Depressive Disorders and Suicide Risk

Depression

Clinical syndrome and diagnostic classification

Depression is a syndromic disorder defined by persistent low mood and/or anhedonia with cognitive, biological and psychomotor symptoms causing functional impairment. For examination purposes, distinguish major depressive disorder from depressive symptoms secondary to bipolar disorder, substance use, endocrine/metabolic disease, neurological disease, medication effects, bereavement and adjustment disorder. A key MRCP trap is failure to screen for past hypomania/mania before prescribing antidepressant monotherapy.

Framework	Core diagnostic requirement	Severity/staging points
DSM-5 major depressive episode	At least 5 of 9 symptoms for ≥2 weeks, including depressed mood or anhedonia; clinically significant distress/impairment; not due to substances/medical illness; no manic/hypomanic episode.	Symptoms: sleep, interest, guilt/worthlessness, energy, concentration, appetite/weight, psychomotor change, suicidal ideation. Specify melancholic, atypical, psychotic, peripartum, seasonal, catatonic.
ICD-10 depressive episode	Core symptoms: depressed mood, loss of interest/enjoyment, reduced energy; usually ≥2 weeks.	Mild: ≥2 core + ≥2 additional; moderate: ≥2 core + ≥3–4 additional; severe: 3 core + ≥4 additional, with or without psychotic symptoms.
Persistent depressive disorder/dysthymia	Chronic depressive symptoms for ≥2 years in adults.	May coexist with major depressive episodes (“double depression”).

Pathophysiology and neurobiology

Depression is not explained by a simple “monoamine deficiency”, although monoaminergic modulation remains therapeutically central. Current models integrate dysregulated serotonergic, noradrenergic and dopaminergic signalling; impaired reward circuitry involving ventral striatum and mesolimbic dopamine; reduced prefrontal top-down regulation of limbic structures including amygdala; and maladaptive cognitive bias. Neuroendocrine findings include hypothalamic–pituitary–adrenal axis activation, impaired glucocorticoid feedback and hypercortisolaemia in severe/melancholic depression. Inflammatory associations include raised CRP, IL-6 and TNF-α in subsets, relevant to sickness behaviour and treatment resistance. Chronic stress may reduce hippocampal neurogenesis and brain-derived neurotrophic factor signalling; antidepressants and ECT appear to modulate synaptic plasticity over weeks, paralleling delayed clinical response.

Assessment, measurement and differential diagnosis

Assessment should quantify symptom severity, longitudinal course, psychotic or catatonic features, substance use, comorbidity, functional impairment and treatment history. Use validated scales to monitor trajectory rather than to replace diagnosis. Response is conventionally ≥50% reduction in symptom score; remission approximates PHQ-9 <5 or HAM-D-17 ≤7.

Scale	Range	Common interpretation
PHQ-9	0–27	5 mild, 10 moderate, 15 moderately severe, 20 severe; score ≥10 has approximately 88% sensitivity and 88% specificity for major depression in primary-care validation studies.
HAM-D-17	0–52	0–7 remission; 8–16 mild; 17–23 moderate; ≥24 severe; widely used in trials.
BDI-II	0–63	14–19 mild, 20–28 moderate, 29–63 severe; self-report, cognitive weighting.

Medical mimics and contributors are common in MRCP contexts: hypothyroidism, Cushing syndrome, Addison disease, anaemia, B12/folate deficiency, hypercalcaemia, chronic kidney/liver disease, Parkinson disease, stroke, dementia, multiple sclerosis, obstructive sleep apnoea and chronic inflammatory disease. Drug causes include corticosteroids, interferon-α, isotretinoin, varenicline, mefloquine, some antiepileptics, beta-blockers and alcohol. Baseline tests are guided by context but commonly include FBC, U&E, LFT, calcium, glucose/HbA1c, TSH, B12/folate and pregnancy testing where relevant.

