• Major depressive disorder (including depression with peripartum onset or other specifiers).
• Anxiety disorders addressed in this review will include generalized anxiety disorder, social anxiety disorder, panic disorder, and anxiety not otherwise specified.
• Suicidal ideation includes suicidal thoughts or plan for suicide.
• Included studies may address these conditions individually or in combination.

• Unselected primary care population.
• Primary care patients without known depression or anxiety disorders or high risk of suicide.
• Other comparable broad-based population recruited from a health care setting.

KQs 4, 5:

• Adults (age ≥19 years), including pregnant and postpartum persons, with depressive disorders, anxiety disorders, or high risk of suicide, or with elevated symptoms of depression or anxiety. Sample must include an estimated 50% or more of participants with an included disorder but may also include some participants with related (e.g., other depressive or anxiety disorders) or subsyndromal conditions (e.g., elevated symptoms but not meeting full criteria).
• For anxiety and depression, evidence will be limited to studies that recruit primary care patients (or comparable broad-based health care recruitment), although treatment can take place in any outpatient setting, including primary care or specialty care (such as mental health). If evidence in primary care-recruited patients is limited for any condition-by-treatment approach combination, evidence will be extended to patients recruited from other settings.

All KQs: A priori subpopulations of interest include pregnant and postpartum persons, individuals identified through population-based screening in primary care or comparable community settings, and subgroups based on age, sex or gender, race or ethnicity, sexual orientation, and socioeconomic status.

• Children and adolescents (age ≤18 years). Trials in which >50% of the population are age ≤18 years will be excluded.
• Studies limited to populations that are not broadly generalizable to primary care (e.g., persons with specific comorbid mental health conditions such as depression and substance use disorder); persons with other mood disorders (e.g., bipolar disorder, persistent depressive disorder/dysthymia); persons with concomitant medical conditions (e.g., cancer, traumatic brain injury, coronary artery disease, or post-cardiovascular disease event); persons with developmental disorders; persons with physical disabilities; persons in the midst of a suicidal crisis, identified through their presentation for health care services related to self-harm in acute care settings (i.e., in the emergency department or inpatient setting); persons in residential, institutional, or inpatient settings.
• Studies of physician-assisted suicide in patients who are terminally ill.

KQ 2: Limited to the most widely recommended or used screening tools:

• For depression: Patient Health Questionnaire (PHQ), 2- and 9-item versions; Center for Epidemiologic Studies Depression Scale (CES-D); Edinburgh Postpartum Depression Scale (EPDS) for perinatal persons; Geriatric Depression Scale (GDS) for older adults.
• For anxiety: Generalized Anxiety Disorder scale (GAD), in any form; PHQ Anxiety scale; EPDS-Anxiety subscale, for perinatal persons; Geriatric Anxiety Inventory (GAI) and Geriatric Anxiety Scale (GAS) for older adults.
• For anxiety and depression: PHQ-ADS (combines the PHQ and GAD).
• For suicide screening: Any brief tools.

KQs 4, 5: Intervention to address depression, anxiety, and/or risk of suicide, including

• Counseling (e.g., psychotherapy, psychoeducation, means restriction)
• First-line pharmacotherapy agents (selective serotonin reuptake inhibitors [SSRIs], selective serotonin norepinephrine reuptake inhibitors [SNRIs], serotonin modulators (e.g., vortioxetine, vilazodone, nefazodone), atypical agents (e.g., bupropion, mirtazapine), tricyclic antidepressants, buspirone, brexanolone (for postpartum depression only), lithium (for suicide risk only), benzodiazepines (for anxiety only).
• Interventions must be conducted in primary care, referable from primary care, or feasible for implementation in a health care setting.

KQs 4, 5:

• Relapse prevention among persons with a history of mood disorders, other treatment modalities (e.g., exercise, light therapy, transcranial magnetic nerve stimulation, electroshock treatment, St. John’s wort, social marketing, policy, system-level interventions, or adjunctive agents to enhance the effects of antidepressants) except as optional adjunctive components to first-line approaches.
• Intervention involving components that could not be replicated in most health care settings, including environmental components (media message, public signage) or that intervenes on groups in closed (pre-existing) social networks (e.g., in worksites, churches, clubs/teams), or involves potential notification or use of authority figures (e.g., military commanders, workplace supervisors).
• Pharmacotherapeutic agents that are not approved by the U.S. Food and Drug Administration for depression or anxiety or are no longer commonly used for anxiety and depression (e.g., monoamine oxidase inhibitors [including reversible monoamine oxidase A inhibitors for anxiety]).

• Usual care/no screening.
• Screening with no feedback of results to providers.

