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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mitra Chitsazan, M.D.[2] Aiden Nguyen[3]
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [4] Template:Your Name
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Major depressive disorder Microchapters |
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Differentiating Major depressive disorder from other Diseases |
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Diagnosis |
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Treatment |
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Follow-up |
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Case Studies |
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Sandbox On the Web |
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American Roentgen Ray Society Images of Sandbox |
Overview
Major depressive disorder (MDD) remains a clinical diagnosis established by a comprehensive psychiatric interview against standardized criteria (DSM-5-TR or ICD-11); no laboratory test, imaging study, or biomarker confirms it. The DSM-5-TR criteria applied through a clinical (or structured) diagnostic interview are the reference standard, while validated self-report scales—chiefly the PHQ-9—are screening and severity-measurement tools, not diagnostic instruments.
Diagnostic Study of Choice
Gold standard or study of choice:
- There is no single diagnostic study of choice for the diagnosis of major depressive disorder; major depressive disorder is mainly diagnosed based on clinical presentation, established through a comprehensive psychiatric interview that applies the DSM-5-TR (or ICD-11) criteria for a major depressive episode. This criteria-based clinical interview is the reference standard for the diagnosis of major depressive disorder.
- No symptom of major depressive disorder is pathognomonic; each occurs in other psychiatric and medical illnesses. Diagnosis of major depressive disorder therefore rests on a syndrome of co-occurring symptoms causing functional impairment, not any single finding.[1]
- Diagnosis of major depressive disorder should not rest on symptom count alone; the degree of functional impairment and disability must be weighed, and the test–retest reliability of the categorical major depressive disorder diagnosis is only fair (κ ≈ 0.40 in DSM-5 field data), reinforcing the value of dimensional severity measures and longitudinal reassessment.[2][3]
- Both DSM-5-TR (predominant in the US and in research) and ICD-11 operationalize the diagnostic syndrome of major depressive disorder.[4][5]
- DSM-5-TR requires a major depressive episode for the diagnosis of major depressive disorder: ≥5 of the following 9 symptoms present during the same 2-week period, nearly every day, representing a change from baseline, with at least one being depressed mood or anhedonia (Criterion A):[4]
- Depressed mood
- Anhedonia (loss of interest/pleasure)
- Significant weight/appetite change
- Insomnia or hypersomnia
- Psychomotor agitation or retardation
- Fatigue
- Worthlessness or excessive guilt
- Diminished concentration or indecisiveness
- Recurrent thoughts of death or suicidal ideation/behavior
- Symptoms of major depressive disorder must cause clinically significant distress or impairment (Criterion B) and must not be attributable to a substance or another medical condition (Criterion C).[4]
- The diagnosis of major depressive disorder additionally requires the absence of any lifetime manic or hypomanic episode and that the episode not be better explained by a psychotic-spectrum disorder (Criterion D).[4]
- The DSM-5 bereavement exclusion has been removed from the diagnosis of major depressive disorder: a major depressive episode may be diagnosed during grief when full criteria are met, using clinical judgment to distinguish normal grief from co-occurring major depressive disorder.[6]
- Investigations for major depressive disorder:
- The Structured Clinical Interview for DSM-5 (SCID-5) is regarded as the reference standard for diagnostic clarity in major depressive disorder, mainly in research; it may have limitations in certain patient populations, and routine clinical diagnosis is instead made by an unstructured but systematic clinical interview mapping symptoms and their course over time.[5][7][8]
- Among patients being evaluated for major depressive disorder, the PHQ-9 is the most widely validated tool. Against semistructured research interviews, a score ≥10 has sensitivity ≈85% and specificity ≈85%. Severity bands: 5–9 mild, 10–14 moderate, 15–19 moderately severe, ≥20 severe.[9][10]
- Among patients being evaluated for major depressive disorder, the PHQ-2 (first two items, cutoff ≥2) can be used as an initial step followed by the full PHQ-9 (≥10), with comparable sensitivity (0.82 vs 0.86 for PHQ-9 alone) and slightly higher specificity, reducing full-questionnaire administration by roughly 57%.[11]
- Other validated instruments used in the evaluation of major depressive disorder include the CES-D, Beck Depression Inventory-II, and Hospital Anxiety and Depression Scale (HADS). HADS was specifically designed for medically ill patients, emphasizing affective over somatic symptoms to avoid confounding by physical illness—a relevant choice when neurovegetative symptoms overlap with medical disease.[7]
- In major depressive disorder, rating scales are also used for measurement-based care—quantifying baseline severity and tracking treatment response and remission over time; this is their primary ongoing clinical value.
