Lurasidone

證據等級: L5

預測適應症: 10 個

Lurasidone: From Schizophrenia to Manic Bipolar Affective Disorder

One-Sentence Summary

Lurasidone (development code SM-13496) is a second-generation atypical antipsychotic originally used to treat schizophrenia. The TxGNN model predicts it may be effective for Manic Bipolar Affective Disorder (Bipolar Disorder), with 15 clinical trials and 19 publications currently supporting this direction.

Quick Overview

Item	Content
Original Indication	Schizophrenia (per literature evidence; no German market authorization data available to confirm approved label indication)
Predicted New Indication	Manic Bipolar Affective Disorder
TxGNN Prediction Score	99.98%
Evidence Level	L1
Germany Market Status	Not Marketed
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, structured mechanism-of-action data is not available in the regulatory record (marked as Data Gap). However, the evidence pack's repurposing rationale confirms that Lurasidone (development code SM-13496) is a second-generation atypical antipsychotic that primarily antagonizes D2 and 5-HT2A/5-HT7 receptors — a receptor profile shared by other agents used in bipolar disorder management.

Schizophrenia and bipolar affective disorder are both severe psychiatric conditions that respond to dopaminergic/serotonergic modulation, and atypical antipsychotics as a class are commonly repurposed across these two indications. Clinically, Lurasidone has already received regulatory approval in multiple countries (including the US) for bipolar I depression, both as monotherapy and as adjunctive therapy with lithium or divalproex — this is independently confirmed in the literature evidence (e.g., PMID 31957501, PMID 24170243), not merely a model-generated hypothesis. This real-world precedent strongly supports the plausibility of the TxGNN prediction.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT01358357	Phase 3	Completed	965	Lurasidone adjunctive to lithium/divalproex for prevention of recurrence in bipolar I disorder
NCT01986101	Phase 3	Completed	525	SM-13496 (lurasidone) vs. placebo, pivotal trial in bipolar I depression
NCT01914393	Phase 3	Completed	702	104-week open-label extension evaluating long-term safety/effectiveness in pediatric bipolar patients
NCT01986114	Phase 3	Completed	495	Long-term efficacy and safety of SM-13496 (lurasidone) in bipolar I disorder
NCT01575561	Phase 3	Completed	377	Open-label extension of lurasidone adjunctive to lithium/divalproex in bipolar I disorder
NCT02046369	Phase 3	Completed	350	Randomized, double-blind, placebo-controlled trial of lurasidone in children/adolescents with bipolar I depression
NCT06433635	Phase 4	Active, not recruiting	2726	Large SMART trial comparing lurasidone, cariprazine, quetiapine, and aripiprazole/escitalopram for bipolar depression
NCT04383691	Phase 3	Terminated	124	Randomized, placebo-controlled flexible-dose study of lurasidone for bipolar I depression (terminated early)
NCT02731612	Phase 3	Completed	100	Lurasidone adjunctive therapy for cognitive functioning in euthymic bipolar I/II patients (ELICE-BD)
NCT02147379	Phase 3	Completed	53	Lurasidone vs. treatment-as-usual for cognitive functioning in euthymic bipolar patients

Literature Evidence

PMID	Year	Type	Journal	Key Findings
39557452	2024	Review (Meta-analysis)	BMJ Mental Health	Systematic review and dose-response meta-analysis of lurasidone efficacy/acceptability in bipolar depression
37595997	2023	Review (Network Meta-analysis)	Lancet Psychiatry	Comparative efficacy/tolerability of pharmacological interventions (incl. lurasidone) for acute bipolar depression
31957501	2020	Review	Expert Opinion on Pharmacotherapy	Evaluates lurasidone as a treatment option for bipolar I depression, monotherapy and adjunct use
29536616	2018	Review (Guideline)	Bipolar Disorders	CANMAT/ISBD 2018 guidelines for management of bipolar disorder
34599629	2021	Review (Guideline)	Bipolar Disorders	CANMAT/ISBD recommendations for bipolar disorder with mixed presentations
37815563	2023	Review	JAMA	Diagnosis and treatment overview of bipolar disorder
24170243	2014	Commentary	American Journal of Psychiatry	Commentary confirming lurasidone's approved use in bipolar disorder
25963405	2016	Review	Asia-Pacific Psychiatry	Discusses lurasidone (with quetiapine) as FDA-approved for bipolar depression
33177610	2021	Review (Network Meta-analysis)	Molecular Psychiatry	Antipsychotics/mood stabilizers for bipolar disorder maintenance phase
40808269	2025	Review (Consensus)	Bipolar Disorders	ISBD Task Force consensus recommendations on treatment-resistant bipolar depression

Germany Market Information

Lurasidone currently has no market authorization on record in Germany (market status: Not Marketed, 0 authorizations). No BfArM license entries are available in this evidence pack to summarize.

Safety Considerations

Please refer to the package insert for safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: The evidence base is strong (L1) — multiple completed Phase 3 RCTs specifically on Lurasidone in bipolar I depression (e.g., NCT01986101, n=525; NCT01358357, n=965; NCT02046369, n=350) plus consistent literature support, and Lurasidone is already approved for bipolar depression in other markets. However, the drug is not currently marketed in Germany and key safety/regulatory data (TFDA/BfArM label warnings, contraindications, MOA confirmation) remain unresolved data gaps that block full safety evaluation (S1).

To proceed, the following is needed:

Official German (BfArM) package insert — warnings, contraindications, and precautions (DG001, blocking)
Confirmed mechanism-of-action documentation from DrugBank or manufacturer (DG002)
Assessment of German market authorization pathway, since the drug is not currently marketed
Drug-drug interaction (DDI) data, as none is currently available
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.