Introduction: Pharmacokinetic and pharmacodynamic drug interactions (DIs) can occur between antiepileptics (AEDs) and second-generation antipsychotics (SGAPs). Some AED and SGAP pharmacodynamic mechanisms are poorly understood. AED-SGAP combinations are used for treating comorbid illnesses or increasing efficacy, particularly in bipolar disorder.
Areas covered: This article provides a comprehensive review of the interactions between antiepileptics and second-generation antipsychotics. The authors cover pharmacokinetic AED-SGAP DI studies, the newest drug pharmacokinetics in addition to the limited pharmacodynamic DI studies.
Expert opinion: Dosing correction factors and measuring SGAP levels can help to compensate for the inductive properties of carbamazepine, phenytoin, phenobarbital and primidone. Further studies are needed to establish the clinical relevance of combining: i) AED strong inducers with amisulpride, asenapine, iloperidone, lurasidone and paliperidone; ii) valproate with aripiprazole, asenapine, clozapine and olanzapine; iii) high doses of oxcarbazepine (≥ 1500 mg/day) or topiramate (≥ 400 mg/day) with aripiprazole, lurasidone, quetiapine, risperidone, asenapine and olanzapine. Two pharmacodynamic DIs are beneficial: i) valproate-SGAP combinations may have additive effects in bipolar disorder, ii) combining topiramate or zonisamide with SGAPs may decrease weight gain. Three pharmacodynamic DIs contributing to decreased safety are common: sedation, weight gain and swallowing disturbances. A few AED-SGAP combinations may increase risk for osteoporosis or nausea. Three potentially lethal but rare pharmacodynamic DIs include pancreatitis, agranulocytosis/leukopenia and heat stroke. The authors believe that collaboration is needed from drug agencies and pharmaceutical companies, the clinicians using these combinations, researchers with expertise in meta-analyses, grant agencies, pharmacoepidemiologists and DI pharmacologists for future progression in this field.