8.1 Affective Disorders: Depression, Bipolar Disorder & Suicide Risk Assessment

Affective Disorders: Depression, Bipolar Disorder & Suicide Risk Assessment

Mood disorders represent common presentations across acute hospital medicine and primary care. Differentiating unipolar depression from bipolar spectrum illness, managing antidepressant pharmacology safely, monitoring narrow-therapeutic-index mood stabilisers, and conducting robust suicide risk stratification are core competencies in clinical practice.

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Major Depressive Disorder (MDD): Diagnostic Criteria & Stratification

Under DSM-5, a major depressive episode needs at least 5 of 9 symptoms for at least 2 weeks, including depressed mood or anhedonia, causing clinically significant distress or impairment. ICD-11 uses a similar threshold (at least 5 symptoms, including at least one affective symptom). The older ICD-10 framing, still common in UK teaching, requires at least 2 of 3 "core" symptoms (low mood, anhedonia, fatigue) plus additional symptoms.

Core & Somatic Features

• Core Symptoms:
  1. Depressed mood: Pervasive low mood for most of the day, nearly every day.
  2. Anhedonia: Markedly diminished interest or pleasure in all or most activities.
  3. Fatigue / Anergia: Decreased energy (a core symptom in ICD-10; one of the nine DSM-5 symptoms).
• Biological & Cognitive Symptoms (Somatic Features):
  • Sleep disruption: Classically early morning awakening (EMA), waking ≥2 hours before habitual wake time; initial or middle insomnia (or hypersomnia) may also occur.
  • Diurnal mood variation: Mood characteristically worst in the morning, improving slightly as the day progresses.
  • Weight and appetite changes: Significant anorexia and weight loss (>5% in a month), or increased appetite.
  • Psychomotor changes: Retardation (slowed speech, delayed responses) or agitation (pacing, hand-wringing).
  • Cognitive symptoms: Feelings of worthlessness, excessive inappropriate guilt, impaired concentration, and recurrent thoughts of death or suicide.

Severity Stratification & Scoring

The Patient Health Questionnaire-9 (PHQ-9) scores 0–27 (5–9 mild, 10–14 moderate, 15–19 moderately severe, 20–27 severe). NICE NG222 (2022) simplifies treatment choice into two groups:

• Less severe depression: PHQ-9 below 16 (covers what was previously called subthreshold and mild depression).
• More severe depression: PHQ-9 16 or more (previously moderate and severe depression). Severe depression may have psychotic features (mood-congruent delusions of poverty, guilt or nihilism, including Cotard's syndrome), which need urgent specialist referral.

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NICE NG222 Management Framework

• Assessment: Exclude organic causes (hypothyroidism, B12 deficiency, Cushing's syndrome, hypercalcaemia, drugs such as corticosteroids), assess suicide risk, and agree a shared treatment decision. Encourage sleep hygiene, physical activity and alcohol reduction.
• Less severe depression: Offer a menu of options in order of cost-effectiveness: guided self-help, group cognitive behavioural therapy (CBT) or group behavioural activation, individual CBT or behavioural activation, group exercise, group mindfulness or meditation, interpersonal psychotherapy (IPT), SSRIs, counselling, and short-term psychodynamic psychotherapy. Do not routinely offer antidepressants first-line for less severe depression unless that is the person's preference.
• More severe depression: Options start with a combination of individual CBT and an antidepressant, then individual CBT, individual behavioural activation, an antidepressant alone (SSRI, SNRI or other), IPT, and others, chosen with the person.
• Chronic, relapsing or treatment-resistant depression, or psychotic features: consider combined treatment, specialist mental health referral and, for severe or life-threatening depression, electroconvulsive therapy (ECT).

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Antidepressant Pharmacotherapy: Classes & Comparison

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SSRI Prescribing Rules, Discontinuation & Serotonin Syndrome

Prescribing & Review Guidelines

• Delayed Onset: SSRIs require 2 to 4 weeks for therapeutic effect. Counsel patients that physical activation often precedes mood elevation, transiently increasing anxiety, agitation, and suicidal thoughts.
• Review Frequency (NICE NG222): Review within 1 week of starting an antidepressant for people aged 18 to 25 or at increased risk of suicide; otherwise usually within 2 weeks, then regularly (for example every 2–4 weeks in the first 3 months).
• Treatment Duration: Continue therapy at full therapeutic dose for at least 6 months after full remission of a first episode to prevent relapse (≥2 years if recurrent depression).

Discontinuation Syndrome

Abrupt cessation (especially short half-life drugs like paroxetine and venlafaxine) causes the FINISH syndrome:

• Flu-like symptoms, Insomnia, Nausea, Imbalance (dizziness/vertigo), Sensory disturbances (electric shock sensations / "brain zaps"), and Hyperarousal (anxiety/agitation). Taper gradually over at least 4 weeks. Fluoxetine carries the lowest risk due to its long-acting metabolite norfluoxetine (half-life 7–14 days).

