lurasidone

General Information

Lurasidone (Latuda) is an second-generation antipsychotic (SGA) approved for schizophrenia in adults and adolescents as well as bipolar I depression in adults and children aged 10–17, notable for low metabolic impact and once-daily dosing.

Therapeutic exposure requires administration with a meal providing at least 350 calories—missed food intake can significantly reduce serum levels and efficacy.

Despite weight neutrality, lurasidone offers limited antimanic protection, so companion mood stabilizers or atypical antipsychotics are often used when manic/hypomanic relapse prevention is needed; longitudinal care can be coordinated through the bipolar disorder hub.

The compare tool to contrast meal requirements, metabolic profiles, and activation traits, and review the lurasidone evidence feed when considering switching therapy or adjusting augmentation.

Preferred in patients with cardiometabolic risk or prior weight gain on other SGAs; counseling often focuses on meal timing, managing akathisia/nausea, and avoiding interacting CYP3A4 agents.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Antagonizes dopamine D2/D3 receptors while sparing striatal occupancy compared with more metabolically burdensome SGAs, treating positive symptoms with low EPS risk.

Serotonin 5-HT2A/5-HT7 antagonism plus partial 5-HT1A agonism supports improvements in negative symptoms, mood, and cognition seen in schizophrenia and bipolar depression trials.

• Antagonist at dopamine D2 and D3 receptors.
• Antagonist at serotonin 5-HT2A, 5-HT7, and 5-HT1D receptors; partial agonist at 5-HT1A.
• Low affinity for histamine H1, muscarinic, and adrenergic α1 receptors limits sedation, anticholinergic effects, and orthostasis.

Metabolism and Pharmacokinetics

• Food increases lurasidone exposure roughly twofold; consistent dosing with meals helps avoid subtherapeutic levels.
• Approximately 99% protein bound with a distribution volume near 6.5 L/kg.
• Metabolized primarily by CYP3A4 to active metabolites (e.g., ID-14283, ID-14326) and inactive species.
• Parent half-life ≈18 hours; active metabolites persist 29–37 hours, enabling once-daily dosing.
• Eliminated mainly via feces (~80%) with ~9% urinary excretion as metabolites.

Dosing and Administration

• Adult schizophrenia: start 40 mg once daily with food; titrate in 40 mg increments to 40–160 mg/day based on response and tolerability.
• Adolescent schizophrenia (13–17): start 40 mg once daily with food; adjust to 40–80 mg/day.
• Adult bipolar depression: start 20 mg once daily; increase to 20–60 mg/day for monotherapy or up to 120 mg/day when adjuncting lithium/valproate.
• Pediatric bipolar depression (10–17): start 20 mg once daily; titrate to 20–80 mg/day.
• Moderate CYP3A4 inhibitors necessitate halving the dose (max 80 mg/day); strong CYP3A4 inhibitors/inducers are contraindicated. Limit to 80 mg/day in moderate/severe renal impairment and 40 mg/day in moderate/severe hepatic impairment.
• Missed doses should be taken as soon as remembered with food unless near the next scheduled dose; do not double the next dose.

Adverse Effects

Interactions

• Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) and inducers (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) are contraindicated; grapefruit products are typically avoided.
• Moderate CYP3A4 inhibitors (diltiazem, erythromycin, fluconazole) require dose reduction and close monitoring.
• Additive CNS depression occurs with alcohol, benzodiazepines, opioids, or other sedatives—driving and machinery precautions are commonly discussed.
• May diminish the effect of dopamine agonists in Parkinson’s disease; therapy adjustments are often coordinated with neurology teams.

Other Useful Information

• Meal timing strategies (pair doses with a reliable main meal) are often emphasized to support adherence and reduce GI upset.
• Weight, BMI, fasting lipids, and glucose are typically monitored at baseline and periodically despite favorable averages to remain consistent with SGA safety standards.
• Akathisia is often reassessed within 2–4 weeks of dose changes; early management can support adherence.
• Contraception and pregnancy plans are typically discussed; limited human data exist, so obstetrics coordination is common for risk–benefit decisions.
• Education for patients and care partners often covers recognizing mood changes or suicidality, particularly in younger populations being treated for bipolar depression.

References

1. LATUDA prescribing information — DailyMed (2026)
2. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia — American Psychiatric Association (2020)Guidelineschizophreniaclinical
3. Effectiveness OF Lurasidone VS. Quetiapine XR FOR Relapse Prevention IN Schizophrenia: A 12 Month, Double Blind, Noninferiority Study — Schizophrenia Research (2013)
4. Lurasidone Monotherapy IN Bipolar I Depression: A Randomized, Double Blind, Placebo Controlled Study — American Journal of Psychiatry (2014)
5. Long Term Safety AND Effectiveness OF Lurasidone IN Schizophrenia — Schizophrenia Research (2016)
6. The CANMAT and ISBD Guidelines for the Management of Patients With Bipolar Disorder: 2021 Update — Bipolar Disorders (2021)Guidelinebipolarclinical