Kanglai Li,1,* Qinling Wei,2,* Guanying Li,2 Xiangjun He,2 Yingtao Liao,2 Zhaoyu Gan2 1Very Important Patient Department, 2Department of Psychiatry, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe District, Guangzhou, Guangdong, People’s Republic of China *These authors contributed equally to this work Introduction: Medication nonadherence remains a big challenge for depressive patients. This study aims to assess and compare the medication persistence between unipolar depression (UD) and bipolar depression (BD). Methods: A total of 146 UD and 187 BD patients were recruited at their first index prescription. Time to lack of persistence with pharmacological treatment (defined as a gap of at least 60 days without taking any medication) was calculated, and clinical characteristics were collected. Final diagnosis was made at the end of 1-year follow-up. Results: A total of 101 (69.2%) UD and 126 (67.4%) BD patients discontinued the treatment, with a median duration of 36 days and 27 days, respectively. No significant difference was found between UD and BD in terms of time to lack of persistence with pharmacological treatment. The highest discontinuation rate (>40%) occurred in the first 3 months for both groups of patients. For UD patients, those with a higher risk of suicide (odds ratio [OR] =0.696, P=0.035) or comorbidity of any anxiety disorder (OR =0.159, P