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Background: The relationship between depression and beta-blockers (BBs) use is a controversial topic for many decades. Due to the interference with adrenergic and serotonin receptors, BB use has been linked to depression in many early cross-sectional and case studies. Others have investigated the indirect relationship between BB use and novice antidepressant use. However, larger trials have yielded inconsistent findings. The objective of this study is to identify the presence of depression and depressive symptoms among patients using BBs in the internal medicine, cardiology, and psychiatry Departments in King Khalid University Hospital (KKUH) and to measure its prevalence. Research Design and Methods: A cross-sectional study included patients visiting Internal Medicine, Cardiology, and Psychiatry clinics at the KKUH in Riyadh, Saudi Arabia, who is known using BBs for any indication and excluded patients previously diagnosed with depression before taking BBs. This study was carried out from December 2018 to October 2019. Either physically or over the phone, patients were requested to complete the Patient Health Questionnaire-9 questionnaire. Drug names and pictures were provided for ease of drug identification. The sample size was 291, with a confidence interval of 95% and 5% margin of error. Written consent was acquired from all participants. Results: Two hundred and ninety-one surveys were collected, among 151 (52%) were females and 140 (48%) were males. Females were more likely to report depressive symptoms and had higher scores of symptom severity on average (P < 0.016). Only 17 patients (5.8%) were found to report no depressive symptoms, while most patients reported mild depressive symptoms (35%). We have not found a statistically significant relationship between BB type and the magnitude of depressive symptoms severity. Conclusions: Although the usage of BBs and the prevalence of depressive symptoms were not directly correlated in our study, compared to the local prevalence, our patients demonstrated a higher prevalence trend of depressed symptoms. In addition, our observations did reveal fascinating information on the gender disparity in depression. [ABSTRACT FROM AUTHOR]