Lurasidone (Latuda)

SGA • Last reviewed 2025-09-23

General information

Lurasidone is an atypical antipsychotic approved for schizophrenia in adults and adolescents, and bipolar depression (monotherapy or adjunct to lithium/valproate). Marketed as LATUDA, it was approved in 2010 (schizophrenia) and 2013 (bipolar depression).

Available as tablets (20, 40, 60, 80, 120 mg), lurasidone must be taken with food (at least 350 calories) to ensure adequate absorption. Schizophrenia dosing starts at 40 mg once daily and can be titrated to 80-160 mg/day. Bipolar depression dosing typically ranges from 20-120 mg/day.

Mechanistically, lurasidone is a potent D2 and 5-HT2A antagonist with high affinity for 5-HT7 receptors (antagonist) and partial agonist at 5-HT1A receptors. It has low affinity for H1 and M1 receptors, leading to minimal sedation and anticholinergic effects.

Lurasidone is metabolized primarily by CYP3A4; the elimination half-life is about 18 hours. Active metabolites contribute minimally to efficacy.

Dosing & administration

Schizophrenia: start 40 mg once daily with food; usual range 40-160 mg/day.

Bipolar depression: start 20 mg once daily with food; titrate to 20-120 mg/day based on response.

CYP3A4 inhibitors require dose reduction; avoid strong inducers.

Renal or hepatic impairment necessitates lower starting and maximum doses.

Dose adjustments

Moderate renal impairment (CrCl 30-<50): Start 20 mg/day; maximum 80 mg/day.
Moderate hepatic impairment: Start 20 mg/day; maximum 80 mg/day.
Severe hepatic impairment: Start 20 mg/day; maximum 40 mg/day.
Strong CYP3A4 inhibitors: Reduce dose to half; do not exceed 40 mg/day.

Mechanism of action

Lurasidone antagonizes dopamine D2 receptors, reducing positive symptoms, and antagonizes 5-HT2A receptors, mitigating EPS. High affinity for 5-HT7 receptors may improve cognition and circadian regulation.

Partial agonism at 5-HT1A receptors contributes to anxiolytic and antidepressant effects, supporting efficacy in bipolar depression.

D2 Ki ~1.7 nM, 5-HT2A Ki ~0.5 nM.
5-HT7 Ki ~0.5 nM (antagonist), 5-HT1A partial agonist Ki ~6.4 nM.
Minimal affinity for H1 and M1 receptors -> low sedation and anticholinergic effects.

Metabolism & pharmacokinetics

Bioavailability increases 2-3 fold when taken with food; advise patients to take with at least 350 calories.

Peak concentrations occur 1-3 hours post-dose; half-life ~18 hours; steady state reached in 7 days.

Tmax: 1-3 h
Half-life: ~18 h
Food effect: Cmax/AUC increase 2-3 fold with ≥350-calorie meal

Drug interactions

Strong CYP3A4 inhibitors (ketoconazole) markedly increase exposure; dose reduction or avoidance required.

Strong CYP3A4 inducers (rifampin, carbamazepine) decrease levels; contraindicated.

Moderate inhibitors (diltiazem) require dose reduction.

Mechanism	Agents / factors	Management
CYP3A4 inhibition	Ketoconazole, clarithromycin	Reduce dose to 20 mg/day (max 40 mg).
CYP3A4 induction	Carbamazepine, rifampin	Contraindicated.
Hypotension	Antihypertensives	Monitor blood pressure during titration.

Monitoring & safety checks

Weight, metabolic labs
Baseline and periodically • Weight gain minimal but monitor per guidelines.
Prolactin-related symptoms
Each visit • Slight elevations possible but usually mild.
EPS/akathisia
Each visit • Akathisia occurs in up to ~14%; monitor and manage early.

Advise taking with evening meal to reduce daytime sedation.

Educate about nausea risk when taken without food.

Discontinuation guidance

Taper over 1-2 weeks to reduce relapse risk, though withdrawal symptoms are uncommon.

Monitor for return of depressive or psychotic symptoms within 1-2 weeks.

Special populations

Pregnancy: limited human data; use only if benefits justify risks; consider neonatal monitoring for EPS/withdrawal if exposure late in pregnancy.

Older adults: start at 20 mg/day; monitor for orthostasis and EPS.

Renal/hepatic impairment: adjust per prescribing guidelines (max 80 mg/day in moderate impairment).

Adverse effects

Common: akathisia, nausea, somnolence, agitation.

Weight gain and metabolic changes are modest compared with other SGAs.

Rare: tardive dyskinesia, neuroleptic malignant syndrome.

References

LATUDA (lurasidone) prescribing information — Sunovion Pharmaceuticals (2024)
Lurasidone in schizophrenia and bipolar depression — Journal of Psychopharmacology (2017) DOI: 10.1177/0269881117736914
Randomized controlled trials of lurasidone — Journal of Clinical Psychiatry (2014) DOI: 10.4088/JCP.13m08633

Educational use only — verify details in current prescribing information and authoritative clinical guidelines before making prescribing decisions.