Lurasidone
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
Lurasidone: From Antipsychotic Therapy to Manic Bipolar Affective Disorder
One-Sentence Summary
Lurasidone is a second-generation (atypical) antipsychotic, marketed internationally as Latuda, though this evidence pack shows no current EU marketing authorization on file. The TxGNN model predicts it may be effective for Manic Bipolar Affective Disorder, with 16 clinical trials (several completed Phase 3 studies) and 20 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not documented in EU licensing data (no EMA authorization on file for this drug); internationally known as an atypical antipsychotic |
| Predicted New Indication | Manic Bipolar Affective Disorder |
| TxGNN Prediction Score | 99.98% |
| Evidence Level | L1 |
| EU Market Status | ✗ Not Marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not officially on file for this drug (flagged as a High-severity data gap, DG002). However, the evidence pack’s pharmacological analysis indicates that Lurasidone acts as a D2/5-HT2A receptor antagonist, with high-affinity 5-HT7 antagonism and partial 5-HT1A agonism — a receptor profile characteristic of second-generation antipsychotics used in mood disorder management.
This receptor-modulation mechanism is the pharmacological basis for treating bipolar spectrum disorders. Lurasidone (Latuda) has already been approved in multiple countries for bipolar depression, used both as monotherapy and as adjunctive therapy with lithium or divalproex. Manic bipolar affective disorder sits within the same disease spectrum as bipolar depression — both are phases of bipolar I/II disorder — so the mechanistic rationale for extending use to mania is a disease-spectrum extension rather than a purely novel prediction.
Because the receptor targets involved (D2/5-HT2A/5-HT7/5-HT1A) are central to mood stabilization across manic, depressive, and maintenance phases of bipolar disorder, it is mechanistically plausible that the same drug effective in bipolar depression could extend to mania, particularly as an adjunct to established mood stabilizers.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01358357 | Phase 3 | Completed | 965 | Lurasidone adjunctive to lithium or divalproex for prevention of recurrence in Bipolar I Disorder |
| NCT01986101 | Phase 3 | Completed | 525 | SM-13496 (lurasidone) vs. placebo for treatment of Bipolar I Depression |
| NCT01986114 | Phase 3 | Completed | 495 | Long-term efficacy and safety of SM-13496 (lurasidone) in Bipolar I Disorder |
| NCT01575561 | Phase 3 | Completed | 377 | Extension study of lurasidone adjunctive to lithium/divalproex in Bipolar I Disorder |
| NCT02046369 | Phase 3 | Completed | 350 | Flexibly dosed lurasidone in children/adolescents with Bipolar I Depression |
| NCT01914393 | Phase 3 | Completed | 702 | 104-week long-term safety/effectiveness of lurasidone in pediatric subjects |
| NCT02147379 | Phase 3 | Completed | 53 | Lurasidone vs. treatment-as-usual on cognitive function in euthymic Bipolar-I patients |
| NCT02731612 | Phase 3 | Completed | 100 | Randomized, double-blind, placebo-controlled study of lurasidone adjunctive therapy on cognition in euthymic bipolar disorder (ELICE-BD) |
| NCT04383691 | Phase 3 | Terminated | 124 | Lurasidone vs. placebo for Bipolar I Depression |
| NCT01932541 | Phase 4 | Withdrawn | 0 | Open-label trial of Lurasidone (Latuda) for mania in children/adolescents with Bipolar I, II and spectrum disorders |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39557452 | 2024 | Review (dose-response meta-analysis) | BMJ Mental Health | Efficacy and acceptability of lurasidone for bipolar depression across dose ranges |
| 24170243 | 2014 | Commentary | The American Journal of Psychiatry | Direct discussion of lurasidone in bipolar disorder treatment |
| 38487836 | 2024 | Review (network meta-analysis) | European Psychiatry | Comparative efficacy/tolerability of FDA-approved atypical antipsychotics (incl. lurasidone) for bipolar depression |
| 33975574 | 2021 | Review (network meta-analysis) | BMC Psychiatry | Efficacy/tolerability of atypical antipsychotics for acute bipolar depression |
| 39175136 | 2024 | Review | Bipolar Disorders | Mood stabilizers in pregnancy and neonatal outcomes; notes limited published safety data on lurasidone |
| 39243127 | 2024 | Review | Medical Science Monitor | Advances in mood-stabilizer pharmacotherapy including lurasidone mechanism and clinical role |
| 37595997 | 2023 | Review (network meta-analysis) | The Lancet Psychiatry | Comparative efficacy/tolerability of pharmacological interventions for acute bipolar depression |
| 33177610 | 2021 | Review (network meta-analysis) | Molecular Psychiatry | Antipsychotics/mood stabilizers for bipolar disorder maintenance phase |
| 29536616 | 2018 | Guideline/Review | Bipolar Disorders | CANMAT/ISBD 2018 guidelines for management of bipolar disorder |
| 37815563 | 2023 | Review | JAMA | Diagnosis and treatment overview of bipolar disorder |
EU Market Information
Currently not authorized in the EU market — no EMA marketing authorization is on file for this drug in the current dataset (0 licenses recorded).
Safety Considerations
Please refer to the SmPC for safety information.
Note: Key warnings, contraindications, and drug interaction data are currently flagged as a Blocking-severity data gap (DG001) in this evidence pack — this must be resolved before any Stage 1 safety assessment can proceed.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple completed Phase 3 trials with substantial enrollment (n=965, 702, 525, 495) directly evaluate lurasidone in Bipolar I disorder, and lurasidone already has established international use in bipolar depression — supporting a mechanistically coherent extension to manic bipolar affective disorder. However, most direct efficacy evidence concerns depressive and maintenance phases rather than acute mania specifically (the one pediatric mania trial, NCT01932541, was withdrawn with zero enrollment).
To proceed, the following is needed:
- Official product label / MOA documentation (currently Blocking gap DG001, High-severity gap DG002)
- Full safety data: contraindications, drug-drug interactions, key warnings (all currently Data Gap)
- Confirmation of EU regulatory/marketing status (currently 0 licenses on file)
- Verification of drug identity for “pending”-relevance trials (e.g., NCT02731612 ELICE-BD, NCT04383691)
- Acute mania–specific efficacy data, since most current trials address depressive/maintenance phases rather than mania itself
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.