Table 1.
Currently approved anti-seizure medications in paediatric age.
| Drug formulation | FDA approval for seizure type(s) and/or syndrome (age if specified) | EMA approval for seizure type(s) and/or syndrome (age if specified) | Main mechanism(s) of action |
|---|---|---|---|
| Adrenocorticotropic hormone (ACTH) Injection |
Monotherapy in infantile spasms (<2 y) | NA | Unknown, adrenocortical secretion stimulator |
| Brivaracetam (BRV) Tablets Oral solution Injection |
Partial onset seizures (>1 m) | Adjunctive therapy for partial-onset seizures with or without secondary generalisation (>2 y) | Binding synaptic vesicle SV2A |
| Cannabidiol (CBD) Oral solution |
LGS, DS, TSC (>1 y) | Adjunctive therapy (with CLB) in LGS and DS (>2 y) Adjunctive therapy in TSC (>2 y) |
GPR55 and TPRV1 channels modulator, ENT-1 inhibitor |
| Carbamazepine (CBZ) Tablets(XR) Oral solution |
Partial seizures with complex symptomatology, GTC, mixed seizure patterns (CBZ does not control absences) | Partial seizures with complex symptomatology, GTC, mixed seizure patterns (CBZ does not control absences and myoclonic seizures) | Voltage-gated sodium channels blocker (by stabilizing fast-inactivated state) |
| Cenobamate (CBN) Tablets |
Partial-onset seizures in adult patient (>18 y) | Adjunctive treatment of focal-onset seizures with or without secondary generalisation in adult patients | Voltage-gated sodium channels blocker (by blocking the persistent sodium current), positive allosteric modulation of GABAA receptors |
| Clobazam (CLB) Tablets Oral solution |
Adjunctive treatment in LGS (>2 y) | NA | Positive allosteric modulator of GABAA receptors |
| Clonazepam (CNZ) Tablets Oral solution Injection |
LGS, atonic, myoclonic Absence who have failed succinimides (injection) |
NA | Positive allosteric modulator of GABAA receptors |
| Eslicarbazepine acetate (ESL) Tablet |
Partial-onset seizures (>4 y) | Adjunctive therapy in partial-onset seizures with or without secondary generalisation (>6 y) | Voltage-gated sodium channels blocker (by stabilizing fast-inactivated state) |
| Ethosuximide (ETH) Capsule Oral solution |
Absence epilepsy (>3 y) | Absence epilepsy | Low-voltage activated calcium channels (T-type) blocker |
| Everolimus Tablets |
Adjunctive treatment of partial-onset seizures in TSC (>2 y) | Add-on in partial-onset seizures in TSC that have not responded to other treatments (>2 y) | mTOR inhibitor |
| Felbamate (FBM) Tablet Oral solution |
Adjunctive therapy in partial and generalized seizures associated with LGS (>2 y) | Adjunctive therapy in partial and generalized seizures associated with LGS (>4 y) | NMDA receptors antagonist, positive modulating action on GABAA receptors, voltage-sensitive sodium and calcium channels blocker |
| Fenfluramine (FFA) Oral solution |
Seizures associated with DS and LGS (>2 y) | Adjunctive therapy in seizures associated with DS and LGS (>2 y) | Serotonin-releasing agent |
| Gabapentin (GBP) Tablet Capsule Oral solution |
Adjunctive therapy in partial onset seizures, with and without secondary generalization (>3 y) | Adjunctive therapy in partial onset seizures, with and without secondary generalization (>6 y) Monotherapy in partial onset seizures, with and without secondary generalization (>12 y) |
High voltage-activated calcium channels (P/Q type) blocker, through binding to the α2δ-1 subunit |
| Ganaxolone (GNX) Oral solution |
Seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (>2 y) | Seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (2–17 y) |
Positive allosteric modulator for both synaptic and extrasynaptic GABAA receptors |
| Lacosamide (LCM) Tablet Oral solution Injection |
Partial-onset seizures (>4 y) Partial-onset seizures (>17 y) (injection) |
Monotherapy in partial-onset seizures with or without secondary generalisation (2 y) Adjunctive therapy in partial-onset seizures with or without secondary generalisation (2 y) and primary GTC seizures in patients with IGE (4 y) |
Voltage-gated sodium channels blocker (by stabilizing slow-inactivated state) |
| Lamotrigine (LTG) Tablet |
Adjunctive therapy in partial-onset seizures, primary GTC, generalized seizures of LGS (>2 y) Conversion to monotherapy in partial-onset seizures (>16 y) |
Adjunctive treatment in partial seizures and generalized seizures, including tonic-clonic seizures and seizures associated with LGS (>2 y) Monotherapy of typical absence seizures (>2 y) Adjunctive or monotherapy treatment in partial seizures and generalized seizures, including tonic-clonic seizures and seizures associated with LGS (>13 y) |
Voltage-gated sodium channels blocker (by stabilizing fast-inactivated state and consequently modulating presynaptic transmitter release of excitatory amino acids), calcium channels blocker (N- and P/Q-type, weakly T-type) |
| Levetiracetam (LEV) Tablet Oral solution Injection |
Adjunctive therapy in partial-onset seizures (>1 m), myoclonic seizures in patients with JME (>12 y), primary GTC in patients with IGE (>6 y) | Monotherapy in partial-onset seizures with or without secondary generalisation (>16 y) Adjunctive therapy in partial-onset seizures (>1 m), myoclonic seizures in patients with JME (>12 y), primary GTC in patients with IGE (>12 y) |
Binding synaptic vesicle SV2A |
