Version July 2025
INTRODUCTION —
Symptoms of depression are common in primary care and outpatient specialty settings; their prevalence ranges from 17 to 53 percent [1]. Most individuals with depressive symptoms will not have major depressive disorder (MDD) but will instead have a different depressive disorder or an alternative cause of depressed mood.
Studies suggest that non-psychiatrists do not accurately diagnose depression, with both under- and overdiagnosis occurring [2,3]. Underdiagnosis is common, in part because many patients with major depression do not present with depressed mood [4]. Patients in primary care settings can have a wide spectrum of depressive symptoms, can present with predominantly physical symptoms, and often have comorbid chronic diseases that can contribute to and masquerade as clinical depression. These factors, coupled with time constraints, can make accurate diagnosis challenging.
This topic presents an approach to the evaluation of adults with suspected depression. The epidemiology, clinical features, diagnosis, and treatment of MDD in adults are discussed separately:
●(See "Major depression in adults: Epidemiology".)
●(See "Depression in adults: Clinical features and diagnosis".)
●(See "Major depressive disorder in adults: Approach to initial management".)
●(See "Diagnosis and management of late-life depression".)
DEFINITIONS OF DEPRESSION —
The term "depression" can be used in multiple ways, which can be confusing for conversations about diagnosis. Depression can refer to a mood state, syndrome, or psychiatric disorder, as detailed in the table (table 1) [5,6]. In this topic, "depressed mood" denotes a mood state, and "depression" or "depressive episode" denotes a syndrome. "Depressive disorder" or "major depression" denotes a psychiatric disorder, such as major depressive disorder or premenstrual dysphoric disorder [6].
WHEN TO SUSPECT A DEPRESSIVE DISORDER —
Several common clinical scenarios can raise suspicion of an underlying depressive disorder.
Positive depression screening — A positive test on depression screening raises the index of suspicion for major depressive disorder (MDD) but does not confirm its diagnosis. Screening tests for depression are sensitive but can lack specificity. A negative result with most depression screening instruments effectively rules out a diagnosis of major depression. However, in primary care settings, between one-half and two-thirds of "positive" depression screening tests will be false positives (ie, have a diagnosis other than MDD) [7].
Screening for depression in adults is discussed separately. (See "Screening for depression in adults".)
Depressed mood — Depressed mood is a common symptom in primary care patients that should raise the suspicion of MDD. Patients may describe feeling "sad" or "blue," appear tearful or sad, or endorse frequent tearfulness or crying "for no reason." Other mood symptoms that may suggest depression include decreased interest or pleasure in activities (anhedonia), anger, irritability, and anxiety. (See "Depression in adults: Clinical features and diagnosis", section on 'Emotional'.)
Unexplained physical symptoms — Clinicians should have a low threshold for investigating the possibility of depression in individuals who present with multiple unexplained physical symptoms, especially symptoms of nonspecific "weakness," headache, sleep disturbances, or musculoskeletal pain. Physical symptoms require evaluation for general medical etiologies; however, they should also prompt an evaluation for major depression, particularly if alternative diagnoses are unlikely. Major depression is more likely to go undetected when patients present with physical, rather than emotional or cognitive, symptoms.
●Physical presentations of depression are common – Individuals with depressive disorders in primary care settings most commonly present with physical, rather than emotional, symptoms [8-13]. One multicenter study evaluated 1146 individuals with major depression from primary care clinics in 14 countries [8]. The proportion of participants who reported only physical symptoms ranged from 45 to 95 percent (mean 69 percent). Eleven percent denied psychologic symptoms of depression when asked directly.
Males may be less likely to endorse depressed mood or other psychologic symptoms [14]. Patients seen in settings where they do not have an ongoing therapeutic relationship with a clinician also present more commonly with somatic symptoms, compared with patients seen in settings where they have a personal clinician [8].
●Specific physical symptoms – Symptoms that may correlate more strongly with the presence of major depression include fatigue, sleep disturbance, back pain, headache, and nonspecific musculoskeletal complaints [10,12,15]. Depression is also common among individuals with chronic pain [16,17]. Additionally, individuals who rate their symptoms as more severe or their health as only "fair or poor" have a greater probability of a depressive disorder [18].
●Multiple physical symptoms – Multiple physical symptoms increase the likelihood of a depressive disorder [18-20]. As an example, in a cohort of 1000 adult primary care patients, the prevalence of a depressive disorder ranged from 2 percent (in those with zero to one physical symptoms) to 60 percent (in those with nine or more physical symptoms) [21]. Patient concerns about their physical health that exceed the magnitude or severity of their physical symptoms may also suggest an underlying depressive disorder.
Clues in older adults — Assessing older adults (ie, age >65 years) for possible depression is challenging, especially in those with medical comorbidities. Depressed mood may be a less reliable indicator of depression in older adults.
Clues that should prompt consideration of a depressive disorder in older individuals include mood or physical symptoms out of proportion to those expected from the patient's medical conditions, poor response to standard medical treatments, poor motivation to participate in treatment, or lack of engagement with care providers. Specific risk factors for depression in older adults include cognitive impairment and transfer to a skilled nursing facility, especially during the first year of residence.
