Summary
Phenytoin has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Epilepsy would be drug repurposing rather than first-in-human development. This does not mean it is approved for Epilepsy. ClinicalTrials.gov lists 8 registered trials linking Phenytoin to Epilepsy: 6 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT00510783). The largest enrolment is 172 participants (NCT02056236). Registration activity spans 2005 to 2019. The literature layer holds 17 publications for this pair: 5 Cochrane reviews, 4 meta-analyses, 3 systematic reviews and 5 clinical trial publications. Publication years run from 2023 to 2026. Because at least one synthesis-level source exists (systematic review, meta-analysis or Cochrane review), this pair has been assessed beyond single studies, although the synthesis may concern a different indication.
The RepurpOS disease-intelligence file for Epilepsy ranks 187 candidate therapeutics from Open Targets, ChEMBL, DGIdb and PubMed; only a minority carry direct clinical evidence, and this page covers one of those. Spontaneous remission context recorded for the condition: 60-85% achieve seizure freedom on medication; of those, 50-75% remain seizure-free after withdrawal (varies by syndrome and duration of freedom).
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 73.5 (trials 23.5, literature 30.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 0 recruiting, 0 active / not yet recruiting, 6 completed, 2 other |
| Linked publications | 17 (5 Cochrane reviews, 5 clinical trial publications, 4 meta-analyses, 3 systematic reviews) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | Not recorded |
| Data sources | Open Targets, ChEMBL |
| Linked via biomarker / target | AARS1 |
How the evidence score is calculated
- Each registered trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5). The trial component is capped at 30.
- Each literature item scores by design (Cochrane review 5, meta-analysis 4, systematic review 3, RCT 3, clinical trial publication 2, curated reference 1.5, other PubMed record 1). The literature component is capped at 30.
- The existing evidence tier adds 15 (A / Strong), 10 (B / Moderate), 5 (C / Preliminary) or 0 (D / Anecdotal).
- Agents approved for any indication (max clinical phase 4) add 5, because an approved agent has an established safety profile that lowers the barrier to repurposing trials.
- The score ranks what has been studied, not what works. It does not read effect sizes or directions of effect.
Registered clinical trials
| NCT ID | Title | Status | Phase | Enrolment |
|---|---|---|---|---|
| NCT00510783 | IV Keppra in the Emergency Department for Prevention of Early Recurrent Seizures 2007 | completed | Phase 4 | 158 |
| NCT00552526 | Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy 2007 | status unknown | Phase 4 | 60 |
| NCT03325439 | A Study to Test the Pharmacokinetics, Efficacy, and Safety of Brivaracetam in Newborns With Repeated Electroencephalographic Seizures 2019 | terminated | Phase 3 | 9 |
| NCT00426673 | An Open-Label Interaction Study to Look at the Effects of Brivaracetam on Phenytoin When Taken Together in 15 Adult Patients With Epilepsy. 2005 | completed | Phase 1 | 15 |
| NCT00627575 | AED/Statin Interaction Study 2008 | completed | Phase 1 | 119 |
| NCT02056236 | TELSTAR: Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resuscitation 2014 | completed | Not applicable | 172 |
| NCT05236166 | Multicentre Study on Rapid Versus Slow Withdrawal of Antiepileptic Monotherapy 2017 | completed | Not applicable | 48 |
| NCT00612235 | Premenstrual Dysphoric Disorder and Antiepileptic Drugs 2008 | completed | Not applicable | 80 |
Published literature
- Cochrane review Breaking the resistance: a narrative review of the evolution from traditional drugs to precision therapies in epilepsyPatel T, Henna F, Ahmad A et al. · Annals of medicine and surgery (2012) · 2026 · PMID 41496926
- Systematic review Pharmacogenomics of anti-seizure medications in epilepsy: a systematic review of genetic predictors of response and toleranceBarguilla A, Riera P, Ros-Castelló V et al. · Expert review of neurotherapeutics · 2026 · PMID 41875007
- Clinical trial publication Pentoxifylline as Adjuvant Therapy in Patients with Generalized Epilepsy Treated with Phenytoin: A Randomized Controlled StudyYounis MA, El-Haggar SM, Mustafa W et al. · Molecular neurobiology · 2025 · PMID 40739381
- Cochrane review Psychiatric and behavioural side effects of antiseizure medications in epilepsyLyndon S, Dworetzky BA, Baslet G · Journal of neurology · 2025 · PMID 41432787
