INTRODUCTION — Depression is the most common psychiatric disorder in the general population  and the most common mental health condition in patients seen in primary care [2-5]. Although symptoms of depression are prevalent among primary care patients, few patients discuss these symptoms directly with their primary care clinicians. Instead, two-thirds of primary care patients with depression present with somatic symptoms (eg, headache, back problems, or chronic pain), making detection of depression more difficult [6,7].
In the absence of screening, it is estimated that only 50 percent of patients with major depression are identified . Unless directly asked about their mood, patients omit information about depressive symptoms for a variety of reasons, including fear of stigmatization, belief that depression falls outside the purview of primary care, belief that depression isn't a "real" illness but rather a personal flaw, concerns about medical record confidentiality, and concerns about being prescribed antidepressant medication or being referred to a psychiatrist .
Systematic screening carries the potential for substantial benefit. Untreated depression is associated with decreased quality of life , increased risk of suicide , and poor physiological outcomes when depression co-occurs with chronic medical conditions . Compared with non-depressed persons, patients with depression have an increased risk of mortality (relative risk [RR] 1.52) . Each year lived with depression has been calculated to detract approximately 20 to 40 percent from a quality-adjusted life year (QALY) [14-17]. Furthermore, depression imposes a significant economic burden, accounting for billions of dollars annually in the United States . The effects of depression extend beyond the individual patient, with negative impact on patients' employers , spouses [20,21], and children [22,23]. (See "Unipolar depression in adults: Assessment and diagnosis".)
This topic will review evidence of the effectiveness of screening adults and recommendations for screening for depression in primary care.
Depression screening in pregnancy, postpartum individuals and new parents, children and adolescents, older adults, and oncology patients are discussed in detail separately.
DEFINITIONS — Depressive syndromes are defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) . The term "major depression" in this topic refers to unipolar depression.
A major depressive syndrome or episode manifests with five or more of the following symptoms, present most of the day nearly every day for a minimum of two consecutive weeks (table 1). At least one symptom is either depressed mood or loss of interest or pleasure.
●Loss of interest or pleasure in most or all activities
●Insomnia or hypersomnia
●Change in appetite or weight
●Psychomotor retardation or agitation
●Thoughts of worthlessness or guilt
●Recurrent thoughts about death or suicide
The symptoms cause substantial distress or impair psychosocial functioning, and they are not the direct result of the physiological effect of a substance or general medical disorder. Further, the symptoms cannot be explained by response to significant loss, though the clinician should still carefully consider the possibility of depression if symptoms extend beyond what is normative following a loss. (See "Prolonged grief disorder in adults: Epidemiology, clinical features, assessment, and diagnosis".)
Persistent depressive disorder (dysthymia), a related condition, is characterized by depressive symptoms that last for at least two years, with depressed mood present for most of the day and for more days than not. The depressed mood is accompanied by two or more of the following symptoms (see "Unipolar depression in adults: Assessment and diagnosis", section on 'Diagnostic criteria and classification'):
●Decreased or increased appetite
●Insomnia or hypersomnia
EPIDEMIOLOGY AND RISK FACTORS — Depression is highly prevalent throughout the world, and the prevalence appears to be increasing. Community surveys of adults living in 10 countries (Brazil, Canada, Chile, Czech Republic, Germany, Japan, Mexico, Netherlands, Turkey, and the United States) found that the lifetime prevalence of major depression varied from 3 percent in Japan to 17 percent in the United States, with most rates in the range of 8 to 12 percent . Reasons for the lower prevalence of depression in some countries may reflect true variation in the determinants of depression due to cultural or genetic factors, sample selection biases, and problems with the cross-cultural portability of diagnostic criteria [26,27]. Depression is more difficult to detect in cultures where patients are more likely to present with somatic symptoms rather than emotional symptoms . (See "Unipolar depression in adults: Epidemiology", section on 'Prevalence'.)
