Background Depression among tuberculosis patients remains a significant public health concern. Its burden and severity is increasing in low-income countries, especially in sub-Saharan Africa. Although it has negative impacts on quality of life, depression among tuberculosis patients is rarely studied in Ethiopia, particularly in the study area. Therefore, this study aimed to determine the magnitude of depression and associated factors among tuberculosis patients in Eastern Ethiopia. Methods A facility-based cross-sectional study was conducted from April 15 to May 15, 2021, among 213 tuberculosis patients in public health facilities of the Harari Regional State, Eastern Ethiopia. Study participants were selected using a systematic sampling technique. Data were collected using interviewer-administered questionnaire. Depression was assessed using Patients Health Questionnaire-9 (PHQ-9). Epi-data and SPSS were used for data processing and analysis. Bi-variable and multivariable logistic regressions were employed to determine the effects of predictors on depression. Statistical significance was considered at a p-value <0.05. Results The magnitude of depression among tuberculosis patients was 52.1% [95% CI (45.4, 58.8%)]. Patient’s age of 25–34 years [AOR = 0.31, 95% CI (0.128, 0.75)], female sex [AOR = 5.04; 95% CI (2.18, 11.62)], intensive phase of tuberculosis treatment [AOR = 2.56; 95% CI (1.118, 5.876)], HIV-positive status [AOR = 7.143; 95% CI (1.55, 32.93)], smoking history [AOR = 9.08; 95% CI (3.35, 24.61)] and having poor social support [AOR = 4.13; 95% CI (1.29, 13.22)] were factors statistically associated with depression. Conclusion In this study, the magnitude of depression was relatively high as more than half of the participants had depression. Advanced age, female sex, intensive phase of tuberculosis treatment, HIV-positive status, smoking history, and poor social support were identified as associated factors with depression. Therefore, this result calls all stakeholders to give duly emphasis on incorporating and integrating mental health support programs as routine practice in tuberculosis follow-up clinics, as screening, early detection and treatment, and training for all health care providers are very crucial in tackling depression among tuberculosis patients.
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