What diagnoses indicate the need for Lurasidone (lurasidone) in adults and adolescents?

Diagnoses Indicating Need for Lurasidone

Lurasidone is FDA-approved for two specific indications: depressive episodes associated with Bipolar I Disorder (bipolar depression) in adults and pediatric patients (10-17 years) as monotherapy, and as adjunctive therapy with lithium or valproate in adults with bipolar depression. 1

FDA-Approved Indications

Bipolar I Disorder - Depressive Episodes

Primary indication: Lurasidone is specifically indicated for treating depressive episodes in patients with Bipolar I Disorder, not for acute mania or maintenance therapy 1, 2.

Adult Patients

• Monotherapy: 20-120 mg per day for bipolar depression 1
• Adjunctive therapy: Combined with lithium or valproate for bipolar depression 1
• Must be taken with food (at least 350 calories) to ensure adequate absorption 1

Pediatric Patients (Ages 10-17)

• Monotherapy only: 20-80 mg per day for bipolar depression 1
• Starting dose: 20 mg per day 1
• No FDA approval for adjunctive therapy in this age group 1

Clinical Evidence for Bipolar Depression

Lurasidone demonstrated significant efficacy in two large 6-week trials for bipolar I depression, improving Montgomery-Åsberg Depression Rating Scale (MADRS) scores and Clinical Global Impression-Bipolar Severity depression scores compared to placebo. 2

• Discontinuation rates due to adverse events were small (<7%) and comparable to placebo 2
• Most common adverse events: headache, nausea, somnolence, and akathisia 2
• Minimal changes in lipid profiles, weight, and glycemic control parameters 2

Off-Label Use: Schizophrenia

While lurasidone is FDA-approved for schizophrenia in the United States (October 2010), the evidence provided focuses on its use for this indication 3, 4, 5.

Schizophrenia Treatment Parameters

• Effective dose range: 80-160 mg daily for acute schizophrenia 3
• Initial dosing: Can start at 80 mg, with incremental increases to 160 mg as condition severity increases 3
• Depressive symptoms in schizophrenia: Lurasidone significantly improved depressive symptoms (MADRS scores) in patients with schizophrenia across multiple pooled studies 5

Efficacy Profile in Schizophrenia

• Doses of 80 mg, 120 mg, and 160 mg showed significant improvements in Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression of Severity (CGI-S) scores compared to placebo 3
• The 40 mg dose did not show significant efficacy differences from placebo 3
• Lurasidone is as effective as other atypical antipsychotics, with possible exception of clozapine 4

Critical Contraindications

Lurasidone is absolutely contraindicated in the following situations: 1

• Known hypersensitivity to lurasidone or any formulation components 1
• Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole) 1
• Concomitant use with strong CYP3A4 induces (e.g., rifampin) 1

Special Population Considerations

Renal Impairment

• Moderate to severe renal impairment: Starting dose 20 mg/day, maximum 80 mg/day 1

Hepatic Impairment

• Moderate hepatic impairment: Starting dose 20 mg/day, maximum 80 mg/day 1
• Severe hepatic impairment: Starting dose 20 mg/day, maximum 40 mg/day 1

Drug Interactions

• Moderate CYP3A4 inhibitors (e.g., diltiazem): Reduce lurasidone dose to half the original level; starting dose 20 mg/day, maximum 80 mg/day 1
• Moderate CYP3A4 inducers: May require dose increase 1

Important Safety Warnings

Boxed Warnings

1. Elderly patients with dementia-related psychosis: Increased mortality risk; lurasidone is NOT approved for this population 1
2. Suicidal thoughts and behaviors: Increased risk in pediatric and young adult patients; requires close monitoring for clinical worsening 1

Common Adverse Reactions (≥5% incidence, at least twice placebo rate)

• Adults with bipolar depression: Akathisia, extrapyramidal symptoms, somnolence 1
• Pediatric patients (10-17 years) with bipolar depression: Nausea, weight increase, insomnia 1

Clinical Context from Guidelines

The American Academy of Child and Adolescent Psychiatry recognizes lurasidone as a rational first-line choice for patients with bipolar depression who have had previous positive response to the medication. 6

• Antipsychotic agents are recommended for psychotic symptoms associated with schizophrenia, with atypical antipsychotics being at least as effective as traditional neuroleptics for positive symptoms 7
• For bipolar disorder, combination therapy with mood stabilizers may be appropriate, though lurasidone's FDA approval includes both monotherapy and adjunctive use 6, 1

Common Pitfalls to Avoid

• Never use lurasidone for acute mania: It is only indicated for the depressive phase of Bipolar I Disorder 1
• Always administer with food: Absorption is substantially increased with at least 350 calories 1
• Avoid in dementia-related psychosis: This carries a boxed warning for increased mortality 1
• Monitor for akathisia and extrapyramidal symptoms: These occur in a minority but can be managed with dose adjustment 4
• Do not combine with strong CYP3A4 inhibitors or inducers: This is an absolute contraindication 1