Lurasidone
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Lurasidone: From Schizophrenia/Bipolar I Depression to Manic Bipolar Affective Disorder
One-Sentence Summary
Lurasidone (DrugBank DB08815) is an atypical antipsychotic whose established use, per the literature retrieved in this pack, spans schizophrenia and acute bipolar I depression. TxGNN additionally flags manic bipolar affective disorder as a high-scoring indication, backed by 15 clinical trials and 19 publications — though most of this evidence actually documents lurasidone’s depressive-episode indication rather than pure mania, a discrepancy worth flagging before acting on the label.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not confirmed via a formal license record in this pack (original_indications is empty, total_licenses = 0). One retrieved publication (PMID 31957501) states lurasidone is approved in the US for schizophrenia and adjunctively for acute bipolar I depression. |
| Predicted New Indication | Manic bipolar affective disorder |
| TxGNN Prediction Score | 99.98% |
| Evidence Level | L1 |
| US Market Status | Not marketed (per this pack’s regulatory query; 0 licenses on file — see caveat below, this conflicts with literature describing lurasidone as a marketed US drug) |
| Number of NDAs | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed formal MOA data for lurasidone is marked as a data gap in this pack (DG002). However, the repurposing rationale attached to this candidate does describe the pharmacology: lurasidone is a benzisothiazole-class atypical antipsychotic with high-affinity antagonism at D2 and 5-HT2A receptors, plus 5-HT7 antagonism and partial agonism at 5-HT1A. This receptor combination is the standard mechanistic basis by which antipsychotics function as mood stabilizers in bipolar disorder — it is not a mechanism specific to mania versus depression.
That mechanistic non-specificity is exactly the caveat that needs to be flagged: nearly all of the supporting Phase 3 trials (e.g., NCT01986101/SM-13496, NCT02046369, NCT01358357) enrolled patients with bipolar I depression, not manic episodes. The one trial explicitly designed around mania (NCT01932541, “Latuda for the Treatment of Mania in Children and Adolescents”) was withdrawn with zero enrollment. This suggests the TxGNN “manic bipolar affective disorder” label likely reflects proximity to the broader bipolar-disorder disease node in the knowledge graph rather than direct evidence of anti-manic efficacy — the underlying evidence base supports lurasidone in bipolar depression, a use that (per literature) may already be established rather than genuinely novel.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01986101 | Phase 3 | Completed | 525 | Pivotal RCT of SM-13496 (lurasidone development code) vs. placebo in Bipolar I Depression |
| NCT01358357 | Phase 3 | Completed | 965 | Lurasidone adjunctive to lithium/divalproex for prevention of recurrence in Bipolar I Disorder |
| NCT01914393 | Phase 3 | Completed | 702 | 104-week open-label extension evaluating long-term safety/effectiveness in pediatric subjects |
| NCT01575561 | Phase 3 | Completed | 377 | Extension study of lurasidone adjunctive to lithium/divalproex in Bipolar I Disorder |
| NCT02046369 | Phase 3 | Completed | 350 | 6-week double-blind, placebo-controlled RCT in children/adolescents with Bipolar I Depression |
| NCT01986114 | Phase 3 | Completed | 495 | Long-term efficacy/safety study of SM-13496 (lurasidone) in Bipolar I Disorder |
| NCT04383691 | Phase 3 | Terminated | 124 | Double-blind, placebo-controlled RCT of lurasidone in Bipolar I Depression — terminated, reason not documented in this pack |
| NCT06433635 | Phase 4 | Active, not recruiting | 2726 | SMART pragmatic trial comparing lurasidone against cariprazine, quetiapine, and aripiprazole/escitalopram for bipolar depression |
| NCT02731612 | Phase 3 | Completed | 100 | ELICE-BD: RCT of lurasidone adjunctive therapy for cognitive functioning in euthymic Bipolar I/II patients |
| NCT01932541 | Phase 4 | Withdrawn | 0 | Open-label trial of Latuda (lurasidone) for mania in children/adolescents — the only trial targeting mania specifically, but never enrolled |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39557452 | 2024 | Review (dose-response meta-analysis) | BMJ Mental Health | Systematic review/meta-analysis of lurasidone’s efficacy and acceptability for bipolar depression across doses |
| 31957501 | 2020 | Review | Expert Opinion on Pharmacotherapy | States lurasidone is approved for bipolar I depression and schizophrenia; explicitly notes it has not been studied in mania or bipolar psychosis |
| 24170243 | 2014 | Commentary | American Journal of Psychiatry | Early commentary on lurasidone’s role in bipolar disorder |
| 37595997 | 2023 | Review (network meta-analysis) | The Lancet Psychiatry | Comparative efficacy/tolerability of pharmacological interventions (incl. lurasidone) for acute bipolar depression |
| 37815563 | 2023 | Review | JAMA | General review of bipolar disorder diagnosis and treatment |
| 29536616 | 2018 | Guideline | Bipolar Disorders | CANMAT/ISBD 2018 bipolar disorder management guidelines |
| 34599629 | 2021 | Guideline | Bipolar Disorders | CANMAT/ISBD recommendations for bipolar disorder with mixed features |
| 33177610 | 2021 | Review (network meta-analysis) | Molecular Psychiatry | Mood stabilizers vs. antipsychotics for maintenance-phase bipolar disorder |
| 40808269 | 2025 | Consensus/Task Force | Bipolar Disorders | ISBD Task Force definition of treatment-resistant bipolar depression |
| 25963405 | 2016 | Review | Asia-Pacific Psychiatry | Notes lurasidone (with quetiapine) is FDA-approved specifically for bipolar depression, not as a general antidepressant |
Safety Considerations
Please refer to the package insert for safety information. (Key warnings, contraindications, and DDI data are all marked as data gaps in this pack; the DDI query returned not_found.)
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple completed Phase 3 RCTs (e.g., NCT01986101, n=525; NCT01358357, n=965) meet the L1 evidence bar and consistently support lurasidone’s efficacy — but for bipolar I depression, not the manic-episode label TxGNN surfaced. The only trial designed around mania was withdrawn with no enrollment, so the “manic” framing should not be taken as validated without further review.
To proceed, the following is needed:
- TFDA/regulatory label data (blocking gap DG001) to run a safety screen before any clinical use
- Resolution of the mismatch between the predicted “manic bipolar affective disorder” label and the depression-focused trial evidence — clarify whether the intended indication is actually bipolar depression (where existing approval may already apply) or genuinely untested manic-episode use
- Formal MOA documentation (DG002)
- A working DDI data source, since the current query returned no results
- Verification of why NCT04383691 was terminated
- Confirmation of actual US/Taiwan market and license status, since the “not marketed / 0 licenses” record in this pack appears inconsistent with literature describing lurasidone as a marketed US drug (Latuda®)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.