Lurasidone

• Schizophrenia
• Bipolar Depression
• Bipolar I Disorder

Lurasidone is an atypical antipsychotic medication approved for the treatment of schizophrenia and bipolar depression. It offers a favorable metabolic profile compared to many other second-generation antipsychotics, making it an attractive option for patients requiring long-term antipsychotic therapy.

Mechanism of Action

Lurasidone functions as an antagonist at multiple receptor types:

• Dopamine D2 receptors: Primary mechanism for antipsychotic effects
• Serotonin 5-HT2A receptors: Contributes to reduced extrapyramidal symptoms
• Serotonin 5-HT7 receptors: May contribute to antidepressant and procognitive effects
• Alpha-2C adrenergic receptors: May enhance cognitive function

The drug has minimal affinity for histamine H1 and muscarinic M1 receptors, which accounts for its favorable metabolic and anticholinergic profile.

Available Formulations

Lurasidone is available as oral tablets:

• 20 mg tablets
• 40 mg tablets
• 60 mg tablets
• 80 mg tablets
• 120 mg tablets

All tablets should be taken with food (at least 350 calories) to ensure adequate absorption.

Medical Uses

FDA-Approved Indications:

• Schizophrenia in adults and adolescents (13-17 years)
• Bipolar depression (depressive episodes associated with bipolar I disorder) as monotherapy or adjunctive therapy with lithium or valproate in adults
• Bipolar depression in children and adolescents (10-17 years)

Lurasidone is particularly valuable for bipolar depression given limited treatment options for this phase of the illness.

Dosing Guidelines

Schizophrenia (Adults):

• Starting dose: 40 mg once daily
• Recommended range: 40-160 mg once daily
• Maximum: 160 mg/day

Schizophrenia (Adolescents 13-17 years):

• Starting dose: 40 mg once daily
• Recommended range: 40-80 mg once daily
• Maximum: 80 mg/day

Bipolar Depression:

• Starting dose: 20 mg once daily
• Recommended range: 20-120 mg once daily (monotherapy) or 20-80 mg (adjunctive)

Important Safety Information

Black Box Warnings:

• Increased risk of death in elderly patients with dementia-related psychosis
• Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults

Contraindications:

• Known hypersensitivity to lurasidone
• Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole) or inducers (e.g., rifampin)

Warnings and Precautions:

• Neuroleptic malignant syndrome
• Tardive dyskinesia
• Metabolic changes (monitor weight, glucose, lipids)
• Orthostatic hypotension
• Leukopenia and neutropenia
• Seizures

Drug Interactions

• Strong CYP3A4 inhibitors (ketoconazole, clarithromycin): Contraindicated
• Strong CYP3A4 inducers (rifampin, carbamazepine): Contraindicated
• Moderate CYP3A4 inhibitors (diltiazem): Reduce lurasidone dose by half
• Grapefruit and grapefruit juice: Avoid

Special Populations

• Hepatic Impairment: Reduce dose; maximum 80 mg/day for moderate impairment, 40 mg/day for severe
• Renal Impairment: Maximum 80 mg/day for moderate to severe impairment
• Elderly: Use lower starting doses
• Pregnancy: May cause extrapyramidal symptoms and withdrawal in neonates