Last reviewed: 28 Oct 2021
Last updated: 10 Mar 2021



History and exam

Key diagnostic factors

  • presence of risk factors
  • depressed mood
  • anhedonia
  • functional impairment

Other diagnostic factors

  • weight change
  • libido changes
  • sleep disturbance
  • changes in movement
  • low energy
  • excessive guilt
  • poor concentration
  • suicidal ideation
  • bipolar disorder excluded
  • substance abuse/medication side effects excluded
  • medical illness excluded
  • schizophrenia excluded

Risk factors

  • postnatal status
  • personal or family history of depressive disorder or suicide
  • dementia
  • corticosteroids
  • interferon
  • propranolol
  • oral contraceptives
  • co-existing medical conditions
  • isotretinoin
  • comorbid substance use
  • personality disorders
  • gene-environment interaction
  • obesity

Diagnostic investigations

1st investigations to order

  • clinical diagnosis
  • metabolic panel
  • FBC
  • thyroid function tests
  • Patient Health Questionnaire-2 (PHQ-2)
  • Patient Health Questionnaire-9 (PHQ-9)
  • Edinburgh Postnatal Depression Scale
  • Geriatric Depression Scale
  • Cornell Scale for Depression in Dementia

Investigations to consider

  • 24-hour free cortisol
  • vitamin B12
  • folic acid

Treatment algorithm



Dean F. MacKinnon, MD

Associate Professor

Psychiatry and Behavioral Sciences

The Johns Hopkins Hospital




DFM declares that he has no competing interests.


Dr Dean F. MacKinnon would like to gratefully acknowledge Dr Roger S. McIntyre, Dr Tonya Fancher, and Dr Richard Kravitz, the previous contributors to this topic.


RSM has received research funds from Stanley Medical Research Institute and National Alliance for Research on Schizophrenia and Depression (NARSAD). RSM is on the advisory board for AstraZeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline, Janssen-Ortho, Solvay/Wyeth, Eli Lilly, Organon, Lundbeck, Biovail, Pfizer, Shire, and Schering-Plough. RSM is on the Speakers Bureau for Janssen-Ortho, AstraZeneca, Eli Lilly, Lundbeck, Biovail, and Wyeth. RSM has received research grants from Eli Lilly, Janssen-Ortho, Shire, and AstraZeneca. RSM has received travel funds from Bristol-Myers Squibb. TF declares that she has no competing interests. RK has received research grants from Pfizer on non-depression-related topics.

Peer reviewers

Scott McAfee, MD


Residency Training

St Vincent's Hospital




SM declares that he has no competing interests.

Dietmar Winkler, MD

Department of Psychiatry and Psychotherapy

Medical University of Vienna




DW has received lecture fees from CSC Pharmaceuticals, GlaxoSmithKline, and Pfizer, and has served as a consultant for GlaxoSmithKline.

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