Table 1 Therapeutic relevance of VGSC inhibitors in the treatment of epilepsies, DS and other pharmacoresistant epilepsies, and limitations of specific inhibitors
From: Therapeutic efficacy of voltage-gated sodium channel inhibitors in epilepsy
VGSC inhibitor | Form of epilepsy | Clinical efficacy | Limitation of inhibitors |
|---|---|---|---|
Phenytoin | Status epilepticus | More efficacious than levetiracetam in treating SE | Exacerbate Dravet syndrome and other SCNA1 related epilepsies |
EIEE | Most effective in treatment of EIEE | Aggravate Juvenile myoclonic epilepsy | |
Rufinamide | LGS | Adjunctive for the treatment of LGS | Numerous adverse side effects: Hyperkinesia, hypotension, locomomotor dysfunction, megaloblastic anemia, SJS, hypotension, hyperkinesia, cardiovascular collapse, peripheral neuropathy |
EIMFS | Effective in treating migrating focal seizures | Â | |
SCN8A encephalopathy | Effective against SCN8A encephalopathy Mitigate SCN1B mutation-related epilepsy | Â | |
| Â | (Epileptic encephalopathy, early infantile, EIEE52) | Â | |
| Â | Moderate efficacy in treatment of benign familial infantile, EIEE5 | Â | |
GTCS | Used to treat general tonic-colonic seizures | Â | |
CPS | Remission of complex partial seizures | Â | |
Myoclonic seizures | PHT should not be used to treat myoclonic seizures | Â | |
Carbamazepine | SCN2A epilepsy | Effective in some SCN2A epileptic | May aggravate Juvenile myoclonic epilepsy and DS |
| Â | Patients at high doses | Â | |
TLE | Most effective against TLE | Exacerbate generalized atypical absence seizure | |
Bilateral tonic clonic seizure | Ameliorate bilateral tonic clonic seizure | Â | |
Simple partial seizure | Remission of simple partial seizure | Some side effects may include: | |
Tonic–clonic seizure | Alleviate Tonic–clonic seizures | Blurry or double vision | |
DS | Contraindicated in DS | Nausea, headache, dizziness | |
Valproic acid | Juvenile myoclonic epilepsy | Control of seizures in 70% to 85% of patients treated with valproic acid monotherapy or polytherapy | VPA therapy induces hypoadiponectinemia which correlates negatively with insulin resistance |
DS | First-line agent to cause remission in DS but not effective to cause total seizure freedom | Â | |
Lennox-Gastaut syndrome | One of the first-line therapies for the treatment of Lennox-Gastaut Syndrome | Induced weight, seems to be appetite-related than metabolic | |
Temporal lobe epilepsy | Effective in the treatment of TLE when combined with CBZ and PTH | potent teratogen | |
Myoclonic seizures | Often exquisitely responsive to treatment with valproic | Rarely used in the elder ly because of its hepatotoxic effects | |
Refractory seizures | Causes seizure freedom in patients with refractory seizures | Â | |
Tonic–clonic seizures | Effective for primary generally tonic–clonic seizures compared to lamotrigine | Its use is accompanied with numerous side effects: | |
Focal aware seizure | Relative efficacious in the treatment of FAS | VPA encephalopathy, coagulopathies, diarrhea, vomiting, bone marrow anomaly ataxia, tremor | |
Bilateral tonic clonic seizure | Equal efficacy with ethosuximide but more efficacious than lamotrigine in the management of BTCS | Valproic acid-induced hyperammonemia in children | |
Complex partial seizures | Effective in the control of CPS | Â | |
Lamotrigine | Subtle seizures/Focal seizures | Very favorable drug for treating epilepsy in people with intellectual disability | Highly tolerable with few adverse side effects: diplopia, headache, ataxia |
DS | LCM is contraindicated in DS | Â | |
Refractory Seizures/GTS/ Absence | Lamotrigine has certain advantages over Carbamazepine because it has less side effects and high tolerability | Â | |
LGS | Cause remission in patients with LGS | Â | |
