Lacosamide
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Lacosamide: From Epilepsy to Manic Bipolar Affective Disorder
One-Sentence Summary
Lacosamide is a third-generation antiepileptic drug (AED), used in the management of partial-onset (focal) seizures in epilepsy. The TxGNN model predicts it may be effective for Manic Bipolar Affective Disorder, but this direction is currently supported by only 1 ongoing clinical trial and 14 publications, most of which are small, indirect, or focused on the depressive (rather than manic) pole of bipolar disorder.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Epilepsy (partial-onset seizures) — inferred from supporting literature; no formal UK licence data available in this evidence pack |
| Predicted New Indication | Manic Bipolar Affective Disorder |
| TxGNN Prediction Score | 99.96% |
| Evidence Level | L3 |
| UK Market Status | Not marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in this evidence pack (data gap DG002). Based on the supporting literature, Lacosamide is known to act by selectively enhancing the slow inactivation of voltage-gated sodium channels — a distinct mechanism from the fast-inactivation blockade used by older sodium channel drugs. Its efficacy in partial-onset seizures is well established as an AED.
Several other sodium-channel-modulating anticonvulsants (lamotrigine, carbamazepine, valproate) are established mood stabilisers in bipolar disorder, which provides a plausible class-level rationale for exploring Lacosamide in mood disorders. Consistent with this, the literature includes early open-label and retrospective observations suggesting mood-stabilising and antidepressant effects of Lacosamide in bipolar disorder patients.
However, a key caveat applies: the only Phase 3 trial identified (NCT07412132) targets major depressive episodes in bipolar disorder, not manic episodes as specified by the TxGNN prediction. This represents a polarity mismatch between the strongest available trial evidence and the predicted indication, which weakens the direct applicability of this evidence and should be treated as a significant caveat when interpreting the evidence level.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT07412132 | Phase 3 | Recruiting | 40 | Randomised, double-blind trial evaluating Lacosamide as an augmentation treatment for major depressive episodes in bipolar I/II disorder; based on earlier open-label findings of improvement in depressive and manic symptoms. Note: targets depressive rather than manic episodes, a partial mismatch with the predicted indication. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 33666402 | 2021 | Open-label pilot trial | J Clin Psychopharmacol | 12-week open-label pilot study of Lacosamide’s efficacy and safety specifically in bipolar depression. |
| 30251375 | 2018 | Retrospective cohort | Psychiatry Clin Neurosci | 30-day comparison of Lacosamide against a retrospective control group treated with other antiepileptics in bipolar disorder without epilepsy. |
| 30275630 | 2018 | Case report (adverse event) | Indian J Psychol Med | Reports Lacosamide-precipitated neutropenia in a patient with bipolar disorder and comorbid epilepsy — an important safety signal. |
| 28845834 | 2017 | Case report | Acta Biomed | Clinical stabilisation of a mood disorder comorbid with PTSD and fronto-temporal epilepsy using Lacosamide, attributed to its sodium-channel stabilising mechanism. |
| 38304661 | 2024 | Case report | Cureus | Case management of a pregnant patient with bipolar I disorder and multiple comorbidities, including seizure-like presentations. |
| 29253680 | 2018 | Prospective multicentre study | Epilepsy Behav | Lacosamide improved depression and anxiety symptoms in patients with focal epilepsy, suggesting a mood effect independent of seizure control. |
| 29957667 | 2018 | Review | Ther Drug Monit | Notes the expanding off-label use of AEDs, including for bipolar disorder management, in the context of therapeutic drug monitoring. |
| 32693579 | 2020 | Mechanistic review | ACS Chem Neurosci | Reviews druggability of CRMP2, a proposed molecular target through which Lacosamide may act beyond simple sodium channel blockade. |
| 37782796 | 2023 | Structural study | PNAS | Cryo-EM structures of Nav channels bound to antiepileptic drugs, providing structural insight relevant to sodium-channel-targeted mood modulation. |
| 22210279 | 2012 | Review | Adv Drug Deliv Rev | Overview of the chemical and pharmacokinetic properties of newer AEDs, including Lacosamide, contextualising its drug class. |
UK Market Information
No UK marketing authorisation is currently registered for Lacosamide in this evidence pack (market status: Not marketed; 0 licences on file). This should be verified against the current MHRA product register and BNF before any decision is finalised.
Safety Considerations
Please refer to the SmPC and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.
(Note: one case report in the literature above describes Lacosamide-precipitated neutropenia in a bipolar disorder patient — this should be flagged for haematological monitoring if this indication is pursued further, pending formal SmPC warning data.)
Conclusion and Next Steps
Decision: Hold
Rationale: Evidence level is L3, and the only Phase 3 trial identified targets depressive rather than manic episodes — a polarity mismatch with the TxGNN-predicted indication. Remaining support comes from small open-label, retrospective, and case-report-level studies, including a documented neutropenia safety signal, which is insufficient to justify progression without further targeted evidence.
To proceed, the following is needed:
- Confirmed mechanism of action data from DrugBank (data gap DG002, High severity)
- SmPC/TFDA-equivalent warnings and contraindications (data gap DG001, Blocking severity)
- A dedicated RCT in manic (not depressive) episodes of bipolar disorder to resolve the current indication/evidence mismatch
- Formal UK licensing and market status verification
- A haematological monitoring plan addressing the reported neutropenia signal
Additional note: Among the other TxGNN-predicted indications reviewed for this drug, migraine disorder (rank 5) shows substantially stronger evidence (L1, multiple completed Phase 3 RCTs directly testing Lacosamide) and may warrant separate evaluation as a higher-priority repurposing candidate.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.