Management principles and pharmacology

NICE guidance emphasises stepped care: psychoeducation, sleep/activity scheduling and guided self-help for less severe depression; high-intensity psychological therapy and/or antidepressants for more severe, persistent or recurrent depression. CBT, behavioural activation and interpersonal therapy have robust evidence. Antidepressants usually require 2–4 weeks for early improvement and 6–8 weeks for an adequate trial at therapeutic dose. Continue treatment for at least 6 months after remission; extend to ≥2 years after recurrent episodes, residual symptoms, severe episodes or high relapse risk.

Drug/class	Typical adult dose	Key pharmacology and cautions
Sertraline	50 mg daily; titrate to 100–200 mg daily	SSRI; half-life ~26 h; first-line in cardiovascular disease; GI upset, sexual dysfunction, hyponatraemia/SIADH, bleeding risk with NSAIDs/anticoagulants.
Citalopram/escitalopram	Citalopram 20–40 mg daily; escitalopram 10–20 mg daily	Dose-dependent QT prolongation; citalopram maximum 20 mg daily in age >65 years or hepatic impairment.
Fluoxetine	20–60 mg daily	Long half-life: fluoxetine 2–4 days, norfluoxetine 7–15 days; CYP2D6 inhibition; activating; useful when adherence/withdrawal issues.
Mirtazapine	15–45 mg nocte	Noradrenergic/5-HT modulation; sedating and appetite-stimulating; less sexual dysfunction; weight gain.
Venlafaxine	75–225 mg daily MR	SNRI; monitor BP, discontinuation symptoms; greater toxicity in overdose than SSRIs.
Amitriptyline	75–150 mg daily in depression	TCA; anticholinergic effects, postural hypotension, QT/QRS widening, arrhythmogenic and dangerous in overdose.

Switching requires attention to serotonin toxicity and half-life. Avoid combining serotonergic agents with MAOIs; after irreversible MAOIs, allow a 14-day washout before SSRI/SNRI, and after fluoxetine allow at least 5 weeks before MAOI. Serotonin syndrome presents with mental-state change, autonomic instability and neuromuscular hyperactivity, especially clonus and hyperreflexia.

Treatment resistance, psychotic depression and ECT

Treatment-resistant depression is commonly defined as non-response to two adequate antidepressant trials from different classes. The STAR*D programme demonstrated diminishing remission rates across sequential steps, with cumulative remission around two-thirds but increasing relapse and intolerance at later stages. Options include switching antidepressant, combining with psychological therapy, or augmentation with lithium, atypical antipsychotics, mirtazapine or thyroid hormone under specialist supervision. Lithium augmentation targets serum lithium typically 0.4–0.8 mmol/L, requiring renal, thyroid and calcium monitoring.

Psychotic depression involves mood-congruent or mood-incongruent delusions/hallucinations and carries high morbidity; treatment usually requires antidepressant plus antipsychotic or ECT. ECT is indicated for severe depression with psychosis, stupor/catatonia, life-threatening refusal of food/fluids, severe treatment resistance, or need for rapid response. Modern bilateral or unilateral ECT under anaesthesia has response rates often 70–90% in severe depression, with transient cognitive adverse effects, particularly anterograde and retrograde memory impairment.

Suicide Risk

Epidemiology and clinical significance

Suicide is a low-frequency but high-impact outcome; in UK practice it is a central MRCP topic because it intersects depression, substance misuse, personality disorder, psychosis and general medical illness. UK annual suicide rates are approximately 10–12 per 100,000 population, with male rates around 3 times female rates. The highest absolute rates occur in middle-aged men, while older adults have higher case fatality due to planning, isolation and more lethal methods. For examination purposes, the key principle is that suicide risk is dynamic: acute intent may fluctuate over hours, particularly with intoxication, insomnia, agitation, interpersonal crisis or access to lethal means.