The assessment and diagnosis of depression in older adults is discussed in detail separately. (See "Diagnosis and management of late-life depression", section on 'Diagnosis'.)
INITIAL EVALUATION
Practical tips — The accurate diagnosis of patients with suspected depression relies on a nuanced history; however, clinician, patient, and system factors can make it challenging to conduct a thorough, efficient evaluation. We use the following techniques to address these factors:
●Using symptom scales to frame the discussion – Clinicians may fear "opening Pandora's box" or not know how best to approach the diagnostic evaluation in a thorough, time-efficient manner. Validated self-report symptom scales, such as the nine-item Patient Health Questionnaire (PHQ-9) (table 2), can help to efficiently document the presence of depressive symptoms, including suicidal thoughts, and set the stage for more in-depth questioning.
Symptom scales also enable clinicians to prioritize the urgency of assessment. As an example, for individuals with minimal to mild symptoms (eg, PHQ-9 score <10 and no suicidal ideation), portions of the assessment can be deferred to a subsequent visit if other patient problems require urgent attention. By contrast, individuals with more severe symptoms (eg, PHQ-9 score ≥15 and/or suicidal ideation) warrant same-day evaluation. Regardless of symptom severity, all individuals with suspected depression should have prompt follow-up to monitor symptom evolution over time and/or complete a thorough evaluation. The follow-up interval should be based on the severity of the patient's symptoms and functional impairment. (See 'Assess for features requiring urgent management' below.)
●Normalizing symptoms – Patients may be reluctant to disclose depressive symptoms because they perceive depression as a moral or personal "flaw," fear the stigma of a depression diagnosis, or have a different explanatory model for their symptoms. To address such concerns, clinicians can inform patients that depression is a medical condition with physical, cognitive, and emotional symptoms that respond to treatment.
●Tailoring history to patient symptoms – The patient's initial presentation guides the approach to eliciting depressive symptoms.
•In individuals who present with depressed mood or are identified by a positive depression screening, we start by asking about mood-related symptoms and then progress to inquire about physical and cognitive symptoms of depression and the impact of the symptoms on functioning. With these individuals, administering the PHQ-9 early on can help guide the assessment.
•Individuals who present with physical symptoms may not experience or endorse mood symptoms [8]. With these patients, we first evaluate their specific physical symptoms and then ask about somatic symptoms of depression (eg, fatigue, low energy). Because these individuals may be more likely to endorse symptoms of anhedonia than depressed mood, it is important to ask explicitly about loss of interest or pleasure in activities.
Because these individuals may be reluctant to accept a diagnosis of depression, using the PHQ-9 early in the assessment may make them uncomfortable or less trusting. Pursuing the possibility of a medical problem in parallel with the evaluation for depression, rather than exploring the diagnosis of depression only after eliminating other medical diagnoses, can maximize efficiency and build rapport.
When discussing a possible diagnosis of depression, clinicians can emphasize that the relationship between depression and other medical illnesses is often bidirectional (ie, depression can worsen symptoms of other diseases and, conversely, other diseases can trigger depression).
Assess for clinically significant depression — To determine whether the patient with suspected depression has a depressive disorder or another condition, clinicians should first assess for the presence of clinically significant depressive symptoms (algorithm 1).
●History – To determine whether the patient has clinically significant depressive symptoms, clinicians should consider the following:
•Is the depressed mood due to sadness? – Periods of sadness and irritability represent normal, adaptive responses to loss, disappointment, or perceived failure and are often intermittent. By contrast, depressed mood that occurs as part of a depressive disorder is usually pervasive and persistent (ie, lasts for at least two weeks).
•Are other depressive symptoms present? – Clinicians should ask about the presence, severity, and frequency of other depressive symptoms (table 3) [6]. The diagnosis of a depressive disorder requires multiple concurrent, persistent depressive symptoms with associated functional impairment. (See "Depression in adults: Clinical features and diagnosis" and "Depression in adults: Clinical features and diagnosis", section on 'Symptoms and signs'.)
•What is the duration and pattern of symptoms? – The duration and time course of symptoms help to narrow the differential diagnosis, estimate prognosis, and inform the urgency and type of treatment.
A current episode that has lasted less than two years is consistent with major depressive disorder (MDD), whereas symptoms that last two or more years suggest the diagnosis of persistent depressive disorder.
Clinicians can assess for symptom remission by asking: "During the last two years, have you had a period of two or more consecutive months when you had none of the problems you just described?" Two months with minimal to no symptoms is consistent with remission from a depressive episode. (See "Major depressive disorder in adults: Continuation and maintenance treatment", section on 'Continuation and maintenance treatment'.)
It is important to inquire about temporal precipitants, such as seasonal recurrences (suggesting seasonal affective disorder) or symptoms that coincide with menses (suggesting premenstrual dysphoric disorder).