| Oxcarbazepine (OXC) Tablet Oral solution |
Partial seizures (adjunctive therapy >2 y, monotherapy >4 y) | Monotherapy or adjunctive therapy in partial seizures with or without secondarily GTC seizures (>6 y) | Voltage-gated sodium channels blocker (by stabilizing fast-inactivated state) |
| Perampanel (PER) Tablet |
Partial-onset seizures with or without secondarily generalized seizures (>4 y); Adjunctive therapy in primary GTC (>12 y) |
Adjunctive treatment in partial-onset seizures with or without secondarily generalized seizures (>4 y) Primary GTC seizures in patients with IGE (>7 y) |
Non-competitive AMPA glutamate receptor antagonist |
| Phenobarbital (PHB) Tablet Oral solution Injection |
Treatment of neonatal seizures in term and preterm infants (injection form) | NA | Positive allosteric modulator of GABAA receptors (agonist effect at high doses) |
| Phenytoin (PHT) Tablet Capsule Oral solution Injection |
GTC and complex partial seizures; prevention or treatment of seizures occurring during or following neurosurgery | GTC, partial seizures or a combination of these; prevention and treatment of seizures occurring during or following neurosurgery and/or severe head injury Status epilepticus of the tonic-clonic type and prevention and treatment of seizures occurring during or following neurosurgery and/or severe head injury |
Voltage-gated sodium channels blocker (by stabilizing fast-inactivated state) |
| Pregabalin (PGB) Tablet Capsule Oral solution |
Adjunctive therapy for the treatment of partial onset seizures (>4 y) | Add-on to existing treatment in patients who have partial seizures | High voltage-activated calcium channels (P/Q type) blocker, through binding to the α2δ-1 subunit |
| Primidone (PRM) Tablet |
Alone or add-on in GTC, psychomotor and focal seizures | Grand mal and psychomotor (temporal lobe) epilepsy; management of focal or Jacksonian seizures, myoclonic jerks and akinetic attacks | Antiseizure activity per se, as do its two metabolites, phenobarbital and phenylethylmalonamide |
| Rufinamide (RUF) Tablet Oral solution |
Adjunctive treatment in LGS (>1 y) | Adjunctive treatment in LGS (>1 y) | Voltage-gated sodium channels blocker (by stabilizing fast-inactivated state) |
| Stiripentol (STP) Tablet Powder for oral solution |
Adjunctive in DS with CLB (>2 y) | Adjunctive therapy with CLB and VPA for refractory GTC in patients with severe myoclonic epilepsy in infancy | Positive allosteric modulator of GABAA receptors, GABA transmission enhancer |
| Tiagabine hydrochloride (TGB) Tablet |
Adjunctive therapy in partial seizures (>12 y) | Add-on therapy for partial seizures with or without secondary generalisation (>12 y) | GABA transporter 1 inhibitor |
| Topiramate (TPM) Tablet Capsule Sprinkle |
Monotherapy in partial onset or primary GTC (>2 y) Adjunctive therapy in partial onset seizures or primary GTC seizures, seizures associated with LGS (>2 y) |
Monotherapy in partial seizures with or without secondary generalisation and primary GTC (>6 y) Adjunctive therapy for partial onset Seizures with or without secondary generalization or primary GTC And for the seizures associated with LGS (>2 y) |
Voltage-dependent sodium channels blocker, GABA transmission enhancer, AMPA/kainate receptor antagonist, carbonic anhydrase inhibitor (particularly isozymes II and IV) |
| Valproic acid (VPA) Tablet Oral solution Capsule Sprinkle Injection |
Monotherapy and adjunctive therapy in complex partial seizures Monotherapy and adjunctive therapy in simple and complex absence seizures Adjunctive therapy in multiple seizure types that include absence seizures |
Treatment of generalized epilepsy: Clonic, tonic, tonic-clonic, absence, myoclonic and atonic seizures Treatment of partial epilepsy: Partial seizures with or without secondary generalisation Treatment of specific syndromes (West, LGS) |
GABA transmission enhancer, voltage-gated sodium channels blocker, T-type calcium currents inhibitor, NMDA-receptor antagonist, histone deacetylase inhibitor |
| Vigabatrin (VGB) Tablet Powder for oral solution |
Monotherapy in infantile spasms (1 m–2 y) Adjunctive therapy in refractory complex partial seizures (>10 y) |
Monotherapy in infantile spasms Adjunctive therapy in resistant partial epilepsy (focal onset seizures) with or without secondary generalisation where all other appropriate medicinal product combinations have proved inadequate or have not been tolerated (1 m–7 y) |
GABA transaminase inhibitor |
| Zonisamide (ZNS) Tablet Oral solution |
Adjunctive therapy in partial-onset seizures (>16 y) | Adjunctive therapy in partial seizures, with or without secondary generalisation (>6 y) | Voltage-gated sodium channels and T-type calcium channels blocker, carbonic anhydrase inhibitor |
Legend: ASMs, anti-seizure medications; DRE drug-resistant epilepsy; EMA, European Medicines Agency; DS, Dravet syndrome; FDA, Food and Drug Administration; ENT-1, equilibrative nucleoside transporter 1; GPR55, (G protein-coupled receptor 55; GTC, generalized tonic-clonic; IGE, idiopathic generalized epilepsy; LGS, Lennox-Gastaut syndrome; m, month(s); NA, not available; TRPV1, transient receptor potential vanilloid 1; TSC, tuberous sclerosis complex; (XR), extended release available; y, year(s).