What is the recommended dosage and treatment approach for Lurasidone (Lurasidone) in patients with schizophrenia or bipolar disorder?

Lurasidone Dosage and Treatment Approach for Schizophrenia and Bipolar Disorder

For patients with schizophrenia, lurasidone should be started at 40 mg once daily with food, with a recommended dose range of 40-160 mg/day, while for bipolar depression, the recommended starting dose is 20 mg once daily with a maximum of 120 mg/day for adults and 80 mg/day for pediatric patients (10-17 years). 1

Dosing for Schizophrenia

• The recommended starting dose for schizophrenia is 40 mg once daily 1, 2
• Dose range of 40-160 mg/day has been established as effective in multiple 6-week clinical trials 3
• Initial dose titration is not required, but dose adjustments may be made based on clinical response 1, 2
• Doses above 80 mg/day may not provide additional benefits for some patients and could increase the risk of adverse effects such as somnolence and akathisia 2
• For treatment-resistant schizophrenia, an adequate trial should last at least 6 weeks at therapeutic doses before considering it a failed trial 4

Dosing for Bipolar Disorder

• For adults with bipolar depression, the recommended starting dose is 20 mg once daily, either as monotherapy or as adjunctive therapy with lithium or valproate 1
• Effective dose range for adults is 20-120 mg/day, with the maximum recommended dose being 120 mg/day 1
• For pediatric patients (10-17 years) with bipolar depression, the starting dose is 20 mg once daily as monotherapy, with a maximum dose of 80 mg/day 1
• Most pediatric patients (67%) in clinical trials received 20-40 mg once daily 1
• Lurasidone has not been established as effective for the treatment of mania in bipolar disorder 1

Administration Requirements

• Lurasidone must be taken with food (at least 350 calories) 1, 2
• Administration with food substantially increases absorption, with approximately 2-fold increase in AUC and 3-fold increase in Cmax 1
• Once-daily dosing regimen is a principal advantage over some other antipsychotics 3

Dose Adjustments for Special Populations

• For patients with moderate renal impairment (creatinine clearance: 30 to <50 mL/min) or severe renal impairment (creatinine clearance <30 mL/min):

  • Starting dose should be 20 mg/day
  • Maximum dose should not exceed 80 mg/day 1

• For patients with moderate hepatic impairment (Child-Pugh Score = 7 to 9):

  • Starting dose should be 20 mg/day
  • Maximum dose should not exceed 80 mg/day 1

• For patients with severe hepatic impairment (Child-Pugh Score = 10 to 15):

  • Starting dose should be 20 mg/day
  • Maximum dose should not exceed 40 mg/day 1

Drug Interactions

• Lurasidone should not be used concomitantly with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir) 1, 2
• When used with moderate CYP3A4 inhibitors (e.g., diltiazem, erythromycin):
  • Reduce lurasidone dose to half of the original dose
  • If adding lurasidone to a moderate CYP3A4 inhibitor, start at 20 mg/day with a maximum of 80 mg/day 1
• Strong CYP3A4 inducers (e.g., rifampin) are contraindicated with lurasidone 2

Treatment Duration and Monitoring

• The effectiveness of lurasidone for longer-term use (more than 6 weeks) has not been established in controlled studies for schizophrenia 1
• Physicians should periodically re-evaluate the long-term usefulness of the drug for individual patients 1
• For bipolar disorder, lithium is approved for maintenance therapy in patients aged 12 years and older 4
• Long-term studies have shown that lurasidone was noninferior to quetiapine extended-release in preventing relapse and superior in avoiding hospitalization (NNT 8) and achieving remission (NNT 7) 5

Safety Profile and Side Effects

• Most common adverse events with lurasidone are somnolence, akathisia, nausea, and parkinsonism 3, 6
• Lurasidone has a favorable metabolic profile with minimal weight gain and no clinically meaningful alterations in glucose, lipids, or ECG QT interval 3, 2, 6
• Higher rates of akathisia, parkinsonism, and hyperprolactinemia may occur compared to some other atypical antipsychotics 6, 7
• Lower risk for sedation and weight gain compared to other atypical antipsychotics 6, 7

Treatment Approach Algorithm

1. Confirm diagnosis of schizophrenia or bipolar depression

2. Assess for contraindications and potential drug interactions

3. For schizophrenia:

   • Start with 40 mg once daily with food
   • Evaluate response after 4-6 weeks
   • If inadequate response, consider dose adjustment up to 160 mg/day 4
   • If still inadequate after two antipsychotic trials, consider clozapine 4

4. For bipolar depression:

   • Start with 20 mg once daily with food
   • For adults, may increase up to 120 mg/day based on response
   • For pediatric patients (10-17 years), may increase up to 80 mg/day 1
   • Consider as monotherapy or adjunctive therapy with lithium or valproate 1

5. Monitor for common side effects, particularly akathisia, and adjust dose if needed

6. Regularly assess metabolic parameters, though risks are lower than with many other antipsychotics 3, 2