Clinicians should also ask whether the current episode is the initial presentation or a recurrent episode. For recurrent episodes, we establish their course, severity, triggers, and treatment, including whether the patient was hospitalized, took medications, or participated in psychotherapy.
•Are there triggers or risk factors? – Interpersonal, occupational, and financial stressors can be triggers or risk factors for a depressive disorder or clues to an alternative diagnosis.
-Recent loss – Clinicians should inquire if anyone close to the patient has recently died or if the patient has recently lost an intimate partner through divorce or separation because such losses cause grief and increase the risk of MDD. (See "Bereavement and grief in adults: Clinical features" and "Prolonged grief disorder in adults: Epidemiology, clinical features, assessment, and diagnosis", section on 'Clinical features'.)
-Medical illness – Many general medical illnesses increase the risk of MDD, especially if they are recently diagnosed or severe, or cause functional impairment or pain. (See "Depression in adults: Clinical features and diagnosis", section on 'Medical illnesses'.)
-Job and financial stressors – Job strain, financial stressors, and work-related burnout are risk factors for a depressive disorder [22].
-Lack of social support – Social isolation and loneliness may increase the risk of MDD; support systems and family functioning may affect prognosis and approaches to treatment. (See "Unipolar depression in adults: Family and couples therapy", section on 'Assessment'.)
-Exposure to violence – Intimate partner violence, family violence, and a history of childhood abuse or adversity are associated with an increased risk of MDD [23,24]. (See "Intimate partner violence: Epidemiology and health consequences", section on 'Psychologic'.)
-Family history of mental illness – A family history of depression, bipolar disorder, suicide, and psychosis increases the risk of depressive disorders and suicide. (See "Bipolar disorder in adults: Assessment and diagnosis", section on 'Unipolar major depression'.)
Risk factors for MDD are discussed in detail separately. (See "Unipolar depression: Pathogenesis", section on 'Pathogenesis' and "Major depression in adults: Epidemiology", section on 'Demographic risk factors'.)
●Mental status examination – The mental status examination complements the patient's history by documenting signs of depression. These include abnormal mood or affect, changes in cognition (eg, attention, concentration, and memory) or speech, abnormal psychomotor activity, ruminative thought processes, and suicidal thoughts. Although these features may support a diagnosis of MDD, they can also be observed in patients with other disorders (eg, flat affect in Parkinson disease); no single sign is pathognomonic for major depression.
It is important to observe the patient's affect (ie, outward expression of their mood) and speech. Individuals with depressive disorders can display a withdrawn affect (ie, poor eye contact, emotional blunting), tearfulness, and/or anxiety. Paucity of speech or movement or hypophonia also supports a diagnosis of depression.
Psychomotor retardation (eg, slowed speech or movements or decreased speech output) suggests the possibility of severe depression. Agitation (eg, restlessness, handwringing, inability to sit still, or pulling on clothing or skin) suggests the possibility of mania, hypomania, or substance use. (See "The mental status examination in adults", section on 'Mood, thought content, and social cognition'.)
Assess for features requiring urgent management — The initial evaluation should include questions that assess the risk of suicide or harming others and the level of functional impairment because this determines the urgency of evaluation and management. Most individuals with suspected depression can undergo evaluation in an outpatient setting.
However, a subset requires expedited workup and management that often involves same-day assessment in an emergency department and expedited treatment from a psychiatrist, ideally in a partial hospital or inpatient setting. This includes individuals who are at imminent risk of self-harm (ie, those with suicidal behavior or suicidal intent and plan, markedly impaired judgment, or inability to care for themselves), are at imminent risk of harming others, or have psychosis or mania.
Risk of suicide — Clinicians should ask all individuals with clinically significant depressive symptoms about suicidal ideation and behavior and send those at imminent risk of suicide to the emergency department for evaluation and possible hospitalization [25]. Identifying which individuals are at imminent risk of danger from self-harm can be challenging because suicidal thoughts are common in those with depression, but most do not act on them [26]. The PHQ-9 may help to identify those who require further assessment (ie, question "thoughts that you would be better off dead or of hurting yourself").
Assessment should include asking about risk factors for suicide, such as prior suicide attempts, comorbid psychiatric disorders, and childhood maltreatment. Clinicians should also explore specific details regarding the suicidal thoughts, intent, plans, and behaviors and ask about the availability of firearms or other means for self-harm (algorithm 2). Patients who have a specific plan, the means available to carry it out, and the intent to do so are at high risk, and they should be referred for emergency evaluation and management. The availability of firearms is a potent risk factor (see "Suicidal ideation and behavior in adults", section on 'Firearms'). Additional information about suicidal ideation, behavior, risk factors, and evaluation is discussed separately. (See "Suicidal ideation and behavior in adults".)
Risk of harming others — The absolute risk of violence in individuals with depression is low. However, patients who demonstrate aggressive or violent behavior or communicate an imminent plan to harm specific others need urgent referral to the emergency department. Intoxication may increase the risk of impulsive behavior.
The risk of harming others includes situations in which a depressed patient demonstrates a profound inability to care for dependent others such that they are at imminent risk of harm. (See "The acutely agitated or violent adult: Overview, assessment, and nonpharmacologic management".)
