Can I stop taking Cariprazine (cariprazine) and start taking Amisulpride (amisulpride) the next day?

Switching from Cariprazine to Amisulpride

You should perform a gradual cross-titration over approximately 4 weeks rather than stopping cariprazine and starting amisulpride the next day. 1, 2

Why Gradual Cross-Titration is Essential

Cariprazine has an exceptionally long elimination half-life that makes abrupt switching problematic:

• Cariprazine itself has a half-life of 2-5 days 3
• Its active metabolite (didesmethyl-cariprazine) has a half-life of 2-3 weeks 3
• The active metabolite reaches several times higher exposure than the parent compound and does not reach steady state even after 3 weeks of dosing 3
• This means cariprazine continues exerting antipsychotic effects for weeks after discontinuation

Abrupt switching risks two major problems:

1. Overlapping dopaminergic effects: Starting amisulpride while cariprazine is still active creates unpredictable combined dopamine receptor modulation (partial agonism from cariprazine plus antagonism from amisulpride) 3, 4
2. Symptom destabilization: Abrupt changes in antipsychotic coverage can precipitate relapse 1

Recommended Cross-Titration Strategy

Week 1-2:

• Begin reducing cariprazine dose by 25-50% 1
• Start amisulpride at 400 mg/day (or 50 mg twice daily if targeting negative symptoms) 5, 2

Week 2-3:

• Continue reducing cariprazine by another 25-50% 1
• Increase amisulpride toward target dose (400-800 mg/day for positive symptoms; 50-100 mg/day for negative symptoms) 5, 6

Week 3-4:

• Discontinue cariprazine completely 1, 2
• Reach full therapeutic dose of amisulpride 5

Important consideration: Because of cariprazine's prolonged half-life, you may need to extend the cross-titration period beyond 4 weeks if tolerability issues emerge 3

Key Monitoring Points

During the switch, watch for:

• Extrapyramidal symptoms (EPS), as amisulpride can cause EPS in up to 35% of patients at higher doses 7
• Hyperprolactinemia, which occurs in approximately 86% of patients on amisulpride 7
• Symptom breakthrough, particularly in weeks 2-4 when both medications are at subtherapeutic levels 1

Target Amisulpride Dosing

For predominantly positive symptoms:

• Start at 400-800 mg/day, with evidence supporting 800 mg/day from day one for maximal efficacy 5, 7
• Maintain therapeutic dose for at least 6 weeks before assessing response 5

For predominantly negative symptoms:

• Use 50 mg twice daily (100 mg/day total) 1, 5
• This low dose selectively blocks presynaptic D2/D3 autoreceptors, enhancing dopamine release 8, 4

Common Pitfalls to Avoid

• Never stop cariprazine abruptly and start amisulpride the next day - the long half-life of cariprazine's metabolites makes this pharmacologically unsound 3
• Don't rush the cross-titration - allow at least 4 weeks, potentially longer given cariprazine's pharmacokinetics 1, 3
• Don't underdose amisulpride - ensure you reach therapeutic doses (400-800 mg/day for positive symptoms) rather than stopping at subtherapeutic levels 5, 6
• Don't assess treatment failure prematurely - maintain amisulpride at therapeutic dose for at least 6 weeks before concluding inadequate response 5