Cycloserine did not increase depression incidence or severity at standard dosing for MDR-TB

In 2018 cycloserine was elevated to World Health Organization (WHO) group B status for multidrug-resistant tuberculosis (MDR-TB), and is recommended in longer MDR-TB treatment regimens [1]. Inclusion of cycloserine is associated with improved MDR-TB treatment success and reduced mortality, but is limited by treatment-associated depression, psychosis and neuropathy, forcing 9% of patients to stop therapy [1–3]. Cycloserine also demonstrates wide interindividual pharmacokinetic variation, with significant food and drug interactions, leaving nearly half of patients with inappropriate drug levels [4, 5]. Optimal dosing is unknown [6], but modelling studies suggest doses from 250 mg to 750 mg twice daily, with 500 mg twice daily for paucibacillary disease and 750 mg twice daily for cavitary pulmonary disease [7]. Therefore, clinicians must balance the known benefits of cycloserine with the dearth of susceptibility- and drug-monitoring capacity and the spectre of treatment-limiting side-effects. To evaluate the impact of cycloserine prescription and dose on incident depression during MDR-TB treatment, we analysed longitudinal cohort data from India.