Introduction
Latuda (lurasidone hydrochloride) is an atypical antipsychotic medication approved by the FDA in 2010. It belongs to the benzisothiazole class and is primarily indicated for the treatment of schizophrenia and bipolar depression. Latuda offers a favorable metabolic profile compared to some other antipsychotics, making it an important option in psychiatric pharmacotherapy.
Mechanism of Action
Lurasidone exerts its therapeutic effects through antagonism at dopamine D₂ and serotonin 5-HT₂A receptors. It also has partial agonist activity at serotonin 5-HT₁A receptors and antagonizes adrenergic α₂C and α₂A receptors. Unlike many other atypical antipsychotics, lurasidone has minimal affinity for muscarinic M₁ receptors, which accounts for its low incidence of anticholinergic side effects. The drug's antidepressant effects in bipolar disorder are thought to be mediated through its combined serotonergic and dopaminergic activity.
Indications
- Treatment of schizophrenia in adults and adolescents (13-17 years)
- Monotherapy treatment of bipolar I depression in adults and pediatric patients (10-17 years)
- Adjunctive therapy with lithium or valproate for bipolar I depression in adults
Dosage and Administration
Schizophrenia:- Adults: Initial dose 40 mg once daily, maximum 80 mg/day
- Adolescents: Initial dose 40 mg once daily, maximum 80 mg/day
- Adults: Initial dose 20 mg once daily, range 20-120 mg/day
- Pediatrics (10-17 years): Initial dose 20 mg once daily, maximum 80 mg/day
- Must be taken with food (at least 350 calories)
- Tablet should be swallowed whole
- Dosage adjustments required in moderate-to-severe renal/hepatic impairment
- Elderly patients: Consider lower starting doses
Pharmacokinetics
Absorption: Time to peak concentration (Tmax) 1-3 hours; bioavailability 9-19% (increased with food) Distribution: Volume of distribution ~6173 L; >99% protein bound Metabolism: Primarily via CYP3A4; main metabolites are inactive Elimination: Half-life ~18 hours; excreted primarily in feces (80%) and urine (9%)Contraindications
- Known hypersensitivity to lurasidone or any component of the formulation
- Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole) or inducers (e.g., rifampin)
- Patients with preexisting severe gastrointestinal narrowing
Warnings and Precautions
Boxed Warning: Increased mortality in elderly patients with dementia-related psychosis- Suicidal thoughts and behaviors
- Cerebrovascular adverse events in elderly patients with dementia
- Neuroleptic malignant syndrome
- Tardive dyskinesia
- Metabolic changes (hyperglycemia, dyslipidemia, weight gain)
- Orthostatic hypotension and syncope
- Leukopenia, neutropenia, agranulocytosis
- Seizures
- Cognitive and motor impairment
- Dysphagia
- Hyperprolactinemia
Drug Interactions
Major Interactions:- Strong CYP3A4 inhibitors: Contraindicated (increase lurasidone exposure)
- Strong CYP3A4 inducers: Contraindicated (decrease lurasidone exposure)
- Moderate CYP3A4 inhibitors: Reduce lurasidone dose by 50%
- Other CNS depressants: Additive sedation
Adverse Effects
Common (≥5%):- Somnolence (22-27%)
- Akathisia (13-22%)
- Nausea (10-17%)
- Parkinsonism (5-11%)
- Neuroleptic malignant syndrome
- Tardive dyskinesia
- Metabolic syndrome
- Hyperglycemia/diabetes mellitus
- Orthostatic hypotension
- Seizures
- Leukopenia/neutropenia
Monitoring Parameters
- Mental status and symptom improvement
- Extrapyramidal symptoms and akathisia
- Weight and BMI at baseline and regularly
- Fasting blood glucose and lipid panel at baseline and periodically
- Blood pressure (sitting and standing)
- CBC with differential (if clinical signs of infection)
- Prolactin levels if symptoms emerge
- Assessment for tardive dyskinesia
Patient Education
- Take with food (at least 350 calories) to ensure proper absorption
- Do not crush or chew tablets
- Avoid alcohol and other CNS depressants
- Rise slowly from sitting/lying position to prevent dizziness
- Report any unusual movements, muscle stiffness, or fever immediately
- Monitor for changes in mood or behavior, especially suicidal thoughts
- Be aware of potential sedation and avoid driving until effects are known
- Notify all healthcare providers about Latuda use
- Do not stop taking abruptly without medical supervision
References
1. FDA Prescribing Information: Latuda (lurasidone hydrochloride) 2. Loebel A, et al. Efficacy and safety of lurasidone 80 mg/day and 160 mg/day in the treatment of schizophrenia. J Clin Psychiatry. 2013;74(8):80-812. 3. Sanford M. Lurasidone: in bipolar I depression. CNS Drugs. 2013;27(1):67-79. 4. Citrome L. Lurasidone for schizophrenia: a review of the efficacy and safety profile for this newly approved second-generation antipsychotic. Int J Clin Pract. 2011;65(2):189-210. 5. Nakamura M, et al. Lurasidone in the treatment of bipolar depression: systematic review and meta-analysis. J Clin Psychopharmacol. 2020;40(4):386-393. 6. Meyer JM, et al. The metabolic safety of lurasidone. J Clin Psychiatry. 2021;82(2):20m13533.