Abstracts

Rationale: Patients with epilepsy are likely to suffer from psychiatric comorbidities, including depression and anxiety. They often require treatment with multiple psychotropic drugs. While it is clear that CYP inducing AEDs (EIAEDs) can increase the oral clearance of multiple medications (thus lowering systemic exposure), it is less clear that all PK interactions are clinically meaningful (e.g. lower efficacy). As a first step in addressing this issue, this study sought to quantify the potential impact of AED choice, whether EIAED or non-inducer (NIAED), on surrogate markers of  suggestive of clinical use, including resultant antidepressant (AD) or antipsychotic (AP) dose, frequency of combination use of AD & AP, and number of multiple drug switches of PDs. Our hypothesis is that because of PK interactions, EIAED treatment would be associated with higher psychotropic drug doses, more frequent Rx adjustments and poly psychotropic comedication, all in order to optimize therapeutic response. Methods: Using VA pharmacy and national encounter databases, Veterans with Epilepsy were identified based on having a seizure diagnosis and being prescribed concomitantly an AED and a psychotropic drug for at least 365 days between Oct, 01, 2010 and Sep 30, 2014 . Patients for whom psychotropic drugs were prescribed any time between beginning and end prescriptions dates of AEDs were considered. Among those, patients prescribed only EIAEDs or NIAEDs were considered for final analysis. Patients were evaluated for AD only, AP only and both (AD & AP). To compute average drug doses per day, averages for each patient were computed and averaged again. Multiple drug switches were defined to be for patients who had been prescribed more than three psychotropic drugs during an observation period. Pearson’s Chi-Square test was used to compare relative proportions of AD, AP and AD+AP in both groups.  Results: In all, 12,516 patients were identified (44.4% on EIAED, 55.6% on NIAED) with a mean age of 59.5 years ( 91.8% male) . A larger proportion of patients on EIAED received mono treatment with any psychotropic drug, as compared to NIAED (47.2 vs 36.1%).  Among all, 61.3% received AD only, 6.6% received AP only, and 32.1% received both concurrently.  Of EIAED, 68.1% were on AD, 5.6% on AP, and 26.3% on both AP & AD. For NIAED, 55.9% received AD, 7.4% AP, and 36.7% on AD & AP. Chi-square showed that the distribution of PD was statistically different between EIAED and NIAED groups. Z tests showed that each difference (AD, AP and both) in proportions was statistically significant (p values (4 tests, one Chi-square, 3 Z tests < 0.001) between EIAED vs NIAED. Interestingly, mean doses of AD or AP did not appear to differ between AED groups. Data for multiple drug switches, demonstrating more switches in NIAED group is shown in Table 1.     Conclusions: Concurrent psychotropic drug use is quite common in the VA epilepsy population, and a large number of patients still receive enzyme inducing AEDs that may complicate other medical therapies.  Interestingly, in seeming contradiction to our hypothesis, mean daily doses of either AD or AP did not appear to differ between inducers vs non-inducers.  Similarly, use of polytherapy, and/or multiple trials of various psychotropic drugs did not appear increased in the CYP induced group. In fact, combination therapy of AD+AP was higher in NIAED than EIAED. These data suggest that perhaps these types of PK interactions may not in fact result in meaningful clinical differences. Since the present analyses did not include clinical psychiatric measures, future analyses examing direct clinical outcomes are clearly warrented Funding: VA Epilepsy Center of Excellence