Non-Cochrane · intervention · PM42220289
Slow-inactivated sodium channels as a therapeutic target in trigeminal neuralgia: evidence from a systematic review and meta-analysis of lacosamide.
Meechumnarn Tonporn, Phutinart Somkiat, Anukoolwittaya Prakit, et al. · Journal of oral & facial pain and headache · 2026 · PubMed · doi:10.22514/jofph.2026.037
Findings
Population Adults with trigeminal neuralgia (ICHD-3 or ICOP-1)
38 findings
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Inattention All | Proportion (%) 1.7 [0.4, 6.4] GRADE not reported 3 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Instability Sensitivity analysis: excluding Munoz-Vendrell 2025 (retaining Munoz-Vendrell 2023 and Lappichetpaiboon 2024) | Proportion (%) 3.1 [1.0, 9.1] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Diplopia Sensitivity analysis: excluding Munoz-Vendrell 2023 (retaining Munoz-Vendrell 2025 and Lappichetpaiboon 2024) | Proportion (%) 0.0 [0.0, 100.0] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Dizziness Sensitivity analysis: excluding Munoz-Vendrell 2023 (retaining Munoz-Vendrell 2025 and Lappichetpaiboon 2024) | Proportion (%) 29.4 [16.6, 46.6] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Sleepiness/somnolence All | Proportion (%) 24.6 [0.4, 96.1] GRADE not reported 3 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Inattention Sensitivity analysis: excluding Munoz-Vendrell 2023 (retaining Munoz-Vendrell 2025 and Lappichetpaiboon 2024) | Proportion (%) 0.0 [0.0, 100.0] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Tremor All | Proportion (%) 0.8 [0.1, 5.7] GRADE not reported 3 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Instability All | Proportion (%) 2.5 [0.8, 7.5] GRADE not reported 3 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Nausea Sensitivity analysis: excluding Munoz-Vendrell 2023 (retaining Munoz-Vendrell 2025 and Lappichetpaiboon 2024) | Proportion (%) 0.0 [0.0, 100.0] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Bradycardia All | Proportion (%) 0.8 [0.1, 5.7] GRADE not reported 3 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Instability Sensitivity analysis: excluding Munoz-Vendrell 2023 (retaining Munoz-Vendrell 2025 and Lappichetpaiboon 2024) | Proportion (%) 0.0 [0.0, 100.0] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Bradycardia Sensitivity analysis: excluding Munoz-Vendrell 2023 (retaining Munoz-Vendrell 2025 and Lappichetpaiboon 2024) | Proportion (%) 0.0 [0.0, 100.0] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: First-degree atrioventricular block Sensitivity analysis: excluding Munoz-Vendrell 2025 (retaining Munoz-Vendrell 2023 and Lappichetpaiboon 2024) | Proportion (%) 1.0 [0.1, 6.9] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Itchiness Sensitivity analysis: excluding Munoz-Vendrell 2023 (retaining Munoz-Vendrell 2025 and Lappichetpaiboon 2024) | Proportion (%) 0.0 [0.0, 100.0] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Dizziness Sensitivity analysis: excluding Munoz-Vendrell 2025 (retaining Munoz-Vendrell 2023 and Lappichetpaiboon 2024) | Proportion (%) 21.4 [1.2, 86.2] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Dizziness All | Proportion (%) 21.7 [9.6, 41.8] GRADE not reported 3 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Pain relief (improvement without additional treatment) Within 3 months · All | Proportion (%) 66.7 [57.3, 74.9] Very low Downgraded: risk of bias, imprecision, indirectness 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Cutaneous rash Sensitivity analysis: excluding Munoz-Vendrell 2023 (retaining Munoz-Vendrell 2025 and Lappichetpaiboon 2024) | Proportion (%) 0.0 [0.0, 100.0] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Insomnia All | Proportion (%) 