KQ 2 (Diagnostic accuracy):

• Reference standard (structured or semistructured diagnostic interview or a nonbrief [>5 minutes] unstructured interview with mental health clinician) within 2 weeks of screening in populations that include a full spectrum of patient severity for the given setting (i.e., studies cannot limit the patient pool to only nondepressed and known/highly likely depressed patients). Reference conditions include major depressive disorder, generalized anxiety disorder, social anxiety disorder, suicidal ideation, or any combination of the above.

KQs 4, 5 (Counseling):

• Usual care/no intervention.
• Waitlist.
• Attention control.
• Minimal intervention (e.g., usual care limited to no more than 15 minutes of information).

KQs 4, 5 (Pharmacotherapy):

• Placebo (including placebo along with counseling, when compared with the active agent plus the same counseling intervention).
• All those listed under “Counseling” above.

• Depression or anxiety symptoms, remission or diagnosis, or response.
• Suicide deaths, self-harm (i.e., suicide attempts), or suicidal ideation.
• All-cause mortality.
• Quality of life.
• Functioning (including vocational).
• Change in health status (e.g., improvement in comorbid conditions or reduction in physical complaints).
• Pregnancy outcomes (e.g., preterm birth)
• Child/infant outcomes (continuation of breastfeeding, achievement of recognized developmental milestones, reduced abuse or neglect).
• Emergency department visits or inpatient stays.
• Hopelessness.

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

KQs 3, 5:

• Treatment avoidance.
• Deterioration in patient-provider relationship.
• Labeling stigma and negative consequences of false-positive and false-negative test results.
• Inappropriate or unnecessary treatment.
• Other harms reported by screening and treatment trials.
• Paradoxical worsening of mental health symptoms.

KQ 5 (Pharmacotherapy only):

• Serious adverse effects.
• Withdrawals due to adverse effects.
• Suicidality.
• Serotonin syndrome.
• Cardiac effects.
• Seizures (bupropion only).
• Dependence (benzodiazepines only).
• Thyroid or renal toxicity (lithium only).
• For pregnant persons only: fetal/infant harms (neonatal death, major malformations, small for gestational age/low birth weight, preeclampsia).

KQ 5 (Harms of pharmacotherapy): No minimum followup.

• Primary care settings (e.g., internal medicine, family medicine, obstetrics/gynecology, pediatrics [for postpartum screening], family planning, military health clinics, university-based health clinics) or comparable (e.g., identification through health plan administrative databases).
• Emergency department setting, if screening is universal rather than targeted to persons presenting with mental health concerns.

KQs 4, 5:

• Intervention may be implemented in outpatient health care (primary or specialty, including mental health).
• Participants must be recruited from a primary care or comparable broad health care setting. If evidence in these patients is limited, evidence in patients recruited from other low-acuity outpatient settings (e.g., mental health, virtual, or community settings) will be used.

• Community settings.
• Mental health clinics (unless recruitment is through primary care screening).
• Inpatient settings, residential care facilities, assisted living facilities, adult foster care, or intermediate care facilities (e.g., nursing homes, rehabilitation facilities, subacute care facilities).
• Correctional facilities.
• Schools (other than school-based health clinics).

KQs 4, 5:

• Correctional facilities.
• Schools (other than school-based health clinics).
• Worksites.
• Inpatient/residential facilities (unless identified through primary care–based screening for suicide).
• Emergency departments (unless identified through primary care–based screening for suicide).

KQ 2: Systematic reviews and studies of diagnostic accuracy reporting sensitivity and specificity (or comparable statistics) compared with an independently assessed gold standard (structured or semistructured diagnostic interview or a nonbrief [>5 minutes] unstructured interview with mental health clinician) within 2 weeks of screening in populations that include a full spectrum of patient severity for the given setting (i.e., studies cannot limit the patient pool to only nondepressed and known/highly likely depressed patients).

KQ 4:

• Systematic reviews of controlled trials of interventions for depression, comparing active agents with control groups.
• Randomized, controlled trials of anxiety interventions in primary care populations.
• Systematic reviews of controlled trials of anxiety interventions, comparing active agents with control groups, if primary literature in primary care populations is insufficient.
• Randomized, controlled trials of suicide prevention interventions.

KQ 5:

• Randomized, controlled trials of anxiety and suicide prevention interventions in primary care populations.
• Systematic reviews of controlled trials comparing active agents with control groups
• Systematic reviews of comparative cohort and case-control observational studies
• (Harms of pharmacotherapy only): large comparative cohort and case-control observational studies published after identified systematic reviews that include observational studies.

KQ 2: If unable to limit to existing systematic reviews, case-control studies will be used (i.e., studies that limit the study sample to only participants with and without known mental health symptoms).