Serotonin Syndrome

Caused by excessive 5-HT receptor stimulation, typically when combining serotonergic agents (SSRI + MAOI, tramadol, St John's Wort, linezolid, triptans).

• Hunter Criteria Triad:
  1. Neuromuscular excitation: Spontaneous clonus, inducible clonus, ocular clonus, hyperreflexia, and tremor.
  2. Autonomic instability: Hyperthermia (>38°C), profuse diaphoresis, tachycardia, labile BP, and diarrhoea.
  3. Altered mental status: Agitation, restlessness, delirium.
• Management: Stop all serotonergic agents immediately; supportive IV fluids (0.9% normal saline); IV benzodiazepines for agitation; cyproheptadine (5-HT2A antagonist) for moderate-to-severe cases; ICU admission and paralysis if temperature >41°C.

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Bipolar Affective Disorder: Subtypes & Management

• Bipolar I Disorder: At least one episode of mania. Manic episodes involve elevated/irritable mood and increased energy lasting ≥7 days (or requiring hospitalisation), with grandiosity, decreased need for sleep, pressured speech, flight of ideas, distractibility, and reckless spending/disinhibition. Often features psychotic symptoms.
• Bipolar II Disorder: At least one episode of hypomania (lasting ≥4 days, without severe functional impairment, hospitalisation, or psychotic symptoms) alternating with major depressive episodes.

Acute Mania Management

1. Stop Antidepressants: Discontinue all antidepressants immediately to avoid fueling manic excitation.
2. First-Line Pharmacotherapy: Initiate an oral atypical antipsychotic (olanzapine, risperidone, quetiapine) or haloperidol.
3. Alternative / Mood Stabiliser: Oral semi-sodium valproate or lithium.

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Lithium Carbonate: Monitoring Protocol & Toxicity Management

Lithium is the gold-standard maintenance mood stabiliser, uniquely proven to reduce completed suicide rates.

Therapeutic Window & Routine Monitoring

• Therapeutic Levels: Maintenance target 0.6 to 0.8 mmol/L (0.8 to 1.0 mmol/L in acute mania or frequent relapses).
• Timing: Draw blood samples precisely 12 hours post-dose (trough level).
• Frequency (NICE CG185): Measure 1 week after starting and after each dose change, then weekly until stable; then every 3 months for the first year, and every 6 months after that (every 3 months for higher-risk groups such as older people, those on interacting drugs, or with impaired renal or thyroid function).
• Organ Surveillance: Check renal function (eGFR/creatinine), thyroid function (TSH) and calcium every 6 months, plus weight or BMI. Long-term risks include nephrogenic diabetes insipidus (polyuria/polydipsia), hypothyroidism, hyperparathyroidism, and first-trimester teratogenicity (Ebstein's anomaly).

Lithium Toxicity Precipitants & Management

Precipitated by dehydration, sodium depletion, and drugs reducing renal clearance: thiazide diuretics (highest risk), NSAIDs, and ACE inhibitors / ARBs.

• Toxicity Features:
  • Mild-to-Moderate (1.5–2.0 mmol/L): Coarse tremor, ataxia, dysarthria, nausea, vomiting, diarrhoea.
  • Severe (>2.0 mmol/L): Hyperreflexia, seizures, arrhythmias, acute renal failure, coma.
• Management: Stop lithium; aggressive IV rehydration with 0.9% normal saline (promotes lithium excretion); discuss extracorporeal treatment (haemodialysis) with TOXBASE or the National Poisons Information Service; the EXTRIP workgroup recommends it if lithium is above 4.0 mmol/L with impaired kidney function, or with decreased consciousness, seizures or life-threatening dysrhythmias whatever the level.

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Suicide & Self-Harm Risk Assessment

NICE NG225 (Self-harm, 2022) changed UK practice: do not use risk assessment tools or scales, or global stratification into low, medium or high risk, to predict future suicide or repeat self-harm, or to decide who receives treatment or is discharged. Instead, carry out a psychosocial assessment of needs and risks and plan care around them:

• Assessment Domains: Intent (desire to die versus self-harm), plan, lethality of method, access to means (medications, firearms, ligature points), preparations (suicide note, updating a will, sorting finances), previous self-harm or suicide attempts (the strongest single predictor of future suicide), hopelessness, mental disorder, substance misuse, social circumstances and protective factors (children, family support, beliefs).
• Safety Planning: Develop a written safety plan with the person (warning signs, coping strategies, people and places that help, crisis contacts such as NHS 111 option 2, Samaritans 116 123, the GP) and agree means restriction (for example limited quantities of medication).
• Escalation According to Needs: Clinical judgement about current needs and safety, not a risk category, decides the setting: follow-up in primary care; urgent referral to the Crisis Resolution and Home Treatment Team (CRHTT) or liaison psychiatry; or admission. Admission is informal if the person has capacity and consents; detention under the Mental Health Act 1983 (Section 2, 3 or 4) may be needed if a person with a mental disorder refuses admission and is at serious risk.