Draft Research Plan

Anxiety in Children and Adolescents: Screening

March 29, 2022

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This figure is an analytic framework depicting the key questions within the context of the populations, interventions, comparisons, outcomes, time frames, and settings (PICOTS) relative to the effectiveness and harms of screening and treatment for depression, anxiety, and suicide risk in children and adolescents. The figure illustrates screening of adolescents and children in populations representative of primary care, followed by possible harms of screening; diagnosis of major depressive disorder, anxiety disorder, or high risk for suicide; treatment; possible harms of treatment; and health outcomes.

  1. Do screening programs for depression, anxiety, and increased risk of suicide in primary care or comparable settings result in improved health outcomes in children and adolescents?
  2. Do instruments to screen for depression, anxiety, or increased risk of suicide accurately identify children and adolescents with depression, anxiety, and increased risk of suicide in primary care or comparable settings?
  3. What are the harms associated with screening for depression, anxiety, or increased risk of suicide in primary care or comparable settings in children and adolescents?
  4. Does treatment (psychotherapy, pharmacotherapy, or collaborative care) of depression, anxiety, or increased risk of suicide result in improved health outcomes in children and adolescents?
  5. What are the harms of treatment (psychotherapy, pharmacotherapy, or collaborative care) in children and adolescents who are treated for depression, anxiety, or increased risk of suicide?

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

  1. What is the diagnostic yield from screening for depression, anxiety, or increased suicide risk in typical primary care practice settings?
  2. What are the minimal clinically important differences for symptoms and functioning on the most common instruments used to measure treatment of depression, anxiety, or increased suicide risk?
  3. What are the U.S. Food and Drug Administration boxed warnings for pharmacotherapy for the treatment of depression, anxiety, or increased suicide risk?
  4. What psychotherapies other than cognitive behavioral therapy are used to treat anxiety in children?
  5. What is the effectiveness of treatment in children and adolescents with persistent depressive disorder and depressive disorders not otherwise specified?
  6. What proportion of children and adolescents who screen positive for depression, anxiety, or increased suicide risk engage with care?

The Proposed Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the key questions.

Criteria Include Exclude
Condition definition Major depressive disorder, as defined by DSM criteria (present in at least 50% of the enrolled study population)

Anxiety disorders include generalized anxiety disorder, social anxiety disorder, panic disorder, agoraphobia, specific phobias, separation anxiety disorder, and selective mutism

Definitions for increased risk of suicide may vary by study but may include suicidal ideation (suicidal thoughts or plan for suicide), history of suicide attempts (nonfatal, self-directed, and potentially injurious behavior that is intended to result in death), and deliberate self-harm

Included studies may address these conditions individually or in combination

 Other mental health disorders (e.g., obsessive compulsive disorder, posttraumatic stress disorder, psychotic disorders, bipolar disorder, cyclothymia, adjustment disorder with depressed mood), persistent depressive disorder/dysthymia, disruptive mood dysregulation disorder, premenstrual dysphoric disorder, substance/medication-induced depressive disorder, depressive disorder due to another medical condition, and depression not otherwise specified; substance/medication-induced anxiety disorder, anxiety disorder due to another medical condition, and anxiety not otherwise specified
Population KQs 1–3: Children and adolescents (age ≤18 years). Studies may include:
  • Unselected primary care population
  • Primary care patients without known depression, anxiety disorders, or increased risk of suicide
  • Comparable community-based population

KQs 4, 5: Children and adolescents (age ≤18 years) with major depressive disorder, anxiety disorders, or increased risk of suicide

A priori subpopulations of interest include by age (children vs. adolescents), race/ethnicity, gender identity, and sexuality
  • Adults (age ≥19 years)
  • Studies in which more than 50% of the population are age 19 years or older
  • Studies limited to populations that are not broadly generalizable to primary care populations (e.g., populations with mental health conditions other than anxiety, depression, and increased suicide risk); persons with treatment-resistant depression; persons in residential, institutional, or inpatient settings; persons with developmental disorders; persons in the midst of a suicidal crisis that are identified through their use of health care services related to a suicide attempt (e.g., in the emergency department)
Interventions KQs 1–3: Screening interventions with or without additional provider or patient-facing elements such as referral support, treatment guidelines, symptoms monitoring, and standardized treatment. Screening tools must be brief standardized instruments designed to identify persons with major depressive disorder, anxiety disorders, or an increased risk of suicide; self-report, clinician administered, or electronically delivered (<5 minutes if clinician administered, <15 minutes if self-administered) instruments are eligible

KQs 4, 5 (depression and suicide):

  • Counseling (e.g., psychotherapy, psychoeducation, suicide means restriction)
  • Care delivery models targeting improved mental health outcomes (e.g., collaborative care, care management)
  • First-line pharmacotherapy agents approved for pediatric use (e.g., duloxetine, fluoxetine, escitalopram, sertraline, fluvoxamine, clomipramine)

KQs 4, 5 (anxiety):

