Key Facts

Depression is one of the most common mental health conditions and a leading cause of disability worldwide. It affects all age groups and is associated with significant morbidity, mortality (suicide), and socioeconomic impact.

Epidemiology

Depression affects approximately 1 in 6 adults in England at any given time. Women are twice as likely as men to be affected. Approximately 6,000 people die by suicide annually in the UK, with depression being the most common associated diagnosis. Depression costs the UK economy an estimated £12 billion per year.

Aetiology

Biopsychosocial model:

• Biological: Monoamine deficiency (serotonin, noradrenaline, dopamine), HPA axis dysregulation (raised cortisol), genetic predisposition (heritability ~37%), neuroplasticity changes (reduced BDNF, hippocampal volume)
• Psychological: Negative cognitive triad (Beck) — negative views of self, world, future; learned helplessness (Seligman); early adverse experiences
• Social: Bereavement, relationship breakdown, unemployment, financial difficulties, social isolation, chronic illness

Pathophysiology

• Monoamine hypothesis: Reduced synaptic 5-HT, NA, dopamine — supported by mechanism of antidepressants but does not fully explain the 2-4 week lag in treatment response
• HPA axis dysregulation: Elevated cortisol → hippocampal damage → impaired negative feedback
• Neuroinflammation: Raised pro-inflammatory cytokines (IL-6, TNF-α, CRP) found in depression
• Neuroplasticity: Reduced BDNF, hippocampal atrophy, prefrontal cortex hypofunction

Core Symptoms (≥2 for ≥2 weeks)

• Low mood: Persistent, most of the day, nearly every day
• Anhedonia: Loss of interest or pleasure in activities
• Reduced energy: Fatigue, decreased activity

Associated Symptoms

• Disturbed sleep (early morning waking is characteristic; or hypersomnia)
• Reduced appetite and weight loss (or increased appetite/weight gain in atypical depression)
• Reduced concentration and attention
• Low self-esteem and self-confidence
• Ideas of guilt and unworthiness
• Psychomotor agitation or retardation
• Suicidal ideation or acts

Severity Classification (ICD-11)

• Mild: 2 core + 2 associated symptoms; can usually continue activities
• Moderate: 2 core + 3-4 associated symptoms; difficulty continuing activities
• Severe: 3 core + ≥4 associated symptoms; marked functional impairment; may have psychotic features

Red Flags

• Active suicidal ideation with plan and intent — immediate risk assessment, consider urgent referral
• Psychotic features (delusions of guilt, nihilism, auditory hallucinations) — antipsychotic may be needed
• Severe self-neglect, catatonia, refusal to eat or drink
• Postpartum depression with thoughts of harming baby — urgent perinatal mental health referral

Bedside

• PHQ-9: 9-item screening questionnaire — 0-4 minimal, 5-9 mild, 10-14 moderate, 15-19 moderately severe, 20-27 severe
• GAD-7: Anxiety screening (common comorbidity)
• Risk assessment: Suicidal ideation, self-harm, plans, protective factors
• Functional assessment: Impact on work, relationships, daily activities

Bloods

• TFTs: Exclude hypothyroidism
• FBC: Exclude anaemia
• HbA1c, glucose: Diabetes (associated comorbidity)
• Calcium: Hypercalcaemia can cause low mood
• Vitamin D, B12, folate: Deficiency may contribute to symptoms
• LFTs: Baseline before certain medications; alcohol-related liver disease
• U&Es: Baseline for SSRI monitoring (hyponatraemia risk, especially in elderly)

Special Tests

• Neuroimaging: Not routine; consider if atypical features or cognitive decline
• Formal cognitive testing: If dementia suspected (distinguish pseudodementia from true dementia)

Non-pharmacological

• Mild depression: Active monitoring, guided self-help, computerised CBT, structured exercise, behavioural activation
• Moderate-severe: CBT (16-20 sessions), behavioural activation, interpersonal therapy (IPT)
• All severities: Psychoeducation, sleep hygiene, social prescribing, exercise

Pharmacological (NICE NG222)

First-line antidepressants:

• Sertraline 50mg OD (first choice — best evidence base, safe in cardiac disease)
• Fluoxetine 20mg OD (long half-life, good in younger adults)
• Citalopram 20mg OD (max 40mg; max 20mg if >65 years or hepatic impairment — QTc prolongation risk)
• Mirtazapine 15mg ON (sedating, good if insomnia/poor appetite; weight gain)
• Venlafaxine 75mg OD (SNRI — monitor BP; higher doses more effective)

Treatment duration: Continue for ≥6 months after remission (≥2 years if recurrent episodes) Switching: If no response at adequate dose after 4-6 weeks, switch to alternative class or within class Augmentation: Lithium, quetiapine, or aripiprazole added to antidepressant in refractory cases

Referral Criteria

• Severe depression with psychotic features — secondary care psychiatry
• Active suicidal intent — crisis team or emergency admission
• Treatment-resistant depression (failed 2 adequate antidepressant trials) — secondary care
• Bipolar depression suspected — psychiatry (avoid SSRI monotherapy)
• Postpartum depression — perinatal mental health team

• Single episode: ~50% recover within 6 months; ~85% within 1 year with treatment
• Recurrence: ~50% after first episode; ~80% after third episode
• Chronic course: ~20% develop chronic/persistent depression (>2 years)
• Suicide: Lifetime risk approximately 4-7% in those hospitalised with depression; ~15% in severe recurrent depression
• Functional outcomes: Depression is a leading cause of disability worldwide (WHO Global Burden of Disease)
• Adequate treatment significantly improves outcomes — NNT for antidepressants ≈ 7 for response vs placebo

PHQ-9 Scoring

Antidepressant Side Effects