Clinical Neurology · Epilepsy & EEG
AED Side Effects
Anti-seizure drug mechanism, indications, key side effects, clinical pearls, metabolism, and pregnancy category. Red = the most important (dangerous) effects. Indications: P = partial, G = generalized, A = absence, M = myoclonic.
| Drug & MOA | Indications | Key side effects | Clinical pearl | Metabolism | Preg |
|---|---|---|---|---|---|
| First-generation | |||||
| Carbamazepine Na-channel blocker | P, G | SJS/TEN (HLA-B*1502) Heme: aplastic anemia, leukopenia Neuro: nystagmus, dizziness, diplopia Hyponatremia; teratogenic (NTD) | Test HLA-B*1502 in Asians first; auto-induction → levels drop over 2–4 wk. | Hepatic (auto-induction) | D |
| Ethosuximide T-type Ca-channel blocker | A | Neuro: drowsiness, headache GI: N/V, hiccups Heme: aplastic anemia, leukopenia | First-line for absence; no effect on tonic-clonic. | Hepatic | D |
| Valproate ↑GABA; Na/Ca-channel; HDAC inhibitor | P, G, A, M | GI: hepatotoxicity (<2 y), pancreatitis, ↑ammonia Teratogenic (NTD, ↓IQ) Heme: thrombocytopenia Weight gain, PCOS, alopecia, tremor | Broadest spectrum; avoid in women of childbearing age; check LFTs/ammonia. | Hepatic | X |
| Phenytoin Na-channel blocker | P, G (not absence) | CV: hypotension/arrhythmia (IV) Skin: SJS/TEN; gingival hyperplasia, hirsutism Neuro: ataxia, nystagmus, tremor Fetal hydantoin syndrome | Zero-order kinetics — small dose ↑ → big level ↑; correct level for albumin. | Hepatic (zero-order) | D |
| Phenobarbital GABA-A agonist | P, G, M | Respiratory depression / dependence Neuro: sedation; hyperactivity (kids) Heme: megaloblastic anemia; vit-K coagulopathy | Neonatal seizures first-line; potent enzyme inducer. | Hepatic | D |
| Second-generation | |||||
| Gabapentin α2δ Ca-channel binding | P (adjunct) | DRESS, angioedema Neuro: sedation, dizziness, ataxia Behavioral (kids); leg edema | Renally cleared, no interactions; also for neuropathic pain. | Renal | C |
| Topiramate Na-channel; ↑GABA; ↓AMPA; CA inhibitor | P, G, M | Renal: kidney stones; metabolic acidosis Eye: acute glaucoma Cognitive: word-finding, paresthesia; weight loss; hypohidrosis (kids) | Bonus: migraine prophylaxis + weight loss; avoid other CA inhibitors. | Renal (70%) | D |
| Lamotrigine Na-channel blocker | P, G (± absence) | SJS/TEN 0.8% (fast titration / valproate), DRESS Rare: HLH, aseptic meningitis Neuro: dizziness, headache, diplopia, insomnia | Titrate SLOWLY (rash); halve dose with valproate; good in pregnancy/mood. | Hepatic (glucuronidation) | D |
| Levetiracetam SV2A binding | P, G, M | Psych: irritability, aggression, depression Neuro: somnolence, asthenia | No interactions + IV load → go-to in status/ICU; watch mood. | Renal | C |
| Oxcarbazepine Na-channel blocker | P, G | Endo: hyponatremia (> CBZ) Skin: SJS/TEN; rash (25% cross-react CBZ) Neuro: dizziness, diplopia, sedation | Check Na; less enzyme induction than CBZ; ~25% rash cross-reactivity. | Hepatic | C |
| Zonisamide Na/T-Ca channel; CA inhibitor | P, G, M | Skin: SJS, DRESS (sulfa) Renal: kidney stones, oligohidrosis, metabolic acidosis Neuro: sedation, cognitive slowing, ataxia | Once-daily; sulfa-allergy caution; weight loss. | Hepatic / renal | D |