0.8 [0.1, 5.7] GRADE not reported 3 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Tremor Sensitivity analysis: excluding Munoz-Vendrell 2023 (retaining Munoz-Vendrell 2025 and Lappichetpaiboon 2024) | Proportion (%) 0.0 [0.0, 100.0] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Diplopia All | Proportion (%) 0.8 [0.1, 5.7] GRADE not reported 3 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse events (overall incidence) All | Proportion (%) 35.2 [26.8, 44.6] Very low Downgraded: risk of bias, imprecision, inconsistency, indirectness 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Cutaneous rash All | Proportion (%) 0.8 [0.1, 5.7] GRADE not reported 3 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Inattention Sensitivity analysis: excluding Munoz-Vendrell 2025 (retaining Munoz-Vendrell 2023 and Lappichetpaiboon 2024) | Proportion (%) 2.0 [0.5, 7.8] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Diplopia Sensitivity analysis: excluding Munoz-Vendrell 2025 (retaining Munoz-Vendrell 2023 and Lappichetpaiboon 2024) | Proportion (%) 1.0 [0.1, 6.9] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Sleepiness/somnolence Sensitivity analysis: excluding Munoz-Vendrell 2023 (retaining Munoz-Vendrell 2025 and Lappichetpaiboon 2024) | Proportion (%) 46.8 [0.0, 100.0] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Tremor Sensitivity analysis: excluding Munoz-Vendrell 2025 (retaining Munoz-Vendrell 2023 and Lappichetpaiboon 2024) | Proportion (%) 1.0 [0.1, 6.9] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: First-degree atrioventricular block Sensitivity analysis: excluding Munoz-Vendrell 2023 (retaining Munoz-Vendrell 2025 and Lappichetpaiboon 2024) | Proportion (%) 2.9 [0.4, 18.1] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: First-degree atrioventricular block All | Proportion (%) 1.7 [0.4, 6.4] GRADE not reported 3 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Nausea Sensitivity analysis: excluding Munoz-Vendrell 2025 (retaining Munoz-Vendrell 2023 and Lappichetpaiboon 2024) | Proportion (%) 1.0 [0.1, 6.9] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Insomnia Sensitivity analysis: excluding Munoz-Vendrell 2025 (retaining Munoz-Vendrell 2023 and Lappichetpaiboon 2024) | Proportion (%) 1.0 [0.1, 6.9] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Insomnia Sensitivity analysis: excluding Munoz-Vendrell 2023 (retaining Munoz-Vendrell 2025 and Lappichetpaiboon 2024) | Proportion (%) 0.0 [0.0, 100.0] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Bradycardia Sensitivity analysis: excluding Munoz-Vendrell 2025 (retaining Munoz-Vendrell 2023 and Lappichetpaiboon 2024) | Proportion (%) 1.0 [0.1, 6.9] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Itchiness Sensitivity analysis: excluding Munoz-Vendrell 2025 (retaining Munoz-Vendrell 2023 and Lappichetpaiboon 2024) | Proportion (%) 1.0 [0.1, 6.9] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Itchiness All | Proportion (%) 0.8 [0.1, 5.7] GRADE not reported 3 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Sleepiness/somnolence Sensitivity analysis: excluding Munoz-Vendrell 2025 (retaining Munoz-Vendrell 2023 and Lappichetpaiboon 2024) | Proportion (%) 26.7 [0.0, 100.0] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Cutaneous rash Sensitivity analysis: excluding Munoz-Vendrell 2025 (retaining Munoz-Vendrell 2023 and Lappichetpaiboon 2024) | Proportion (%) 1.0 [0.1, 6.9] GRADE not reported 2 studies |
| Oral lacosamide (any dose, monotherapy or adjunctive) | None (single-arm proportion) | Adverse event: Nausea All | Proportion (%) 0.8 [0.1, 5.7] GRADE not reported 3 studies |
Included primary studies 8
