Psych · General adult psychiatry — mood disorders
Major depressive disorder
Also known as MDD · Unipolar depression · Clinical depression · Major depression · Depressive episode · Treatment-resistant depression · Psychotic depression · Melancholic depression
Exam-exhaustive fellowship reference on major depressive disorder — DSM-5-TR and ICD-11 criteria and specifiers; epidemiology and suicide risk; monoamine and circuit models; differentials including bipolar and medical mimics; PHQ-9 and HAM-D in measurement-based care; STAR*D, antidepressant NMA, psychotherapy and ECT evidence; stepped care (RANZCP/NICE/APA/CANMAT); special populations. FRANZCP-primary, globally tagged.
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Target exams
Red flags
- Active suicidal intent, plan or recent attempt — same-day senior review, means restriction, documented safety plan; do not discharge to an empty plan
- Psychotic depression, catatonic features, or severe melancholia with refusal of food/fluids — urgent escalation; ECT may be first-line
- New or worsening suicidal ideation after starting or increasing an antidepressant — reassess risk, akathisia/activation, and care intensity immediately
- Mixed features or prior hypomania/mania — do not treat as uncomplicated unipolar MDD with antidepressant monotherapy
- Serotonin syndrome (clonus, hyperreflexia, fever, agitation) or TCA overdose — medical emergency
- Elderly patient with confusion, falls or seizures on SSRI — check sodium; hyponatraemia is a classic trap
Meet the patient
A 46-year-old accountant is brought in by his wife. He has woken at 4am every day for six weeks, lost weight he did not have to lose, and answers each question after a three-second delay. He says he is "a burden" and that the family "would be tidier without me".[9][10]
His GP started citalopram nine days ago at half the starting dose and told him to come back in three months. His wife adds, almost as an afterthought, that one summer in his twenties he redecorated the whole house in a weekend and did not sleep.[2][17]
Two exam questions are now live and you must answer both: is this unipolar? and is he safe to go home tonight? Everything below exists to answer those two questions at consultant depth.[1][17]
References20ShowHide
- [1]Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report Am J Psychiatry, 2006.PMID 17074942
- [2]Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice Am J Psychiatry, 2006.PMID 16390886
- [3]Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, Thase ME, et al. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression N Engl J Med, 2006.PMID 16554525
- [4]Nierenberg AA, Fava M, Trivedi MH, Wisniewski SR, Thase ME, McGrath PJ, et al. A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report Am J Psychiatry, 2006.PMID 16946176
- [5]McGrath PJ, Stewart JW, Fava M, Trivedi MH, Wisniewski SR, Nierenberg AA, et al. Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report Am J Psychiatry, 2006.PMID 16946177
- [6]Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis Lancet, 2018.PMID 29477251
- [7]Geddes JR, Carney SM, Davies C, Furukawa TA, Kupfer DJ, Frank E, et al. Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review Lancet, 2003.PMID 12606176
- [8]UK ECT Review Group Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis Lancet, 2003.PMID 12642045
- [9]Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R) JAMA, 2003.PMID 12813115
- [10]Kroenke K, Spitzer RL, Williams JB The PHQ-9: validity of a brief depression severity measure J Gen Intern Med, 2001.PMID 11556941
- [11]Hamilton M A rating scale for depression J Neurol Neurosurg Psychiatry, 1960.PMID 14399272
- [12]Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression Arch Gen Psychiatry, 2006.PMID 16894061
- [13]Popova V, Daly EJ, Trivedi M, Cooper K, Lane R, Lim P, et al. Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Am J Psychiatry, 2019.PMID 31109201
- [14]Daly EJ, Trivedi MH, Janik A, Li H, Zhang Y, Li X, et al. Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial JAMA Psychiatry, 2019.PMID 31166571
- [15]March J, Silva S, Petrycki S, Curry J, Wells K, Fairbank J, et al. Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial JAMA, 2004.PMID 15315995
- [16]Kennedy SH, Lam RW, McIntyre RS, Tourjman SV, Bhat V, Blier P, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments Can J Psychiatry, 2016.PMID 27486148
- [17]Malhi GS, Bell E, Bassett D, Boyce P, Bryant R, Hazell P, et al. The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders Aust N Z J Psychiatry, 2021.PMID 33353391
- [18]Cuijpers P, Quero S, Noma H, Ciharova M, Miguel C, Karyotaki E, et al. Psychotherapies for depression: a network meta-analysis covering efficacy, acceptability and long-term outcomes of all main treatment types World Psychiatry, 2021.PMID 34002502
- [19]Nelson JC, Papakostas GI Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials Am J Psychiatry, 2009.PMID 19687129
- [20]DeRubeis RJ, Hollon SD, Amsterdam JD, Shelton RC, Young PR, Salomon RM, et al. Cognitive therapy vs medications in the treatment of moderate to severe depression Arch Gen Psychiatry, 2005.PMID 15809408