurrence rate. In Chile, the prevalence of adolescent MDD is estimated at 8.3%, but only a fraction receive treatment. Post-COVID-19 studies indicate a deterioration in adolescent mental health globally. Treatments for MDD include various psychotherapies, medications like Selective Serotonin Reuptake Inhibitors (SSRIs), and combined approaches, though many adolescents remain untreated or receive non-specific care. Integrated Care Pathways (ICPs), such as the CARIBOU, show promise in providing structured, multidisciplinary care. The CARIBOU model includes components like individual and group Cognitive Behavior Therapy (CBT), caregiver support, and medication algorithms within a Measurement-Based Care (MBC) framework. Pilot studies indicate the feasibility of such interventions, but further research is needed, particularly in resource- limited settings like Chile. Recent initiatives by the Chilean Ministry of Health, underscore the urgency and potential for implementing ICPs like CARIBOU in primary care to address adolescent depression effectively. General Objective: To evaluate the acceptability, feasibility, and explore the efficacy of CARIBOU pathway in treating adolescent depression in primary care. Specific Objectives (SO) 1. To assess the acceptability of the various components of the CARIBOU care model among adolescents, parents/caregivers, and healthcare professionals involved in the treatment of depression in primary care. 2. To assess the feasibility of implementing the different components of the CARIBOU care model for adolescents in the treatment of depression in primary care settings. For example, determine if the research team can recruit a sufficient number of participants at each participating health center within the time of the pilot cluster Randomized Controlled Trial (cRCT) study, evaluate the adherence of healthcare professionals in offering and implementing the proposed interventions, and estimate the participation level of students, parents/caregivers, and healthcare professionals in completing multiple longitudinal outcome assessments to provide sufficient data for a valid analysis. 3. To explore the efficacy of the ICP CARIBOU in reducing depressive symptoms, as measured by the short form of Mood and Feelings Questionnaire (MFQ), compared to treatment as usual (TAU) over 24 weeks. Similarly, determine if the use and implementation of CARIBOU are more effective in reducing anxiety symptoms, measured by the Generalized Anxiety Disorder 7 (GAD-7), and in improving quality of life, measured by the KIDSCREEN-27, family functioning measured by the The McMaster Family Assessment Device - General Functioning Subscale (MFAD-GF), and the overall functionality using the Columbia Impairment Scale, Youth Version (CIS-Y). Methodology. To achieve these objectives, the project will be divided into two phases. I) Formative work: a) the Translation and cultural adaptation of the program of the different components CARIBOU ICP, and b) Youth and family engagement in enhancing the design and relevance of CARIBOU interventions for adolescent depression. And II) The Intervention evaluation phase: a) a Pilot cluster Randomized Controlled Trial study to assess the acceptability and feasibility of implementation CARIBOU ICP in primary care centers and to explore the efficacy of the intervention in reducing depressive and anxiety symptoms and functional impairment and improving quality of life in primary care settings in Chile. This study will involve 72 depressed adolescents and their families randomly allocated to the CARIBOU ICP group (n=36, in two CESFAMs) and to the Treatment As Usual (TAU) (n=36, in two CESFAMs) Expected outcomes. The research project is anticipated to deliver several key outcomes across two phases. In the formative phase, the project will successfully translate and culturally adapt the CARIBOU intervention materials for Chile. This phase will ensure the intervention and assessment tools are culturally relevant and reliable. In the evaluation phase, a pilot cRCT will assess the acceptability and feasibility of implementation of CARIBOU and will explore the intervention's efficacy, aiming to show significant reductions in depression and anxiety symptoms and improvements in overall well-being and social functioning among adolescents. The successful dissemination of findings will inform clinical practices and policymakers, potentially leading to a larger evaluation and dissemination of the CARIBOU intervention in primary care settings, thereby benefiting adolescent mental health in Chile.
