Overview

1. These are generally benign in OD, requiring only supportive care. Mild sedation, HR, & orthostatic hypoBP common. E.g. Clozapine, risperidone, olanzapine, quetiapine, amisulpride.

Toxic mechanism

1. D2, 5HT, peripheral 1, H1, M1 antagonism. Risperidone & amisulpride have affinity for H1, M1.

Toxicokinetics

1. Clozapine, risperidone, olanzepine: Rapidly abs. 1st pass metabolism – Cyt P450.
2. Olanzapine: Large Vd. Abs by SL route too and also has some hepatic conjugation to glucuronide.
3. Quetiapine: Large Vd. Protein bound. Hepatic met by Cyt P450
4. Amisulpride: 2 abs peaks (1hr, 4hr). Mod Vd. Most excreted unchanged in faeces & urine.

Clinical features

1. All but amisulpride: Intoxication within 4hrs. Mild confusion, sedation, HR, & orthostatic hypoBP common. Miosis. Coma & _cardiotoxicity, rare. EPE more common in children.
2. Clozapine: Hypersalivation, anticholinergic effects (incl mydriasis). Fits in 5–10%.
3. Olanzapine: agitated delirium & urine retention common with mod OD. 15% have non-specific ST-T wave changes.
4. Quetiapine: <5% fit. Although may have QT, torsade de pointes very rare.
5. Amisulpride: Higher risk of cardiotoxicity with QT & HR → risk of torsade de pointes up to 36h. BBB possible. Coma uncommon. Large ingestions may delay onset of toxicity.

Investigations

1. Screening: BSL, ECG, paracetamol
2. Other: Rpt ECG, cardiac monitoring. QT can occur with some ODs. UEC if ECG abnormal.

Risk assessment

Clozapine & risperidone

1. Usually benign. OD>2.5mg/kg clozapine may significant symptoms.

Olanzapine

1. <40mg
   1. Therapeutic sedation and antipsychotic effects
2. 40–100mg (child>0.5mg/kg)
   1. Mild-mod sedation with possible anticholinergic effects
3. 100–300mg
   1. Sedation with intermittent marked agitation
4. >300mg
   1. Coma possible, hypoBP with peripheral alpha blockade, rarely seizures

Quetiapine

1. <3g
   1. Mild-mod sedation and sinus tachycardia
2. >3g
   1. Risk of CNS depression, coma & BP. Delirium or seizures possible

Amisulpride

1. <8g
   1. Mild-mod sedation and sinus tachycardia. QTc & TdP reported >4g
2. 8–15g
   1. Risk of delayed CNS depression, cardiotoxicity (BP,QRS,QTc,BBB & TdP)
3. >15g
   1. Expected delayed CNS depression, cardiotoxicity (BP,QRS,QTc,BBB & TdP)

Management

1. Resus, supportive care & monitoring:
   1. ABCs incl. fluid management for BP.
2. Watch for urinary retention.
3. Manage delirium with non-pharmacological & BDZ rather than physostigmine.
4. Treat seizures with BDZ and acute dystonic reactions (EPE) with benztropine ± BDZ.
5. Treat Na blockade cardiotoxicity with **bicarbonate ± hyperventilation, and TdP with MgSO4/pacing.
6. Decontamination:
   1. Activated charcoal not advised except if >4g amisulpride ingested within 1–2h.

Disposition

1. If remain asymptomatic at 4–6h (16h for amisulpride) post OD with normal ECG can be d/c else monitor until normal & below QT nomogram line. Advise child’s parents of risk of EPE for 1wk.