  • Cognitive behavioral therapy*
  • First-line pharmacotherapy agents approved for pediatric use (e.g., duloxetine, fluoxetine, escitalopram, sertraline, fluvoxamine, clomipramine)
 KQ 1–3: Studies reporting on a screening instrument that does not have established validity and scoring mechanism for use within clinical practice

KQs 4, 5 (all disorders): Other treatment modalities (e.g., exercise, light therapy, transcranial magnetic nerve stimulation, electroshock treatment, diet and herbal supplements such as St. John’s wort and other complementary and alternative medicine, social marketing, policy, system-level interventions, or adjunctive agents to enhance the effects of antidepressants) except as optional adjunctive components to counseling, care delivery models, or first-line pharmacotherapy agents

Interventions involving components that could not be replicated in most health care settings, including environmental components (media messages, public signage) or interventions on groups in closed (preexisting) social networks (e.g., in daycares, schools)

Pharmacotherapeutic agents that are not FDA approved for pediatric use (e.g., paroxetine)

KQs 4, 5 (anxiety): Psychotherapy other than cognitive behavioral therapy
Comparators KQs 1, 3 (screening): Usual care/no screening

KQ 2 (depression and anxiety): Clinical diagnosis based on structured clinical interview by qualified professional using standard diagnostic criteria in place at the time of the study (e.g., DSM-IV or DSM-5)

KQ 2 (suicide): Assessment of increased suicide risk based on clinical interview by qualified professional

KQs 4, 5 (psychotherapy and care delivery model):

  • Usual care/no intervention
  • Waitlist
  • Attention control

KQs 4, 5 (pharmacotherapy): Placebo (including placebo along with psychotherapy, when compared with the active agent plus the same psychotherapy intervention)

 KQs 1, 3: No comparator

KQ 2: Another screening instrument, nonstandardized clinical diagnosis (i.e., diagnosis not made based on existing DSM criteria at the time of the study)

KQs 4, 5: Active intervention (i.e., comparative effectiveness), no comparator
Outcomes KQs 1, 4:
  • Depression or anxiety symptoms, remission or diagnosis, or response
  • Suicide deaths, suicide attempts and deliberate self-harm, or suicidal ideation
  • All-cause mortality
  • Quality of life measured using validated scales or instruments
  • Functioning (including days of missed school)

KQ 2: Sensitivity, specificity, or data to calculate one or both

KQs 3, 5:

  • Treatment avoidance
  • Deterioration in patient-provider relationship
  • Labeling or stigma
  • Inappropriate/unnecessary treatment

KQ 5 (pharmacotherapy only):

  • Serious adverse effects
  • Withdrawals due to adverse effects
  • Suicidality
 All KQs: All other outcomes
Outcome assessment timing No minimum followup Not applicable
Setting KQs 1–3:
  • Primary care settings (e.g., pediatrics, family medicine, school, or university-based health clinics)
  • Virtual or community setting, if population comparable to general primary care (i.e., focus on “healthy” children or adolescents, or broad spectrum of medical and mental health conditions in rates comparable to primary care setting)
  • General emergency departments
KQs 4, 5: 50% or more of the study participants are recruited from primary care, virtual, or community-based settings		 KQs 1–3:
  • Mental health clinics (unless recruitment is through primary care screening)
  • Inpatient/residential facilities
  • Correctional facilities
  • Schools (other than school-based health clinics)
  • Psychiatric emergency departments

KQs 4, 5:

  • Correctional facilities
  • Schools (other than school-based health clinics)
  • Inpatient/residential facilities
  • Emergency departments
Study design KQs 1, 3: RCTs, CCTs

KQ 2: Studies of diagnostic test accuracy**

KQ 3: Observational studies

KQ 4: RCTs

KQ 5:

  • RCTs
  • Systematic reviews of comparative cohort and case-control observational studies
  • Harms of pharmacotherapy only: large (>1,000 participants) comparative cohort and case-control observational studies published after identified systematic reviews that include observational studies
 All other study designs

KQ 2: Psychometric development and internal (e.g., split sample) validation studies of new instruments; case-control studies (i.e., studies that limit the study sample to only those with and without known mental health symptoms)

KQs 1–4: Systematic reviews of RCTs (reviews will only be used to identify relevant studies)
Study geography Primary studies that primarily take place in countries categorized as “Very High” on the 2019 Human Development Index (as defined by the United Nations Development Programme) Reviews in which >50% of included studies take place in countries not categorized as “Very High” on the Human Development Index
Publication language English Any language other than English
Quality rating Fair- or good-quality studies Fair- or good-quality studies

* We will summarize the effect of other non-CBT interventions as a contextual question, using a best-evidence approach.

** We will catalog all studies reporting on instruments that otherwise meet all eligibility criteria, but our synthesis will focus on the instruments that are reported in more than one study.

Abbreviations: CBT=cognitive behavioral therapy; CCT=controlled, clinical trial; DSM=Diagnostic and Statistical Manual of Mental Disorders; FDA=U.S. Food and Drug Administration; KQ=key question; RCT=randomized, controlled trial.