What is the recommended dosing strategy when switching from aripiprazole (Abilify) 5mg to lurasidone (Latuda)?

Switching from Aripiprazole 5mg to Lurasidone

Start lurasidone at 20 mg once daily with food (at least 350 calories), while tapering aripiprazole to 50% of the original dose by day 7 and discontinuing it completely by the end of week 2. 1, 2

Lurasidone Initiation Strategy

Starting Dose and Administration

• Begin lurasidone at 20 mg once daily taken with food containing at least 350 calories, as food increases absorption approximately 2-fold for AUC and 3-fold for Cmax 1
• No initial dose titration is required when starting lurasidone 1
• The dose may be increased after one week based on clinical response 1

Aripiprazole Taper Schedule

Based on evidence from switching studies, the recommended cross-titration approach is: 2

• Week 1: Continue aripiprazole 5mg while starting lurasidone 20mg
• Day 7: Reduce aripiprazole to 2.5mg (50% of original dose)
• End of Week 2: Discontinue aripiprazole completely
• Weeks 3-6: Flexibly dose lurasidone between 20-120 mg/day based on response 2

Dosing Considerations

Target Dose Range

• The effective dose range for lurasidone is 20-120 mg/day for bipolar depression 1
• Most patients respond adequately to 20-40 mg daily 1
• The maximum recommended dose is 120 mg/day 1
• Higher doses (80-120 mg/day) do not consistently provide additional efficacy compared to lower doses (20-60 mg/day) 1, 3

Special Populations Requiring Dose Adjustment

If any of the following apply, start at 20 mg/day with a maximum of 80 mg/day: 1

• Moderate renal impairment (creatinine clearance 30 to <50 mL/min)
• Severe renal impairment (creatinine clearance <30 mL/min)
• Moderate hepatic impairment (Child-Pugh Score 7-9)

For severe hepatic impairment (Child-Pugh Score 10-15), the maximum dose should not exceed 40 mg/day 1

Drug Interaction Considerations

CYP3A4 Inhibitors

• Contraindicated with strong CYP3A4 inhibitors (ketoconazole, clarithromycin, ritonavir) 1
• If taking moderate CYP3A4 inhibitors (diltiazem, erythromycin, fluconazole, verapamil), reduce lurasidone dose to half the original level, with a starting dose of 20 mg/day and maximum of 80 mg/day 1

CYP3A4 Inducers

• May require dose increases when used with moderate CYP3A4 inducers 1

Rationale for This Approach

Why Start at 20mg Rather Than 40mg

Given the patient is currently on a low dose of aripiprazole (5mg), starting lurasidone at the lower end of the therapeutic range (20mg) minimizes the risk of adverse effects during the transition period 1. This is particularly important because:

• Aripiprazole 5mg is a relatively low dose (typical range 10-30mg for schizophrenia) 4
• The patient may be sensitive to antipsychotic effects
• Common lurasidone adverse effects include somnolence, akathisia, nausea, and parkinsonism, which are dose-related 5, 3, 6

Cross-Titration Strategy

The gradual taper of aripiprazole over 2 weeks while initiating lurasidone is based on a randomized switching study that demonstrated this approach successfully minimizes treatment failure 2. This study found:

• Treatment failure occurred in only 7.9% of patients using this switching strategy 2
• The gradual cross-titration allows time for receptor adaptation, as aripiprazole is a partial D2 agonist while lurasidone is a full D2 antagonist 4
• Abrupt discontinuation of aripiprazole could lead to withdrawal symptoms or symptom exacerbation

Monitoring During the Switch

Adverse Effects to Monitor

Watch for dose-related adverse effects, particularly: 5, 3, 6

• Akathisia (reported in 12.5% of patients, though discontinuation due to akathisia is rare at 0.4%) 2
• Somnolence (especially in the first 2 weeks)
• Nausea
• Parkinsonism/extrapyramidal symptoms

Metabolic Advantages

Lurasidone has a favorable metabolic profile compared to many antipsychotics: 5, 3, 6, 2

• Minimal weight gain
• No clinically meaningful alterations in glucose or lipids
• No QTc prolongation
• Mean improvements in weight and lipids have been observed during switching studies 2

Dose Titration After Initial Switch

If symptoms are not adequately controlled after the first week on lurasidone 20mg, the dose can be increased to 40mg, then further titrated in 20-40mg increments based on response and tolerability 1, 2. Flexible dosing between 20-120 mg/day can be implemented after the initial 2-week cross-titration period 2.