Prescription trends and psychiatric symptoms following first receipt of one of seven common antiepileptic drugs in general practice Colin B. Josephson a,b,c,d, ⁎, Jordan D.T. Engbers e , Nathalie Jette f , Scott B. Patten b,c,d,g , Tolulope T. Sajobi b,c,d , Deborah Marshall b,d , Mark Lowerison h , Samuel Wiebe a,b,c,d,h a Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada b Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, AB, Canada c Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada d O'Brien Institute for Public Health, University of Calgary, Calgary, AB, Canada e Desid Labs Inc., Calgary, AB, Canada f Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA g Department of Psychiatry, University of Calgary, Calgary, AB, Canada h Clinical Research Unit, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada abstract article info Article history: Received 6 February 2018 Revised 2 April 2018 Accepted 16 April 2018 Available online xxxx We sought to examine the risk of psychiatric symptoms associated with a first prescription for specific antiepi- leptic drugs (AEDs) used in monotherapy in a general cohort of patients with epilepsy. We used The Health Improvement Network database (comprising the years 2000–2012) to identify incident patients with epilepsy. The index date was that on which they met the case definition for epilepsy, and analyses only included patients who remained on monotherapy or received no AED therapy following diagnosis to avoid confounding by polytherapy. Psychiatric symptoms were defined using mental health clinical or treatment (medical or therapeu- tic) code. We analyzed the AED of interest as a time-varying covariate in multivariate Cox proportional hazard regression models controlling for confounding factors. We identified 9595 patients with incident epilepsy, 7400 of whom (77%) received a first-recorded AED prescription. Prescriptions for newer generation AEDs (lamotrigine and levetiracetam) steadily increased (constituting over 30% of all AED prescriptions by 2012) while valproate use significantly declined in females (~40% in 2002 to just over 20% by 2012). A total of 2190 patients were first exposed to carbamazepine (29.3%) and 222 to lamotrigine (3%), both of which were associated with a lower hazard of any coded psychiatric symptom or disorder in multivariate analyses (hazard ratio [HR]: 0.84, 95% confidence interval [95% CI]: 0.73–0.97; p = 0.02 and HR: 0.83, 95% CI: 0.70–0.99; p = 0.03, respectively, for carba- mazepine and lamotrigine). Carbamazepine was also associated with a lower hazard for depression (HR: 0.81; 95% CI: 0.69–0.96; p = 0.013) and anxiety (HR: 0.77; 95% CI: 0.63–0.95; p = 0.013) in secondary analyses. This study provides evidence that carbamazepine and lamotrigine are associated with lower hazards for psychiatric symptoms following a diagnosis of epilepsy. These estimates can be used in clinical settings, and the precision should improve with more contemporary data that include larger proportions of newer generation AEDs. © 2018 Elsevier Inc. All rights reserved. Keywords: Cohort studies Epilepsy/seizures Antiepileptic drugs Psychiatric disorders Medication adverse effects 1. Introduction Psychiatric disorders are common in people with epilepsy. Approx- imately 23% of patients with epilepsy have active depression [1]. Furthermore, the odds of reporting anxiety and suicidal thoughts are 2.4-fold (95% confidence interval [95% CI]: 1.5–3.8) and 2.2-fold (95% CI: 1.4–3.3) higher, respectively, in people with epilepsy compared with the general population [2]. Not surprisingly, psychiatric comorbidities are also a major determinant of quality of life in those with epilepsy [3]. In addition to comorbidities, antiepileptic drugs (AEDs) themselves can unmask subclinical psychiatric disorders or elicit de novo affective symptoms [4]. In particular, there is evidence that in select populations with epilepsy, levetiracetam, clobazam, barbiturates, and phenytoin are associated with a variety of psychiatric adverse effects that include affective disorders, psychosis, and irritability/aggression [5]. Prior studies using data from large administrative and electronic medical records (EMR) have typically focused on AEDs as a class, rather than as individual medications, or examined their association with a limited range of conditions focusing primarily on the association Epilepsy & Behavior 84 (2018) 49–55 ⁎ Corresponding author at: Neurology, Cumming School of Medicine, University of Calgary, Foothills Medical Centre, 1403 - 29 St NW, Calgary, Alberta T2N 2T9, Canada. E-mail addresses: cbjoseph@ucalgary.ca (C.B. Josephson), jordan@desidlabs.com (J.D.T. Engbers), nathalie.jette@mssm.edu (N. Jette), patten@ucalgary.ca (S.B. Patten), tolu.sajobi@ucalgary.ca (T.T. Sajobi), damarsha@ucalgary.ca (D. Marshall), mwloweri@ucalgary.ca (M. Lowerison), swiebe@ucalgary.ca (S. Wiebe). https://doi.org/10.1016/j.yebeh.2018.04.012 1525-5050/© 2018 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh