Key Facts

Depression is a common mental health disorder characterised by persistent low mood, loss of interest or pleasure (anhedonia), and a range of cognitive, behavioural, and physical symptoms. It is a leading cause of disability worldwide and is predominantly managed in primary care.

Epidemiology

• Lifetime prevalence: 15-20%; point prevalence: 5-10%
• Female:male ratio 2:1
• Peak onset: 20-30 years; second peak in elderly
• Recurrence: 50% after first episode; 80% after third episode
• Only one-third of depressed individuals seek help
• Associated with significant morbidity, reduced productivity, and increased mortality

Aetiology

• Biopsychosocial model: biological, psychological, and social factors interact
• Biological: monoamine hypothesis (serotonin, noradrenaline, dopamine deficiency), genetic predisposition (heritability ~40%), HPA axis dysregulation, neuroinflammation, structural brain changes
• Psychological: cognitive distortions (Beck), learned helplessness (Seligman), attachment difficulties
• Social: life events (bereavement, job loss, relationship breakdown), social isolation, childhood adversity, poverty, chronic illness

Pathophysiology

• Reduced serotonergic, noradrenergic, and dopaminergic neurotransmission
• HPA axis overactivity: elevated cortisol
• Reduced hippocampal neurogenesis and BDNF (brain-derived neurotrophic factor)
• Neuroinflammation: elevated pro-inflammatory cytokines (IL-6, TNF-α)
• Antidepressants increase monoamine availability and promote neuroplasticity

Core Symptoms (ICD-11)

• Persistent low mood (most of the day, nearly every day, for ≥2 weeks)
• Anhedonia (loss of interest or pleasure in activities)
• Fatigue/reduced energy

Associated Symptoms

• Reduced concentration and attention
• Reduced self-esteem and confidence
• Ideas of guilt and unworthiness
• Disturbed sleep (insomnia or hypersomnia)
• Appetite and weight change (reduced or increased)
• Psychomotor agitation or retardation
• Suicidal ideation or acts of self-harm

Severity Classification

• Mild: 2 core + 2 associated symptoms; minimal functional impairment
• Moderate: 2 core + 3-4 associated symptoms; considerable difficulty with daily activities
• Severe: 3 core + ≥4 associated symptoms; marked functional impairment; may have psychotic features

Red Flags

• Active suicidal ideation with plan and intent
• Psychotic features (hallucinations, delusions of guilt/worthlessness)
• Self-neglect (not eating, drinking, personal hygiene)
• Catatonia
• Severe agitation
• Risk to children/dependants

Screening/Assessment Tools

• PHQ-9 (Patient Health Questionnaire-9): scores 0-27; ≥5 mild, ≥10 moderate, ≥15 moderately severe, ≥20 severe
• PHQ-2: 2-item screen (first 2 questions of PHQ-9); ≥3 warrants full PHQ-9
• GAD-7: for comorbid anxiety
• Suicide risk assessment: direct questioning about suicidal thoughts, plans, means, protective factors

Bloods (Exclude Organic Causes)

• TFTs: hypothyroidism
• FBC: anaemia
• Vitamin B12 and folate: deficiency
• Glucose/HbA1c: diabetes
• U&Es, LFTs: baseline
• Calcium: hypercalcaemia

Special Tests

• ECG: before starting certain antidepressants (citalopram QTc prolongation risk)
• Drug and alcohol screening if substance misuse suspected
• Cognitive assessment (ACE-III): if depression in elderly (differentiate from dementia)

NICE NG222 Stepped-Care Model

• Step 1: Recognition, assessment, watchful waiting for subthreshold/mild depression
• Step 2: Low-intensity psychological interventions (guided self-help, computerised CBT, group physical activity, behavioural activation)
• Step 3: High-intensity psychological therapy (individual CBT, IPT, EMDR, couples therapy) OR antidepressant medication, or combination
• Step 4: Complex/crisis: specialist mental health services, inpatient care, ECT

Pharmacological

• First-line SSRI: sertraline 50mg OD (start 50mg, increase to 100-200mg); or fluoxetine 20mg OD (start 20mg, increase to 40-60mg)
• Alternative SSRIs: citalopram 20mg OD (max 40mg; 20mg if >65 years — QTc risk), escitalopram 10-20mg OD
• Second-line: switch SSRI, or consider SNRI (venlafaxine 75-375mg/day, duloxetine 60-120mg/day), mirtazapine 15-45mg ON (sedating, appetite stimulating)
• Augmentation (specialist): lithium, atypical antipsychotic (quetiapine, aripiprazole)
• Duration: continue for ≥6 months after remission (first episode); ≥2 years for recurrent depression
• Taper gradually when discontinuing (over 4+ weeks) to avoid discontinuation syndrome
• Warn about: delayed onset of benefit (2-4 weeks), initial anxiety increase, SSRI side effects (nausea, sexual dysfunction, headache)

Psychological Therapies

• CBT: 16-20 sessions; as effective as antidepressants for moderate depression (NICE NG222)
• IPT (Interpersonal Therapy): 16 sessions; focuses on relationships
• Behavioural Activation: structured increase in rewarding activities
• MBCT (Mindfulness-Based Cognitive Therapy): for relapse prevention (NICE recommended)

Referral Criteria

• Crisis/home treatment team: active suicidal ideation with plan, psychotic features, severe self-neglect
• Community mental health team: treatment-resistant depression (failed ≥2 adequate antidepressant trials), complex comorbidity
• Psychiatrist: diagnostic uncertainty, bipolar suspected, augmentation strategies
• IAPT (Improving Access to Psychological Therapies): for Steps 2-3 psychological therapies
• Emergency: immediate risk to self or others

• 60-70% respond to first-line antidepressant treatment (STAR*D: 33% remission with first trial)
• Average episode duration: 6-9 months if untreated; shorter with treatment
• 50% relapse after first episode; 80% after third episode
• With continuation treatment (≥6 months), relapse rate reduced to 25%
• Chronic (persistent) depression: 20% of cases
• Depression is associated with 2× increased risk of cardiovascular disease and 4× increased risk of completed suicide
• CBT has comparable long-term efficacy to antidepressants and may have lasting protective effect after therapy ends
• Suicide risk: 6% lifetime risk in severe depression

PHQ-9 Scoring

SSRI Side Effects and Comparison

Serotonin Syndrome — Key Features