Conceptual model of suicide risk

Suicidal behaviour is best conceptualised as the interaction between baseline vulnerability and proximal precipitants. Baseline vulnerability includes genetic loading, early adversity, impulsivity, chronic psychiatric illness, substance dependence and neurobiological dysregulation of serotonergic, noradrenergic and hypothalamic–pituitary–adrenal axis systems. Proximal precipitants include acute depressive relapse, psychotic command hallucinations, intoxication, unbearable pain, shame, financial or relationship loss, and recent discharge from psychiatric care. Low central serotonergic function, reflected historically by reduced cerebrospinal fluid 5-hydroxyindoleacetic acid, is associated with impulsive and violent suicidal behaviour, although it is not clinically used as a test.

Major risk factors

Domain	High-yield risk factors	Exam relevance
Psychiatric	Major depressive episode, bipolar depression or mixed affective state, schizophrenia, anorexia nervosa, alcohol or drug dependence, severe anxiety, personality disorder	Bipolar mixed states and agitated depression are particularly dangerous because energy and impulsivity coexist with despair
Historical	Previous suicide attempt, especially violent method or high intent; family history of suicide; childhood trauma	Previous attempt is among the strongest predictors; risk is greatest in the first weeks to months after an attempt
Demographic	Male sex, older age, social isolation, unemployment, homelessness, imprisonment, military veteran status	Women attempt more often; men die more often due to higher-lethality methods
Clinical state	Hopelessness, anhedonia, guilt, insomnia, agitation, panic, psychosis, intoxication, chronic pain, terminal or disabling illness	Hopelessness is a stronger predictor than depressive severity alone
Access and context	Access to firearms, ligatures, high places, railway lines, large medication supplies; recent bereavement, relationship breakdown or financial crisis	Means restriction is one of the most effective population-level interventions

Risk periods in mood disorders

In depressive disorders, suicide risk rises with severity, psychotic symptoms, agitation, insomnia, comorbid substance misuse and perceived burdensomeness. The risk is not confined to the nadir of mood: it may increase early in recovery when psychomotor retardation improves before hopelessness has resolved. After psychiatric inpatient discharge, suicide risk is markedly elevated, particularly during the first 1–4 weeks; follow-up within 7 days is a widely used safety standard in UK services, with more urgent review for high-risk patients. In bipolar disorder, depressive and mixed episodes confer more risk than pure mania; long-term lithium treatment is associated with reduced suicide and self-harm compared with several alternative mood stabilisers, with meta-analytic estimates suggesting an approximately 50–60% reduction in suicide risk, though confounding and toxicity considerations remain important.

Assessment principles and limitations of scoring

Risk assessment should be structured but not reduced to a numerical score. NICE guidance on self-harm and suicide prevention advises against using risk scales to predict suicide or to determine discharge, because positive predictive value is poor when the outcome is rare. Common instruments such as the SAD PERSONS scale have low sensitivity and should not be used as gatekeeping tools. A clinically defensible formulation integrates static risk, dynamic risk, protective factors and foreseeable scenarios.

• Static risk: sex, age, previous attempts, family history, long-standing psychiatric disorder.
• Dynamic risk: current intent, hopelessness, intoxication, agitation, psychosis, insomnia, pain, recent losses, treatment non-adherence.
• Protective factors: dependent children, supportive relationships, religious or cultural objections, future plans, therapeutic alliance; these are protective only if subjectively meaningful to the patient.
• Access to means: quantity of prescribed drugs, opioids, tricyclic antidepressants, insulin, firearms, ligature points, high places and transport routes.

Clinical features suggesting imminent risk

Imminent risk is suggested by a specific plan, available means, preparatory acts, suicide note, concealment, finalising affairs, recent rehearsal, command hallucinations, severe agitation, intoxication, or inability to agree to immediate safety measures. A sudden calmness after marked distress may indicate resolved intent rather than improvement. Persistent denial of suicidal ideation is not reassuring if collateral evidence indicates preparation or the mental state examination shows severe hopelessness, nihilistic delusions or psychotic depression.

