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Johanna Schr€ oder is a PhD candidate studying novel modes in delivering psychotherapy. SUMMARYObjective: Depression is the most prevalent psychiatric disorder in persons with epilepsy (PWEs). Despite its major impact on quality of life and risk of suicide, most PWEs are not treated for depression. A current challenge in mental health care is how to close this treatment gap and increase access to psychological services. Psychological online interventions (POIs) have shown efficacy in improving depression among individuals without neurologic disorders. This pilot study aimed to assess the feasibility and efficacy of a psychological online intervention for depression (Deprexis) in PWEs who have symptoms of depression. Methods: Participants with self-reported epilepsy and subjective complaints of depressive symptoms were randomized to an intervention condition (Deprexis) or to a waiting list control (WLC) condition. After 9 weeks, participants were invited to complete an online reassessment. Results: Relative to the waiting list group, program users experienced a significant symptom decline on the Beck Depression Inventory -I (BDI-I, primary outcome) with a moderate effect size in the complete observations analysis and a small effect size in the intention-to-treat analysis. Furthermore, there was a significant improvement with a moderate effect size on the "energy/fatigue" subscale of the Quality of Life In Epilepsy Inventory -31 (QOLIE-31). Significance: The results of this trial suggest that POIs may be a feasible and beneficial tool for PWEs who have comorbid depressive symptoms. KEY WORDS: Depression, Epilepsy, Internet intervention, iCBT, Deprexis.Depressive disorders are the most frequent comorbid psychological conditions in persons with epilepsy (PWEs), with lifetime prevalence rates of 30-35%. 1Patients with uncontrolled seizures are diagnosed with major depression twice as often as patients with controlled seizures.2 Depressive symptoms, as well as seizure worry, have a major impact on the quality of life of affected individuals, 3 irrespective of the type of recent epileptic seizures. 4A recent systematic review suggests that psychological interventions, such as cognitive behavioral therapy (CBT), are effective if they are particularly focused on the reduction of depressive symptoms rather than on the reduction of seizure frequency.5 Given physician-related treatment barriers related to fears of lowering seizure threshold and adverse drug interactions between antidepressants and antiepileptic drugs (such as, reciprocal inhibitory or excitatory effects on PWEs are often interested in exploring novel approaches, but unfortunately, research on the applicability and efficacy of such approaches for depression in PWEs is rare, 9 in contrast to the well-grounded evidence on psychological online interventions (POIs) for depression in general. A metaanalysis that included seven randomized controlled trials (RCTs) of self-guided psychological interventions for depression (one self-help book and six Internet-based s...