In the United States, the National Epidemiologic Survey on Alcohol and Related Conditions III identified an annual major depressive disorder (MDD) prevalence rate of 10 percent and a lifetime rate of 21 percent . Among patients with chronic medical illness, the annual prevalence rate is significantly higher, approximately 25 percent . Rates of depression may be particularly high in patients with diseases of the central nervous system (eg, stroke, traumatic brain injury, Parkinson disease) [31-33], cardiovascular disorders [34-36], cancer , and conditions involving immune and inflammatory mechanisms (eg, systemic lupus erythematosus ).
Risk factors for depression involve genetic, medical, environmental, and social influences and include  (see "Unipolar depression in adults: Epidemiology", section on 'Demographic risk factors'):
●Prior depressive episode
●Childbirth (ie, postpartum depression)
●Stressful life events
●Poor social support
●Serious medical illness
●Substance use disorder
Although knowledge of risk factors can be clinically helpful, it is not sufficient to guide clinical practice or the decision to screen for depression.
PRESENTATION, NATURAL HISTORY, AND COURSE OF ILLNESS — Patients with depressive syndromes may present with mood, cognitive, neurovegetative, or somatic symptoms. Mood manifestations include sadness, emotional distress, emotional numbness, or sometimes anxiety or irritability. Neurovegetative symptoms include loss of energy, changes in sleep, appetite, or weight. Certain patient populations are more likely to present with somatic symptoms (headache, abdominal or pelvic pain, back pain, or other physical complaints), which can impede the diagnosis of depression. Populations in which somatic symptoms often predominate include pregnant individuals, older adults, incarcerated individuals, some cultural ethnicities, patients with low incomes, and patients with coexisting medical conditions .
Most individuals with depressive syndromes eventually remit, such that approximately half will be in remission after one year  and three-quarters after two years . However, subsyndromal symptoms of depression often persist even after full criteria for depression are no longer met. The most common symptom to persist after remission is insomnia, followed by sad mood and decreased concentration . Persistence of such symptoms heightens the risk for recurrence of the full depressive syndrome. (See "Unipolar depression in adults: Course of illness".)
Individuals who have suffered from one episode of depression frequently have recurrences; among patients with a history of depression, 72 percent report having more than one episode . The average age of onset for unipolar major depression among patients seen in clinical settings is in the thirties, with earlier age of onset associated with a range of negative biopsychosocial outcomes .
Effective treatments for depression include pharmacotherapy and psychotherapy. Chronic depression is associated with poorer treatment response , underscoring the importance of early identification and treatment. (See "Unipolar major depression in adults: Choosing initial treatment" and "Unipolar depression in adults: Choosing treatment for resistant depression".)
RATIONALE FOR SCREENING — Several factors related to depression would seem to lead to a cogent argument for population screening:
●Depression is often difficult to detect since patients often present with a variety of somatic symptoms and may be reluctant to acknowledge symptoms of depression.
●Untreated depression is associated with decreased quality of life, increased mortality, and increased economic burden.
●Depression can be successfully treated, and treatment is more effective when started early in the course.
However, the true test of whether or not screening is effective is a trial in which patients are randomly assigned to a screening group or to a non-screened control group, and the two groups compared over time for outcomes related to the condition being screened. Only two relatively short-term randomized trials have evaluated screening alone without additional supports for the treatment of depression [45,46]. These studies found conflicting results. Thus, there is disagreement among experts on how best to interpret the available evidence.
EFFECTIVENESS OF SCREENING — The effectiveness of screening depends upon multiple factors [47,48]:
●Whether a condition is sufficiently common in the general population to merit screening
●Whether there is an asymptomatic or early phase of the condition that can be detected by screening and for which treatment is more effective than if started at a later and more symptomatic time
●Whether there is a screening test with acceptable performance characteristics (high sensitivity and relatively high specificity)
●Whether the screening test is easily administered, inexpensive, and well tolerated by the patient
●Whether outcomes of screening result in clinically meaningful benefits that outweigh potential harms to the patient
In considering screening for depression in primary care, there is good evidence that depression is both a common condition and frequently undetected in the absence of screening. There is evidence that response rates to treatment are better if treatment is initiated earlier in the course of depression. Screening instruments are available that are relatively easy to administer and have been validated for use in primary care. Less well confirmed, however, is whether screening leads to improved patient outcomes that outweigh the potential harms of false-positive test results and unnecessary treatment.
