What is the recommended protocol for switching from Abilify (aripiprazole) to Caplyta (lumateperone)?

Switching from Abilify (Aripiprazole) to Caplyta (Lumateperone)

Perform a gradual cross-titration over 2 weeks, tapering aripiprazole by approximately 10% per week while simultaneously initiating lumateperone at 42 mg daily, to minimize withdrawal symptoms and allow for receptor adaptation between these pharmacologically distinct agents. 1, 2

Rationale for Gradual Cross-Titration

The switch from aripiprazole to lumateperone requires careful consideration of their distinct pharmacological profiles:

• Aripiprazole is a dopamine D2 partial agonist, while lumateperone is a full D2 antagonist, necessitating gradual transition to allow receptor adaptation and prevent treatment failure 2
• Abrupt discontinuation of aripiprazole can lead to withdrawal symptoms (anxiety, insomnia, irritability, mood changes) or symptom exacerbation 3
• The gradual taper minimizes these risks while maintaining antipsychotic coverage throughout the transition 1

Specific Switching Protocol

Week 1:

• Start lumateperone 42 mg once daily (taken with food, as required for absorption) 4, 5
• Reduce aripiprazole to 50% of current dose (e.g., if on 10 mg, reduce to 5 mg) 3

Week 2:

• Continue lumateperone 42 mg daily 4
• Reduce aripiprazole to 25% of original dose (e.g., if originally on 10 mg, reduce to 2.5 mg) 3

Week 3 and Beyond:

• Discontinue aripiprazole completely 3
• Continue lumateperone 42 mg daily as monotherapy 4, 5

Critical Monitoring Parameters

Extrapyramidal Symptoms (EPS):

• Monitor closely for parkinsonism, akathisia, and restlessness, particularly during weeks 1-4 of the transition 2, 4
• Lumateperone has demonstrated low EPS risk (1.0% in switching studies), significantly lower than traditional antipsychotics 4

Common Adverse Effects of Lumateperone:

• Somnolence (24.1%), sedation, dry mouth (5%), and headache (5.3%) are the most frequent treatment-emergent adverse events 6, 4, 5
• These effects are typically mild to moderate and dose-related 6

Metabolic and Endocrine Benefits:

• Expect improvements in metabolic parameters including total cholesterol, LDL cholesterol, body weight, and prolactin levels during the switch to lumateperone 4
• This represents a significant advantage over many other antipsychotics 4

Special Populations and Dosing Adjustments

Renal Impairment:

• For severe renal impairment (CrCl <30 mL/min), lumateperone is not recommended as it has not been studied in this population 5
• Moderate renal impairment does not require dose adjustment 5

Hepatic Impairment:

• No dose adjustment needed for mild to moderate hepatic impairment 5
• Lumateperone has not been studied in severe hepatic impairment 5

Drug Interactions:

• Avoid strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin) as they may reduce lumateperone efficacy 5
• Use caution with moderate to strong CYP3A4 inhibitors, though dose adjustment is typically not required 5

Symptom Stability During Transition

• PANSS Total scores remain stable or improve during the switch to lumateperone in outpatients with stable schizophrenia 4
• The 42 mg dose has demonstrated statistically significant reduction in positive and negative symptoms compared to placebo in clinical trials 6, 5
• Therapeutic effects are maintained throughout the switching period when using gradual cross-titration 4

Common Pitfalls to Avoid

• Do not abruptly discontinue aripiprazole, as its long half-life (75 hours) means plasma levels will persist, but sudden cessation increases withdrawal risk 7, 3
• Do not use faster tapers than 10% per week for aripiprazole, as this increases the risk of withdrawal symptoms and symptom exacerbation 3
• Ensure lumateperone is taken with food (at least 350 calories) to ensure adequate absorption, as bioavailability is significantly reduced when taken fasting 5
• Do not assume all patients will tolerate the same taper speed—if withdrawal symptoms emerge, pause the taper and restart when the patient stabilizes 3