Pharmacological and treatment-related considerations

Antidepressants reduce suicide risk at population level by treating depression, but early activation, akathisia, insomnia and agitation can transiently increase risk, particularly in younger patients. Regulatory warnings emphasise increased suicidal thoughts and behaviours in people aged under 25 years during initial antidepressant treatment; close review is recommended within 1 week for young adults or those at increased suicide risk, and within 2 weeks for others when starting treatment. Tricyclic antidepressants are substantially more lethal in overdose than SSRIs; dosulepin and amitriptyline are particularly hazardous and generally avoided in suicidal patients. SSRIs such as sertraline and fluoxetine are preferred when overdose risk is relevant, though citalopram and escitalopram have dose-dependent QT prolongation concerns. Clozapine reduces suicidal behaviour in schizophrenia; the InterSePT trial showed clozapine superiority over olanzapine for preventing suicidal behaviour in high-risk schizophrenia or schizoaffective disorder.

Population prevention and systems approach

Effective suicide prevention combines individual treatment with systems interventions: rapid post-discharge follow-up, crisis planning, reduction of access to lethal means, safer prescribing with limited quantities, assertive management of alcohol and substance misuse, and robust communication between primary care, emergency medicine and mental health services. From an MRCP perspective, the safest answer is rarely “risk score and discharge”; it is a documented formulation, collateral information where possible, treatment of the underlying disorder, means restriction, and escalation when intent, psychosis, intoxication or lack of support makes risk unmanageable in the community.

Self-Harm Assessment

Self-harm is defined by NICE as any act of self-poisoning or self-injury, irrespective of apparent suicidal intent. This definition is deliberately broad: intent is often ambivalent, fluctuating, concealed, or retrospectively reconstructed. For MRCP purposes, the assessment has two parallel priorities: medical toxicity/physical injury and psychosocial formulation of risk, needs, and safeguarding. Self-harm is one of the strongest predictors of subsequent suicide; approximately 1–2% die by suicide within 1 year and 3–5% within 5–10 years, with highest risk in older men, violent methods, high intent, psychiatric illness, substance misuse, and social isolation.

Immediate assessment: safety, physiology, and treatable toxicity

Initial management follows an ABCDE approach, with early treatment of hypoxia, shock, seizures, hypoglycaemia, hyperthermia, and reduced consciousness. Do not delay antidotes or decontamination while awaiting psychiatric review. Record observations, Glasgow Coma Scale, capillary glucose, temperature, ECG, pregnancy status where relevant, and obtain collateral history from ambulance crew, relatives, drug packets, electronic prescribing records, and GP summary.

Clinical issue	Exam-relevant thresholds and actions
Activated charcoal	Usually 50 g orally if presentation within 1 hour of potentially toxic ingestion; consider later for modified-release preparations, carbamazepine, dapsone, phenobarbital, quinine, theophylline. Avoid if unprotected airway.
Paracetamol overdose	Toxic dose traditionally >150 mg/kg. Measure plasma concentration at ≥4 hours post-ingestion and treat using the UK nomogram; since 2012 the single treatment line is 100 mg/L at 4 hours. Start acetylcysteine immediately if staggered overdose, uncertain timing, >8 hours since ingestion, or high-risk history.
Tricyclic antidepressants	ECG is crucial. QRS >100 ms predicts seizures; QRS >160 ms predicts ventricular arrhythmias. Treat broad-complex tachycardia or hypotension with IV sodium bicarbonate.
Salicylates	Check serial levels, acid–base status, U&E. Severe toxicity suggested by metabolic acidosis, pulmonary oedema, renal failure, CNS features, or levels often >700 mg/L; consider alkalinisation and haemodialysis.
Lithium	Delayed absorption and redistribution require serial levels. Severe toxicity often >2.5 mmol/L or neurological impairment; haemodialysis may be indicated.

