Psychiatric and behavioral side effects of antiepileptic drugs in adults with epilepsy
Introduction
Psychiatric and behavioral side effects (PBSEs) are highly prevalent in patients taking antiepileptic drugs (AEDs). These adverse effects can lead to suboptimal dosing for seizure control, as well as poor adherence to AEDs and early AED discontinuation in up 25% of patients [1], [2]. Between 15% and 20% of adult patients with epilepsy taking AEDs experience PBSEs; these include depressive mood, psychosis, increase in irritability, and aggressive behavior [3]. Psychiatric and behavioral side effects are some of the most common adverse effects associated with AED use and have a higher cost per patient per year compared with other adverse-effect categories [4], [5]. To our knowledge, no previous study has compared PBSEs of both newer and older AEDs while controlling for potential non-AED-related factors [6]. A better understanding of the PBSE profiles of different AEDs available today is important clinically, as it could help provide practical recommendations and guidelines for physicians to weigh the cost–benefit ratio when prescribing AEDs.
Of particular importance is that psychiatric and behavioral comorbidities result from the social and structural implications of epilepsy, as well as from the AEDs themselves [4]. Thus, individual susceptibility highlights the necessity of understanding patient-related, dose-independent factors that contribute to the onset of PBSEs [7], [8]. Yet, our knowledge of the influence of these factors is still very limited [9]. In the current study, we compared PBSE profiles of older and newer AEDs using a large patient database. We also looked at the influence of patient demographics and medical histories, as well as AED dose and drug load, on the onset of PBSEs.
Section snippets
Methods
We examined the medical records of 4085 adult patients (≥ 18 years old) using the Columbia and Yale Antiepileptic Drug Database. We included patients seen at both the Columbia Comprehensive Epilepsy Center and the Yale Comprehensive Epilepsy Center, all of whom had been newly started on one or more of the following AEDs between January 1, 2000 and January 1, 2015, and were followed up for at least 1 year: carbamazepine (CBZ), clobazam (CLB), felbamate (FBM), gabapentin (GBP), lacosamide (LCM),
Results
Our study population consisted of 4085 patients with epilepsy that started an AED at the age of 18 or older. Most of the patients were diagnosed with focal epilepsy (71.1%), followed by idiopathic generalized epilepsy (17.4%) and symptomatic generalized epilepsy (3.6%) (Table 1). A total of 79.8% (3261/4085) of our study population had seizures that failed to improve with two or more AEDs.
Overall, 17.2% (701/4085) of patients developed PBSE attributed to an AED, and 13.8% (565/4085) experienced
Discussion
Previous literature has shown that the presence of psychiatric history is a strong predictor of PBSE with AED use in adult patients with epilepsy [3], [4], [13], [14], [15]. This finding was confirmed by our study. In addition, our study also found that patients with intractable epilepsy (seizures failing to improve with two or more AEDs), secondarily generalized seizures, or absence seizures are more likely to have PBSE when taking AEDs. History of static encephalopathy was also moderately
Acknowledgments
The Columbia and Yale AED Database has been supported by Elan, GlaxoSmithKline, Ortho-McNeil, Pfizer, Lundbeck, Esai, and UCB Pharma. Dr. Hirsch has received honoraria, consultation fees, and/or speaker fees from all the supporting companies. Dr. Detyniecki and Dr. Choi have both received research support for investigator-initiated studies from Acorda Therapeutics.
Other coauthors have no relevant disclosures.
Dr. Gustavo Patino, Assistant Professor of Neuroscience at the Oakland University
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