In patients with epilepsy taking antiseizure and psychotropic medications, drug-drug interactions may not substantially impact outcomes as expected.

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Patients with epilepsy often have psychiatric comorbidities, such as depression and anxiety. As a result, a single patient can receive several pharmacologic interventions. Limited data are available regarding drug-drug interactions and their effect on successfully treating patients with epilepsy and mental health comorbidities.

To explore the drug-drug interactions experienced by patients with epilepsy, Barry E. Gidal, PharmD, FAES, Ariela Karasov, MD, and colleagues completed a statistical analysis of veterans with epilepsy based on information extracted from the US Department of Veterans Affairs Pharmacy Benefits Management Services and Veterans Support Service Center databases. They discussed their findings with Physician’s Weekly.

PW: What prompted this research?

Dr. Gidal: It has been well established that many older antiseizure medications perpetrate drug-drug interactions. These enzyme-inducers increase the drug-metabolizing enzymes in our liver and in the gut that can chew up other medicines. The question is: Does this really matter? In some cases, it clearly does. In this study, we wanted to explore the management of common mental health disorders such as depression. We decided to look at other potential surrogate markers to see if patients with epilepsy were requiring adjustments to antidepressant treatments because of these interactions. These markers included changes in psychotropic drug dosing (ie, using higher doses in patients receiving an enzyme-inducing antiseizure medication), or frequency of psychotropic drug combinations.

Dr. Karasov: Providers can understandably be anxious about drug-drug interactions, and sometimes we may avoid certain medications because of these concerns. Sometimes that’s warranted and other times maybe not so much. Having a better idea of what plays out naturalistically may be helpful in terms of guiding our practices. In an observational study like this, there are inherently many limitations on the conclusions you may draw. But the information gathered is reflective of what’s going on in the real world, so it is valuable.

Dr. Gidal: Under-treating depression or anxiety because of a fear of drug-drug interactions is serious in all patients, but especially in our patients with epilepsy.

What were the most surprising findings of this study?

Dr. Gidal: What I expected to find was that patients receiving enzyme-inducing antiseizure medicines compared with the cohort of patients receiving other antiseizure medicines for the same indication were going to receive much higher doses of antidepressants, multiple drugs, switches, augmentation therapy, etc, because of the metabolic factors discussed earlier. It was surprising to me when we saw none of that at all.

Dr. Karasov: I was similarly surprised. We didn’t see any trends toward differences between patients on the drug-drug interactions that we would expect.

Dr. Gidal: We also looked at the data considering sex and age. We didn’t see any group skewing the data.

How can a clinician apply this information in their practice?

Dr. Karasov: I hope that this study might relieve some of the anxiety or hesitation we have as clinicians regarding drug-drug interactions. I think we still need to be cautious, thoughtful, and aware of these pharmacokinetic concerns, but with reasonable clinical practices, we may be able to release a little bit of the handwringing. In all patients with epilepsy, we should start low and go slow when adjusting medications, ideally with close monitoring and the use of standardized measures to track symptoms. This study’s findings suggest that some of these drug-drug interactions may be less profoundly impacting actual clinical outcomes and clinical patterns than we previously thought.

What should be explored next?

Dr. Karasov: I think we need randomized controlled trials targeting mental health disorders in patients with epilepsy. Studies focused on drug-drug interactions, applying standardized measures, and looking at treatment responses while providing actual data about the indication for each medication would be productive.

Dr. Gidal: I would add that the purpose of research is not to provide the final answer; there are no final answers. Medicine is largely [about] managing uncertainty. We need studies to challenge hypotheses and take the next step in design.

Is there anything else you would like to add?

Dr. Gidal: Mood disorders and epilepsy go hand-in-hand—not just within the veteran population. Up to 30% to 40% of our patients with epilepsy have some comorbid mood disorder. I think it gets under-treated and under-identified, and there needs to be a better awareness of this. It’s a big deal.

Dr. Karasov: We must continue to do our best to thoughtfully acknowledge the deficits in our knowledge base in our discussions with our patients. We need to use what we know in treating our [patients with] epilepsy to reduce their suffering, and we need to be aware of drug-drug interactions, but not be paralyzed by them. Those concerns should not be a barrier to providing optimal care to your patients.