Psychiatry/First-generation antipsychotic

First-generation (typical) antipsychotics

also: haloperidol · chlorpromazine · typical antipsychotic · flupentixol

Overview

The older "typical" antipsychotics — strong dopamine blockade, so prominent extrapyramidal side effects and hyperprolactinaemia.

Mechanism

Potent dopamine D₂-receptor antagonism in the mesolimbic pathway (antipsychotic). Non-selective D₂ blockade in the nigrostriatal (→ EPSEs) and tuberoinfundibular (→ ↑prolactin) pathways causes the side effects.

Indications

Schizophrenia / psychosis
Acute severe agitation / delirium (haloperidol — short term)
Nausea (some)

The agents

Haloperidolhigh-potency

PO/IM

Acute agitation; marked EPSEs; QT prolongation.

Chlorpromazinelow-potency

More sedation/anticholinergic/postural drop; photosensitivity.

Flupentixol / zuclopenthixoldepot

long-acting injection

Maintenance/adherence.

Adverse effects

Extrapyramidal side effects ("ADAPT")classic

Acute Dystonia (→ procyclidine), Akathisia, Parkinsonism, Tardive dyskinesia (late, often irreversible).

Hyperprolactinaemia (galactorrhoea, ↓libido, amenorrhoea)classic

Neuroleptic malignant syndromeserious

Fever, rigidity, autonomic instability, ↑CK — stop drug; supportive ± dantrolene/bromocriptine.

QT prolongation; sedationcommon

Cautions & contraindications

Parkinson's / Lewy body dementiaall

Worsen parkinsonism / severe neuroleptic sensitivity.

Elderly with dementia (unless severe distress)elderly

↑stroke + mortality.

Interactions

QT-prolonging drugs; other dopamine antagonists

Monitoring & kinetics

EPSEs, ECG (QT), prolactin

Oral / IM / depot.

Source: NICE NG178 — Psychosis & schizophrenia · BNF — Antipsychotics