A) THEORETICAL-CONCEPTUAL FOUNDATIONS AND STATE OF THE ART Definition and magnitude of the problem Major Depressive Disorder (MDD) is a distinct diagnosis outlined in the DSM-5, characterized by episodes lasting at least two weeks, often much longer, with changes in mood, thinking, and neurovegetative functions (sleep, appetite, and energy) and periods of remission between episodes. MDD symptoms are consistent and valid, classified into mild, moderate, and severe forms based on nine specific symptoms. Severity is determined by symptom count, intensity, and impairment level, with this classification method widely used in population studies and primary care settings. Mild depression involves fewer symptoms and minimal impairment, while severe depression includes all DSM-5 symptoms or severe impairment. Moderate depression falls in between. Most episodes last 3-6 months in community samples and 5-8 months in referred samples. However, 20% of adolescents may experience episodes lasting two years or more, with more than half having a recurrence within five years. Predictors of recurrence include poor treatment response, symptom severity and chronicity, previous episodes, comorbidity, negative cognitive style, family problems, low socioeconomic status, and exposure to family conflict or violence. Major Depressive Disorder in adolescents (MDD-A) is common, with the National Comorbidity Survey-Adolescent Supplement (NCS-A) showing lifetime and 12-month prevalence rates of 11.0% and 7.5%, respectively, among adolescents aged 13 to 18. Prevalence increases significantly during adolescence, especially among females. Most cases involve psychiatric comorbidity and severe role impairment, with many reporting suicidality. Adolescents are considered to have severe MDD if they have at least five criteria plus a specific suicide plan, psychotic symptoms, a family history of bipolar disorder, or severe functional impairment. Several studies have alerted about a significant deterioration in mental health among adolescents in the post-COVID-19 period. For instance, a recent study including 5,368 Canadian secondary school students who participated in three consecutive waves during the 2018-19, 2019-20, and 2020-21 school years, found that the proportion of adolescents with significant depressive (29.4%) and moderate-to-severe anxiety (17.6%) symptoms at baseline increased by 1.5 times, reaching 44.8% and 29.8% in the ongoing pandemic period, respectively. In Chile, it is estimated that the prevalence at the national level of MDD in the adolescent population is 8.3%. There is concern regarding these figures because only between 20% and 50% of depressed adolescents finally access treatment. In a more recent study, 2,022 students from the first to the third grades of secondary education (9th to 11th grade) from 8 schools (average age, 15.2 years; 49.5% were women) were surveyed. Using the Patient Health Questionnaire-9 (PHQ-9) to explore depressive symptoms, 35.2% of the students had a score to be classified at risk of having a MDD-A (PHQ-9\>10). There is no data on the prevalence of MDD-A in the post-COVID-19 period. An MDD-A is debilitating, impacting the development in several areas. A recent meta-analysis of longitudinal studies found that adolescent depression was associated with outcomes including, but not limited to, failure to complete secondary school, unemployment, and pregnancy/parenthood. Additionally, MDD-A is also a risk factor for suicide. Some studies have shown that in primary care (PC), as many as 2 in 3 youth with depression are not identified and fail to receive any care. Treatment in any form was received by most adolescents with 12-month DSM-IV MDD (60.4%), but only a minority received treatment that was disorder-specific or from the mental health sector. Another study showed that 62% of individuals with a psychiatric disorder had not accessed any mental health services in the past year. This study also showed that these individuals exhibited fewer antisocial traits and disorders, more anxiety disorders, and less comorbidity compared to those receiving treatment. This suggests that individuals with anxiety disorders may be less likely to seek services and highlights that access to Child and Adolescent Mental Health Services (CAMHS) often requires more complex cases with high levels of comorbidity and impairment. In addition, the same longitudinal study found that among 14-year-old adolescents with a DSM-IV psychiatric disorder, those who used mental health services experienced a substantial reduction in depressive symptoms by the 36-month follow-up. By contrast, by age 17, adolescents who did not access mental health services were seven times more likely to report clinical-level depression symptoms compared to those who did seek help. Legal tools and Clinical Guidelines for