Lurasidone (Latuda) Clinical Indications
FDA-Approved Indications
Lurasidone is FDA-approved for bipolar I depression in adults and adolescents (10-17 years), both as monotherapy and as adjunctive therapy with lithium or valproate. 1
Bipolar I Depression (Primary Indication)
- Adult dosing: Start at 20 mg once daily with food (at least 350 calories); effective range 20-120 mg/day, with no initial titration required 1
- Pediatric dosing (10-17 years): Start at 20 mg once daily; may increase after one week based on response; effective range 20-80 mg/day, with most patients (67%) maintained on 20-40 mg/day 1
- Adjunctive therapy: When combined with lithium or valproate, use the same dosing strategy (20-120 mg/day in adults) 1
- Food administration is mandatory—absorption increases 2-fold (AUC) and 3-fold (Cmax) when taken with food 1
Schizophrenia (Off-Label in This Context)
- Lurasidone is approved for schizophrenia in the US and Europe, with an effective dose range of 40-160 mg/day 2, 3
- The recommended starting dose for schizophrenia is 40 mg/day, with no initial titration required 2
Clinical Scenarios Where Lurasidone Excels
Metabolic Syndrome or Weight Concerns
Lurasidone is the most weight-neutral atypical antipsychotic, making it the preferred first-line choice for patients with obesity, diabetes, or metabolic syndrome. 4
- Minimal weight gain compared to olanzapine, quetiapine, or risperidone 2, 3
- No clinically meaningful alterations in glucose, lipids, or ECG QTc interval 2
- Metabolic syndrome rates comparable to placebo 5
Previous Positive Response
Lurasidone is a rational first-line choice for patients with previous positive response, as prior response is a strong predictor of future response. 4
First-Episode Psychosis (Emerging Evidence)
- Lurasidone shows promise in cannabis-induced psychosis, with effective doses of 74-128 mg/day demonstrating good tolerability and remission of positive/negative symptoms 6
- Its favorable metabolic and neurocognitive profile makes it particularly suitable for youth with first-episode psychosis 3, 6
Cognitive Function Preservation
- Lurasidone has a relatively benign neurocognitive side effect profile compared to other atypicals 3
- Patients switching to lurasidone may experience improvements in ability to focus/concentrate 3
Important Clinical Considerations
Administration Requirements
- Must be taken with food (≥350 calories) to ensure adequate absorption—this is non-negotiable 1
- Once-daily dosing improves adherence 2
Dose Adjustments
- Renal impairment: Start at 20 mg/day; maximum 80 mg/day in moderate (CrCl 30-50 mL/min) or severe (CrCl <30 mL/min) impairment 1
- No initial titration required in bipolar depression, unlike many other antipsychotics 1
Common Side Effects
- Most common adverse events: somnolence, akathisia, nausea, and parkinsonism 2
- Most side effects are transitory and manageable with dose adjustment 3
- Akathisia and extrapyramidal symptoms occur in a minority but respond to dose adjustment or adjunctive therapy 3
Critical Pitfalls to Avoid
- Never use lurasidone for acute mania—efficacy in mania has not been established 1
- Never administer without food—this dramatically reduces bioavailability 1
- Lurasidone is not approved for dementia-related psychosis due to increased mortality risk 1
- Monitor for suicidal thoughts/behaviors, particularly in pediatric and young adult patients 1
Comparison to Other Atypicals
- Superior metabolic profile compared to olanzapine, quetiapine, and risperidone 4, 2, 3
- Lower propensity for hyperprolactinemia than most other atypicals 3
- As effective as other atypical agents (with possible exception of clozapine) for schizophrenia 3
- Efficacy in bipolar depression demonstrated with clinically meaningful effect sizes (0.51 monotherapy, 0.34 adjunct) and NNT of 5-7 7