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Major
Depressive Disorder

A mood disorder characterized by persistent depressed mood or loss of interest/pleasure, accompanied by cognitive, behavioural, and somatic symptoms that significantly impair functioning.

  • 17%
    Prevalence
  • ~32
    Onset Age
  • 2:1
    Ratio
  • 40-50%
    Response Rate

DSM-5-TR Diagnostic Criteria

  • Core Symptom Requirement

    5+ symptoms during the same 2-week period

    • • At least one must be (1) depressed mood or (2) loss of interest/pleasure

  • Symptom Cluster

    Clinical manifestations:

    • • Depressed Mood (Subjective or observed)
    • • Anhedonia (Markedly diminished interest or pleasure)
    • • Weight/Appetite Change (Significant loss or gain)
    • • Sleep Disturbance (Insomnia or hypersomnia)
    • • Psychomotor Agitation/Retardation (Observable)
    • • Fatigue/Loss of Energy
    • • Worthlessness/Guilt (Excessive or inappropriate)
    • • Concentration Difficulties (or indecisiveness)
    • • Suicidal Ideation (Recurrent thoughts of death)

  • Additional Requirements

    Diagnostic caveats:

    • • Symptoms cause significant distress or impairment
    • • Not attributable to substance use or medical condition
    • • No history of manic or hypomanic episodes

Assessment Protocols

Validated tools for screening and severity tracking

  • PHQ-9

    Patient Health Questionnaire-9

    Brief 9-item self-report measure directly corresponding to DSM-5-TR depression criteria; one of the most widely used screeners in primary care.

    Scoring:

    0-4 minimal, 5-9 mild, 10-14 moderate, 15-19 moderately severe, 20-27 severe depression

    Time:2-5 minutes

  • BDI-II

    Beck Depression Inventory-II

    21-item self-report assessing cognitive, affective, somatic, and vegetative symptoms over past 2 weeks.

    Scoring:

    0-13 minimal, 14-19 mild, 20-28 moderate, 29-63 severe depression

    Time:5-10 minutes

  • MADRS

    Montgomery-Åsberg Depression Rating Scale

    Clinician-rated 10-item scale sensitive to change; preferred for treatment trials and monitoring.

    Scoring:

    0-6 normal, 7-19 mild, 20-34 moderate, >34 severe; change ≥50% indicates response

    Time:15-20 minutes

  • QIDS-SR16

    Quick Inventory of Depressive Symptomatology

    16-item self-report covering all 9 DSM symptom domains; sensitive to change, useful for monitoring.

    Scoring:

    0-5 none, 6-10 mild, 11-15 moderate, 16-20 severe, 21-27 very severe

    Time:5-7 minutes

Causes & Etiology

  • Neurobiological

    • Monoamine dysregulation (serotonin, norepinephrine, dopamine)
    • Reduced hippocampal volume and neurogenesis
    • Prefrontal cortex hypoactivity
    • Amygdala hyperactivity (negative emotional processing)
    • HPA axis dysfunction (cortisol dysregulation)
    • Neuroinflammation and cytokine elevation

  • Genetic

    • Heritability: 30-40% (moderate genetic component)
    • Polygenic risk involving 100+ genes
    • 5-HTTLPR polymorphism (serotonin transporter)
    • BDNF gene variants (neuroplasticity)
    • First-degree relatives have 2-3x increased risk

  • Environmental

    • Early childhood adversity and trauma
    • Chronic stress and major life events
    • Social isolation and lack of support
    • Socioeconomic disadvantage
    • Medical illness (stroke, cancer, chronic pain)
    • Substance use (alcohol, sedatives)

  • Psychological

    • Negative cognitive schemas (Beck's cognitive triad)
    • Rumination and cognitive inflexibility
    • Learned helplessness and external locus of control
    • Perfectionism and self-criticism
    • Reduced reward sensitivity (anhedonia)

Common Comorbidities

  • Anxiety Disorders

    50-60%

    GAD, panic disorder, social anxiety frequently co-occur; shared neurobiological pathways

  • Substance Use Disorders

    20-30%

    Alcohol and cannabis most common; self-medication hypothesis; worsens depression course

  • PTSD

    Varies by sample

    Higher in trauma-exposed and military samples; screen for trauma history

  • Chronic Pain

    Common

    Pain is more common in depressed cohorts and predicts worse depression outcomes; shared pathways proposed

  • Obsessive-Compulsive Disorder

    ~5-10%

    OCD may come before or after the mood disorder; onset order is close to even

  • Eating Disorders

    5-10%

    More often diagnosed in women; binge eating disorder and bulimia nervosa most common

Evidence-Based Treatments

  • Cognitive Behavioural Therapy (CBT)

    First-line

    Structured therapy targeting negative thought patterns, behavioural activation, and skill-building for depression.

    Evidence

    About 40% response in trials; g 0.71 vs control (0.53 in higher-quality trials); comparable to antidepressants

    In practice

    12-16 sessions; gains often maintained after treatment ends

  • SSRIs/SNRIs

    First-line

    Selective serotonin reuptake inhibitors (fluoxetine, sertraline, escitalopram) and serotonin-norepinephrine reuptake inhibitors (venlafaxine, duloxetine).

