🔑 Key Learning

  • Antipsychotics are divided into typical and atypical classes, each with distinct side effect profiles
    • Typical - EPSEs
      • Acute dystonias e.g. OG Crisis - Management: procyclidine / benzatropine
    • Atypical - Metabolic syndrome
  • SSRIs are 1st-line antidepressants but can be complicated by serotonin syndrome and discontinuation effects
  • Lithium requires close biochemical monitoring due to narrow therapeutic index. Coarse tremor suggests toxicity. 
  • Benzodiazepines must be withdrawn slowly to avoid withdrawal seizures - 1/8th every 2-3 weeks 

🧪 Antipsychotic Medications

Typical (first-generation) antipsychotics

Examples
Haloperidol, chlorpromazine

Mechanism
Dopamine D2 receptor antagonists

Side effects

  • Hyperprolactinaemia: amenorrhoea, galactorrhoea, reduced libido, erectile dysfunction
    • Dopamine inhibits prolactin release - therefore antipyschotics increase prolactin
  • Extrapyramidal side effects (EPSEs): parkinsonism, dystonias, akathisia, tardive dyskinesia
  • Antimuscarinic effects: dry mouth, blurred vision, urinary retention, constipation
  • Impaired glucose tolerance
  • Lowered seizure threshold

Extrapyramidal Side Effects

Drug-induced parkinsonism

  • Rapid onset, symmetrical, tremor may be absent
  • Differentiated from idiopathic Parkinson’s (gradual, asymmetrical)

Akathisia

  • Severe restlessness

Tardive dyskinesia

  • Slow, writhing movements
  • Common signs: lip-smacking, tongue protrusion, grimacing

Dystonias

  • Sustained muscle contraction
  • Torticolis - also referred to as 'wry neck' - severe neck muscle spasm/contraction resulting in involuntary head tilting
  • Oculogyric Crisis - involuntary, extreme upward deviation of gaze +/- the presence of torticolis, tongue protrusion, jaw spasm
  • Management of acute dystonias: Procyclidine (anticholinergic) or Benzatropine

Other complications

  • Increased stroke and VTE risk in elderly
  • Neuroleptic malignant syndrome
  • QTc prolongation → risk of torsades de pointes (especially haloperidol)

Atypical (second-generation) antipsychotics

Examples
Olanzapine, risperidone, quetiapine, aripiprazole, clozapine, amisulpride

Mechanism
Act on multiple receptors: D2, D3, D4, 5-HT

Advantages
Lower risk of extrapyramidal side effects compared to typical agents

Side effects

  • Metabolic syndrome: weight gain, insulin resistance, dyslipidaemia
    • Therefore, monitoring BMI, HbA1c, lipid profile is extremely important. Patients at high risk of cardiovascular disease. 
  • Stroke and VTE (especially in elderly)
  • Hyperprolactinaemia and EPSEs: less common but can occur

💊 Clozapine

Indication
Treatment-resistant schizophrenia (failure of ≥2 antipsychotics for 6–8 weeks)

Key side effects

  • Agranulocytosis: requires regular FBC monitoring
  • Seizures
  • Myocarditis: ECG required prior to starting
  • Constipation
  • Hypersalivation: may affect up to 1/3 of patients, treat with hyoscine butylbromide

🌡 Neuroleptic Malignant Syndrome (NMS)

Triggers
Antipsychotics, abrupt withdrawal of Parkinson’s medications (e.g. levodopa)

Clinical features

  • Pyrexia
  • Muscle rigidity
  • Agitation and delirium
  • Autonomic dysfunction: tachycardia, hypertension

Examination findings

  • Reduced or absent reflexes
  • Normal pupils

Differential
Serotonin syndrome (dilated pupils, myoclonus, brisk reflexes)

Complications
Rhabdomyolysis → acute kidney injury

Management

  • Stop antipsychotics
  • IV fluids
  • Dantrolene
  • Bromocriptine (dopamine agonist)

💊 Antidepressants

Selective Serotonin Reuptake Inhibitors (SSRIs)

Examples
Sertraline, fluoxetine, citalopram

Mechanism
Block serotonin reuptake → increase synaptic serotonin

Contraindications

  • Current mania
  • Poorly controlled epilepsy
  • Avoid citalopram/escitalopram if QT prolongation
  • Avoid sertraline in severe hepatic impairment

Cardiovascular disease
Sertraline is safest

Side effects

  • Common: GI symptoms (nausea, diarrhoea)
  • Consider PPI if co-prescribed with NSAIDs

