Lurasidone
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Lurasidone: From Bipolar Depression/Schizophrenia to Manic Bipolar Affective Disorder
One-Sentence Summary
Lurasidone is an atypical antipsychotic internationally approved for schizophrenia and bipolar I depression. The TxGNN model predicts it may also be effective for manic episodes of bipolar affective disorder, with 15 clinical trials and 19 publications currently supporting the broader bipolar I disorder indication — though very few of these directly address the acute manic phase itself.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not documented in local regulatory filings (drug not marketed); internationally established for schizophrenia and bipolar I depression |
| Predicted New Indication | Manic Bipolar Affective Disorder |
| TxGNN Prediction Score | 99.98% |
| Evidence Level | L1 |
| Norway Market Status | ✗ Not Marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in this evidence pack. Based on known pharmacology, lurasidone is a D2/5‑HT2A/5‑HT7 receptor antagonist — a receptor profile shared by other atypical antipsychotics used across the full spectrum of bipolar disorder (manic, mixed, and depressive episodes, as well as maintenance therapy).
Lurasidone's established indications (schizophrenia, bipolar I depression) and the predicted new indication (manic bipolar affective disorder) sit within the same disease category — bipolar I disorder — just different mood phases. Since D2/5‑HT2A antagonism is the pharmacological basis for antimanic efficacy in essentially all approved second-generation antipsychotics, there is reasonable mechanistic plausibility for extending lurasidone's use to the manic phase.
However, the evidence base has an important caveat: the highest-quality completed Phase 3 trials for lurasidone specifically studied bipolar I depression and maintenance/relapse-prevention (adjunctive to lithium/divalproex), not acute mania as a standalone indication. One review (PMID 31957501) explicitly notes that "lurasidone has not been studied in patients with mania or bipolar psychosis." A dedicated pediatric mania trial (NCT01932541) was withdrawn with zero enrollment. This means the prediction is directionally reasonable (same disease category, same drug class mechanism) but requires confirmatory acute-mania efficacy data before being treated as clinically validated.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01986114 | Phase 3 | Completed | 495 | Long-term efficacy and safety of lurasidone (SM-13496) in Bipolar I Disorder — direct drug-disease evidence |
| NCT01358357 | Phase 3 | Completed | 965 | PREVAIL series: lurasidone adjunctive to lithium/divalproex for prevention of recurrence in Bipolar I Disorder (with/without rapid cycling or psychotic features) |
| NCT01914393 | Phase 3 | Completed | 702 | 104-week open-label extension evaluating long-term safety/effectiveness of flexibly-dosed lurasidone in pediatric subjects |
| NCT04383691 | Phase 3 | Terminated | 124 | RCT of lurasidone vs placebo for Bipolar I Depression — terminated, reason not specified in this evidence pack |
| NCT02046369 | Phase 3 | Completed | 350 | Efficacy and safety of lurasidone in children/adolescents with Bipolar I Depression |
| NCT01575561 | Phase 3 | Completed | 377 | Open-label extension of lurasidone adjunctive to lithium/divalproex in Bipolar I Disorder |
| NCT02731612 | Phase 3 | Completed | 100 | ELICE-BD: lurasidone adjunctive therapy for cognitive functioning in euthymic Bipolar I/II patients |
| NCT02147379 | Phase 3 | Completed | 53 | Cognitive functioning changes with lurasidone vs treatment-as-usual in euthymic Bipolar I patients |
| NCT01986101 | Phase 3 | Completed | 525 | RCT of lurasidone (SM-13496) vs placebo for Bipolar I Depression |
| NCT01932541 | Phase 4 | Withdrawn | 0 | Open-label trial of lurasidone specifically for mania in children/adolescents — withdrawn before enrollment, no data generated |
Note: Additional trials in the evidence pack involve other drugs (vortioxetine, cariprazine, ketamine/D-cycloserine) or are only indirectly related (antenatal antipsychotic exposure, SMART trial design) and were excluded from this table as lower relevance (Grade C).
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39557452 | 2024 | Systematic Review / Dose-Response Meta-analysis | BMJ Mental Health | Dose-response relationship for lurasidone efficacy, acceptability, and metabolic/endocrine profile in bipolar depression |
| 31957501 | 2020 | Review | Expert Opin Pharmacother | Evaluates lurasidone in bipolar disorder; explicitly notes it has not been studied in mania or bipolar psychosis |
| 33177610 | 2021 | Systematic Review / Network Meta-analysis | Molecular Psychiatry | Compares antipsychotics/mood stabilizers (incl. lurasidone) for bipolar disorder maintenance phase |
| 37595997 | 2023 | Network Meta-analysis | Lancet Psychiatry | Comparative efficacy/tolerability of pharmacological interventions for acute bipolar depression |
| 29536616 | 2018 | Guideline (CANMAT/ISBD) | Bipolar Disorders | Standard treatment guideline for bipolar disorder management |
| 34599629 | 2021 | Guideline (CANMAT/ISBD) | Bipolar Disorders | Recommendations for bipolar disorder with mixed presentations (closer to manic/mixed phase) |
| 24170243 | 2014 | Commentary | Am J Psychiatry | "Lurasidone and bipolar disorder" |
| 39243127 | 2024 | Review | Med Sci Monit | Narrative review of new antipsychotics/mood stabilizers for bipolar disorder and schizophrenia, incl. lurasidone |
| 25963405 | 2016 | Review | Asia-Pac Psychiatry | Antipsychotics as antidepressants; notes lurasidone approved specifically for bipolar depression |
| 37815563 | 2023 | Review | JAMA | General diagnosis and treatment review of bipolar disorder |
Norway Market Information
Lurasidone is currently not marketed in Norway (market status: 未上市, 0 authorizations). No product license or approved indication text is available for this drug in the local regulatory dataset.
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Lurasidone has a substantial body of completed Phase 3 evidence (L1) supporting its use across bipolar I disorder — including depression treatment and maintenance/relapse prevention — which shares mechanistic and diagnostic overlap with the manic phase. However, evidence specifically demonstrating efficacy in acute mania is weak (the only dedicated pediatric mania trial was withdrawn), and the drug is not currently marketed locally, so no local safety labeling exists yet.
To proceed, the following is needed:
- Local regulatory/package insert data (warnings, contraindications, DDI) — currently blocking (DG001)
- Confirmed mechanism of action detail from DrugBank (DG002)
- Dedicated efficacy/safety data for lurasidone in acute manic or mixed episodes (current evidence is predominantly for the depressive/maintenance phase)
- Regulatory pathway assessment for market entry, since lurasidone holds zero authorizations in this market
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.