Lacosamide

證據等級: L5

預測適應症: 10 個

Lacosamide: From Epilepsy (Focal/Partial-Onset Seizures) to Manic Bipolar Affective Disorder

One-Sentence Summary

Lacosamide is an antiseizure medication established for focal (partial-onset) seizures/epilepsy, referenced throughout the supporting trial and literature records in this evidence pack. The TxGNN model predicts it may be effective for Manic Bipolar Affective Disorder, with 1 clinical trial and 14 publications currently identified, though most of the clinical evidence to date addresses the depressive rather than the manic phase of bipolar disorder.

Quick Overview

Item	Content
Original Indication	Not established in the New Zealand label (drug not marketed); international trial/literature context indicates use in focal/partial-onset seizure epilepsy
Predicted New Indication	Manic Bipolar Affective Disorder
TxGNN Prediction Score	99.96%
Evidence Level	L3
New Zealand Market Status	✗ Not marketed (未上市)
Number of Authorizations	0
Recommended Decision	Research Question

Why is This Prediction Reasonable?

Structured mechanism-of-action data for lacosamide was not returned from DrugBank in this evidence pack. Based on the supporting literature that was retrieved, lacosamide's known pharmacological action is selective enhancement of the slow inactivation of voltage-gated sodium (Nav) channels, together with an interaction with CRMP2 (collapsin response mediator protein 2) that affects trafficking of voltage- and ligand-gated ion channels (PMID 32693579). This is the same general mechanistic family as other membrane-stabilising antiepileptic drugs (e.g., lamotrigine, carbamazepine, valproate) that are already established mood stabilisers in bipolar disorder.

Epilepsy and bipolar disorder share a plausible mechanistic link through neuronal membrane hyperexcitability, and psychiatric mood comorbidity is well documented in epilepsy populations. Retrospective and open-label data (PMID 30251375, 33666402) and case reports of mood stabilisation in comorbid epilepsy/mood-disorder patients (PMID 28845834) support a signal for lacosamide affecting mood symptoms.

An important caveat: the strongest available clinical evidence (the retrospective cohort and the 12-week open-label pilot) and the currently recruiting Phase 3 trial (NCT07412132) are focused on the depressive episodes of bipolar disorder, not the manic phase named in this predicted indication. The mechanistic rationale for a specific antimanic effect is therefore indirect and should be treated cautiously.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT07412132	Phase 3	Recruiting	40	Randomized, controlled, double-blind trial evaluating lacosamide as augmentation therapy for major depressive episodes in Bipolar Disorder Types I and II; based on prior observational and open-label signals of effect on depressive/manic symptoms in epilepsy and bipolar disorder. No results yet available.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
30251375	2018	Retrospective Cohort	Psychiatry and Clinical Neurosciences	30-day comparison of lacosamide vs. other antiepileptics in bipolar disorder patients without epilepsy — first dedicated assessment of lacosamide in BD
33666402	2021	Open-Label Pilot Trial	Journal of Clinical Psychopharmacology	12-week open-label pilot showing efficacy/safety signal for lacosamide in bipolar depression
29253680	2018	Prospective multicenter study	Epilepsy & Behavior	Lacosamide associated with improved depression/anxiety symptoms in focal epilepsy patients
28845834	2017	Case report	Acta Bio-Medica	Clinical stabilisation of mood disorder comorbid with PTSD and fronto-temporal epilepsy using lacosamide
32693579	2020	Mechanistic review	ACS Chemical Neuroscience	Reviews CRMP2 as a druggable target relevant to lacosamide's channel-trafficking mechanism
30275630	2018	Case report (AE)	Indian Journal of Psychological Medicine	Lacosamide-precipitated neutropenia in a patient with bipolar disorder and comorbid epilepsy — safety signal
38304661	2024	Case report	Cureus	Case of bipolar I disorder with multiple comorbidities including epilepsy/PNES, relevant population overlap
37782796	2023	Structural biology	PNAS	Cryo-EM structural study of Nav1.7 channel binding by antiepileptic drugs, supports Nav-channel MOA class
26220372	2015	Preclinical	Epilepsy Research	Lacosamide modulates interictal spiking/high-frequency oscillations in a mesial temporal lobe epilepsy model
22210279	2012	Review	Advanced Drug Delivery Reviews	Overview of chemical properties of AEDs including lacosamide, background pharmacology

New Zealand Market Information

Lacosamide is currently not marketed in New Zealand (0 authorizations on record); no license or approved-indication data is available for this evidence pack.

Safety Considerations

Please refer to the package insert for safety information.

Conclusion and Next Steps

Decision: Research Question

Rationale: The mechanistic rationale (Nav-channel/CRMP2 modulation, shared with established mood-stabilising AEDs) is plausible, and a Phase 3 trial is now recruiting, but existing clinical evidence predominantly addresses bipolar depression rather than the manic phase named in this prediction, and it consists mainly of retrospective/open-label data (Evidence Level L3) rather than confirmatory RCTs.

To proceed, the following is needed:

Formal TFDA/DrugBank mechanism-of-action data (currently flagged as a Blocking/High-severity data gap)
Package insert warnings, contraindications, and drug-interaction data (all currently unavailable)
Results from the ongoing Phase 3 trial (NCT07412132) once available
Clarification of whether the mood-stabilising signal extends specifically to manic (not just depressive) episodes before advancing beyond a research question
Disclaimer

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