Myoclonic Seizures | LCM aggravates myoclonic seizures | ||
TPM | GTCS/Absence/Focal seizures | Has efficacy as monotherapy or adjunctive therapy in adult and paediatric patients with GTCS, absence and focal seizures | Mild side effect of cognitive impairment |
Myoclonic seizures | TPM appears effective in neonatal seizure Like myoclonic seizure | Â | |
LGS | Adjunctive therapy in patients with LGS | Undefined sleep disturbances | |
Dravet syndrome | TPM is useful as an adjunctive therapy in patients with DS and carry additional benefits in other refractory cases of epilepsies | Â | |
Oxcarbazepine | Partial-onset seizures | Effective in alone or in combination with other ASMs in the treatment of partial-onset seizures | Fewer side effects compared to its other family member of CBZ and ESL |
GTCS | Monotherapy is as effective as phenytoin and vaiproic acid at reducing generalised tonic–clonic and partial seizure frequency | Side effects include: hyponatremia, thyroid abnormalities double vision, mental-depression, crying, clumsiness | |
| Â | more favorable pharmacokinetic and metabolic profile when used in the treatment of GTCS | Â | |
Myoclonic seizures | Oxcarbazepine worsen myoclonic seizures | Should be avoided in patients with myoclonic | |
Dravet syndrome | should be avoided, as they typically exacerbate DS type of seizure | Â | |
Eslicarbazepine | TLE | More effective in reducing TLE seizure frequency than a placebo | Similar side effects with other family members of CBZ and ZNS such as: |
FIAS | Suppress seizure activity but may also inhibit the generation of a hyperexcitable network | Diplopia | |
SGS | Effective, safe and well tolerated third-generation ASM for the treatment of focal epilepsies | Â | |
DS | Beneficial in some DS patients | Â | |
Zonisamide | LGS | Effective due to its broad spectrum of anticonvulsant activity | Â |
FIAS | Long-term use of adjunctive zonisamide therapy may be beneficial with FIAS | Â | |
Dravet syndrome | Fails to decrease seizures in all SCN1A-positive cases | Â | |
Lacosamide | Focal aware seizure/GTCS | Favorable tolerability and pharmacokinetic profiles when used in the treatment of partial-onset seizures and generalized tonic–clonic seizures | LCM therapy has a higher level of suicidal thought and actions |
MTLE | Early LCM treatment has effective anti-ictogenic properties in the pilocarpine model of MTLE | Increase chances of development of atrial fibrillation | |
DS | Not effective in tackling DS | Â | |
SPS/ idiopathic generalized epilepsy | Adjunctive treatment for uncontrolled primary generalized tonic–clonic seizures in those with idiopathic generalized epilepsy |  | |
DRE | Effective in the treatment of focal DRE | Rarely, a drop in White blood cell is Seen in patients | |
Fosphenytoin | GTCS | Alternative to intravenous phenytoin for acute. treatment of seizures | Â |
| Â | Advantages include more convenient and rapid intravenous administration, availability for intramuscular injection, and low potential for adverse local reactions at injection sites | Drawbacks include the occurrence of transient paraesthesias and pruritus at infusion rates and cost | |
DS | Just like its prodrug phenytoin, Fosphenytoin should be avoided as medication for DS but may be useful in the treatment of SE | Â | |
Cenobamate | DS | May lead to a clinically meaningful reduction of seizure frequency in a few adult patients with DS | It is unclear, if all patients with DSÂ benefit, requiring further investigations and functional experiments |
Focal-onset seizures | Effective in the treatment of focal-onset seizures | Complex drug–drug interactions which decrease plasma concentrations of LCM and CBZ and increase levels of PHT | |
LGS | CNB may represent a promising therapeutic option in patients with drug-resistant epilepsy associated with LGS | Â |