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 (Latuda) is a second-generation atypical antipsychotic approved in the US and multiple markets for schizophrenia and bipolar I depression, but not yet registered in India. The TxGNN model predicts it may be effective for Manic Bipolar Affective Disorder, with 15 clinical trials and 20 publications currently supporting this direction.

Quick Overview

Item	Content
Original Indication	Schizophrenia / Bipolar I Depression (global approval; not registered in India)
Predicted New Indication	Manic Bipolar Affective Disorder
TxGNN Prediction Score	99.98%
Evidence Level	L1
India Market Status	✗ Not Marketed
Number of Registrations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Formal DrugBank MOA data was not retrieved in this Evidence Pack; however, Lurasidone’s pharmacological profile is well characterised in the clinical literature. It acts as a high-affinity antagonist at dopamine D2 receptors, serotonin 5-HT2A and 5-HT7 receptors, and as a partial agonist at 5-HT1A receptors. D2 antagonism suppresses dopamine hyperactivation that drives manic symptoms; 5-HT7 antagonism confers antidepressant properties during the depressive phases of bipolar illness; 5-HT2A antagonism promotes mood stabilisation and improved sleep architecture; and 5-HT1A partial agonism provides a degree of cognitive protection. This multi-receptor profile maps closely onto the neurobiological substrate of bipolar disorder and explains the high TxGNN prediction score.

The conceptual leap from schizophrenia to manic bipolar affective disorder is small: both conditions share dysregulated dopaminergic and serotonergic circuits, and second-generation antipsychotics are already first-line agents for acute mania in international guidelines (CANMAT/ISBD 2018). Lurasidone’s relatively neutral metabolic profile — lower weight gain and minimal QTc prolongation compared to quetiapine or olanzapine — gives it a practical advantage for long-term use in a patient population already at elevated cardiometabolic risk.

Crucially, Lurasidone has already obtained regulatory approval for bipolar I depression in the US (FDA, 2013) and Japan (2020), and multiple Phase 3 RCTs covering both the depressive and maintenance phases of bipolar I disorder have been completed successfully. The TxGNN prediction for the broader manic bipolar affective disorder classification is therefore not a speculative extrapolation but is robustly anchored in a mature and expanding clinical evidence base.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT01358357	Phase 3	Completed	965	Largest RCT: Lurasidone adjunctive to lithium or divalproex for prevention of recurrence in Bipolar I Disorder, with or without rapid cycling
NCT06433635	Phase 4	Active, not recruiting	2,726	SMART pragmatic trial comparing Lurasidone, Cariprazine, Quetiapine, and Aripiprazole/Escitalopram for bipolar depression; real-world comparative effectiveness
NCT01986101	Phase 3	Completed	525	SM-13496 (Japanese development code for Lurasidone) vs placebo in Bipolar I Depression; double-blind, pivotal Asian registration trial
NCT01986114	Phase 3	Completed	495	Long-term efficacy and safety of SM-13496 in Bipolar I Disorder; supports sustained benefit and tolerability over extended treatment
NCT01914393	Phase 3	Completed	702	104-week open-label extension evaluating long-term safety and effectiveness of Lurasidone in paediatric subjects across multiple studies
NCT02046369	Phase 3	Completed	350	Lurasidone in children and adolescents (6–17 years) with Bipolar I Depression; double-blind, placebo-controlled, flexible dose
NCT01575561	Phase 3	Completed	377	Open-label 12-week extension of the adjunctive Lurasidone + Li/VPA study; longer-term safety and tolerability in Bipolar I
NCT02731612	Phase 3	Completed	100	ELICE-BD: randomised, double-blind assessment of Lurasidone’s cognitive effects in euthymic Bipolar I/II patients; adjunctive design
NCT02147379	Phase 3	Completed	53	Open-label randomised study of Lurasidone add-on vs treatment-as-usual on cognitive functioning in remitted Bipolar I patients
NCT04383691	Phase 3	Terminated	124	Lurasidone vs placebo in Bipolar I Depression; terminated early (non-safety reason), limiting standalone evidential weight