depression among adolescents in Chile in a nutshell In 2001, the Program for Screening, Diagnosis, and Comprehensive Treatment of Depression (PSDCTD) was established to provide effective treatment for depressive disorders in primary care clinics. By 2005, the program was extended to all primary care clinics nationwide. In 2006, it was supplemented by the Explicit Health Guarantees (GES) plan, which included coverage for depressive disorders in individuals over 15 years old. The GES plan guarantees coverage by Fonasa and Isapres, ensuring timely and comprehensive treatment by accredited providers. Financial coverage varies by income, covering 100% for the lowest income households and up to 80% for higher income groups and Isapre affiliates. Patients are informed about GES coverage options for depression and can choose between private providers and the free-choice system. In 2013, the Clinical Guide for Depression (CGD) for individuals aged 15 and older provided treatment recommendations, including active detection of at-risk individuals, reducing complications and relapses through early and continuous evidence-based treatment, and promoting cost-effective interventions tailored to patients' specific conditions. However, it lacked recommendations for adolescents. The Chilean Ministry of Health recently introduced the Clinical Practice Guideline for Addressing Depression in Adolescents (CGD-A), offering detailed recommendations for all healthcare professionals involved in adolescent depression care, such as general practitioners, psychiatrists, psychologists, and others. The PSDCTD, GES Plan, CGD, and CGD-A are good tools for health professionals to help adolescents with depression. However, no evaluation of their effectiveness and implementation has been done. Treatment of Depression for Adolescents: Several treatments are available for depression, including different types of psychotherapy, medications, family involvement, or a combination of these. Treatment may also involve collaboration with the adolescent's school or participation in peer support or self-help groups. The professionals in charge of the treatment should create a comprehensive treatment plan tailored to the specific situation and adolescent's needs, incorporating the recommended treatment approaches. Additionally, the professionals should thoroughly explain the treatment plan's risks and benefits to you and your child. There are limited studies on the effectiveness of medications for depression in adolescents. Fluoxetine (Prozac) and escitalopram (Lexapro) are Selective Serotonin Reuptake Inhibitors (SSRIs) and the only medications approved by the FDA for treating depression in children and adolescents aged 8 and older and 12 and older, respectively. Other SSRIs, like sertraline, and non-SSRIs, such as venlafaxine, although not FDA-approved for this age group, are commonly used off-label by physicians to treat depression in children and adolescents, which is a standard clinical practice. On the other hand, the efficacy of psychological treatments for depression in children and adolescents gained traction in 1980 following the American Psychiatric Association's clarification on the similarity of major depressive episodes across age groups. That year, the first trial on the treatment of childhood depression was published, and six years later, the first study of the treatment of depression in adolescents was published. Initial trials indicated cognitive behavioral therapy (CBT) as an effective treatment adapted for adolescents, though early comparisons with relaxation training showed no significant differences in outcomes. The first randomized controlled trial (RCT) in adolescents diagnosed with depression was conducted in 1990. A recent meta-analysis revealed that psychotherapies are effective compared to control conditions. Yet, over 60% of youths receiving therapy do not respond, indicating the need for more effective treatments and strategies. Additionally, a gap exists between research-based interventions and their clinical implementation. Despite approximately 20% of adolescents experiencing major depression, evidence-based treatments remain underutilized, highlighting the need to bridge the gap between research findings and clinical application. Effectiveness of medication and when combined with psychotherapy The Treatment for Adolescents with Depression Study (TADS), funded by the National Institute of Mental Health and published in 2004, evaluated fluoxetine (Prozac), cognitive-behavioral therapy (CBT), and their combination in treating moderate to severe depression in adolescents. After 12 weeks, 71% of those receiving the combined treatment improved significantly, compared to 35% for placebo, 43% for psychotherapy, and 61% for medication alone. The combined treatment also enhanced functioning and quality