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Atypical (Second-generation) Antipsychotic — Dopamine D3/D2 Partial Agonist Pregnancy: Avoid — limited data; potential for neonatal EPS with third-trimester exposure. Long-acting metabolite makes timing of discontinuation important.

Cariprazine

Brand names: Reagila

Adult dose

Dose: Schizophrenia: 1.5mg OD initially; increase by 1.5mg every 1–2 weeks; usual maintenance 1.5–6mg OD. Maximum 6mg OD.
Route: Oral
Frequency: Once daily (with or without food)
Max: 6mg OD
Unique mechanism: partial agonist at D3 and D2 receptors (like aripiprazole) but with preferential D3 affinity — D3 receptors are implicated in cognitive function, motivation, and reward processing. May improve negative symptoms and cognition in schizophrenia more than older antipsychotics. Also 5-HT1A partial agonist and 5-HT2A antagonist. NICE approved for schizophrenia where other antipsychotics have failed or caused intolerable side effects.

Paediatric dose

Route: Oral
Frequency: Once daily
Max: Not applicable
Not licensed under 18 years. Seek specialist child and adolescent psychiatry opinion.

Dose adjustments

Renal

Mild-moderate renal impairment: no adjustment. Severe (eGFR <30): use with caution — limited data.

Hepatic

Mild-moderate hepatic impairment: no adjustment. Severe hepatic impairment: avoid.

Clinical pearls

  • Active metabolite (DDCAR) has a very long half-life (1–3 weeks) — when stopping cariprazine, adverse effects such as akathisia may persist for weeks; conversely, after stopping, residual therapeutic effect persists for weeks
  • Negative symptoms: emerging evidence that cariprazine's D3 preference improves negative symptoms (avolition, alogia, anhedonia) and cognition more than predominantly D2 blockers — may be preferred when negative symptoms are the primary concern
  • Akathisia: most common side effect — usually responds to dose reduction; propranolol 10–30mg BD or low-dose diazepam can be used if dose reduction not possible
  • NICE TA810: cariprazine approved for schizophrenia in adults when other antipsychotics not tolerated or insufficient response

Contraindications

  • Concomitant strong CYP3A4 inhibitors (ketoconazole, clarithromycin — markedly increase cariprazine and active metabolite levels)
  • Concomitant strong CYP3A4 inducers (carbamazepine, rifampicin — reduce cariprazine levels)
  • Hypersensitivity to cariprazine

Side effects

  • Akathisia (most common — dose-dependent)
  • Parkinsonism / EPSE
  • Headache
  • Somnolence (less than quetiapine/olanzapine)
  • Nausea
  • Weight gain (less than olanzapine)
  • Restlessness

Interactions

  • Strong CYP3A4 inhibitors — contraindicated or use half dose; cariprazine and DDCAR (active metabolite) levels rise significantly
  • Strong CYP3A4 inducers — avoid; significant reduction in efficacy
  • CNS depressants — additive sedation

Monitoring

  • EPSE assessment (akathisia scale — Barnes Akathisia Scale)
  • Weight and metabolic parameters
  • Mood response
  • ECG if cardiac risk factors

Reference: BNFc; BNF 90; NICE TA810 (Cariprazine for Schizophrenia); Reagila SPC. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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