Abstract: Introduction Experts agree that there is a need for protocols to guide health professionals on how to best manage psychiatric comorbidities in patients with epilepsy (PWE). We aimed to develop practical recommendations for key issues in the management of depression in PWE. Methods This was a qualitative study conducted in four steps: (1) development of a questionnaire on the management of depression in PWE to be answered; (2) literature review and, if evidence from guidelines/consensus or systematic reviews was available, drafting initial recommendations; (3) a nominal group methodology for reviewing initial recommendations and formulating new recommendations on those issues without available evidence; and (4) drafting and approving the final recommendations. A scientific committee (one neurologist and one psychiatrist) was responsible for the development of the project and its scientific integrity. The scientific committee selected a panel of experts (nine neurologists and nine psychiatrists with experience in this field) to be involved in the nominal group meetings and to formulate final recommendations. Results Fifteen recommendations were formulated. Four on the screening and diagnosis: screening and diagnosis of depression, evaluation of the risk of suicide, and diagnosis of depression secondary to epilepsy; nine on the management of depression: referral to a psychiatrist, selection of the antiseizure medication, change of antiseizure medication, antidepressant treatment initiation, selection of antidepressant, use of antidepressants during pregnancy, use of psychotherapy, antidepressant treatment duration, and discontinuation of antidepressant treatment; two on the follow-up: duration of the follow-up under usual conditions, and follow-up of patients at risk of suicide. Conclusion We provide recommendations based on expert opinion consensus to help healthcare professionals assess depression in PWE. The detection and treatment of major depressive disorders are key factors in improving epilepsy outcomes and avoiding suicide risk.

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