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Lappichetpaiboon 2025 Efficacy and safety of lacosamide in patients with trigeminal neuralgia: an 8-week pilot dose-escalation study DOI:10.22514/jofph.2025.011 | 2025 | this review only | not stated | not extracted yet |
| Lappichetpaiboon 2025 Efficacy and safety of lacosamide in patients with trigeminal neuralgia: an 8-week pilot dose-escalation study. PMID:40129429 | 2025 | this review only | not stated | not extracted yet |
| Munoz-Vendrell 2022 Intravenous lacosamide and phenytoin for the treatment of acute exacerbations of trigeminal neuralgia: A retrospective analysis of 144… PMID:35469475 | 2022 | this review only | not stated | not extracted yet |
| Muñoz-Vendrell 2022 Intravenous lacosamide and phenytoin for the treatment of acute exacerbations of trigeminal neuralgia: A retrospective analysis of 144 cases DOI:10.1177/03331024221092435 | 2022 | this review only | not stated | not extracted yet |
| Munoz-Vendrell 2023 Oral lacosamide for the treatment of refractory trigeminal neuralgia: A retrospective analysis of 86 cases. PMID:37036126 | 2023 | this review only | not stated | not extracted yet |
| Muñoz-Vendrell 2023 Oral lacosamide for the treatment of refractory trigeminal neuralgia: A retrospective analysis of 86 cases DOI:10.1111/head.14505 | 2023 | this review only | not stated | not extracted yet |
| Munoz-Vendrell 2025 Second-line pharmacological treatment strategies for trigeminal neuralgia: A retrospective comparison of lacosamide, gabapentin and… PMID:40341553 | 2025 | this review only | not stated | not extracted yet |
| Muñoz-Vendrell 2025 Second‐line pharmacological treatment strategies for trigeminal neuralgia: A retrospective comparison of lacosamide, gabapentin and baclofen DOI:10.1111/head.14952 | 2025 | this review only | not stated | not extracted yet |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Adults diagnosed with trigeminal neuralgia (ICHD-3 or ICOP-1) | Adults with trigeminal neuralgia (n=284 participants in 4 studies) |
| Intervention | Lacosamide, any dose, route or regimen, as monotherapy or adjunctive therapy | Oral lacosamide (3 studies); intravenous lacosamide (1 study) |
| Comparison | Active pharmacologic agents (carbamazepine, oxcarbazepine, gabapentin, baclofen, phenytoin) or usual care, when present | Phenytoin IV, carbamazepine, gabapentin or baclofen in some studies; not pooled |
| Outcomes | Pain outcomes (at least 50% pain relief, VAS/NRS, BPI-F change) or safety outcomes (adverse events, serious adverse events, withdrawals due to adverse events) | Pain relief (k=2 pooled); overall adverse events (k=2 pooled); 12 individual adverse events (k=3 pooled) |
| Study designs | Prospective or retrospective cohort studies | Cohort studies: 3 retrospective cohorts and 1 prospective controlled pilot clinical trial (n=4) |
| Timing | Not specified | Pain improvement within 3 months (pooled); 4-week BPI-F reduction and IV pain absence within 10 hours (not pooled) |
AMSTAR 2 items
Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | Partial Yes | Partial Yes | yes |
| 3Choice of study designs explained | No | No | yes |
| 4Comprehensive literature searchcritical | Partial Yes | Partial Yes | yes |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | No | No | yes |
| 8Included studies described in detail | Partial Yes | Partial Yes | yes |
| 9Risk of bias assessed satisfactorilycritical | NRSI: Yes · RCT: N/A | RCT: N/A · NRSI: Yes | no |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | NRSI: Yes · RCT: N/A | RCT: N/A · NRSI: Yes | no |
| 12Impact of risk of bias on the pooled results | No | No | yes |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | Yes | Yes | yes |
| 15Publication bias investigatedcritical | Yes | Yes | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Low | Low | yes |