AbstractObjectiveWe studied the impact of depressive symptoms on adverse effects (AEs) in people with epilepsy (PWE) on antiseizure medication (ASM) therapy. An effect of depression on the AE burden has already been reported. We studied the correlation of various depressive symptoms with specific AEs to assess which AEs are especially prone to being confounded by particular depressive symptoms.MethodsPWE filled in a variety of questionnaires including the “Neurological Disorder Depression Inventory for Epilepsy” (NDDI‐E), “Emotional Thermometers 4” (ET4) and “Liverpool Adverse Events Profile” (LAEP). Depression was defined by a NDDI‐E score > 13. Depressive symptoms consisted of NDDI‐E and ET4 items. Discriminant analysis identified those AEs (=LAEP items) that were most highly influenced by depression. Logistic regression analysis yielded correlations of different depressive symptoms with specific AEs.ResultsWe included 432 PWE. The strongest discriminators for depression were the LAEP items “Depression”, “Nervousness/agitation,” and “Tiredness”. Out of all depressive symptoms “Everything I do is a struggle” most strongly correlated with total LAEP score (odds ratio [OR] = 3.1) and correlated with all but one LAEP item. Other depressive symptoms correlated to varying degrees with total LAEP and item scores. The number of ASMs, lack of seizure remission, and female gender correlated with high LAEP scores.SignificanceTo the best of our knowledge, we are the first to show that various depressive symptoms correlate with specific LAEP items. This information can be helpful for quick evaluation of whether the reporting of different LAEP items may be confounded by particular depressive symptoms. This is relevant because changes in therapy may differ depending on if AEs are confounded by depressive symptoms. Simply reporting a particular depressive symptom may give a clue to whether specific AEs are confounded by depression. Our findings confirm the importance of screening for depression in all PWE.Plain Language SummaryIn this study we measured depressive disorder and side effects caused by medication used to treat epilepsy with self‐reported questionnaires in a cohort of people with epilepsy. We found depressive disorder to influence the perception of side effects that are caused by drugs used to treat epilepsy. This knowledge can help to identify if the reporting of side effects is influenced by depression. Treating depression may help to reduce side effects and may thus increase the tolerability of anti‐epileptic medication. People who tolerate their medication are more likely to take it and are thus less likely to develop epileptic seizure.