Psychiatry/Third-generation antipsychotic

Third-generation antipsychotics (aripiprazole)

also: aripiprazole · cariprazine · dopamine partial agonist

Overview

The newest class — dopamine partial agonists, which "stabilise" dopamine and so cause the least weight gain, prolactin elevation and sedation.

Mechanism

Partial agonists at the dopamine D₂ receptor (and 5-HT₁A) — act as functional antagonists where dopamine is high (mesolimbic) but provide some tone where it is low → "dopamine system stabiliser" with fewer EPSEs/prolactin/metabolic effects.

Indications

Schizophrenia / psychosis
Bipolar (mania)
Useful when metabolic effects / prolactin are a concern

The agents

AripiprazoleD₂ partial agonist

oral/depot

Least weight gain/prolactin/sedation; can cause akathisia.

CariprazineD₃/D₂ partial agonist

Newer option.

Adverse effects

Akathisia (restlessness)common

Most characteristic of aripiprazole.

Less weight gain / prolactin / sedationcommon

The selling point.

Nausea, insomniacommon

Cautions & contraindications

Elderly with dementia (class effect)elderly

↑stroke/mortality.

Interactions

CYP3A4/2D6 metabolism — dose-adjust with inhibitors/inducers

Monitoring & kinetics

As antipsychotics (metabolic) but lower burden; akathisia

Oral / long-acting depot.

Choosing it

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Source: BNF — Aripiprazole