The comparison table for diagnostic studies of choice for major depressive disorder
| Sensitivity | Specificity | |
|---|---|---|
| PHQ-9 (cutoff ≥10) | ✔ ~85% | ~85% |
| PHQ-2 (cutoff ≥2) | ~82% | ✔ Slightly higher than PHQ-9 |
✔= The best test based on the feature. Sensitivity and specificity are reported against semistructured diagnostic interviews applying DSM-5 criteria (the reference standard); the Structured Clinical Interview for DSM-5 (SCID-5) itself has no published sensitivity/specificity figures because it defines the standard against which these instruments are measured.
Diagnostic results
The following result of the clinical diagnostic interview is confirmatory of major depressive disorder:[4]
- ≥5 of the 9 DSM-5-TR symptoms present during the same 2-week period, nearly every day, representing a change from baseline, with at least one being depressed mood or anhedonia (Criterion A)
- Symptoms causing clinically significant distress or impairment (Criterion B)
- Symptoms not attributable to a substance or another medical condition (Criterion C)
- No lifetime manic or hypomanic episode, and the episode not better explained by a psychotic-spectrum disorder (Criterion D)
Sequence of Diagnostic Studies
The clinical evaluation for major depressive disorder should proceed through the following sequence:
- Maintain suspicion — patients seldom present spontaneously with low mood; they more often report general distress, sleep disturbance, pain, and fatigue, so mood and anhedonia must be probed routinely in the evaluation of major depressive disorder. Failure to probe for accompanying depressive symptoms is a recognized cause of underdiagnosis.[8][4]
- Screen (if indicated by USPSTF-endorsed practice) with PHQ-2/PHQ-9; a positive screen for major depressive disorder is not a diagnosis. (See Screening microchapter for population-level screening policy.)[5]
- Confirm against DSM-5-TR/ICD-11 via clinical interview, establishing the 2-week duration, ≥5 symptoms, and functional impairment required for major depressive disorder.[4]
- Exclude bipolarity — screen for any lifetime manic/hypomanic episode before diagnosing major depressive disorder and before starting antidepressants.[4]
- Rule out substance/medical causes and psychotic-spectrum disorders (Criteria C/D) before confirming major depressive disorder.[4]
- Assess safety — suicidal ideation, plan, or intent.
- Characterize severity and specifiers of major depressive disorder (mild/moderate/severe; anxious distress, mixed features, melancholic, atypical, psychotic, peripartum, seasonal — see Classification microchapter for full definitions) to guide treatment.
- Corroborate and re-evaluate — enlist family/carers where possible; if the picture is evolving, assign a provisional diagnosis of major depressive disorder and reassess at a scheduled follow-up.
