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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Core symptoms: persistent low mood, anhedonia (loss of pleasure), reduced energy — for ≥2 weeks
- PHQ-9 for severity screening: 5–9 mild, 10–14 moderate, 15–19 moderately severe, ≥20 severe
- NICE stepped care: subthreshold/mild → guided self-help, exercise, CBT; moderate-severe → SSRI + CBT
- First-line SSRI: sertraline (good safety profile, licensed in cardiac disease). Alternative: citalopram, fluoxetine
- Safety: always assess suicide risk. SSRIs take 4–6 weeks for effect. Warn about initial anxiety/activation
- SSRI discontinuation syndrome: dizziness, GI upset, "electric shock" sensations — taper gradually, do not stop abruptly
Overview
Depression (major depressive disorder) is a common, serious mood disorder characterised by persistent low mood, loss of interest or pleasure (anhedonia), and a range of cognitive, behavioural, and somatic symptoms that cause significant functional impairment. It is distinct from normal sadness by its severity, duration (≥2 weeks), and impact on daily functioning. Depression is one of the leading causes of disability worldwide. The biopsychosocial model informs understanding: biological (serotonin/noradrenaline, HPA axis), psychological (cognitive distortions, early adversity), and social (isolation, unemployment, relationships) factors all contribute.
Epidemiology
Depression is one of the most common mental health conditions, with a UK point prevalence of approximately 5–10% of adults. Lifetime risk is approximately 10–20% (higher in women — 2:1 ratio). Peak incidence is in early adulthood but occurs across all ages. Major risk factors include female sex, family history, adverse childhood experiences, chronic physical illness, social isolation, unemployment, and substance misuse. Depression frequently coexists with anxiety disorders (~50%), chronic pain, cardiovascular disease, and diabetes.
Clinical Features
Symptoms
Persistent low mood — present most of the day, nearly every day
Anhedonia — loss of interest or pleasure in previously enjoyed activities
Reduced energy, fatigue, psychomotor retardation
Disturbed sleep — insomnia (early morning waking is classic) or hypersomnia
Appetite change — reduced or increased (atypical depression)
Poor concentration and indecisiveness
Feelings of worthlessness, guilt, hopelessness
Suicidal ideation, thoughts of self-harm, or intent/plan
Psychotic symptoms (severe depression): nihilistic delusions, auditory hallucinations
Signs
Psychomotor retardation: slow speech, reduced movement, flat affect
Poor eye contact, tearfulness
Self-neglect: unkempt appearance, poor hygiene
Psychomotor agitation (less common): restlessness, hand-wringing
Investigations
First-line
PHQ-9 questionnaireValidated screening and severity measure. 9 items scored 0–3. Total: 5–9 mild, 10–14 moderate, 15–19 moderately severe, ≥20 severe
Clinical assessmentStructured psychiatric history: core + additional symptoms, duration, functional impact, risk assessment (suicide, self-harm, neglect)
Risk assessmentALWAYS assess: suicidal thoughts, intent, plan, means, protective factors, previous attempts
Second-line
Bloods to exclude organic causesTFTs (hypothyroidism), FBC (anaemia), calcium (hypercalcaemia), glucose/HbA1c, B12/folate, LFTs
Specialist
NeuroimagingNot routine — only if organic brain pathology suspected (late-onset, focal neurology, cognitive decline)
1
Step 1 — Subthreshold/mild depression
- Active monitoring (watchful waiting) with follow-up in 2 weeks
- Guided self-help (workbooks, online CBT programmes)
- Physical exercise (structured exercise programme — NICE recommended)
- Sleep hygiene, social prescribing
2
Step 2 — Moderate depression
- SSRI: sertraline is commonly first-line (or citalopram, fluoxetine)
- Start at low dose and titrate: e.g. sertraline 50 mg → 100 mg → max 200 mg
- Warn: takes 4–6 weeks for full effect; initial side effects (nausea, anxiety, activation) usually settle
- Psychological therapy: CBT (gold standard), behavioural activation, interpersonal therapy
- COMBINATION of SSRI + CBT is more effective than either alone
3
Step 3 — Severe or treatment-resistant depression
- Optimise SSRI dose → switch SSRI → augmentation (mirtazapine, lithium, or atypical antipsychotic)
- Venlafaxine (SNRI) or mirtazapine as alternative antidepressants
- Combined antidepressants: SSRI + mirtazapine (specialist decision)
- ECT (electroconvulsive therapy): for life-threatening depression (suicidality, psychotic depression, severe catatonia, not eating/drinking)
- Psychotic depression: SSRI + antipsychotic (or ECT)
4
Continuing/maintenance treatment
- Continue antidepressant for ≥6 months after remission (first episode)
- If recurrent depression: continue for ≥2 years
- When stopping: taper SSRI gradually over 4+ weeks to avoid discontinuation syndrome
- Never stop abruptly — discontinuation symptoms: dizziness, nausea, electric shock sensations, insomnia, irritability
Complications
- Suicide: ~15% lifetime risk in severe depression. The most feared complication — always assess risk
- Self-harm: Frequently co-occurs — assess at every consultation
- Substance misuse: Self-medication with alcohol/drugs worsens outcomes
- Functional impairment: Work, relationships, self-care — depression is the leading cause of disability worldwide (WHO)
- Physical health decline: Depression worsens outcomes in CVD, diabetes, cancer — bidirectional relationship
- Recurrence: >50% after first episode; >80% after third. Long-term treatment reduces recurrence
UKMLA Exam Tips
- 1Core symptoms: low mood + anhedonia + low energy. Need ≥2 core + additional symptoms for ≥2 weeks
- 2PHQ-9 ≥10 = moderate depression warranting active treatment (SSRI and/or CBT)
- 3ALWAYS ask about suicide — directly asking does NOT increase risk. It is essential, safe, and expected
- 4SSRIs take 4–6 weeks for effect — counsel patients to persevere through initial side effects
- 5Fluoxetine is first-line in children and adolescents (only SSRI licensed for under 18s)
- 6Serotonin syndrome: SSRIs + MAOIs or tramadol → agitation, clonus, hyperthermia, diaphoresis — medical emergency
- 7Early morning waking is the classic sleep disturbance in depression (not initial insomnia)
practicetest your knowledge on depressionApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — psychiatry and beyond.
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