Several high-quality systematic reviews address the effects of depression screening in primary care settings for a broad range of clinically relevant outcomes [49-53]. A review completed for the US Preventive Services Task Force (USPSTF) found that screening in adults, without other practice enhancements to improve depression care, increases the rate of depression diagnosis (absolute increase 10 to 47 percent) [49,54]. A subsequent meta-analysis of 16 studies with 7576 patients found the use of depression screening or case-finding instruments in primary care or other non-mental health settings was associated with a modest increase in clinicians' recognition of depression (relative risk [RR] 1.27, 95% CI 1.02-1.59) and a nonsignificant impact on the initiation of any treatment (RR 1.30; CI 0.97-1.76), with no influence on the prescription of antidepressants (RR 1.20, CI 0.87-1.66) . The seven studies that provided data on clinical outcomes, however, found no evidence of an effect on depressive symptoms . This suggests that although screening is important for detecting depression, it is insufficient to improve clinical outcomes.
Other systematic reviews, including the 2009 review for the USPSTF , included studies that evaluated screening in combination with additional staff support for activities, such as symptom monitoring, self-management plans, or facilitated referral . The USPSTF review identified eight randomized controlled trials and found that intervention patients were more likely to show significant improvement in depressive symptoms than control patients (RR 1.78), improvements that persisted for up to five years [51,54]. Although the independent contribution of screening in these complex interventions is impossible to determine, these data support the conclusion that depression screening, coupled with appropriate follow-up and effective treatment supported by staff in addition to the primary care clinician, is beneficial. Effective treatment requires careful monitoring of treatment adherence and clinical response together with changes in treatment if the clinical response is poor . This is no different from the approach to patients with chronic medical conditions. For example, when a screening blood glucose test reveals diabetes and treatment is initiated, that patient will need subsequent glucose monitoring, titration of therapy, and involvement of a health care team to optimize clinical outcomes.
The 2016 USPSTF systematic review found one trial in the general adult population that reported no adverse events attributed to screening . There were no other trials that reported on the potential harms of screening. Potential harms include false-positive diagnoses with subsequent labeling effects and unnecessary treatment, including the medication costs and adverse effects of medication, as well as opportunity costs (time taken from a patient encounter to screen for depression might be spent on other preventive or therapeutic activities). Depression screening is highly accepted, with few patients finding the process burdensome or upsetting [58-60].
Cost-effectiveness — Data on the cost-effectiveness of depression screening are limited and come from two sources, simulation approaches and randomized trials of enhanced care models that utilized depression screening to identify patients. Limited evidence suggests that depression screening may be cost-effective when conducted in general medical settings with a high prevalence of depression (eg, serving patients with chronic medical conditions) coupled with access to enhanced models of care.
The modeling approach used a sophisticated Markov model to estimate the costs of screening and found high costs for annual screening (USD $192,444 per quality-adjusted life year [QALY]) but lower costs for screening every five years ($85,679/QALY) . Screening was cost-effective only under the optimistic conditions of high prevalence (≥13 percent) and high treatment and remission rates. Cost-effectiveness analyses were reported in two of the seven trials included in USPSTF’s review of depression screening. Costs per QALY were within the proposed threshold of ≤$50,000 per QALY for interventions considered to be cost-effective, ranging from $9478 to $36,467 per QALY [62,63].
An evidence synthesis evaluating the cost-effectiveness of depression screening for postnatal depression found no adequate primary data, and a simulation model did not suggest cost-effectiveness using conventional thresholds [64,65].
Targeted versus general population screening — One approach, recommended by the US Preventive Services Task Force (USPSTF), is to screen all patients during routine visits and then further evaluate those who score above a specified threshold . A more selective approach, known as case-finding, is to evaluate only those patients whose clinical presentation triggers a suspicion of depression. Clinical red flags for depression include :
●Recent life changes or stressors
●Fair or poor self-rated health
●Unexplained physical symptoms
Although the likelihood of a depressive disorder increases by 1.5 to 3.5 times if a patient reports any of these symptoms, this targeted approach is only moderately more efficient than routine screening and misses more patients who have a depressive disorder [67,68]. Compared with screening all adults, case-finding increases specificity but decreases sensitivity (eg, false-positive findings are decreased but fewer patients suffering from clinical depression are identified). Rates of false positives are lower for screening in specialty settings than in primary care because of the increased prevalence of depression in patients with chronic illness (eg, chronic heart disease, chronic obstructive pulmonary disease [COPD], diabetes mellitus).
