Major Depressive Disorder
Summary
Major depressive disorder (MDD) is a common, recurrent mood disorder characterised by persistent low mood, anhedonia, and associated cognitive and somatic symptoms causing significant functional impairment. Diagnosis is clinical using ICD-11/DSM-5 criteria. Severity is graded as mild, moderate, or severe, with or without psychotic features. NICE recommends a stepped care approach: low intensity interventions for mild depression, antidepressants and/or psychological therapy for moderate-severe. SSRIs are first-line pharmacotherapy. Risk assessment for suicide is essential in every consultation.
Key Facts
- Definition: Persistent low mood + anhedonia + associated symptoms for 2+ weeks
- Prevalence: Lifetime 15-20%; point prevalence 5%
- Demographics: F:M 2:1; peak onset 20s-40s
- Classification: Mild, moderate, severe (± psychotic features)
- Gold Standard Investigation: Clinical diagnosis (ICD-11/DSM-5)
- First-line Treatment: Mild: guided self-help/watchful waiting; Moderate-severe: SSRI + psychological therapy
- Prognosis: 70% respond to treatment; 50% recurrence risk
Clinical Pearls
Risk Assessment Pearl: ALWAYS assess suicide risk. Ask directly - it does NOT increase risk and may be lifesaving.
SSRI Pearl: SSRIs take 4-6 weeks for full effect. Warn about initial anxiety/agitation. Continue for 6+ months after remission.
Stepped Care Pearl: Follow NICE stepped care. Don't jump to medication for mild depression.
Discontinuation Pearl: When stopping SSRIs, taper gradually over 4 weeks minimum to avoid discontinuation syndrome.
Prevalence
- Lifetime: 15-20%
- Point prevalence: 5%
- Female:male 2:1
Risk Factors
| Category | Factors |
|---|---|
| Biological | Family history, prior episodes, chronic illness |
| Psychological | Early trauma, personality, negative thinking |
| Social | Unemployment, isolation, poverty, life events |
Theories
- Monoamine hypothesis: Reduced serotonin, noradrenaline, dopamine
- HPA axis dysregulation: Elevated cortisol
- Neuroplasticity: Reduced hippocampal volume
- Inflammation: Elevated cytokines
Core Symptoms
- Low mood (persistent, pervasive)
- Anhedonia (loss of interest/pleasure)
- Reduced energy/fatigue
Associated Symptoms
ICD-11/DSM-5 Criteria
Red Flags
[!CAUTION]
- Active suicidal ideation or plan
- Access to means
- History of attempts
- Psychotic features (delusions, hallucinations)
- Severe self-neglect
Every Consultation
- Screen for suicide risk
- Ask directly: "Are you having thoughts of harming yourself or ending your life?"
- Assess plan, intent, access to means
- Protective factors
High Risk Factors
- Previous attempts
- Male sex
- Social isolation
- Substance misuse
- Recent loss
- Access to lethal means
Management Algorithm (NICE Stepped Care)
DEPRESSION SUSPECTED
↓
┌──────────────────────────────────────────────────────────┐
│ ASSESS SEVERITY + RISK │
│ - PHQ-9, GAD-7 │
│ - Suicide risk assessment │
│ - Functional impairment │
└──────────────────────────────────────────────────────────┘
↓
┌──────────────────────────────────────────────────────────┐
│ MILD DEPRESSION │
│ - Watchful waiting (2 weeks) │
│ - Guided self-help │
│ - Computerised CBT │
│ - Exercise │
└──────────────────────────────────────────────────────────┘
↓
┌──────────────────────────────────────────────────────────┐
│ MODERATE-SEVERE DEPRESSION │
│ - SSRI (first-line antidepressant) │
│ - Psychological therapy (CBT, BA, IPT) │
│ - Combination (SSRI + therapy) most effective │
└──────────────────────────────────────────────────────────┘
↓
┌──────────────────────────────────────────────────────────┐
│ TREATMENT RESISTANT │
│ - Switch antidepressant │
│ - Augment (lithium, aripiprazole) │
│ - Specialist referral │
│ - ECT for severe/life-threatening │
└──────────────────────────────────────────────────────────┘
Antidepressant Therapy
| Class | Examples | Notes |
|---|---|---|
| SSRI (first-line) | Sertraline, citalopram, fluoxetine | Start low, go slow |
| SNRI | Venlafaxine, duloxetine | If SSRI fails |
| Mirtazapine | Good if insomnia, weight loss | |
| TCA | Amitriptyline | More side effects; caution in overdose |
Treatment Duration
- Continue 6+ months after remission (first episode)
- 2+ years if recurrent depression
- Taper gradually when stopping (4+ weeks)
- 70% respond to treatment
- 30% achieve remission with first antidepressant
- 50% recurrence after first episode
- Chronic course in 15-20%
-
NICE Guideline NG222. Depression in adults: treatment and management. 2022.
-
Cipriani A et al. Comparative efficacy and acceptability of 21 antidepressant drugs (network meta-analysis). Lancet. 2018;391(10128):1357-1366. PMID: 29477251
-
Cuijpers P et al. Psychotherapy for depression. World Psychiatry. 2019;18(3):276-286. PMID: 31496089
Viva Points
"Depression is diagnosed clinically: low mood or anhedonia + 5 symptoms for 2 weeks. NICE stepped care: mild = self-help; moderate-severe = SSRI + psychological therapy. SSRIs take 4-6 weeks. Continue 6+ months after remission. ALWAYS assess suicide risk."
Last Reviewed: 2026-01-01 | MedVellum Editorial Team