| Tiagabine (Gabitril) GABA reuptake inhibitor | P (adjunct, >12 yr) | Provokes seizures / NCSE (overdose, off-label) Neuro: dizziness, tremor, cognitive | Can precipitate NCSE; avoid in non-epileptic patients. | Hepatic | C |
| Felbamate NMDA antagonist; Na-channel | Refractory (LGS) | Aplastic anemia (1:5000) Hepatic failure (boxed) GI: anorexia, weight loss, insomnia | Reserved — informed consent + CBC/LFT monitoring. | Hepatic | C |
| Third-generation | |||||
| Lacosamide (Vimpat) Enhances slow Na inactivation | P | CV: PR prolongation, AF (in DM) Neuro: dizziness, ataxia, diplopia | Baseline ECG (PR); IV available; well tolerated. | Renal | C |
| Brivaracetam (Briviact) SV2A (20× affinity vs LEV) | P | Neuro: sedation, dizziness, fatigue Psych: irritability (less than LEV) | Like levetiracetam with less irritability. | Renal | C |
| Clobazam (Onfi) GABA-A potentiation | LGS (adjunct, >2 yr) | Skin: SJS/TEN Neuro: sedation (avoid CNS depressants) | LGS adjunct; less sedation than other benzos. | Hepatic | C |
| Perampanel (Fycompa) AMPA antagonist | P, G | Psych: aggression, homicidal/suicidal ideation (boxed) Neuro: dizziness, gait disturbance, falls | Once-daily at bedtime; counsel re boxed psychiatric warning. | Hepatic | C |
| Vigabatrin (Sabril) Irreversible GABA-transaminase inhibitor | Infantile spasms (refractory CPS) | Permanent peripheral vision loss (boxed) MRI changes / intramyelinic edema (infants) Neuro: sedation | Serial visual-field testing (REMS); first-line for infantile spasms in TSC. | Renal | D |
| Rufinamide (Banzel) Prolongs Na inactivation | LGS | CV: shortened QT (avoid familial short-QT) Neuro: dizziness, somnolence, ataxia | LGS; take with food; check QTc. | Hepatic | C |
| Eslicarbazepine (Aptiom) Na-channel blocker | P | Endo: hyponatremia Neuro: dizziness, diplopia Skin: rash (like oxcarbazepine) | Once-daily, oxcarbazepine-like; check Na. | Hepatic | C |
| Newest agents (2018+) | |||||
| Cannabidiol (Epidiolex) GPR55 / TRPV1 / adenosine modulation | LGS, Dravet, TSC | Hepatotoxicity (↑LFTs) Neuro: somnolence; GI: diarrhea, ↓appetite Interaction: ↑ with clobazam / valproate | Monitor LFTs; ↑ clobazam active metabolite. | Hepatic (CYP3A4/2C19) | — |
| Cenobamate (Xcopri) Persistent Na current + GABA-A modulator | P (adults) | DRESS/DIHS (slow titration) QT shortening Neuro: somnolence, dizziness, diplopia | Very slow titration to avoid DRESS; highly effective for focal. | Hepatic | — |
| Fenfluramine (Fintepla) Serotonin releaser; 5-HT / sigma-1 | Dravet, LGS | Valvulopathy & pulmonary HTN (REMS echo) ↓appetite, somnolence, fatigue | Baseline + q6-month echo (REMS); very effective in Dravet. | Hepatic | — |
| Ganaxolone (Ztalmy) Neuroactive steroid; GABA-A modulator | CDKL5 | Neuro: somnolence, sedation Pyrexia | For CDKL5 deficiency disorder. | Hepatic | — |
Common to all AEDs: suicidal ideation (OR ~1.8), sedation. DRESS = drug reaction with eosinophilia & systemic symptoms. SJS/TEN = Stevens-Johnson syndrome / toxic epidermal necrolysis. CA = carbonic anhydrase. Pregnancy: X = contraindicated, D = known risk, C = risk not excluded, — = no category (PLLR).
Neuro.Wiki by Ahmed Koriesh, MD — Educational only, not a substitute for clinical judgement