Regardless of the approach, further evaluation following screening is essential to confirm a diagnosis of depression. Trials show that screening is associated with improved clinical outcomes when it is coupled with careful diagnostic assessment and treatment [51,54,56,57]. (See "Unipolar depression in adults: Assessment and diagnosis", section on 'Assessment' and "Unipolar major depression in adults: Choosing initial treatment", section on 'Overview of treatment'.)
Screening instruments — A number of attributes should be considered in choosing a questionnaire to screen for depression, including its diagnostic accuracy in the population being screened and the feasibility of its administration. Factors impacting feasibility include the number of questions, scoring and ease of interpretation, and reading level required. These characteristics are summarized in a table about recommended questionnaires (table 2) [69,70].
The diagnostic accuracy of screening questions for depression is validated against structured diagnostic interviews that use consensus criteria, such as the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). Systematic reviews evaluating the performance of screening questionnaires in primary care settings found that the sensitivity is too low (32 percent) if only a single question about depression is posed . However, short questionnaires that range from 2 to 10 questions perform well (table 2) [69,71]. In a meta-analysis of screening instruments in primary care, the median sensitivity and specificity of instruments was 85 and 74 percent respectively, with no significant difference in performance between instruments .
Short screening instruments include the Patient Health Questionnaire-9 (PHQ-9), the Patient Health Questionnaire-2 (PHQ-2), the Beck Depression Inventory for Primary Care (BDI-PC), and the 5-Item World Health Organization Well-Being Index (WHO-5). These can be self-administered by patients preceding their meeting with a clinician or while in the waiting area.
PHQ-9 — The PHQ-9 (table 3) is somewhat more accurate than other screens (sensitivity 88 percent; specificity 85 percent ) and is useful for monitoring a patient's response to treatment [73-76]. The PHQ-9 is scored 0 to 27, with scores ≥10 indicating a possible depressive disorder. It also includes a question to assess whether depressive symptoms are impairing function, a key criterion to establish a DSM-based diagnosis . Similar to other screening questionnaires, the PHQ-9 is not sufficiently accurate to establish a definitive diagnosis for depression . Scores exceeding the threshold for a positive screen should prompt a careful diagnostic assessment. The PHQ-9 can be used to monitor treatment response. (See "Unipolar depression in adults: Assessment and diagnosis", section on 'Unipolar major depression' and "Using scales to monitor symptoms and treat depression (measurement based care)".)
Using a prevalence of 10 percent for major depressive disorder or dysthymia, a score of 10 or higher on the PHQ-9 yields a positive predictive value of 45 percent. Some false-positive screens may lead to other diagnoses that share symptoms with major depressive disorder (MDD), such as anxiety disorder, at-risk alcohol use, or subsyndromal depression, a condition defined by lower-level depressive symptoms that increases the risk for MDD. A score less than 10 on the PHQ-9 yields a negative predictive value of 99 percent.
PHQ-2 — The PHQ-2, also called the “Two-Question Screen,” is comprised of the first two questions from the PHQ-9 (table 4):
●During the past two weeks, have you often been bothered by feeling down, depressed, or hopeless?
●During the past two weeks, have you often been bothered by having little interest or pleasure in doing things?
The PHQ-2 has the advantage of being brief and easy to administer verbally. Responses may be dichotomous (yes/no), or scaled (0 to 3). A single "yes" response, or a score ≥3 (out of a possible score of 0 to 6) indicates possible clinically significant depression. The PHQ-2 has a sensitivity of 76 percent and a specificity of 87 percent .