Severe functional impairment — Individuals with severe depressive symptoms require more urgent evaluation and management. Patients with more severe depression have a greater number and frequency of depressive symptoms that impact their interpersonal and occupational function.
●Moderate to severe functional impairment includes the inability to get dressed, get out of bed, or perform typical work or home responsibilities. This level of impairment necessitates expedited management and close monitoring; however, it does not require referral to the emergency department if the patient has adequate support from family and/or friends.
●Patients with extreme functional impairment may be unable to take in adequate nutrition and have signs of dehydration, volume depletion, or malnutrition. These individuals are at imminent danger from lack of self-care and need inpatient stabilization and treatment.
●Patients with active symptoms of mania or psychosis can demonstrate profound impairment of judgment and often require urgent evaluation and management. (See 'Mania or hypomania' below and 'Psychosis' below.)
The PHQ-9 is useful for assessing symptom severity (table 2 and table 4). Individuals with severe symptoms (ie, PHQ-9 score of ≥20) require more urgent evaluation and management. Additional questioning about functional status is also indicated in patients who indicate that their symptoms make it "very" or "extremely difficult" to carry out daily activities. Family members, close friends, or other clinicians may also provide important information about the patient's self-care and functional status [27]. In such circumstances, clinicians must discuss the involvement of others with the patient, obtain patient consent, and ensure patient confidentiality.
Evaluate for general medical illness — As part of the initial evaluation, we assess patients for general medical conditions and medications that cause symptoms that either masquerade as depression, cause depression, or exacerbate an existing depressive disorder (table 5) [27,28].
●History – Clinicians should assess for specific medical conditions suggested by the patient's symptoms. As examples, if patients note low energy or fatigue, we ascertain if they have other symptoms of hypothyroidism, adrenal insufficiency, cardiopulmonary disease, or anemia. Similarly, symptoms of insomnia or agitation should prompt questions about hyperthyroidism, alcohol or drug withdrawal, or stimulant use. Including questions to assess cognitive status or a mental status examination is important when patients describe impaired memory or concentration.
The history should include a review of the patient's current and past medical history and medications. A number of medications can cause depressive syndromes and/or symptoms (table 5) [29].
●Physical examination – Clinicians should tailor the physical examination to evaluate specific symptoms elicited by the history and assess for the most common medical conditions that can present with depressive symptoms (table 5) [29,30].
Depending on the patient's symptoms and history, potential areas of focus include:
•Vital signs – Heart rate and blood pressure abnormalities can identify potential cardiovascular diseases (eg, heart failure), endocrine conditions (eg, hypothyroidism, adrenal insufficiency, or hypercortisolism), anemia, or substance use disorders (eg, amphetamine intoxication, alcohol withdrawal). Although weight changes can occur in the context of depression, significant, unintentional weight loss should prompt consideration of occult malignancy, dementia, or autoimmune disease (eg, systemic lupus erythematosus).
•General appearance – Poor attention to clothing, personal hygiene, or general appearance may provide insight into their functional status. Cachexia should raise concern for occult malignancy or chronic infection.
•Cardiopulmonary – Symptoms of fatigue or low energy should prompt evaluation for signs of cardiopulmonary disease (eg, heart failure or chronic obstructive lung disease).
•Skin – Dermatologic findings suggestive of underlying systemic diseases that can present with depressive symptoms include skin dryness and hyperkeratosis (hypothyroidism), hyperpigmentation (Wilson disease, adrenal insufficiency), extensive ecchymoses or striae (Cushing syndrome), and palmar or conjunctival rim pallor (anemia).
•Musculoskeletal – This includes evaluating for signs of inflammatory arthritis (eg, from systemic lupus erythematosus, rheumatoid arthritis) and proximal muscle wasting (eg, from Cushing syndrome) when the patient's history suggests these disorders.
•Neurologic – The presence of tremor, ataxia, and bradykinesia suggest Parkinson disease; chorea or athetosis, Wilson or Huntington disease; and focal neurologic deficits, prior stroke or cerebral tumor.
●Laboratory studies for selected patients – Most individuals with suspected depression do not require laboratory testing [31]. The utility of laboratory testing in patients whose history and examination do not suggest an underlying general medical cause of depressive symptoms has not been demonstrated [30]. Avoiding routine laboratory tests may save costs without increasing adverse events [32].
However, we obtain testing in the subset of patients with the following features:
•In new-onset (especially in the absence of clear precipitants and/or risk factors), severe (particularly with melancholic or psychotic features), or treatment-resistant depression, obtain thyroid-stimulating hormone, urine toxicology, and human chorionic gonadotropin (pregnancy) [33].
•Complete blood count in patients with fatigue and/or other symptoms of anemia [28].
•Serum chemistries in those with symptoms or signs of adrenal dysfunction or liver disease.
•Individuals with neuropsychiatric changes, peripheral neuropathy, or gait disturbances should undergo testing for syphilis, B12, and folate.