Diagnostic Criteria
- The diagnosis of major depressive disorder is based on the DSM-5-TR criteria for a major depressive episode, established by the American Psychiatric Association.[4]
- The diagnosis of major depressive disorder is made when at least 5 of the following 9 diagnostic criteria are met during the same 2-week period, nearly every day, representing a change from baseline, with at least one being depressed mood or anhedonia: depressed mood, anhedonia, significant weight/appetite change, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue, worthlessness or excessive guilt, diminished concentration or indecisiveness, and recurrent thoughts of death or suicidal ideation/behavior (Criterion A).[4]
- In addition to Criterion A, the diagnosis of major depressive disorder requires clinically significant distress or impairment (Criterion B), symptoms not attributable to a substance or another medical condition (Criterion C), and absence of any lifetime manic or hypomanic episode with the episode not better explained by a psychotic-spectrum disorder (Criterion D).[4]
- The DSM-5 bereavement exclusion no longer applies to major depressive disorder: a major depressive episode may be diagnosed during grief when full criteria are met.[6]
DSM-5-TR vs ICD-11: Practical differences for major depressive disorder
The diagnostic criteria for major depressive disorder in DSM-5-TR and ICD-11 are now closely harmonized, closer than at any time since ICD-8/DSM-II.[12][13]
| Feature | DSM-5-TR | ICD-11 |
|---|---|---|
| Symptom threshold | ≥5 of 9 symptoms, ≥1 core | ≥5 of 10 features, ≥1 core (raised from ICD-10's ≥4) |
| Core symptoms | Depressed mood, anhedonia | Depressed mood, anhedonia (low energy demoted to accessory) |
| Newer descriptors | Hopelessness added as a descriptor of depressed mood | Hopelessness added as a distinct accompanying feature |
| Guilt/worthlessness | Separate symptom | Combined into a composite feature |
| Overall concordance | Criteria are now closely harmonized; closer to DSM than at any time since ICD-8/DSM-II | |
References
- ↑ Malhi GS, Mann JJ. Depression. Lancet. 2018;392(10161):2299-2312. doi:10.1016/S0140-6736(18)31948-2.
- ↑ Park LT, Zarate CA. Depression in the Primary Care Setting. N Engl J Med. 2019;380(6):559-568. doi:10.1056/NEJMcp1712493.
- ↑ Hasin DS, Sarvet AL, Meyers JL, et al. Epidemiology of Adult DSM-5 Major Depressive Disorder and Its Specifiers in the United States. JAMA Psychiatry. 2018;75(4):336-346. doi:10.1001/jamapsychiatry.2017.4602.
- ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 Diagnostic and Statistical Manual of Mental Disorders. Jeste DV, Lieberman JA, Fassler D, et al. American Psychiatric Association (2022).
- ↑ 5.0 5.1 5.2 Simon GE, Moise N, Mohr DC. Management of Depression in Adults: A Review. JAMA. 2024;332(2):141-152. doi:10.1001/jama.2024.5756.
- ↑ 6.0 6.1 Park SC, Kim K, Kim YK. Diagnostic Constructs of Major Depression in DSM-5: Current Critiques and Future Directions. Adv Exp Med Biol. 2026;1502:3-13. doi:10.1007/978-981-95-6872-7_1.
- ↑ 7.0 7.1 Baumgart P, Garrick T. Assessment of Depressive Symptoms in Medically Ill Patients. JAMA. 2021;325(24):2497-2498. doi:10.1001/jama.2021.2320.
- ↑ 8.0 8.1 Malhi GS, Bell E, Stavdal A, et al. Depression. Lancet. 2026;407(10540):1738-1756. doi:10.1016/S0140-6736(26)00201-1.
- ↑ Negeri ZF, Levis B, Sun Y, et al. Accuracy of the Patient Health Questionnaire-9 for Screening to Detect Major Depression: Updated Systematic Review and Individual Participant Data Meta-Analysis. BMJ. 2021;375:n2183. doi:10.1136/bmj.n2183.
- ↑ Levis B, Benedetti A, Thombs BD. Accuracy of Patient Health Questionnaire-9 (PHQ-9) for Screening to Detect Major Depression: Individual Participant Data Meta-Analysis. BMJ. 2019;365:l1476. doi:10.1136/bmj.l1476.
- ↑ Levis B, Sun Y, He C, et al. Accuracy of the PHQ-2 Alone and in Combination With the PHQ-9 for Screening to Detect Major Depression: Systematic Review and Meta-Analysis. JAMA. 2020;323(22):2290-2300. doi:10.1001/jama.2020.6504.
- ↑ Lundin A, Möller J, Forsell Y. The Major Depression Inventory for diagnosing according to DSM-5 and ICD-11. Int J Methods Psychiatr Res. 2023;32(4):e1966. doi:10.1002/mpr.1966.
- ↑ First MB, Gaebel W, Maj M, et al. An Organization- And Category-Level Comparison of Diagnostic Requirements for Mental Disorders in ICD-11 and DSM-5. World Psychiatry. 2021;20(1):34-51. doi:10.1002/wps.20825.