of life, making it the preferred approach for faster recovery and remission. All treatments reduced suicidal thoughts and behaviors, but fluoxetine alone was linked to increased suicidal ideation. After three months, suicidal thoughts and behaviors significantly decreased across all treatments, with no completed suicides. This study underscores the effectiveness of medication and suggests that combined treatment may help protect against suicidal thoughts and behaviors, though this effect is not consistently found in all studies. Most adolescents with depression (about 60%) improve with initial SSRI antidepressant treatment, but around 40% do not respond. The TORDIA study investigated alternative therapies for these SSRI-resistant adolescents, including switching to a different SSRI, switching to a non-SSRI (venlafaxine), combining a different SSRI with CBT, and combining a non-SSRI with CBT. The most improvement was seen in those who switched medications and added CBT, proving more effective than medication alone. Switching to another SSRI was as effective as switching to venlafaxine but had fewer side effects. These findings suggest that adolescents not responding to initial SSRI treatment may benefit from switching to another SSRI combined with CBT. It is important to allow 6-8 weeks to assess the initial treatment's effectiveness before considering alternatives. Optimal treatment often involves a combination of psychotherapy and medication. What happened in the real world? Treatment approaches used in real-world clinical practice are heterogeneous, often with limited patient follow-up frequency, low resolution, and insufficient evidence support in the primary care system. There are several steps to bridge the gap between research and practice in treating MDD-A. Firstly, to establish a broad consensus on evidence-based treatments for MDD-A. High-quality Clinical Practice Guidelines (CPGs) are designed to fulfill this role; they are defined as "statements that include recommendations aimed at optimizing patient care based on a systematic review of evidence and an assessment of the benefits and harms of alternative care options." Only recently, in Chile (in 2021), the Chilean Ministry of Health published the CPG for adolescents. In 2018, the American Academy of Pediatrics published the Guidelines for Adolescent Depression in Primary Care (GLAD-PC), Part I and Part II. Regarding the GLAD-PC, these guidelines strongly support that Primary Care (PC) clinicians should recommend scientifically tested and proven treatments (i.e., psychotherapies, such as CBT or Interpersonal Psychotherapy, or antidepressant treatment, such as SSRIs) whenever possible to achieve the goals of the treatment plan. These GLAD-PCs also provide recommendations for managing adolescent depression in primary care, including 1) active monitoring of mildly depressed youth, 2) using evidence-based medications and psychotherapeutic methods for moderate and severe depression, 3) closely monitoring side effects, 4) consulting and co-managing care with mental health specialists, 5) continuously tracking outcomes, and 6) taking specific actions in cases of partial or no improvement after starting treatment. One might question whether primary care (PC) clinicians should identify and diagnose adolescent depression, given the limited availability of psychiatric services for referrals. Despite this concern, the growing consensus is that, at the very least, PC clinicians should be equipped with the necessary guidance to support the initial management of adolescent depression. However, due to the varying levels of readiness among practitioners and their clinical settings in identifying and managing adolescent depression, significant time and flexibility will likely be needed before these guidelines are systematically or universally implemented. Secondly, the gap in how CPG recommendations should be implemented in clinical settings must be narrowed. Greater adherence to care standards in the treatment of depressive disorders in adolescents treated in primary care has been associated with improved outcomes. As mentioned above, specific evidence-based treatments, such as antidepressant medication and CBT, have shown limited effectiveness, with up to 40% of adolescents remaining unremitted at follow-up. This is why there has been a call for more comprehensive care, where, in addition to medications and therapy, they could be integrated into other strategies, such as psychoeducation about sleep, exercise, diet, and family involvement. There is evidence that a multifaceted approach to mental health consultation may improve the management of depression in Primary Care settings. In this sense, Integrated Care Pathways (ICPs) serve as an implementation tool: they are decision-support aids based on CPG recommendations designed to