**2.2. Antiepileptic agents**

Several antiepileptic agents are known to have an effect on weight gain [33]. However, two newer antiepileptic agents, topiramate and zonisamide, have shown an associated decrease in weight in patients taking these medications [34]. Therefore, these two drugs are being looked at as potential anorectic agents.

#### *2.2.1. Topiramate (Topamax®)*

Topiramate is a carbonic anhydrase inhibitor (Figure 1c) that is typically used in the treatment of migraines and as an anticonvulsant [35]. Topiramate is proposed to exert its antiepileptic activity via gamma-aminobutyric acid (GABA)-A-mediated inhibition via a benzodiazepine insensitive pathway, although the drug also blocks voltage dependent sodium channels [35-37]. Weight loss has been a commonly reported adverse effect of topiramate; therefore, the drug has recently come into focus as a potential anorectic agent [38-42]. Topiramate has shown promise as a combination low-dose therapy with phentermine (Qsymia(R) (originally Qnexa(R), Vivus Pharmaceuticals, Mountain View, CA, USA) for long term treatment of obesity [43-46]. Despite, safety concerns related to teratogenicity and cardiovascular effects, the product has recently been approved by the U.S. Food and Drug Administration."

Drug interactions with topiramate include coadministration with other antiepileptic agents. Although no changes in carbamazepine or phenytoin levels were seen, topiramate levels decreased by 40% or 48%, respectively [35]. However, there have been two case reports of antiepileptic drug intoxications in patients initiated on topiramate who were already taking the maximum carbamazepine dose [47]. Decrease in carbamazepine dosage resolved the interaction. Hyperammonemia, hypothermia and potentially encephalopathy can result from a synergistic interaction between topiramate, valproic acid, and phenobarbital, although the exact mechanism of this interaction is unknown [35, 48-50]. Levels of ethinyl estradiol can be significantly decreased in patients taking topiramate as an adjunctive therapy with valproic acid [35]. As a carbonic anhydrase inhibitor, topiramate can cause metabolic acidosis, and therefore is contraindicated in patients taking metformin, while patients taking other carbonic anhydrase inhibitors should be monitored due to the potential additive effects when coadmi‐ nistered with topiramate [51-55]. High doses of topiramate (600 mg/day) can increase systemic exposure to lithium. However, since topiramate dosage proposed to anorectic effects is low, this interaction may not be a significant concern when used as anti-obesity treatment [56]. No clinical studies or case studies are available for interactions with CNS depressants (e.g alcohol), although combined use is contraindicated by the manufacturer due to combined CNS depression [35]. No data supporting herb-drug interactions are available specifically related to use of topiramate at low doses as an anorectic agent [27].
