DangerousContraindicated
St. John's Wort
St. John's Wort is a strong CYP3A4 inducer and can markedly lower lurasidone exposure.
Recommendation: Do not combine St. John's Wort with lurasidone.
Lurasidone
Prescription ·Strong evidence ·Reviewed May 2026
Lurasidone is an atypical antipsychotic used for schizophrenia and bipolar depression. It must be taken with a meal of at least 350 calories for adequate absorption and is highly dependent on CYP3A4 metabolism. It carries boxed warnings for increased mortality in elderly patients with dementia-related psychosis and suicidal thoughts and behaviors in younger patients when used for bipolar depression.
What it's good for
The bottom line
Evidence rating strong. Most-documented uses: treatment of schizophrenia in adults and adolescents, treatment of bipolar depression as monotherapy or adjunctive therapy, lower average metabolic burden than some antipsychotics, though monitoring remains necessary. 3 sources indexed (2011–2025), with 4 interaction records on file.
The science
How it works, mechanistically.
Core mechanism
Lurasidone antagonizes dopamine D2 and serotonin 5-HT2A receptors and has additional activity at 5-HT7, 5-HT1A, and alpha-2C receptors. Antipsychotic and mood effects are attributed to dopamine-serotonin modulation. It is primarily metabolized by CYP3A4, so strong CYP3A4 inhibitors or inducers can produce unsafe exposure changes and are contraindicated.1,2
Class
Atypical antipsychotic
Absorption
Water-soluble; take with food
Dosing
Dosing & protocol.
Common range
Schizophrenia: commonly 40-160 mg once daily with food. Bipolar depression: commonly 20-120 mg once daily with food.
Recommended form
Oral tablet taken once daily with at least 350 calories
Must be taken with food containing at least 350 calories; fasting administration markedly lowers exposure and can reduce efficacy.
Safety
Full safety detail.
Side effects
- Somnolence
- Akathisia
- Nausea
- Parkinsonism or extrapyramidal symptoms
- Restlessness
- Insomnia
- Hyperprolactinemia
- Orthostatic hypotension
- Metabolic changes
- Neuroleptic malignant syndrome
- Tardive dyskinesia
Interactions
Interaction records.
ModerateCaution
Melatonin
Melatonin can add to lurasidone-related somnolence or dizziness.
Recommendation: Use cautiously and avoid hazardous activities if sedated.
ModerateCaution
L-Theanine
L-Theanine may add calming or sedating effects to lurasidone.
Recommendation: Use cautiously, especially during dose changes or if already sleepy.
ModerateCaution
Ashwagandha
Ashwagandha can cause sedation in some patients and may add to lurasidone's CNS effects.
Recommendation: Use cautiously and avoid combining with other sedatives unless approved by the prescriber.
Sources
Sources, by evidence tier.
Numbered references. Citations throughout the page link here.
Reviews & position papers
1- 1Lurasidone for the treatment of schizophrenia: a review of the efficacy and safety profileNeeds reviewNo linkCitrome L · Expert Opinion on Pharmacotherapy · 2011
Review summarizes antipsychotic efficacy and common adverse effects including akathisia and somnolence.
Reference material
2- 2LURASIDONE HYDROCHLORIDE tablets, US Prescribing InformationNeeds reviewURLU.S. National Library of Medicine · DailyMed · 2025
Labeling documents 350-calorie administration requirement, dosing, CYP3A4 contraindications, and boxed warnings.
- 3Effect of food on the pharmacokinetics of lurasidoneNeeds reviewNo linkPreskorn SH et al. · Clinical Pharmacology in Drug Development · 2013
Food-effect data support the 350-calorie administration requirement in labeling.
Keep exploring
Deep dives & adjacent profiles.
This page is educational. Do not start, stop, or change a supplement or medication based on it without checking with a qualified healthcare professional.
Use this with your stack
Lurasidone in NutriStack.
Add it to your stack, see how it interacts with everything else you take, and get a Stack Score that updates the moment it does.