    Evidence

    About 1 in 3 remit on a first SSRI (STAR*D); 4-8 weeks for full effect

    In practice

    Titrate slowly; monitor suicidality in first weeks; taper to discontinue

  • Behavioural Activation

    First-line

    Structured increase in rewarding activities and reduction of avoidance; addresses anhedonia and withdrawal.

    Evidence

    Non-inferior to CBT (COBRA trial); matched medication in more severe depression in one RCT

    In practice

    Simpler than CBT; delivered by junior mental health workers in the COBRA trial

  • Interpersonal Therapy (IPT)

    First-line

    Time-limited therapy focusing on interpersonal disputes, role transitions, grief, or interpersonal deficits.

    Evidence

    Comparable to other psychotherapies, including CBT, for acute depression

    In practice

    12-16 sessions; addresses life transitions and relationship conflicts

  • Electroconvulsive Therapy (ECT)

    Adjunct

    Electrical stimulation under anesthesia; among the most effective acute treatments for severe or treatment-resistant depression.

    Evidence

    About 48% remission after medication failure vs 65% without; rapid onset (2-4 weeks)

    In practice

    Reserved for severe, psychotic, or refractory depression; cognitive side effects

  • Transcranial Magnetic Stimulation (TMS)

    Adjunct

    Non-invasive brain stimulation targeting dorsolateral prefrontal cortex; for treatment-resistant depression.

    Evidence

    30-50% response in treatment-resistant; 20-30 sessions over 4-6 weeks

    In practice

    Clinically validated; fewer side effects than ECT; no anesthesia required

Try it with one client

Send a PHQ-9 or GAD-7 by secure link and read the scored result before the session.

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Major Depressive Disorder questions

  • What is Major Depressive Disorder?

    Major Depressive Disorder (MDD) is a mood disorder defined in DSM-5-TR (ICD-10 codes F32.x for single episode, F33.x for recurrent) by persistent depressed mood or loss of interest, plus at least four additional symptoms across cognitive, behavioural, and somatic domains, present nearly every day for at least 2 weeks. Symptoms must produce clinically significant distress or functional impairment. Episodes are classified by severity (mild, moderate, severe) and may include specifiers like with anxious distress, melancholic features, or peripartum onset.

  • What are the symptoms of Major Depressive Disorder?

    Diagnostic criteria require five or more of nine symptoms during the same 2-week period, with at least one being depressed mood or loss of interest. The full symptom list includes depressed mood, anhedonia (loss of interest or pleasure), significant weight or appetite change, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue, feelings of worthlessness or guilt, difficulty concentrating, and recurrent thoughts of death or suicidal ideation. Symptoms must represent a change from baseline functioning.

  • How is Major Depressive Disorder diagnosed?

    Diagnosis is made by a clinician using DSM-5-TR criteria, supported by validated scales. The PHQ-9 (9 items, 2 to 3 minutes) is one of the most widely used screeners; a score of 10 or above has 88% sensitivity and 88% specificity for major depression. The BDI-II is an established alternative. The MADRS (Montgomery-Åsberg Depression Rating Scale) and HAM-D are widely used clinician-rated severity measures. A full clinical evaluation rules out bipolar disorder (the most clinically important differential), substance-induced mood disorder, and depression secondary to medical conditions like hypothyroidism.

  • What causes Major Depressive Disorder?

    MDD has a moderate genetic component with heritability around 35 to 40 percent. Risk is polygenic, spread across many common variants of small effect; single candidate genes such as 5-HTTLPR have not replicated well. Neurobiologically, depression involves dysregulation of monoamine systems (serotonin, norepinephrine, dopamine), HPA axis hyperactivity, hippocampal volume reduction, and altered prefrontal-limbic connectivity. Environmental contributors include childhood adversity, recent stressful life events, chronic medical illness, social isolation, and substance use. Cognitive vulnerability factors include negative attributional style and rumination.

Scientific Sources

Evidence-Based

  • PHQ-9 Validation

    Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606-613.

  • DSM-5-TR Criteria

    American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR). 2022.

  • CBT Efficacy Meta-Analysis

    Cuijpers P, Berking M, Andersson G, et al. A meta-analysis of cognitive-behavioural therapy for adult depression, alone and in comparison with other treatments. Can J Psychiatry. 2013;58(7):376-85. PMID 23870719.

  • Antidepressant Efficacy (STAR*D)

    Rush AJ, Trivedi MH, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: STAR*D trial. Am J Psychiatry. 2006;163(11):1905-1917.

  • Neurobiology of Depression

    Duman RS, Aghajanian GK, et al. Synaptic dysfunction in depression: potential therapeutic targets. Science. 2012;338(6103):68-72.

  • Behavioural Activation

    Dimidjian S, Hollon SD, et al. Randomized trial of behavioural activation, cognitive therapy, and antidepressant medication. J Consult Clin Psychol. 2006;74(4):658-670.