Depression
Exam Tips
- In OSCEs, start with the two NICE case-finding questions, then assess duration (>=2 weeks), functional impact, biological symptoms, and risk.
- Always ask directly about suicide: thoughts, plans, intent, means, and protective factors; document safeguarding concerns for dependents.
- Differentiate unipolar depression from bipolar depression before prescribing antidepressant monotherapy.
- For UK prescribing stations, sertraline is a common first-line SSRI: start 50 mg daily and review in 1-2 weeks for tolerability/risk, then 4-6 weeks for response.
- Know key safety points: early activation/suicidality in younger adults, SSRI discontinuation symptoms, serotonin syndrome interactions, and QT cautions with citalopram/escitalopram.
- For revision diagrams of neurobiology, use your core psychiatry textbook monoamine/HPA-axis figure (e. g, See Figure from page X in your course text).
Definition
Depression is a mood disorder characterised by persistent low mood and/or loss of interest or pleasure, with associated cognitive, emotional, behavioural, and physical symptoms that are present most days for at least 2 weeks. In UK practice, severity is commonly graded with the PHQ-9 (less severe usually <16; more severe usually >=16), and diagnosis depends on symptom burden plus functional impairment rather than questionnaire score alone.
Pathophysiology
The mechanism is multifactorial and involves interaction between genetic vulnerability and psychosocial stressors, with downstream changes in monoaminergic neurotransmission (serotonin, noradrenaline, dopamine), stress-axis dysregulation (HPA-axis hyperactivity), altered inflammatory signalling, and impaired neuroplasticity in fronto-limbic circuits (for example hippocampus and prefrontal cortex). Cognitive models describe persistent negative schemas, rumination, and attentional bias to threat/loss, which maintain symptoms even after the precipitating stressor has resolved.
Risk Factors
- Female sex
- Older age (with possible physical or cognitive presentation)
- Previous depressive episode(s), especially recurrent or recent episodes
- Family history of depression or suicide (first-degree relative risk increased)
- Postpartum period
- Comorbid mental illness (for example anxiety disorders, PTSD, psychosis) or substance/alcohol misuse
- Chronic physical illness with functional impact (for example diabetes, COPD, cardiovascular disease, chronic pain, stroke, epilepsy)
- Adverse social determinants: bereavement, relationship breakdown, unemployment, debt, homelessness, social isolation, childhood maltreatment, domestic abuse
Clinical Features
Symptoms
- Persistent low mood
- Markedly reduced interest or pleasure (anhedonia)
- Sleep disturbance (insomnia or hypersomnia)
- Reduced or increased appetite, with weight change
- Fatigue or low energy
- Poor concentration or indecisiveness
- Feelings of worthlessness, excessive or inappropriate guilt
- Recurrent thoughts of death, self-harm, suicidal ideation, or plans
- Psychomotor slowing or agitation
- In older adults: non-specific somatic complaints or apparent cognitive decline
Signs
- Low-volume, slowed speech
- Psychomotor retardation or agitation on mental state examination
- Reduced eye contact and flattened/reactive affect
- Poor self-care and impaired social/occupational functioning
- Biological features in severe episodes (early morning waking, diurnal variation, reduced libido)
- Possible psychotic features in severe depression (mood-congruent guilt, nihilistic or poverty delusions)
Investigations
Management
Lifestyle Modifications
- Psychoeducation, shared decision-making, and active follow-up
- Structured sleep hygiene, graded physical activity, regular daytime routine, and reduction of alcohol/recreational drug use
- Address social drivers (debt, housing, isolation, safeguarding concerns, carer stress) and signpost to community supports
- For less severe depression: offer low-intensity psychosocial interventions first (guided self-help/CBT-based approaches, behavioural activation, group physical activity) before routine antidepressant prescribing
- Develop a safety plan if any self-harm/suicide risk and ensure urgent escalation when risk is high
Pharmacological Treatment
Selective serotonin reuptake inhibitors (first-line in many adults)
- Sertraline 50 mg once daily initially; increase in steps to 200 mg daily if needed
- Fluoxetine 20 mg once daily initially; usual range 20-60 mg daily
- Citalopram 20 mg once daily initially; usual max 40 mg daily (max 20 mg daily in older adults or hepatic impairment)
- Escitalopram 10 mg once daily initially; usual max 20 mg daily (max 10 mg daily in older adults or hepatic impairment)
Explain delayed onset (typically 2-4 weeks), early adverse effects, and withdrawal risk if stopped abruptly. Monitor for increased suicidal thoughts in younger adults early in treatment. Check interaction risk (serotonergic drugs, anticoagulants/NSAIDs) and hyponatraemia risk, especially in older people. Avoid/monitor QT-prolonging combinations with citalopram/escitalopram.