Psychosocial assessment

NICE NG225 recommends that every presentation with self-harm receives a comprehensive psychosocial assessment by a suitably trained clinician, not simply “medical clearance”. Assessment should occur when the patient is cognitively able to engage; intoxication, delirium, severe pain, or hypoxia may necessitate observation and reassessment. Premature discharge before psychosocial assessment is a common examination and clinical governance pitfall.

Core domains

• Index episode: method, lethality, dose, timing, precautions against discovery, isolation, planning, final acts, suicide note, internet searches, alcohol/drug use, triggers, and whether help was sought.
• Intent: desire to die, expectation of fatality, ambivalence, regret, relief at survival, and current suicidal ideation. Distinguish stated intent from objective lethality.
• Psychiatric morbidity: depressive episode, bipolar disorder, psychosis, PTSD, eating disorder, personality disorder traits, substance dependence, neurodevelopmental disorder, cognitive impairment.
• Past behaviour: previous self-harm, escalating frequency or lethality, previous high-lethality attempts, psychiatric admissions, non-adherence, and family history of suicide.
• Context: relationship breakdown, debt, disciplinary proceedings, domestic abuse, homelessness, bereavement, chronic pain, physical illness, immigration or legal stressors.
• Protective factors: dependants, therapeutic alliance, religious/cultural objections, future plans, problem-solving capacity, stable housing, and willingness to accept support. Protective factors mitigate but do not negate acute risk.
• Safeguarding: children, vulnerable adults, domestic violence, coercion, exploitation, access to firearms, stockpiled medication, ligatures, or high places.

Risk formulation: avoid spurious precision

Risk assessment tools such as SAD PERSONS, Beck Hopelessness Scale, or local checklists must not be used to predict suicide or determine discharge in isolation. NICE explicitly advises against global stratification into “low/medium/high risk” as the sole basis for management, because positive predictive value is poor even when relative risks are elevated: suicide is a statistically rare outcome. A defensible assessment is a dynamic formulation: why this person harmed themselves now, what factors maintain risk, what can change, and what immediate plan reduces foreseeable harm.

Risk component	Examples	Management implication
Static	Male sex, older age, previous self-harm, family suicide, childhood adversity	Informs baseline vulnerability; not modifiable acutely
Dynamic	Current depression, intoxication, psychosis, insomnia, agitation, access to means	Targets immediate intervention and follow-up intensity
Future/contingent	Court case, discharge from ward, anniversary, eviction, relationship contact	Requires anticipatory crisis planning
Protective	Engaged family, children, employment, treatment adherence	Mobilise support, but verify reliability

Capacity, consent, and legal considerations

Assess decision-making capacity specifically for refusal of medical treatment or psychiatric admission: ability to understand, retain, weigh information, and communicate a decision. Intoxication or severe affective/psychotic symptoms may impair capacity transiently. In England and Wales, life-saving treatment for an incapacitated adult may proceed under the Mental Capacity Act in best interests. If a capacitous patient refuses treatment after self-poisoning, senior review is essential; detention under the Mental Health Act may be appropriate if a mental disorder warrants assessment or treatment and risk criteria are met. Confidentiality can be breached proportionately to prevent serious harm, including contacting relatives or removing lethal means.

Disposition and aftercare

Admission is indicated for ongoing medical toxicity, persistent suicidal intent, psychosis, severe depression, inability to maintain safety, lack of support, safeguarding concerns, or need for Mental Health Act assessment. Discharge should include a collaboratively written safety plan, restriction of means, crisis contacts, communication with primary care within 24 hours, and rapid follow-up. NICE recommends aftercare within 48 hours when ongoing safety concerns exist. Repetition prevention is not achieved by “no-suicide contracts”; evidence favours problem-solving approaches, brief psychological interventions, continuity of care, and treatment of underlying psychiatric and substance-use disorders.