23.1 Mood & Psychotic Disorders in Medical Patients

Psychiatric morbidity is prevalent among general medical inpatients, frequently complicating medical management, prolonging hospitalisation, and escalating morbidity. For MRCP(UK) Part 1, candidates must master the diagnostic features of mood and psychotic disorders, the pharmacology and adverse effect profiles of psychotropic medications, emergency toxidromes (Serotonin Syndrome vs Neuroleptic Malignant Syndrome), alcohol withdrawal syndromes, and the statutory legal frameworks governing capacity and compulsory treatment in the United Kingdom.

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1. Mood & Psychotic Disorders in the Medical Setting

Major Depressive Disorder (MDD)

Depression affects up to 20–30% of medical inpatients, particularly those with chronic medical illnesses (e.g. stroke, myocardial infarction, end-stage renal disease, diabetes, and Parkinson's disease).

• Diagnostic Criteria (DSM-5 / ICD-11): Diagnosis requires at least 5 of 9 symptoms present nearly every day for at least 2 weeks, representing a change from previous functioning. At least one symptom must be a core symptom:
  1. Persistent low or depressed mood most of the day.
  2. Anhedonia (markedly diminished interest or pleasure in almost all activities).
  3. Significant unintentional weight loss/gain or change in appetite.
  4. Insomnia (particularly early morning wakening) or hypersomnia.
  5. Psychomotor agitation or retardation (observable by others).
  6. Fatigue or loss of energy.
  7. Feelings of worthlessness or excessive, inappropriate guilt.
  8. Diminished ability to think, concentrate, or indecisiveness.
  9. Recurrent thoughts of death, suicidal ideation, or suicide attempts.
• Somatic Symptom Confounding in Medical Illness: Fatigue, anorexia, weight loss, and psychomotor slowing can stem directly from underlying physical illness (e.g. malignancy, congestive cardiac failure, hypothyroidism, chronic kidney disease). In medical inpatients, diagnostic emphasis must be placed on cognitive and affective symptoms: pervasive anhedonia, excessive guilt, feelings of hopelessness, worthlessness, and suicidal ideation.
• Medical Screening Tools: The Patient Health Questionnaire-9 (PHQ-9) and Hospital Anxiety and Depression Scale (HADS) are validated bedside instruments. HADS specifically omits somatic symptoms to minimize confounding by physical disease.

Bipolar Affective Disorder (BPAD)

• Bipolar I Disorder: Characterized by at least one manic episode. Major depressive episodes are common but not strictly required for diagnosis.
• Bipolar II Disorder: Characterized by at least one hypomanic episode AND at least one major depressive episode, with no history of full manic episodes.
• Mania vs Hypomania:
  • Mania: Elevated, irritable, or expansive mood with increased energy lasting ≥7 days (or any duration if hospitalisation is required); marked impairment in social or occupational functioning; presence of psychotic features (grandiose delusions, auditory hallucinations).
  • Hypomania: Elevated or irritable mood lasting ≥4 consecutive days; clearly observable change in functioning, but without significant functional disruption, no hospitalisation required, and no psychotic symptoms.
• Lithium Carbonate Therapy:
  • Gold standard mood stabilizer for prophylaxis of bipolar affective disorder and acute mania; uniquely reduces long-term completed suicide risk.
  • Narrow Therapeutic Index: Target maintenance serum trough level is 0.6–0.8 mmol/L (0.8–1.0 mmol/L in acute mania). Levels must be drawn exactly 12 hours post-dose.
  • Adverse Effects: Fine resting tremor, polyuria/polydipsia (nephrogenic diabetes insipidus via uncoupling of aquaporin-2 channels), hypothyroidism, goitre, weight gain, hyperparathyroidism/hypercalcaemia, and chronic tubulointerstitial nephropathy.
  • Toxicity Precipitants: Dehydration, low-sodium diets, and medications that decrease renal lithium clearance: NSAIDs, Thiazide diuretics (highest risk via compensatory proximal tubular sodium/lithium reabsorption), ACE inhibitors, and ARBs.
  • Clinical Toxicity: Levels >1.5 mmol/L produce coarse tremor, ataxia, dysarthria, nausea, vomiting, and diarrhoea; levels >2.0 mmol/L trigger hyperreflexia, myoclonus, seizures, stupor, coma, and life-threatening arrhythmias. Management involves aggressive IV 0.9% saline rehydration; haemodialysis is indicated for lithium levels >4.0 mmol/L, or >2.5 mmol/L with severe neurological impairment or renal failure.

Schizophrenia & Psychotic Disorders

Schizophrenia is characterized by positive symptoms (delusions, hallucinations, thought disorganisation), negative symptoms (affective flattening, avolition, alogia, anhedonia, asociality), and cognitive dysfunction.

• Kurt Schneider's First-Rank Symptoms (FRS): Classically tested, highly specific clinical features strongly suggestive of schizophrenia in the absence of organic brain disease:
  1. Auditory Hallucinations:
     • Voices arguing or discussing the patient in the third person.
     • Voices giving a running commentary on the patient's actions.
     • Thought echo (gedankenlautwerden): hearing one's thoughts spoken aloud.
  2. Thought Alienation:
     • Thought insertion: Belief that thoughts are being inserted into one's mind from an external agency.
     • Thought withdrawal: Belief that thoughts are being actively removed or extracted from one's mind.
     • Thought broadcasting: Belief that one's private thoughts are passively escaping and accessible to others.
  3. Passivity Phenomena (Delusions of Control): Belief that one's somatic feelings, bodily sensations, volitional acts, or impulses are controlled or manipulated by an external force.
  4. Delusional Perception: A normal, real sensory perception is abruptly interpreted with profound, self-referential, delusional significance (e.g. seeing a red traffic light and instantly 'knowing' one has been ordained by royalty).

