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BackgroundAdherence to medication for tuberculosis (TB) has been found to be deleteriously affected by psychosocial issues, including internalized and perceived stigma (IPS) and depression, usually resulting in the emergence of multidrug-resistant TB (MDR-TB). The objective of the study was to find the prevalence of depression among patients receiving treatment for pulmonary TB, and how stigma and depression affect the relationship between drug sensitivity status (DSS) and treatment adherence.MethodIt was a cross-sectional observational study conducted between January 2019 and July 2020 in two centers in Sikkim, India. The Patient Health Questionnaire-9 (PHQ-9), Internalized Social Stigma Scale (ISSS), and Tuberculosis Medication Adherence Scale were used to assess depression, IPS, and medication adherence, respectively. A path analysis was performed with DSS, treatment adherence, IPS, and depression. Education in years was included in the model as it was significantly correlated with IPS.ResultsA total of 71 patients who were on drug-sensitive TB (DS-TB) regimen (n = 26) and MDR-TB regimen (n = 45) participated in the study. Notably, 56.3% (n = 40) of the participants were found to have depression. Among the depressed participants, 32.5% were on the DS-TB regimen and 67.5% were on the MDR-TB regimen. The path analysis indicated that IPS and depression were serially mediating the relationship between DSS and treatment adherence (β = −0.06, p < 0.05, 95% CI = −3.20, −0.02). Finally, years of education had an exogenous predictor role, not only directly affecting IPS (β = −0.38, p < 0.001, 95% CI = −0.99, −0.31) but also affecting treatment adherence through IPS and depression (β = 0.08, p = 0.02, 95% CI = 0.03, 0.47). This indicated that with more years of education, the IPS decreases, which decreases depression and ultimately leads to better adherence.ConclusionWe found an important relationship between different psychosocial factors which may affect treatment adherence. Patients who have higher IPS are more likely to develop depression which negatively affect adherence. Patients on the MDR-TB regimen have higher stigma. There is an urgent need to integrate mental health services with TB Control Programs.