The PHQ-2 is often used as a "pre-screening" exam, and, if positive, followed up with a more detailed screening such as the PHQ-9. In a meta-analyses including over 44,000 participants, administration of the PHQ-2 using a cutoff score of ≥2, followed by a PHQ-9 for those who screened positive, reduced the need for a follow-up PHQ-9 by 57 percent compared with screening all patients with a PHQ-9 alone . The sensitivity and specificity of this more efficient two-step strategy was similar to screening all individuals with a PHQ-9. (See 'Screening implementation' below.)
Beck Depression Inventory for Primary Care — The BDI-PC is a seven-item scale  adapted from the extensively validated 21-item Beck Depression Inventory (BDI-II) [81,82]. The 21-item BDI-II is useful for monitoring treatment response. In primary care outpatients, the BDI-PC with a cutoff of four points had 97 percent sensitivity and 99 percent specificity for identifying major depression . However, the BDI is available only by license requiring a fee and thus has limited use for screening, since other instruments are available in the public domain.
Instruments for special populations — Specialized depression questionnaires are available for some patient populations.
●Postpartum individuals (see "Postpartum unipolar major depression: Epidemiology, clinical features, assessment, and diagnosis", section on 'Screening' and "Bipolar disorder in postpartum women: Epidemiology, clinical features, assessment, and diagnosis", section on 'Screening')
●Partners who have recently become parents (see "Postpartum paternal depression", section on 'Screening')
SCREENING IMPLEMENTATION — Based on our interpretation of the available evidence, we suggest general population screening for depression, when the practice setting has adequate systems to ensure accurate diagnosis, effective treatment, and appropriate follow-up. The optimal frequency of screening is not established by evidence. To facilitate ease of implementation, we support screening at the time of a routine health visit.
When personnel or systems are available to assure appropriate follow-up and management of patients who screen positive, screening all adults for depression at the time of a routine visit perhaps is the simplest approach, particularly when using an electronic medical record (EMR) that incorporates clinical reminders. Practices may wish to distribute questionnaires at check-in for patients to complete, or have staff distribute or verbally administer questionnaires along with assessment of vital signs. When using the latter approach, many practices find it most efficient to administer the Patient Health Questionnaire-2 (PHQ-2) verbally and, when positive, distribute a longer questionnaire, such as the Patient Health Questionnaire-9 (PHQ-9), to be completed in the examination room while the patient is waiting for the clinician.
Use of pre-visit videos or interactive computer programs to engage patients in recognition of depression symptoms has also been explored. In one randomized trial, patients with depressive symptoms who used a tailored interactive computer program in the waiting area prior to their clinician visit were more likely to be treated for depression (by antidepressant prescription and/or referral) than control patients; viewing a noninteractive video did not increase treatment . However, there was no difference between groups in mental health outcomes at 12 weeks.
Regardless of the screening approach chosen, changing practice routines can be challenging . To facilitate implementation of depression screening, everyone on staff should understand the following:
●Why depression screening is important
●How to address patients' concerns about confidentiality
●How to introduce depression screening to patients
●The importance of asking the screening questions verbatim
Adequate systems for depression care refers to the support of staff who provide direct clinical care or coordinate care for patients with depression. They may provide support with symptom monitoring, self-management plans, medication adherence, patient education, assessment of patient preferences and goals, and/or referrals. Medicare and many other health insurers reimburse practices for integrated behavioral health services , facilitating the financial viability of offering such services . Examples of system supports for depression care include [52,57,89]:
●A nurse who screens patients for depression, informs the clinician of a positive screen, and facilitates referral for evidence-based behavioral treatment
●Trained care managers who assess patient symptoms at baseline and follow-up, using a standardized instrument, and who assess treatment adherence
●Collaborative care involving direct coordination between mental health specialists and primary care
Care is also facilitated by inclusion of active self-management support and assuring active follow-up for a minimum of 16 weeks .
There is limited evidence to guide the optimal frequency of routine screening for depression. Although screening every five years may be more cost-effective than more frequent screening , annual screening or screening at the time of a health maintenance examination may be easier to incorporate into routine practice.
It bears mentioning that the greatest impact of depression derives from insufficient treatment of patients with known depression, rather than lack of screening to identify depression in less symptomatic patients . Practices should prioritize high-quality treatment, including these practice supports over depression screening.
