There are many different types of issues that must be considered when choosing any particular AED for any specific patient. When considering comorbidities in patients with epilepsy, one must first note the presence of any underlying psychiatric illness, as those with epilepsy are more likely than the general population to have depression and other mood disorders. All AEDs carry the risk of suicidality, but, in the case of existing psychiatric comorbidity, you want to preferentially choose an AED that is at least neutral in that regard. Lamotrigine and carbamazepine are known to have mood-stabilizing properties, while levetiracetam and perampanel may exacerbate issues related to mood. So, you would generally want to avoid the latter in those patients.

With respect to other comorbidities, obesity is also something that an AED can either help or hurt. Topiramate and zonisamide, for example, are associated with weight loss, while valproate is associated with weight gain. Regarding patient age and age-associated comorbidities, the list of concurrent medicines is likely to grow in older patients, and, so, the potential for drug-drug interactions becomes a concern in this group. This is especially true with first-generation AEDs such as valproate, carbamazepine, and phenytoin. Second- and third-generation agents are less likely to have clinically significant drug-drug interactions, making them an attractive option for older patients.

Another aspect of AED profiles to consider is that of cognitive side effects. Topiramate and zonisamide, in particular, can cause word-finding difficulties and other cognitive concerns at higher doses. For cognitively normal patients with jobs that require them to be cognitively spry, such medicines often should be passed by in favor of other AEDs that are not associated with cognitive impairment, such as lamotrigine and perampanel. Perampanel has been studied in this regard and scored well on the validated Cognitive Drug Research scale in adolescent patients with inadequately controlled focal (also known as partial) onset seizures.

Once-daily dosing at night can help to mitigate some of the side effects of AEDs. For instance, with perampanel, which is dosed once daily at bedtime, the time to peak effect is approximately 0.5 to 2.5 hours after dosing. Dizziness is a side effect that some patients experience with this AED, but I have had patients on perampanel who only notice this effect if they happen to get up in the middle of the night (ie, when the time to peak effect occurs).