Lacosamide

證據等級: L5

預測適應症: 10 個

Lacosamide: From Epilepsy to Manic Bipolar Affective Disorder

One-Sentence Summary

Lacosamide is an antiepileptic drug (anticonvulsant) currently used for the treatment of epilepsy, specifically partial-onset seizures. The TxGNN model predicts it may be effective for Manic Bipolar Affective Disorder, with 1 clinical trial and 14 publications currently supporting this direction — though the evidence base remains preliminary, and most of that evidence actually concerns the depressive rather than the manic pole of bipolar disorder.

Quick Overview

Item	Content
Original Indication	Epilepsy (partial-onset seizures) — inferred from trial/literature context in the evidence pack; no formal TFDA license record was found
Predicted New Indication	Manic Bipolar Affective Disorder
TxGNN Prediction Score	99.96%
Evidence Level	L3
Taiwan Market Status	未上市 (Not marketed)
Number of NDAs	0
Recommended Decision	Research Question

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available (MOA marked as a data gap). Based on known information, Lacosamide belongs to the antiepileptic drug (AED) / anticonvulsant class, and its efficacy in epilepsy (partial-onset seizures) has been established; mechanistically, this class may be applicable to mood disorders such as bipolar disorder.

The supporting literature indicates lacosamide’s mechanism consists of selective slow inactivation of voltage-gated sodium channels, promoting extended stabilization of neuronal cell membranes (PMID 28845834). Sodium-channel-blocking anticonvulsants — such as lamotrigine, carbamazepine, and valproate — are an already-established class of mood stabilizers, which is the pharmacological rationale for testing lacosamide in bipolar disorder.

However, an important caveat applies: the direct mechanistic and clinical evidence specifically supports the depressive pole of bipolar disorder rather than the manic pole named in this prediction. The single registered clinical trial (NCT07412132) targets major depressive episodes in bipolar I/II disorder, not mania, and the open-label pilot data (PMID 33666402) similarly concerns bipolar depression. Evidence for a mechanistic link to mania specifically remains weak.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT07412132	Phase 3	Recruiting	40	Evaluates lacosamide as an augmentation treatment for major depressive episodes in bipolar I/II disorder, building on prior observational/open-label signals of improved depressive and manic symptoms in BD; trial targets the depressive pole, not mania directly; results not yet available (est. completion 2027-01)

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 specifically in bipolar depression — the most direct clinical evidence in this evidence pack
30251375	2018	Retrospective cohort	Psychiatry Clin Neurosci	30-day comparison of lacosamide vs. a retrospective control group treated with other antiepileptics in bipolar disorder without epilepsy
30275630	2018	Case report	Indian J Psychol Med	Reports neutropenia precipitated by lacosamide in a patient with bipolar disorder and comorbid epilepsy — a safety signal, not an efficacy signal
28845834	2017	Case report	Acta Biomed	Clinical stabilization with lacosamide of mood disorder comorbid with PTSD and fronto-temporal epilepsy; describes the sodium-channel slow-inactivation mechanism as basis for mood stabilization
29253680	2018	Prospective multicenter study	Epilepsy Behav	Lacosamide’s effect on depression and anxiety symptoms in focal refractory epilepsy patients — indirect mood-related signal in a related population
29957667	2018	Review	Ther Drug Monit	Update on therapeutic drug monitoring of AEDs; notes AEDs including lacosamide are also used in bipolar disorder management
32693579	2020	Mechanistic review	ACS Chem Neurosci	Reviews CRMP2 as a druggable target relevant to lacosamide’s mechanism, providing indirect mechanistic support
22210279	2012	Review	Adv Drug Deliv Rev	Background review of chemical properties of AEDs approved 1990–2011, including lacosamide
16732716	2006	Review	Expert Opin Investig Drugs	Background review of second-generation AEDs
40072331	2025	Database study	Epilepsia	Real-world therapeutic drug monitoring concentration ranges for antiseizure medications — indirect background data

US Market Information

Lacosamide is currently not marketed in Taiwan (未上市) and no license/NDA records were found in this evidence pack (0 authorizations).

Safety Considerations

Formal safety data (key warnings, contraindications, drug-drug interactions) were not available for this candidate — the DDI query returned no results, and this represents a blocking data gap for safety pre-screening (TFDA label/warnings not yet retrieved).

Please refer to the package insert for safety information.

Supplementary note: one case report in the literature above (PMID 30275630) describes lacosamide-precipitated neutropenia in a bipolar patient with comorbid epilepsy. This is a single case report, not formal labeling data, but it is an early hematologic safety signal worth tracking as this candidate advances.

Conclusion and Next Steps

Decision: Research Question

Rationale: Evidence level is L3 (retrospective cohort and open-label pilot data only, no completed RCT), and the sole registered Phase 3 trial (NCT07412132) is still recruiting with results not expected until 2027. Critically, most supporting evidence addresses bipolar depression rather than the manic indication named by the TxGNN prediction, so the mechanistic case for mania specifically is not yet well established.

To proceed, the following is needed:

TFDA label warnings/contraindications (blocking gap, required for S1 safety pre-screening)
Detailed mechanism of action (MOA) documentation from DrugBank or equivalent source
Completion and readout of NCT07412132
Trial or observational data targeting manic (not just depressive) episodes specifically
Formal drug-drug interaction data (current DDI query returned no results)

Note for context: among this drug’s other predicted indications in the same evidence pack, migraine disorder (rank 5) currently has substantially stronger evidence (L1, “Proceed with Guardrails,” including a completed head-to-head Phase 3 RCT vs. propranolol) and may warrant a separate, higher-priority evaluation report.

Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.