Relapse prevention in panic disorder with pharmacotherapy: where are we now? ABSTRACT Introduction: A substantial number of patients with PD experience relapse after the discontinuation of effective pharmacotherapy, leading to detrimental effects on the individuals and considerable societal costs. This suggests the need to optimize pharmacotherapy to minimize relapse risk. Area covered: The present systematic review examines randomized, double-blind, placebo-controlled relapse prevention studies published over the last 20 years involving recommended medications. The authors aim to provide an overview of this topic and evaluate whether recent advances were achieved. Only seven studies were included, providing limited results. One-year maintenance pharmacotherapy with constant doses had protective effects against relapse in patients who had previously exhibited satisfactory responses to the same medication at the same doses. The duration of maintenance treatment did not influence relapse risk. No data were available concerning the use of lower doses or the predictors of relapse. Expert opinion: Relapse prevention in PD has received limited attention. Recent progress and conclusive indications are lacking. Rethinking pharmacological research in PD may be productive. Collecting a wide range of clinical and individual features/biomarkers in large-scale, multicenter longterm naturalistic studies, and implementing recent technological innovations (e.g., electronic medical records/‘big data’ platforms, wearable devices, and machine learning techniques) may help identify reliable predictive models.