Objective We aimed to review and synthesise evidence from randomised controlled trials and prospective non-randomised studies of antidepressants used for treating depression in patients with epilepsy. The primary objectives were to evaluate the efficacy and safety of antidepressants in treating depressive symptoms and the effect on seizure recurrence.

Method A search of the databases was carried. There were no language restrictions. RCTs and prospective non randomised cohort controlled and uncontrolled studies investigating children or adults with epilepsy treated with an antidepressant for depressive symptoms were included. Data were extracted on trial design factors, patient demographics, and outcomes for each study. The primary outcomes were changes in depression scores and change in seizure frequency. Secondary outcomes included the number of patients withdrawing from the study and reasons of withdrawal and also any adverse events. Binary outcomes were presented as risk ratios and 95% CI. Continuous outcomes were presented as the standardised mean differences and 95% CI. Risk of bias was assessed using a version of the extended Cochrane Collaboration's tool for assessing risk of bias in both RCTs and non randomised studies.

Results Eight studies, three RCTs and five prospective cohort studies including 471 patients with epilepsy treated with an antidepressant were included. The RCTs were all single centred studies comparing antidepressant versus active control, placebo or no treatment. The five non randomised prospective cohort studies reported on outcomes mainly in partial epilepsy treated for depression with a selective serotonin reputable inhibitor(SSRI). We were unable to perform any meta analysis for the proportion with a >50% improvement in depression scores because the studies reported on different treatment comparisons. For the mean depression in depression score we were able to perform a limited meta analysis of two prospective cohort studies of citalopram including a total of 88 patients. The effect estimate was 1.17 (CI 0.96–1.38) for the mean difference in depression scores. Seizure frequency data were not reported in any RCTs. The treatment group on three prospective studies didn't report any significant increase in seizure frequency. Patients given an antidepressant were more likely to withdraw due to adverse events than inefficacy.

Conclusion Current evidence suggests antidepressants of various classes are effective in treating depressive symptoms associated with epilepsy. However we have no high quality evidence of informing on the best choice of antidepressant drug or class of drug in treating depression in patients with epilepsy. This review provides low quality evidence that SSRIs are not associated with seizure exacerbation, but there are currently no data comparing antidepressant classes.