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The interplay between tuberculosis and depression has been problematic since the humoralists. Over the centuries similarities in disease management have transpired. With the advent of isoniazid chemotherapy, transformation of tuberculosis patients from morbidly depressive to euphoric was noted. Isoniazid was thereafter widely prescribed for depression: hepatotoxicity ending its use as an antidepressant in 1961. Isoniazid monotherapy led to the emergence of drug resistant tuberculosis, stimulating new drug development. Vastly increased investment into antidepressants ensued thereafter while investment in new drugs for tuberculosis lagged. In the 21st century, both diseases independently contribute significantly to global disease burdens: renewed convergence and the resultant syndemic is detrimental to both patient groups. Ending the global tuberculosis epidemic and decreasing the burden of depression and will require multidisciplinary, patient-centered approaches that consider this combined co-morbidity. The emerging era of big data for health, digital interventions and novel and repurposed compounds promise new ways to treat both diseases and manage the syndemic, but absence of clinical structures to support these innovations may derail the treatment programs for both. New policies are urgently required optimizing use of the current advances in healthcare available in the digital era, to ensure that patient-centered care takes cognizance of both diseases.

The Tuberculosis-Depression Syndemic and Evolution of Pharmaceutical Therapeutics: From Ancient Times to the Future