GUIDELINE RECOMMENDATIONS — Guidelines on depression from several countries vary in their recommendations. Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See 'Society guideline links' below.)
United States — The USPSTF recommends screening for depression in the general adult population, including pregnant and postpartum individuals . The USPSTF also states that screening should be implemented with adequate systems in place to ensure diagnosis, treatment, and appropriate follow-up. The USPSTF notes that the optimal interval for screening is not known. They suggest a pragmatic approach of screening all adults who have not been previously screened and using clinical judgement to determine if additional screening in needed. (See "Postpartum unipolar major depression: Epidemiology, clinical features, assessment, and diagnosis", section on 'Screening' and "Unipolar major depression during pregnancy: Epidemiology, clinical features, assessment, and diagnosis", section on 'Screening'.)
The Department of Veterans Affairs recommends that all patients not currently receiving treatment for depression be screened using the Patient Health Questionnaire (PHQ-2) . The American College of Physicians (ACP) does not make specific recommendations about screening for depression. However, the ACP supports the integration of behavioral health care (including screening, diagnosis, brief treatment, and referral) into primary care and encourages addressing behavioral health issues within the limits of available resources .
Canada — The Canadian Task Force on Preventive Health Care (CTFPHC) recommends not routinely screening for depression in the primary care setting in adults with no history of depression and no apparent symptoms of depression, including not screening those who are at average risk or who may be at increased risk of depression [92,93]. They advise that clinicians remain alert to symptoms of depression (eg, insomnia, low mood, anhedonia, and suicidal thoughts), especially among patients with characteristics that may increase depression risk. CTFPHC based their recommendations on the absence of high-quality evidence of the effectiveness of screening for depression and the concern about false-positive diagnoses leading to unnecessary treatment. This reverses its previous recommendations to screen adults in primary care settings that had integrated feedback to the clinician regarding depression status and a system for managing treatment, and that included access to case management, and/or mental health treatment [49,94].
United Kingdom — Guidelines from the National Institute for Health and Clinical Excellence (NICE) suggest being alert to possible depression, particularly if there is a depression history or chronic physical health problem with functional impairment . They recommend considering asking people who may be depressed two questions from the PHQ-2:
●During the past two weeks, have you often been bothered by feeling down, depressed, or hopeless?
●During the past two weeks, have you often been bothered by having little interest or pleasure in doing things?
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Screening for depression".)
SUMMARY AND RECOMMENDATIONS
●Depression is the most common psychiatric disorder and the most common mental health condition among patients seen in primary care. In the absence of screening, it is estimated that only 50 percent of patients with major depressive disorder (MDD) are identified. (See 'Introduction' above.)
●Patients with depression may present with mood, cognitive, neurovegetative, or somatic symptoms. Diagnosis of depression is more challenging in patients who present with somatic symptoms. Effective treatments for depression include pharmacotherapy and psychotherapy. Chronic depression is associated with poorer treatment response. (See 'Presentation, natural history, and course of illness' above and 'Rationale for screening' above.)
●Depression screening improves diagnosis rates, but clinical outcomes are only improved if screening is part of an enhanced care approach in which staff are available to participate in patient management. There appear to be limited, if any, harms from screening as long as a positive screen is followed by a careful diagnostic assessment. (See 'Effectiveness of screening' above.)
●For practices choosing to screen, the Patient Health Questionnaire-2 (PHQ-2), either as a verbal or written screen, is easily administered with reasonable performance characteristics (table 4). A positive screen should be followed by a clinical interview, facilitated with the Patient Health Questionnaire-9 (PHQ-9) (table 3) or a similar instrument, to diagnose depression. (See 'Screening instruments' above.)
●We suggest screening adults for depression when adequate systems are in place to ensure appropriate diagnosis, treatment, and follow-up (Grade 2C). The optimal frequency of screening is not established by evidence. To facilitate ease of implementation, we support screening at the time of a routine health visit. (See 'Screening implementation' above and 'Guideline recommendations' above.)
●Recommendations for screening for depression vary internationally. (See 'Guideline recommendations' above.)
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