guide clinical choices during patient care. No studies have explored the effectiveness of ICPs in guiding the comprehensive delivery of care for MDD-A in Chile and Latin American countries. ICPs aim to standardize and personalize patient management by enabling comprehensive, multidisciplinary care through a sequence of decision points and treatment steps. The ultimate goal of ICPs is to optimize evidence-based care by balancing research evidence, expert clinical judgment, and patient/family values within the constraints of available resources. Finally, the patient's progress must be monitored following successive CPG recommendations, ensuring that the patient improves or alerts physicians when treatment is ineffective and needs adjustment. Measurement-Based Care (MBC) provides this approach; it "involves systematic administration of symptom rating scales and uses the results to drive clinical decision-making at the individual patient level." To our knowledge, only one ICP has been studied among adolescents with MDD. It is called The CARIBOU pathway, which stands for "Care for Adolescents who Receive Information 'Bout Outcomes" (first iteration), which includes several components for youth: 1) a structured assessment focusing on self-harm risk, bullying exposure, and caregiver mental illness, 2) a group education session called "Mood Foundations" discussing depression, sleep hygiene, exercise, and diet with youth and caregivers, 3) 16 sessions of group CBT, chosen over individual therapy due to resource availability and evidence of similar efficacy, 4) an 8-session caregiver group focusing on validating communication and collaborative problem-solving, 5) a medication algorithm with fluoxetine as the first-line treatment and sertraline as the second-line, and 6) all within a framework of measurement-based care (MBC). In a recent pilot parallel non-randomized controlled clinical trial, two centers participated, one implementing CARIBOU in 35 adolescents and the other assigned to Treatment As Usual (TAU) with 31 participants. Recruitment met the target sample size over 15 months. High clinician fidelity (95%) and adolescent engagement (80%) were observed in the ICP components based on checklists. Baseline and 20-week endpoint data for depressive symptoms as the primary outcome, measured by the Children's Depression Rating Scale-Revised (CDRS-R), were collected for 83% of the participants. Analysis using linear mixed-effects modeling showed a consistent decrease in CDRS-R scores over 4-week intervals up to the 20-week endpoint in both groups (β = -2.07; 95% CI -3.14 to -1.01). The study concluded that implementing CARIBOU was feasible. Still, more research is needed to explore the effectiveness of this ICP model in a larger randomized controlled trial (RCT). There is an urgent need to assess the acceptability, feasibility, and efficacy/effectiveness of Integrated Care Pathways like CARIBOU for treating Major Depressive Disorder (MDD) in adolescents in resource-constrained countries such as Chile and other Latin American nations. In Chile, 18% of individuals needing mental health treatment are underserved. Recent initiatives by the Chilean Ministry of Health, such as an updated national plan to prevent adolescent suicide in educational settings and the promotion of collaboration between schools and primary care clinics to minimize support delays and reach all those in need, give support to this proposal. Furthermore, the Ministry supports the implementation of CARIBOU by advocating for depression screening in primary care settings for adolescents and promoting group over individual psychological interventions to optimize resources in already constrained settings such as primary care clinics.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Enrollment
72
An integrated care pathway for adolescents with major depressive disorder delivered in primary care, including psychoeducation, cognitive behavioral therapy (group or individual) or Brief Psychological Intervention, caregiver support, measurement-based care, and medication management when clinically indicated.
Treatment as usual consists of routine outpatient care provided in Chilean primary care centers. Participants receive standard clinical management according to local practice, which may include assessment, psychotherapy, medication management, referrals, and follow-up, without the structured CARIBOU integrated care pathway or measurement-based care framework.
CESFAM Madre Teresa de Calcuta; CESFAM Juan Pablo II; CESFAM San Alberto Hurtado; CESFAM
Santiago, Santiago Metropolitan, Chile
Acceptability of the CARIBOU Integrated Care Pathway
Acceptability of the intervention will be assessed using a questionnaire developed by the research team and qualitative interviews with adolescents, caregivers, and healthcare professionals.