More extensive testing may be warranted for patients with chronic medical conditions or those at increased risk for medical illnesses, including older adults, individuals who are institutionalized, and those with substance use disorders [30].
Although preliminary studies have examined the utility of serum biomarkers for the diagnosis of MDD, this approach has not shown superiority to focused testing based on the results of history and physical examination findings [34-38].
●Role of neuroimaging – We do not routinely perform neuroimaging as part of the evaluation of individuals with suspected depression. It is reasonable to obtain brain magnetic resonance imaging or head computed tomography in those with new-onset depression in later life (ie, >65 years of age) and those with prominent cognitive symptoms [28,33]. (See "Evaluation of cognitive impairment and dementia", section on 'Neuroimaging'.)
Assess for additional psychiatric symptoms — We assess all individuals with suspected depression for "AMPS," or the presence of anxiety, mania, psychosis, and alcohol or substance use. These can be symptoms of a depressive disorder or manifestations of other psychiatric disorders that can masquerade as depression or co-occur with it. The initial assessment involves asking questions about symptoms and observing the patient for overt signs of agitation, psychosis, mania, intoxication, or withdrawal from alcohol or drugs [31].
The presence of specific symptoms or signs should prompt additional investigation to determine their cause. As an example, agitation can be a manifestation of anxiety, acute mania, psychosis, or use or withdrawal from alcohol or drugs. (See 'Patients with other psychiatric symptoms' below.)
●Mania or hypomania – Patients should be assessed for symptoms and signs of mania (table 6) or hypomania (table 7). Symptoms of mania include euphoric, expansive, or irritable mood that is persistent and abnormal; disinhibition; cognitive impairment (eg, racing thoughts, distractibility, grandiosity); and abnormally increased energy and activity, impulsivity, and risk-taking behavior (table 8). Patients with mania may also exhibit loud, accelerated speech. Symptoms of hypomania resemble those of mania but are less severe. (See 'Mania or hypomania' below and "Bipolar disorder in adults: Clinical features", section on 'Mania' and "Bipolar disorder in adults: Clinical features", section on 'Hypomania'.)
●Psychosis – Individuals with psychosis may endorse hallucinations or false, fixed beliefs (delusions) or demonstrate social withdrawal. Individuals who appear distracted by internal stimuli or exhibit severe agitation or psychomotor retardation should also raise the suspicion of psychosis. (See 'Psychosis' below and "Psychosis in adults: Epidemiology, clinical manifestations, and diagnostic evaluation", section on 'Clinical manifestations'.)
●Anxiety – Symptoms of anxiety include worry, perseveration, body tension, nervousness, and episodic panic attacks. Patients may appear agitated or nervous. (See 'Anxiety' below.)
●Alcohol or substance use disorder – The initial assessment should include questions about alcohol and substance use to identify disorders that can masquerade as, coexist with, or cause a depressive disorder and potentially inform management. (See 'Alcohol or substance use disorder' below.)
Outcome of initial evaluation — The initial evaluation should yield sufficient information to determine whether clinically significant depressive symptoms exist that suggest a depressive disorder or whether the patient's presentation suggests an alternative diagnosis. Patients with a depressive disorder generally have symptoms in multiple domains of function, including emotional (depressed mood or dysphoria and/or anhedonia), physical (fatigue, sleep, or appetite disturbance), and cognitive symptoms (difficulty concentrating or making decisions). When such symptoms are pervasive, persistent, and not readily explained by an underlying physical illness, the patient is likely to have a depressive disorder. (See 'Patients with prominent depressive symptoms' below.)
By contrast, individuals are less likely to have a depressive disorder if they endorse a paucity of depressive symptoms, have symptoms that fluctuate daily, or have diagnostic findings that suggest a general medical cause of their symptoms. With these patients, we explore alternative explanations for their depressed mood or somatic symptoms. (See 'Patients without prominent depressive symptoms' below.)
FURTHER ASSESSMENT AND DIFFERENTIAL DIAGNOSIS —
The subsequent evaluation consists of determining the patient's most likely diagnosis and defining comorbidities that can complicate diagnosis and management.
Patients with prominent depressive symptoms — If the patient does not require urgent management and has depressive symptoms that are prominent and persistent, we pursue a diagnosis of major depressive disorder (MDD) or an alternative depressive disorder (table 9). Some of these patients may additionally require evaluation of other psychiatric or medical symptoms. (See 'Patients with other psychiatric symptoms' below and 'Patients with medical conditions as likely cause of symptoms' below.)
Major depressive disorder — MDD is a syndrome characterized by at least one episode of major depression (table 10) without a history of mania (table 6) or hypomania (table 7) [6]. Although the nine-item Patient Health Questionnaire can facilitate the diagnostic process, we establish the diagnosis of a major depressive episode by using diagnostic criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (table 10). The diagnosis of MDD is discussed separately. (See "Depression in adults: Clinical features and diagnosis", section on 'Major depressive disorder'.)