Literature Evidence

PMID	Year	Type	Journal	Key Findings
39557452	2024	SR + Dose-Response Meta-analysis	BMJ Mental Health	Examined dose-response relationship of Lurasidone for efficacy, acceptability, and metabolic/endocrine profiles in bipolar depression; clarifies optimal dosing strategy
37595997	2023	Network Meta-analysis	Lancet Psychiatry	Comparative efficacy and tolerability of pharmacological interventions for acute bipolar depression; positions Lurasidone among top-ranked agents
38487836	2024	Network Meta-analysis	European Psychiatry	Bayesian NMA of 16 RCTs (n=7,234); compared five FDA-approved atypical antipsychotics for bipolar depression, including Lurasidone
33177610	2021	SR + Network Meta-analysis	Molecular Psychiatry	Compared mood stabilisers and antipsychotics for bipolar disorder maintenance phase; Lurasidone included in adjunctive analyses
33975574	2021	Network Meta-analysis	BMC Psychiatry	Bayesian NMA comparing atypical antipsychotic monotherapy for acute bipolar depression; Lurasidone among agents with established efficacy and tolerability
29536616	2018	Clinical Practice Guideline	Bipolar Disorders	CANMAT/ISBD 2018 guidelines for bipolar disorder management; Lurasidone recommended as first-line for bipolar depression
34599629	2021	Clinical Practice Guideline	Bipolar Disorders	CANMAT/ISBD recommendations for bipolar disorder with mixed presentations; specific treatment selection guidance including atypical antipsychotics
37815563	2023	Narrative Review	JAMA	Broad review of bipolar disorder diagnosis and treatment for ~8 million affected US adults; contextualises pharmacotherapy choices including second-generation antipsychotics
39243127	2024	Narrative Review	Medical Science Monitor	Reviews Lurasidone’s mechanism of action, efficacy, and safety alongside aripiprazole and lamotrigine for bipolar disorder and schizophrenia
36472471	2022	Algorithm/Guideline Review	J Child Adolesc Psychopharmacology	Updated paediatric bipolar disorder treatment algorithms; covers FDA-approved agents including Lurasidone for bipolar depression in youth

India Market Information

Lurasidone currently holds no registrations with the Central Drugs Standard Control Organisation (CDSCO). It is not marketed in India under any trade name or dosage form.

For reference, Lurasidone (Latuda) is approved in the United States (FDA, 2010 for schizophrenia; 2013 for bipolar I depression), the European Union, Japan, and Canada, among other jurisdictions. A formal India registration pathway would require a New Drug Application to CDSCO supported by clinical bridging data for the Indian population.

Safety Considerations

Drug–Drug Interactions: Lurasidone has a documented interaction profile of 179 entries (DDInter database). Key interactions requiring clinical attention:

Major interactions: Bupropion, Clarithromycin, Aprepitant, Morphine. Of particular note, Clarithromycin (a potent CYP3A4 inhibitor) is contraindicated with Lurasidone in prescribing information from other markets due to risk of significantly elevated Lurasidone plasma levels. Bupropion co-administration raises seizure-threshold concerns.
Moderate interactions (selected): Metformin, Pioglitazone, Canagliflozin, Alogliptin, Acarbose — relevant given that antipsychotic-related metabolic effects may compound glycaemic management challenges. Dexamethasone, Epinephrine, Atropine, Hyoscyamine, and Glycopyrronium are also flagged at the moderate level.

For complete warnings, contraindications, and precautions, refer to the originator prescribing information (US label or EU SmPC), as India-specific package insert data was not available in this Evidence Pack.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: The evidence base for Lurasidone in bipolar I disorder (encompassing both depressive and maintenance phases) meets L1 criteria, with multiple completed Phase 3 RCTs enrolling thousands of patients and consistent support from international clinical practice guidelines (CANMAT/ISBD). The mechanistic rationale — multi-receptor modulation of dopaminergic and serotonergic pathways — is well aligned with the neurobiology of manic bipolar affective disorder. However, Lurasidone is not currently registered in India, and India-specific regulatory and safety documentation is absent.

To proceed, the following is needed:

CDSCO New Drug Application: Initiate formal registration in India; assess whether Phase 3 data from US/Japan/EU trials is sufficient or whether an Indian bridging study is required under CDSCO’s accelerated pathway for globally approved drugs
India-specific package insert: Download and review TFDA/FDA labelling to complete the safety matrix (key warnings, contraindications, special population guidance)
Formal MOA documentation: Retrieve DrugBank API data for DB08815 to formally document the mechanism of action and fill the DG002 data gap
Pharmacoeconomic assessment: Evaluate cost-effectiveness relative to quetiapine (widely available in India) for bipolar disorder management
Major DDI risk mitigation plan: Define clinical protocols for managing CYP3A4 interactions (especially macrolide antibiotics) in the Indian prescribing context
Post-marketing pharmacovigilance plan: Design a risk management strategy aligned with CDSCO requirements for a new CNS agent

⚠️ This report is intended for research reference only and does not constitute medical advice. All drug repurposing candidates require formal clinical validation before therapeutic application.

Disclaimer

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