Time frame: week 24
Participant Satisfaction
Satisfaction with the intervention will be assessed using the adapted Client Satisfaction Questionnaire (CSQ-8). This is an 8-item instrument, validated in English and subsequently translated and validated into Spanish, that measures overall satisfaction with health services received across various populations. Responses are Likert-type, with four options each. It also includes space for comments and suggestions. This instrument will be slightly adapted to questions oriented to the context of the study. The CSQ has an internal consistency range of α = 0.83 to α = 0.93
Time frame: Week 24
Recruitment Feasibility
Number of participants recruited who complete the baseline assessment.
Time frame: Up to 30 months
Baseline Assessment Completion
Percentage of participants completing the baseline assessment within 2 hours.
Time frame: Baseline
Clinician Adherence to the CARIBOU Model
Mean clinician adherence score assessed using clinician adherence forms, checklists, and chart reviews.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
Retention of Outcome Assessments
Proportion of completed scheduled Mood and Feelings Questionnaire (MFQ) assessments across all planned time points.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
Depressive Symptoms
Depressive symptoms measured using the Mood and Feelings Questionnaire - Short Version (MFQ). This is a self-report instrument designed to assess mood. It consists of 13 items rated on a Likert scale from 0 = "Not true" to 2 = "True." The total score ranges from 0 to 26 points. Various studies have shown that the scale is unidimensional in samples of girls and boys aged 6 to 18 years. It demonstrates high levels of internal reliability (α = 0.80 to 0.91) and validity in cohorts of children aged 8-16. The MFQ is specifically designed for children and adolescents, which may make it more suitable for this age group compared to the PHQ-9. It has strong psychometric properties, including high internal consistency and reliability, making it a robust tool for screening adolescent depression. The MFQ's ease of use and open-access nature can facilitate its implementation in various settings, including schools and primary care clinics.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
Overall Functioning
Overall functioning measured using the Columbia Impairment Scale - Youth Version (CIS-Y). Is a 13-item questionnaire with versions for both parent (CIS-P) and youth (CIS-Y) ratings. It assesses family and peer relationships, engagement in hobbies, and school involvement over the past weeks using a Likert scale. The scale demonstrates high internal consistency and excellent test-retest reliability and correlates well with established measures of functioning. A score of ≥ 16 indicates significant impairment, making it suitable for inclusion due to its cost-effectiveness, quick administration, and reliable psychometric properties. In this project, we will study the psychometric properties of this instrument.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
Anxiety Symptoms
Anxiety symptoms measured using the Generalized Anxiety Disorder 7-item scale (GAD-7) which is a self-report questionnaire designed to assess the severity of anxiety symptoms in adolescents and adults. It consists of seven items corresponding to the DSM-5 diagnostic criteria for generalized anxiety disorder. Respondents rate the frequency of their symptoms over the past two weeks on a scale from 0 (not at all) to 3 (nearly every day), yielding a total score ranging from 0 to 21. It has been validated among Chilean adolescents with good psychometric properties.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
Health-Related Quality of Life
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Health-related quality of life measured using the KIDSCREEN-27 questionnaire which is a brief questionnaire used to assess the health-related quality of life in children and adolescents aged 8 to 18. It includes 27 items that evaluate physical, emotional, mental, and social well-being, providing a comprehensive overview of a child's overall quality of life. It has been validated among Chilean adolescents with adequate psychometric properties
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
Family Functioning
Family functioning measured using the McMaster Family Assessment Device - General Functioning Subscale (MFAD-GF). consists of 12 items completed by family members aged 12 and above to assess general family functioning. It takes less than 5 minutes to complete and provides an average score across family members. The scale's subscales demonstrate good internal consistency, and a score of 2.0 or higher indicates the need for clinical intervention. This measure was selected based on its established psychometric properties and availability at no cost. Baseline MFAD-GF scores have shown significant associations with outcomes such as suicide attempts in prior research, underscoring its relevance for clinical use in the context of adolescent depression treatment, and it has been studied among Chilean adolescents with good psychometric properties.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24