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2. Psychopharmacology in General Medicine

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs selectively inhibit the presynaptic serotonin transporter (SERT), enhancing central 5-hydroxytryptamine (5-HT) neurotransmission. They are first-line for depression and anxiety disorders.

• Sertraline: The drug of choice in patients with ischaemic heart disease and post-myocardial infarction (MI), supported by the SADHART trial demonstrating cardiovascular safety and minimal arrhythmogenic potential.
• Citalopram and Escitalopram: Associated with dose-dependent QTc prolongation and risk of Torsades de Pointes via block of cardiac hERG potassium channels. Maximum daily dose is capped at 20 mg in adults >65 years or with hepatic impairment, and 40 mg in younger adults. Avoid concurrent prescription with other QT-prolonging drugs (e.g. clarithromycin, amiodarone, haloperidol).
• Upper Gastrointestinal Bleeding Risk: Platelets lack serotonin synthesis machinery and rely entirely on SERT for uptake from plasma; serotonin is essential for platelet aggregation. SSRIs deplete platelet serotonin, increasing upper GI bleeding risk 2- to 3-fold. When combined with NSAIDs, aspirin, or anticoagulants, bleeding risk multiplies synergistically. NICE guidelines mandate co-prescribing a Proton Pump Inhibitor (PPI, e.g. lansoprazole or omeprazole) when SSRIs are used alongside NSAIDs or antiplatelet therapy.
• Hyponatraemia: SSRIs are a leading cause of the Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH), particularly in elderly inpatients on diuretics. Check baseline and routine electrolytes.
• SSRI Discontinuation Syndrome: Abrupt cessation or missed doses (especially with short half-life agents like paroxetine or venlafaxine) precipitates symptoms within 24–72 hours: electric shock-like sensations ('brain zaps'), vertigo, dizziness, ataxia, flu-like myalgias, nausea, insomnia, and intense anxiety. Avoided by slow dose tapering over 4 weeks.

Antipsychotics: Typical vs Atypical

Extrapyramidal Side Effects (EPSE) Spectrum

1. Acute Dystonic Reactions: Rapid onset (hours to days) following initiation or dose escalation; painful involuntary muscle spasms (oculogyric crisis [sustained upward deviation of eyes], torticollis, retrocollis, trismus, laryngeal spasm). Emergency treatment: Intravenous or intramuscular anticholinergic agent (e.g. Procyclidine 5–10 mg).
2. Akathisia: Unbearable subjective motor restlessness and compulsion to move (pacing, shifting feet, inability to sit still); frequently mistaken for psychotic agitation, leading to inappropriate antipsychotic dose escalation. Treatment: Dose reduction, switch to atypical agent, or add Propranolol (first-line) or low-dose clonazepam.
3. Parkinsonism: Onset within weeks; bradykinesia, cogwheel rigidity, masked facies, festinant shuffling gait. Treatment: Reduce antipsychotic dose, or add oral anticholinergic (procyclidine, trihexyphenidyl).
4. Tardive Dyskinesia: Late onset (months to years); choreoathetoid, stereotypic movements of the tongue, lips, and face (lip smacking, grimacing, tongue protrusion) and choreiform limb/trunk movements. Driven by dopamine D2 receptor upregulation and supersensitivity in the striatum. Often irreversible. Anticholinergic drugs paradoxically worsen tardive dyskinesia! Management: Gradual cessation of culprit typical antipsychotic, switch to clozapine (lowest risk of TD), or VMAT2 inhibitors (valbenazine, deutetrabenazine).

Clozapine: Mandatory Clinical Monitoring & Severe Toxicities

• Agranulocytosis / Severe Neutropenia: Occurs in ~1% of patients, peaking in the first 18 weeks. Monitored via centralized registry (CPMS/ZTAS) with absolute neutrophil counts (ANC):
  • Green: ANC ≥ 2.0 × 10^9/L, WBC ≥ 3.5 × 10^9/L (continue therapy).
  • Amber: ANC 1.5–2.0 × 10^9/L, WBC 3.0–3.5 × 10^9/L (increase monitoring to twice weekly; continue therapy).
  • Red: ANC < 1.5 × 10^9/L or WBC < 3.0 × 10^9/L (IMMEDIATE CESSATION; never re-challenge with clozapine).
• Myocarditis & Cardiomyopathy: Most common within the first 2 months. Baseline and regular troponin, CRP, and echocardiograms are required. Any unexplained tachycardia, chest pain, dyspnoea, or heart failure mandates immediate discontinuation.
• Gastrointestinal Hypomotility: Potent anticholinergic and antiserotonergic activity induces severe constipation, paralytic ileus, faecal impaction, and fatal bowel necrosis. Prophylactic stimulant/osmotic laxatives (macrogol, senna) are routinely required.
• Hypersalivation (Sialorrhoea): Paradoxical muscarinic M4 agonism and impaired swallowing; treated with sublingual ipratropium spray or hyoscine hydrobromide drops.

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