Other depressive disorders — Some individuals have clinically significant symptoms of depression that differ from MDD with respect to time course, symptom severity, or existence of a precipitating medical factor. These disorders include:
●Persistent depressive disorder
●Premenstrual dysphoric disorder
●Depressive disorder due to another medical condition
●Substance- or medication-induced depressive disorder
●Adjustment disorder with depressed features
These disorders are discussed separately. (See "Depression in adults: Clinical features and diagnosis", section on 'Other depressive disorders and subtypes'.)
Patients with medical conditions as likely cause of symptoms — In some individuals with suspected depression, the initial assessment suggests that a general medical illness or medication is causing or contributing to the patient's symptoms (see 'Evaluate for general medical illness' above). These individuals require additional evaluation to determine if a primary depressive disorder exists.
●With depressed mood – A primary depressive disorder is likely when the symptom of depressed mood predominates and is accompanied by other emotional, cognitive, and physical manifestations of depression. Because MDD is common among individuals with chronic medical conditions, most of these patients will have two separate diagnoses (eg, the general medical condition plus a depressive disorder). Less commonly, when the onset of the patient's depressive symptoms coincides with that of a new medication or medical condition that can cause depression, the depressive disorder is "secondary to" the medication or medical condition (table 5). (See "Depression in adults: Clinical features and diagnosis", section on 'Temporal pattern or context'.)
In either scenario, management requires treating both the depressive disorder and the general medical condition. However, in some circumstances in which the medical condition can be treated relatively quickly (eg, hypothyroidism) or the offending medication can be discontinued, clinicians might wait to assess whether this resolves the depressive symptoms prior to treating the depressive disorder.
●Without depressed mood – When depressed mood is not a prominent feature of the clinical presentation and the patient's symptoms are largely explained by the medical illness (eg, weight loss and fatigue in a patient with chronic obstructive pulmonary disease), a depressive disorder is unlikely. In these situations, the clinician should optimize management of the general medical condition.
Patients with other psychiatric symptoms — Individuals with prominent depressive symptoms who also have additional psychiatric symptoms require further evaluation to determine whether these symptoms are due to a primary depressive disorder, a different psychiatric disorder, or both. Several psychiatric disorders can be misdiagnosed as a depressive disorder or coexist with it. Common psychiatric disorders that can be mistaken for MDD include bipolar disorder, generalized anxiety disorder (GAD), substance use disorders, and some personality disorders, such as borderline personality disorder. (See 'Borderline personality disorder' below.)
Conversely, up to three-quarters of individuals with MDD have at least one psychiatric comorbidity. The most common of these include anxiety disorders, substance use disorders, posttraumatic stress disorder, attention deficit hyperactivity disorder (ADHD), and personality disorders. Psychiatric comorbidities in patients with MDD are discussed in detail separately. (See "Depression in adults: Clinical features and diagnosis", section on 'Psychiatric' and "Comorbid anxiety and depression in adults: Epidemiology, clinical manifestations, and diagnosis".)
Mania or hypomania — If the initial evaluation suggests significant depressive symptoms, it is crucial to ascertain if the patient has current symptoms of mania (table 6) or hypomania (table 7) or has had them in the past. (See 'Assess for additional psychiatric symptoms' above.)
Patients with current or past symptoms of mania or hypomania require evaluation for bipolar disorder (see "Bipolar disorder in adults: Assessment and diagnosis"). The management of bipolar disorder differs from that of MDD. Patients with mania often exhibit profoundly impaired judgment and engage in behaviors that put themselves or others at risk; such individuals require urgent management [27].
Bipolar disorder often presents with depression, and multiple episodes of bipolar depression may occur prior to the first lifetime episode of mania/hypomania. This frequently results in delayed or missed diagnoses and inappropriate treatment. The differentiation of bipolar disorder from MDD is discussed separately. (See "Bipolar disorder in adults: Assessment and diagnosis", section on 'Unipolar major depression'.)
Psychosis — Individuals with symptoms of psychosis require expedited psychiatric evaluation and treatment, ideally in an inpatient setting. Hallucinations and delusions are associated with a higher risk of self-harm and suicide attempts. (See 'Assess for additional psychiatric symptoms' above and "Psychosis in adults: Epidemiology, clinical manifestations, and diagnostic evaluation", section on 'Clinical manifestations'.)
Psychotic symptoms can occur in the context of a mood disorder (eg, bipolar disorder or MDD with psychotic features) or a primary psychotic disorder (eg, schizophrenia, schizoaffective disorder, or brief psychotic disorder) (algorithm 3). In MDD with psychotic features, delusions and hallucinations occur only during an episode of major depression [6]. By contrast, in schizophrenia and schizoaffective disorder, psychotic symptoms can occur in the absence of major depression. The clinical features and diagnosis of MDD with psychotic features, schizophrenia (table 11), and schizoaffective disorder are discussed separately, as is the assessment of depression in patients with schizophrenia. (See "Unipolar major depression with psychotic features: Epidemiology, clinical features, assessment, and diagnosis" and "Schizophrenia in adults: Clinical features, assessment, and diagnosis" and "Schizophrenia in adults: Assessment and treatment of co-occurring depression".)