Other antidepressants
- Mirtazapine 15 mg at night initially; increase to 30-45 mg at night
- Venlafaxine modified-release 75 mg once daily initially; titrate according to response (often up to 225 mg daily; higher doses usually specialist-led)
- Duloxetine 60 mg once daily; may increase to 120 mg daily
- Amitriptyline 25-50 mg at night initially (TCA use generally specialist/selected cases due to toxicity)
Choose by previous response, comorbidity, side-effect profile, overdose risk, and patient preference. Venlafaxine can raise blood pressure (monitor). TCAs are dangerous in overdose and have anticholinergic/cardiac adverse effects; avoid in significant suicide risk where possible.
Augmentation/specialist pharmacology for treatment-resistant depression
- Lithium augmentation (dose adjusted to serum level under specialist care)
- Second-generation antipsychotic augmentation such as quetiapine (specialist advice)
- Aripiprazole augmentation in selected cases (specialist advice)
Use in secondary care with monitoring. Screen for bipolar disorder before antidepressant monotherapy to reduce risk of precipitating mania/hypomania.
Complications
- Self-harm and suicide (major morbidity/mortality risk)
- Functional decline affecting education, work, relationships, and parenting/caring roles
- Self-neglect and reduced quality of life
- Alcohol/substance misuse and dependence
- Worse outcomes in coexisting physical illnesses and mental disorders
- Relapse and recurrence, including chronic depressive symptoms
Prognosis
Course is variable but often episodic: with treatment, many episodes improve over 3-6 months and many people recover within about 12 months. Recurrence is common and risk increases with each episode; a substantial minority develop persistent/chronic symptoms, particularly with comorbid anxiety, residual symptoms, or ongoing psychosocial adversity.
Sources & References
🏥BMJ Best Practice(2)
💊BNF Drug References(50)
- Acitretin[cautions]
- Alitretinoin[cautions]
- Amisulpride[cautions]
- Apraclonidine[cautions]
- Aripiprazole[cautions]
- Asenapine[cautions]
- Benperidol[cautions]
- Brimonidine tartrate[cautions]
- Buserelin[cautions]
- Cariprazine[cautions]
- Chlorpromazine hydrochloride[cautions]
- Clonidine hydrochloride[cautions]
- Clozapine[cautions]
- Co-cyprindiol[cautions]
- Cycloserine[contraindications]
- Daridorexant[cautions]
- Dienogest[cautions]
- Droperidol[cautions]
- Eszopiclone[cautions]
- Flupentixol[cautions]
- Flupentixol decanoate[cautions]
- Goserelin[cautions]
- Haloperidol decanoate[cautions]
- Indoramin[cautions]
- Isotretinoin[cautions]
- Levomepromazine[cautions]
- Lofexidine hydrochloride[cautions]
- Loxapine[cautions]
- Lurasidone hydrochloride[cautions]
- Methyldopa[contraindications]
- Modafinil[cautions]
- Olanzapine[cautions]
- Olanzapine embonate[cautions]
- Paliperidone[cautions]
- Peginterferon beta-1a[contraindications]
- Pericyazine[cautions]
- Pimozide[cautions]
- Prochlorperazine[cautions]
- Progesterone[cautions]
- Promazine hydrochloride[cautions]
- Quetiapine[cautions]
- Risperidone[cautions]
- Sulpiride[cautions]
- Tetrabenazine[contraindications]
- Trifluoperazine[cautions]
- Vigabatrin[cautions]
- Zolpidem tartrate[cautions]
- Zopiclone[cautions]
- Zuclopenthixol acetate[cautions]
- Zuclopenthixol decanoate[cautions]
✅NICE Guidelines(1)
- Depression[overview]
📖Textbook References(2)
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1059)[context]
- Oxford Handbook of Clinical Diagnosis (Huw Llewelyn, Hock Aun Ang, Keir Lewis etc.) (Z-Library).pdf(pp. 478, 479)[context]