- Cochrane review Effects of Antiseizure Medications on Lipid Profile and Weight in Patients with Epilepsy: A Systematic Review with Meta-analysisChochoł P, Arturo N, Łajczak PM et al. · CNS drugs · 2025 · PMID 41032224
- Meta-analysis Role of different anti-seizure medications on carotid intima-media thickness: A systematic review and meta-analysisDavari A, Bahadori AR, Mohammadi-Asl A et al. · Medicine · 2025 · PMID 41204548
- Meta-analysis Efficacy and safety of levetiracetam for pediatric convulsive status epilepticus in emergency settings: a systematic review and meta-analysisAlsabri M, Elsayed SM, Rath S et al. · BMC neurology · 2025 · PMID 40739189
- Meta-analysis Valproic acid-induced hyperammonemia with encephalopathy in adults: A meta-analysisHuang TK, Su YC, Shih CS · International journal of clinical pharmacology and therapeutics · 2025 · PMID 39873559
- Meta-analysis Guidelines for Seizure Prophylaxis in Patients Hospitalized with Nontraumatic Intracerebral Hemorrhage: A Clinical Practice Guideline for Health Care Professionals from the Neurocritical Care SocietyFrontera JA, Rayi A, Tesoro E et al. · Neurocritical care · 2025 · PMID 39707127
- Systematic review Optimizing phenytoin therapy: a systematic review of clinically relevant food and herb interactionsOrellana-Paucar AM, Mosquera-Lopez ET, Bustamante-Alvarez NM et al. · Frontiers in pharmacology · 2025 · PMID 41560756
- Systematic review Cytotoxic lesions of the corpus callosum related to epilepsy or anti-seizure medications: a systematic reviewCutillo G, Bonelli G, Rubin M et al. · Seizure · 2025 · PMID 41237482
- Clinical trial publication Efficacy and safety of phenytoin and levetiracetam for acute symptomatic seizures in children with acute encephalitis syndrome: an open label, randomised controlled trialSharawat IK DM, Murugan VK MD, Bhardwaj S MD et al. · Seizure · 2024 · PMID 38678766
- Clinical trial publication Efficacy and Tolerability of Adjunctive Brivaracetam in Patients with Focal-Onset Seizures on Specific Concomitant Antiseizure Medications: Pooled Analysis of Double-Blind, Placebo-Controlled TrialsMoseley B, Bourikas D, Dimova S et al. · Advances in therapy · 2024 · PMID 38356105
- Cochrane review Seizure control and adverse outcomes of lamotrigine use during pregnancy: A systematic review and meta-analysisWan X, Wu Y, Zou Q et al. · Epilepsy & behavior : E&B · 2024 · PMID 38945077
- Clinical trial publication Efficacy Of Levetiracetam Versus Phenytoin As A Second-Line Antiepileptic Drug In The Management Of Benzodiazepine-Refractory Status Epilepticus Among ChildrenNaeem B, Ashfaq M, Qureshi MA · Journal of Ayub Medical College, Abbottabad : JAMC · 2023 · PMID 38404082
- Clinical trial publication Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for adult convulsive status epilepticus: a multicentre non-inferiority randomised control trialNakamura K, Marushima A, Takahashi Y et al. · Journal of neurology, neurosurgery, and psychiatry · 2023 · PMID 36207063
- Cochrane review Anti-seizure medications for neonates with seizuresAbiramalatha T, Thanigainathan S, Ramaswamy VV et al. · The Cochrane database of systematic reviews · 2023 · PMID 37873971
Mechanism and notes
No mechanism of action is recorded for this pair in the source databases.
OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in Open Targets and ChEMBL, in this case via the biomarker or target AARS1. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Phenytoin approved for Epilepsy?
Phenytoin has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Epilepsy would be drug repurposing rather than first-in-human development. This does not mean it is approved for Epilepsy. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Phenytoin in clinical trials for Epilepsy?
ClinicalTrials.gov lists 8 registered trials linking Phenytoin to Epilepsy: 6 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT00510783). The largest enrolment is 172 participants (NCT02056236). Registration activity spans 2005 to 2019.
What does the evidence show for Phenytoin in Epilepsy?
Phenytoin has both completed registered trials and synthesis-level publications linked to Epilepsy. That is the strongest profile in this database, but the summaries here do not extract effect sizes, so read the linked reviews for direction and magnitude of benefit. OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in Open Targets and ChEMBL, in this case via the biomarker or target AARS1. The tier describes how well the drug-disease link is documented, not how well the drug works.
Cite this page
Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-07-05. Page built 2026-10-07.