Anxiety — Anxiety in individuals with depressive symptoms can occur as a manifestation of MDD (eg, "anxious depression"), a primary anxiety disorder (eg, GAD or panic disorder), or a comorbid anxiety disorder (ie, in a patient who also has MDD). Anxious depression accounts for up to one-half of major depressive episodes, and its characteristic features include worry, panic attacks, rumination, difficulty concentrating, and psychomotor agitation. (See "Depression in adults: Clinical features and diagnosis", section on 'Specific symptom constellations'.)
Some primary anxiety disorders, such as GAD, can be difficult to differentiate from depressive disorders. GAD shares features of MDD, including sleep and appetite disturbances, dysphoria, impaired concentration, and anxiety. Although worry characterizes both disorders, patients with GAD tend to worry about the future, whereas those with major depression often perseverate on past events. Symptoms of MDD that are uncommon in GAD include early morning awakening, suicidal ideation, and pronounced guilt or self-criticism. The clinical manifestations and diagnosis of GAD are discussed separately. (See "Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis".)
Comorbid anxiety disorders are common in individuals with MDD, and their presence complicates management and portends a worse prognosis. Anxiety disorders occur frequently in patients with MDD and include GAD (most common), panic disorder, and social anxiety disorder [39]. Comorbid anxiety and depression and how to differentiate GAD from depression are discussed separately. (See "Comorbid anxiety and depression in adults: Epidemiology, clinical manifestations, and diagnosis".)
Alcohol or substance use disorder — Alcohol and other substance use disorders can masquerade as depression, coexist with MDD, or cause a depressive disorder. Symptoms resembling those of MDD can occur from intoxication with or withdrawal from a wide range of substances, including alcohol, cannabis, and stimulants. Features common to MDD and substance misuse include disturbed sleep or appetite, loss of interest in pleasurable activities, agitation, fatigue, or dysphoria. Impaired occupational and psychosocial functioning can also occur in both. The timing and predominance of depressive symptoms can help to differentiate between a primary or comorbid substance use disorder or a depressive disorder caused by exposure to alcohol or drugs. (See "Depression in adults: Clinical features and diagnosis", section on '"Secondary" depressive disorders'.)
Patients without prominent depressive symptoms — Individuals who endorse a paucity of depressive symptoms or whose symptoms fluctuate daily are less likely to have a depressive disorder (table 9). For these individuals, we explore alternative diagnoses that include the following:
Sadness — Periods of sadness and irritability (dysphoria) in the absence of other symptoms do not warrant the diagnosis of a depressive disorder. Sadness and irritability are generally a normal, adaptive part of the human condition, particularly in response to loss, disappointment, or perceived failure. By contrast, the symptoms of a depressive disorder are persistent and pervasive and result in significant impairment of functioning.
Grief — Both acute and prolonged grief have symptoms that overlap with those of MDD, such as sadness, disrupted sleep and/or appetite, social withdrawal and disinterest, and suicidal ideation. However, grief is characterized by a preoccupation with intense thoughts and memories of the deceased person and a profound yearning for the deceased, which are not features of depressive disorders.
Acute grief is a normal human reaction to the death or loss of a loved one or other important relationship, identity, job, or other support. Prolonged grief disorder is a form of acute grief that is abnormally intense, prolonged, and disabling. The disabling symptoms persist for at least 12 months after the death or loss and can be distinguished from depression. Bereavement, acute grief, prolonged grief disorder, and their differentiation from major depression are discussed separately. (See "Bereavement and grief in adults: Clinical features", section on 'Typical acute grief' and "Bereavement and grief in adults: Clinical features", section on 'Major depression' and "Prolonged grief disorder in adults: Epidemiology, clinical features, assessment, and diagnosis", section on 'Unipolar major depression'.)
Burnout — Burnout is a work-related condition that is characterized by emotional exhaustion, dissatisfaction with one's accomplishments, and depersonalization (detachment from one's job) [40,41]. The condition can occur in the context of chronic job-related stress, including medical practice.
Conversely, job-related stressors can also lead to depression, and symptoms that may be observed in both burnout and major depression include dysphoria, fatigue, and suicidal ideation. Distinguishing burnout from major depression is based primarily upon determining whether the individual meets diagnostic criteria for MDD (table 10) because burnout is not a single, standardized syndrome and is often poorly defined [42]. Several validated scales exist to assist with the assessment of burnout.
Borderline personality disorder — Symptoms that are common to borderline personality disorder and MDD include dysphoria and recurrent suicidal ideation [6]. However, borderline personality disorder is characterized by episodic mood states that vary within a short period of time (often within a single day), whereas major depression is marked by dysphoria that is pervasive and persistent and accompanied by other depressive symptoms. (Other personality disorders, such as histrionic and narcissistic, can also include varying mood states.)
