**3. Gastrointestinal problems associated with antiepileptic drugs**

AEDs have a relatively narrow therapeutic index, and their adverse effects can impact on any organ or system. Some 10–30% of patients with epilepsy discontinue their first prescribed AED due to adverse effects and intolerance [43]. Many AEDs cause gastrointestinal side effects. Multi-AEDs in particular may increase the potential side effects in intractable seizures. The most common AED-related side effects are vomiting and nausea [44]. Some important adverse gastrointestinal side effects of AEDs are mentioned below.

*Valproic acid* (*VA*) may cause gastrointestinal side effects such as nausea, diarrhea, abdominal pain, and vomiting. This problem may be seen particularly when the initial doses are taken. The meal time ingestion and slow release form of the drug will be tolerated by most patients [45]. Acute pancreatitis is also related to VA ingestion, and the clinician should suspect this in case of severe abdominal pain during VA therapy. Hepatotoxicity is a life-threatening condition related to VA therapy. Patients with organic brain disease, treated with several antiepileptic drugs, and younger than 2 years old have the highest risk for developing hepatotoxicity during VA treatment. Liver function tests, ammonia, and other tests are not reliable for assessing VA-related hepatotoxicity. However, clinical symptoms such as vomiting, nausea, anorexia, and lethargy may be an indicator of fatal hepatotoxicity [46].

*Benzodiazepines* are commonly prescribed drugs particularly in childhood epileptic syndromes. Although they exhibit sedation-related adverse effects, benzodiazepines are usually well tolerated in the gastrointestinal system and do not lead to hepatic damage unless combined with other AEDs [47].

*Carbamazepine* (*CBZ*) is well tolerated in the gastrointestinal system, but idiosyncratic reaction due to CBZ might be related to granulomatous hepatitis, fever, and rash [48].

*Ethosuximide* (*ESM*) has reversible, adverse gastrointestinal effects, such as abdominal discomfort, vomiting, diarrhea, and hiccups, but these can all be prevented if ESM is taken after meals [49].

Felbamate and *topiramate* (*TPM*) may cause anorexia, thus promoting weight loss, and there are reports of fatal hepatotoxicity due to felbamate [50, 51].
