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Major depressive disorder

MDD is a mood disorder characterized by a persistent feeling of sadness that represents a change from previous functioning, often accompanied by loss of interest and alterations in cognition, sleep, and appetite.
The pathogenesis of MDD is complex, and remains poorly understood. Heritability is estimated at 35%. Predisposing genetic vulnerabilities interact with adverse and protective environmental factors to produce disease. At least some of the environmental effects are mediated through epigenetic mechanisms.
In the US, the 12-month and lifetime prevalence of MDD are estimated at 10.4% and 20.6%, respectively.
Disease course
Key clinical manifestations include alterations in behavior and mood, impaired cognitive function, and suicidal ideation.
Prognosis and risk of recurrence
MDD increases the risk of mortality by 60-80%. The contribution of MDD to all-cause mortality is estimated at up to 10%.
Key sources
The following summarized guidelines for the evaluation and management of major depressive disorder are prepared by our editorial team based on guidelines from the World Health Organization (WHO 2023), the American College of Physicians (ACP 2023), the U.S. Preventive Services Task Force (USPSTF 2023; 2019; 2016), the American Academy of Family Physicians (AAFP 2023; 2009), the European Society of Medical Oncology (ESMO 2023), the American Society of Clinical Oncology (ASCO 2023), the Society for Integrative Oncology (SIO/ASCO 2023), the United States Department of Defense (DoD/VA 2022), the American Psychiatric Association (APA 2019; 2010), the American Academy of Pediatrics (AAP 2018), the Canadian Task Force on Preventive Health Care (CTFPHC 2013), and the The Scottish Intercollegiate Guidelines Network (SIGN 2012).


1.Screening and diagnosis

Indications for screening, adults, USPSTF: obtain screening for depression in the adult population, including pregnant and postpartum women and older adults.
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  • Indications for screening (children and adolescents)

2.Classification and risk stratification

Assessment of severity: consider using a quantitative measure of depression severity in the initial treatment planning and monitoring treatment progress at regular intervals to guide shared treatment decision-making in patients with MDD.

3.Diagnostic investigations

Initial evaluation: obtain a thorough diagnostic assessment to establish the diagnosis of MDD, identify other psychiatric or general medical conditions requiring attention, and develop a comprehensive plan for treatment.
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  • Functional evaluation

  • Psychosocial evaluation

  • Patient safety evaluation

  • Pharmacogenetic testing

  • Screening for HIV

4.Medical management

General principles: collaborate with the patient in decision-making and attend to the patient's preferences and concerns about treatment.
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  • Setting of care

  • Initial therapy

  • Maintenance therapy

  • Management of inadequate response

  • Therapies with no evidence for benefit

5.Nonpharmacologic interventions

Exercise: as per VA 2022 guidelines, advise practicing exercise (such as yoga, tai chi, qi gong, resistance, and aerobics) as an adjunct in patients with MDD.

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  • Bright light therapy

  • Bibliotherapy

  • Herbal products

  • Acupuncture

6.Therapeutic procedures

Electroconvulsive therapy: as per VA 2022 guidelines, offer electroconvulsive therapy, with or without psychotherapy, in patients with severe MDD and any of the following conditions:
psychotic depression
severe suicidality
history of a good response to electroconvulsive therapy
need for rapid, definitive treatment response on either medical or psychiatric grounds
risks associated with other treatments are greater than the risks of electroconvulsive therapy for the specific patient (co-occurring medical conditions make electroconvulsive therapy the safest MDD treatment alternative)
history of poor response or intolerable adverse effects to multiple antidepressants.

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7.Specific circumstances

Pediatric and adolescent patients, prevention: offer psychosocial interventions, including CBT, psychoeducation, and family-focused treatment approaches, for the prevention of depression and anxiety in children whose parents have mental health conditions.

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  • Pediatric and adolescent patients (evaluation)

  • Pediatric and adolescent patients (counseling and treatment plan)

  • Pediatric and adolescent patients (psychotherapy)

  • Pediatric and adolescent patients (pharmacotherapy)

  • Pediatric and adolescent patients (management of comorbidities)

  • Pediatric and adolescent patients (monitoring)

  • Pregnant patients

  • Peripartum depression (screening)

  • Peripartum depression (evaluation)

  • Peripartum depression (psychotherapy)

  • Peripartum depression (antidepressants)

  • Elderly patients (management of minor depression)

  • Elderly patients (management of major depression)

  • Elderly patients (secondary prevention of major depression)

  • Elderly patients (patients with cognitive impairment)

  • Elderly patients (patients with other comorbidities)

  • Patients with subclinical depression

  • Patients with relationship distress

  • Patients with post-myocardial infarction depression

  • Patients with cancer (evaluation)

  • Patients with cancer (psychotherapy and pharmacotherapy)

  • Patients with cancer (alternative and complementary therapies)

8.Patient education

Patient education: provide education about the symptoms and treatment of MDD in language readily understandable to the patient. Consider providing education about the illness, its effects on functioning (including family and other interpersonal relationships), and its treatment with the patient's permission, family members, and others involved in the patient's day-to-day life.
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9.Follow-up and surveillance

Assessment of treatment response: obtain careful monitoring of response to treatment. Obtain continued monitoring of co-occurring psychiatric and/or medical conditions to develop and refine the treatment plan.
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  • Enhancing treatment adherence

  • Discontinuation of treatment

10.Quality improvement

Cultural considerations
Assess the impact of language barriers, as well as cultural variables influencing symptom presentation, treatment preferences, and the degree to which psychiatric illness is stigmatized in the assessment and treatment of MDD.
Recognize that ethnic groups may differ in their metabolism and response to antidepressant medications.