Features of borderline personality disorder that additionally differentiate it from MDD include identity disturbance, frantic efforts to avoid abandonment, and chronic feelings of emptiness [6]. Conversely, major depression includes symptoms that are not predominant features of borderline personality disorder, such as insomnia or hypersomnia, weight loss or weight gain, and low energy. The clinical features and diagnosis of borderline and other personality disorders are discussed separately. (See "Borderline personality disorder: Epidemiology, pathogenesis, clinical features, course, assessment, and diagnosis" and "Overview of personality disorders".)
Borderline and other personality disorders commonly co-occur with MDD and other depressive disorders. (See "Depression in adults: Clinical features and diagnosis", section on 'Psychiatric'.)
Attention deficit hyperactivity disorder — Impaired concentration, inattention, and fidgeting can occur in both ADHD and depressive disorders [6]. However, in ADHD, these symptoms are pervasive and continuous, whereas in depressive disorders, these symptoms appear only during active depressive episodes. In addition, the disruptions in sleep and appetite that characterize MDD are not present in ADHD. (See "Attention deficit hyperactivity disorder in adults: Epidemiology, clinical features, assessment, and diagnosis".)
ADHD can also be comorbid with depressive disorders. (See "Depression in adults: Clinical features and diagnosis", section on 'Psychiatric'.)
Delirium — Delirium and major depression can both manifest as difficulty with attention or concentration, poor sleep, psychomotor retardation or agitation, affect constriction, and social withdrawal [29]. However, delirium is marked by decreased level of alertness and consciousness, significant impairment of other neurocognitive functions, and marked fluctuation of symptoms, which are not characteristic of depression. (See "Diagnosis of delirium and confusional states".)
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: Depressive disorders".)
INFORMATION FOR PATIENTS —
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Depression in adults (The Basics)")
●Beyond the Basics topics (see "Patient education: Depression in adults (Beyond the Basics)" and "Patient education: Depression in children and adolescents (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Terminology – Depression can refer to a mood state, syndrome, or specific clinical disorder (table 1). (See 'Definitions of depression' above.)
●When to suspect depression – We suspect a depressive disorder in individuals who screen positive for depression, experience depressed mood or anhedonia, or have multiple unexplained physical symptoms. (See 'When to suspect a depressive disorder' above.)
●Initial evaluation – The initial evaluation should determine if clinically significant depression exists (table 3); investigate medical conditions that might account for the patient's symptoms; assess for suicidal ideation and behavior, mania, psychosis, and alcohol or substance abuse; and determine the need for urgent management (algorithm 1). (See 'Initial evaluation' above.)
•Features that suggest clinically significant depression include pervasive, persistent symptoms of depressed mood; other depressive symptoms; and specific risk factors for depression. (See 'Assess for clinically significant depression' above.)
•We use a targeted history and physical examination to evaluate for conditions and medications that cause symptoms that can masquerade as, cause, or exacerbate depressive symptoms (table 5). Most individuals with suspected depression do not require laboratory testing or neuroimaging unless the history and physical examination suggest an underlying medical cause. (See 'Evaluate for general medical illness' above.)
•Using self-report symptom scales and tailoring the history to the patient's clinical presentation can optimize the assessment's efficiency and accuracy (table 2). (See 'Practical tips' above.)
●Patients with prominent depressive symptoms on initial assessment – Individuals with prominent depressive symptoms require further assessment to:
•Assess the need for urgent management – Most individuals with suspected depression can undergo outpatient evaluation. However, patients who are at imminent risk of self-harm (ie, those with active suicidal intent and behavior, markedly impaired judgment, or inability to care for themselves), are at imminent risk of harming others, or have psychosis or mania require urgent assessment and psychiatric treatment (table 4). (See 'Assess for features requiring urgent management' above.)
•Determine the most likely diagnosis – If the patient does not require urgent management, we pursue a diagnosis of major depressive disorder (table 10) or an alternative depressive disorder (table 9 and algorithm 4). (See "Depression in adults: Clinical features and diagnosis", section on 'Diagnosis'.)
•Assess for other symptoms and disorders – Some individuals with prominent depressive symptoms may require additional evaluation of symptoms that can complicate diagnosis and treatment.
-Psychiatric – In individuals with symptoms of other psychiatric disorders, we determine whether the symptoms are due to a primary depressive disorder, a different psychiatric disorder, or both. (See 'Patients with other psychiatric symptoms' above.)
-Medical – Individuals whose initial assessment suggests that a general medical illness or medication is contributing to the patient's symptoms require additional evaluation to determine if a primary depressive disorder exists (table 5). (See 'Patients with medical conditions as likely cause of symptoms' above.)
●Patients without prominent depressive symptoms on initial assessment – Individuals are less likely to have a depressive disorder if they endorse a paucity of depressive symptoms, have symptoms that fluctuate daily, or have diagnostic findings that suggest a general medical cause of their symptoms. With these patients, we explore alternative explanations for their depressed mood or somatic symptoms (table 9). (See 'Patients without prominent depressive symptoms' above.)
ACKNOWLEDGMENT —
The UpToDate editorial staff acknowledges Jeffrey M Lyness, MD, who contributed to earlier versions of this topic review.