Cautions

  • SSRIs + NSAIDs/aspirin: GI bleed risk
  • SSRIs + anticoagulants: avoid due to bleeding risk
  • Avoid with MAOIs or triptans: risk of serotonin syndrome

Follow-up

  • Age <30: review within 1 week
  • Age ≥30: review in 2 weeks

Duration

  • Continue for at least 6 months after symptom improvement
  • Discontinuation syndrome if stopped abruptly
    • Features: agitation, anxiety, diarrhoea
    • Gradual withdrawal over 4 weeks
    • Paroxetine has highest risk of withdrawal symptoms

Serotonin Syndrome

Causes

  • SSRIs
  • MAOIs
  • Triptans
  • Ecstasy, methamphetamines
  • St John’s Wort

Clinical features

  • Neuromuscular: myoclonus, hyperreflexia, rigidity
  • Autonomic: tachycardia, hypertension, fever
  • Cognitive: agitation, confusion

Management

  • IV fluids
  • Benzodiazepines
  • Severe cases: cyproheptadine or chlorpromazine

SNRIs

Examples
Venlafaxine, duloxetine

Mechanism
Inhibit reuptake of serotonin and noradrenaline

Monoamine Oxidase Inhibitors (MAOIs)

Example
Phenelzine

Mechanism
Inhibit breakdown of serotonin and noradrenaline

Side effects

  • Risk of hypertensive crisis if combined with tyramine-containing foods (cheese, herring, broad beans)

Tricyclic Antidepressants (TCAs)

Examples
Amitriptyline, dosulepin

Uses
Also prescribed for neuropathic pain and migraine prophylaxis

Side effects

  • Anticholinergic: dry mouth, blurred vision, constipation, urinary retention
  • Drowsiness
  • QT prolongation (risk of torsades)

Toxicity in overdose

  • Most dangerous class in overdose
  • Features: dilated pupils, seizures, coma, arrhythmia
  • ECG: prolonged QT, wide QRS, broad complex tachycardia

Management

  • IV sodium bicarbonate
  • Indicated if QRS >100 ms or ventricular arrhythmias

💊 Benzodiazepines

Mechanism
Increase GABA activity by increasing chloride channel opening frequency

Withdrawal

  • Taper gradually: reduce by 1/8th every few weeks
  • Symptoms: anxiety, tremor, insomnia, tinnitus, seizures
  • Withdrawal symptoms may last up to 3 weeks

💊 Lithium

Indication
Mood stabiliser for bipolar affective disorder

Side effects

  • Nausea, vomiting
  • Fine tremor (coarse tremor = toxicity)
  • Nephrogenic diabetes insipidus
  • Hypothyroidism
  • Weight gain
  • Idiopathic intracranial hypertension
  • Hyperparathyroidism and hypercalcaemia

Monitoring

  • Lithium levels: 1 week after initiation and after dose changes
  • Once stable: every 3 months
  • Every 6 months: BMI, U&Es, calcium, TSH
  • If worsening renal function, monitor lithium more frequently

📝 Exam Clues & Clinchers

  • Parkinsonism that is symmetrical and of rapid onset → likely 1st gen antipsychotic
  • Lip-smacking and tongue protrusion in a patient on haloperidol → tardive dyskinesia
  • Oculogyric crisis or torticollis after starting antipsychotic → acute dystonia
    • Management: Procyclidine, benzatropine
  • Fever, rigidity, confusion, and autonomic instability → neuroleptic malignant syndrome
  • Myoclonus and hyperreflexia after SSRI + triptan → serotonin syndrome
  • Hyperprolactinaemia with antipsychotics → especially risperidone or typicals
  • Schizophrenia resistant to ≥2 antipsychotics → initiate clozapine (check ECG + FBC)
    • Risk of agranulocytosis
  • SSRI started in under-30s → follow up in 1 week due to suicide risk
  • Restlessness, diarrhoea, agitation after abrupt SSRI withdrawal → discontinuation syndrome
  • Hypertensive crisis after MAOI + cheese → tyramine interaction
  • ECG: Broad complex tachycardia, dilated pupils, coma, seizures after OD → think TCA toxicity
  • Lithium + fine tremor = expected; coarse tremor + vomiting = toxicity
  • SSRI + NSAID → risk of GI bleed, consider PPI
  • Benzodiazepine withdrawal after long-term use → seizures, tinnitus, anxiety - 1/8th every 2 weeks