Lacosamide
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Lacosamide: From Partial-Onset Seizures to Manic Bipolar Affective Disorder
One-Sentence Summary
Lacosamide is an antiseizure medication; the literature in the Evidence Pack describes it as an adjunctive treatment for partial-onset seizures. The TxGNN model predicts it may be useful for manic bipolar affective disorder. Support is early: 1 Phase 3 trial (recruiting, no results) and a small set of publications, mostly a retrospective cohort, an open-label pilot and case reports. Those studies concern bipolar depression rather than mania.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not listed in the US label data provided (literature describes partial-onset seizures) |
| Predicted New Indication | Manic bipolar affective disorder |
| TxGNN Prediction Score | 99.96% |
| Evidence Level | L3 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 (the authorizations listed are generic ANDAs) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Lacosamide enhances slow inactivation of voltage-gated sodium channels and modulates CRMP2. Both actions stabilize neuronal membranes, and they are plausibly related to mood-stabilizing anticonvulsants such as lamotrigine and valproate. Anticonvulsants have been used in psychiatry as mood stabilizers since the 1950s, which gives the prediction a reasonable pharmacological basis.
The match to the predicted disease is only partial. The clinical signals so far come from bipolar depression: an open-label pilot, a retrospective cohort and the ongoing Phase 3 trial. None of them tests lacosamide in acute mania. Detailed official mechanism-of-action data was not available in the pack, so the mechanism above comes from the literature and the model’s rationale.
Of the 10 predictions for this drug, rank 5 (migraine disorder) has much stronger direct evidence (completed Phase 3 RCTs, evidence level L1). It is worth a separate evaluation.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT07412132 | Phase 3 | Recruiting | 40 | Randomized, double-blind, parallel-group trial of lacosamide as augmentation to standard treatment in moderate to severe major depressive episodes of bipolar I and II disorder. Targets the depressive pole, not mania. No results yet. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 33666402 | 2021 | Open-label pilot trial | J Clin Psychopharmacol | 12-week open-label pilot of lacosamide for bipolar depression. Results not in the retrieved text. |
| 30251375 | 2018 | Retrospective cohort | Psychiatry Clin Neurosci | 30-day comparison of lacosamide vs other antiepileptics in bipolar patients without epilepsy. Described as the first test of lacosamide in bipolar disorder. |
| 30275630 | 2018 | Case report (safety) | Indian J Psychol Med | Lacosamide-precipitated neutropenia in a patient with bipolar disorder and epilepsy. |
| 28845834 | 2017 | Case report | Acta Biomed | Clinical stabilisation with lacosamide of a mood disorder comorbid with PTSD and fronto-temporal epilepsy. |
| 29253680 | 2018 | Prospective multicenter study | Epilepsy Behav | Effect of lacosamide on depression and anxiety symptoms in focal refractory epilepsy. Indirect evidence for mood effects. |
| 32693579 | 2020 | Review | ACS Chem Neurosci | Review of CRMP2 as a drug target. Supports the CRMP2 mechanism. |
| 38304661 | 2024 | Case report | Cureus | Management of a pregnant patient with bipolar I disorder and multiple comorbidities. Lacosamide use is not confirmed in the retrieved text. |
| 29957667 | 2018 | Review | Ther Drug Monit | Antiepileptic drug monitoring update. Notes AEDs are also used for bipolar disorder. Background only. |
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA214695 | Lacosamide | Tablet, film coated | Not listed in the data |
| ANDA208308 | Lacosamide | Tablet | Not listed in the data |
| ANDA216335 | Lacosamide | Injection | Not listed in the data |
| ANDA216151 | Lacosamide | Solution | Not listed in the data |
| ANDA204974 | Lacosamide | Tablet, film coated | Not listed in the data |
Oral, injectable and solution forms are all available, so route of administration is unlikely to be a barrier.
Safety Considerations
- Neutropenia signal: one case report describes neutropenia precipitated by lacosamide in a patient with bipolar disorder and epilepsy (PMID 30275630). This is a single case, but it is relevant to a psychiatric population.
- Drug interactions: no interaction records were found in the database query.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The only trial is a small (n=40), still-recruiting Phase 3 study in bipolar depression, and the supporting literature is an open-label pilot, a retrospective cohort and case reports. Nothing tests lacosamide in mania, the predicted indication, and a neutropenia case report adds a safety question. Evidence is consistent with a research question, not a development decision.
To proceed, the following is needed:
- Results from NCT07412132 and the full results of the 12-week open-label pilot (PMID 33666402)
- Data specific to acute mania, or a decision to reframe the indication as bipolar depression
- US package insert warnings and contraindications (not in the current data)
- A haematological monitoring plan, given the neutropenia report
- A separate evaluation of the migraine prediction (rank 5), which has stronger evidence
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any clinical use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.