Antiepileptics are drugs that are used to prevent and treat seizures by controlling abnormal electrical activity in the brain. They are also known as anticonvulsants or AEDs. Epilepsy is a chronic disorder characterized by recurring seizures. Seizures are caused due to dysregulated electrical activity in the brain, either localized or generalized. AEDs regulate and stop disorderly electrical activity by acting on ion channels like sodium channels, GABA mediated chloride channels, and calcium channels. Some block glutamate mediated electrical currents. Most AEDs have varying effects on multiple ion channels. Phenytoin, topiramate, zonisamide, valproic acid, lamotrigine and carbamazepine are the strongest sodium channel blockers. Drugs from the benzodiazepine class, like clonazepam, have strong GABA blocking activity. Ethosuximide blocks calcium channels. Some antiepileptics like gabapentin, pregabalin and carbamazepine are effective to treat neuropathic pain.
Commonly prescribed antiepileptics and their brand names are listed below:
Antiepileptics are frequently associated with adverse effects, which may make it difficult to adhere to treatment. Common adverse effects include drowsiness, rash, diarrhea, disruption of menstrual cycles, infertility, sexual dysfunction, teratogenicity, cognitive issues, and restlessness. Weight gain occurs with valproic acid, gabapentin, carbamazepine, and pregabalin. Weight loss occurs with topiramate, zonisamide, and felbamate. There may be increased suicidal tendencies, changes in blood counts, and severe allergic reactions. Phenytoin causes gum hyperplasia or overgrowth and hirsutism. Valproate is associated with the highest risk of congenital defects in newborn children. Vision problems occur with vigabatrin, while metabolic disturbances like Vitamin D deficiency and dyslipidemias are seen with carbamazepine, phenytoin, and barbiturates. Liver dysfunction may be caused by felbamate and valproate.
Sold under the brand names Lithobid, Carbolith, and Eskalith, lithium is used in the treatment of bipolar disorder and some cases of schizophrenia. Bipolar disorder is a mood disorder characterized by episodes of mania followed by episodes of depression. Lithium is a mood stabilizer that can control manic symptoms in bipolar disorder. It balances neurotransmitters like GABA and dopamine in the brain, reduces oxidative stress and inhibits enzyme glycogen synthase kinase, and has a neuroprotective effect. Adverse effects include restlessness, tremors, bloating, weight changes, rash, and hair loss. Lithium excess may cause toxicity that begins as nausea, vomiting, abdominal pain, mental status changes like delirium, imbalance, slurred speech, seizures, and coma. Chronic toxicity may cause kidney damage called nephrogenic diabetes insipidus, which causes excessive urination, thirst, and dehydration. It may cause thyroid dysfunction. Lithium is a narrow therapeutic index drug and blood levels have to be monitored regularly.
Drugs used in the treatment of psychotic disorders: Antipsychotics are medications that are used to treat psychosis, which is seen in disorders like schizophrenia, PTSD, and drug-induced psychosis. Based on their activity on neurotransmitter receptors, antipsychotics can be classified as typical and atypical antipsychotics. Atypical antipsychotics have overall greater efficacy and decreased risk of movement disorders, but they carry greater risk of metabolic syndrome.
Typical or conventional or first-generation antipsychotics: They act primarily by blocking D2 dopamine receptors. They include chlorpromazine, thioridazine (Mellaril), trifluoperazine, haloperidol (Haldol), fluphenazine, loxapine (Adusuve), prochlorperazine (Compro), molindone, perphenazine, thiothixene and pimozide (Orap). Long-acting intramuscular formulations are available for haloperidol, perphenazine, fluphenazine, and chlorpromazine. Long acting forms are especially useful for patients in whom compliance is a problem. Typical antipsychotics can control positive symptoms of schizophrenia but are not useful for treating negative symptoms. Positive symptoms include hallucinations, delusions, paranoia, etc. Negative symptoms include lack of emotions, decreased speech, decreased drive, etc.
Adverse effects of typical antipsychotics include sedation, dry mouth, constipation, low blood pressure, cognitive defects, dystonia, muscle stiffness, tremors, galactorrhea and elevated prolactin levels, seizures, movement disorders, and metabolic syndrome (less likely). Some drugs like thioridazine and chlorpromazine may cause retinal or corneal deposits, respectively. Movement disorders may be incapacitating and lead to drug non-compliance and include acute dystonia, akinesia, bradykinesia, akathisia, and tardive dyskinesia.
Atypical or second-generation antipsychotics: They are more selective D2 blockers than typical antipsychotics, and they also block serotonin 5HT2A receptors. They are effective in treating both positive and negative symptoms of schizophrenia. They include clozapine (Clozaril, Versacloz), olanzapine (Zyprexa, Symbyax, Lybalvi), aripiprazole (Abilify, Aristada), asenapine (Saphris, Secuado), brexpiprazole (Rexulti), cariprazine (Vraylar), ziprasidone (Geodon), risperidone (Perseris, Risperdal), lurasidone (Latuda), quetiapine (Seroquel) etc. Second-generation drugs are preferred as they have a low risk of extrapyramidal effects like movement disorders. However, they are associated with higher mortality in older patients with dementia. The advantage of clozapine is its high efficacy. Aripiprazole, olanzapine, and risperidone are available in long-acting injectable formulations.
Adverse effects of clozapine include sedation, hypotension, tachycardia, weight gain, metabolic syndrome, glucose intolerance, and rare but potentially fatal agranulocytosis. WBC count has to be monitored regularly with clozapine therapy. Major adverse effects of second-generation drugs include metabolic syndrome, weight gain, and dyslipidemias. Blood glucose and lipid levels should be monitored.
Next-generation antipsychotics: Xanomeline and trospium combination sold as COBENFY were FDA-approved in 2024. They work by modulating parasympathetic M or muscarinic receptors in the brain. Adverse effects include urinary retention, liver dysfunction, jaundice, glaucoma, angioedema, fast heart rate, constipation, nausea, dizziness, and hypertension.
Antipsychotics that may prolong QTc: They include thioridazine, haloperidol, olanzapine, risperidone, and ziprasidone. That may precipitate cardiac arrest and arrhythmias.