Cycloserine-induced neuropsychiatric toxicity in multidrug-resistant tuberculosis: association with peak plasma concentration

Cycloserine (Cs) is a crucial anti-multidrug-resistant tuberculosis medication with significant clinical efficacy. However, its clinical application is limited by neuropsychiatric-related adverse drug reactions (ADRs). This study retrospectively evaluated the peak plasma concentration (<i>C</i> _max) of Cs and Cs-related neuropsychiatric ADRs and analyzed the risk factors of developing neuropsychiatric ADRs. A multivariable ordinal logistic regression model was built to predict the incidence of neuropsychiatric ADRs. This study enrolled a total of 136 participants, with a cumulative incidence of neuropsychiatric ADRs of 12.5%. Patients experiencing ADRs had significantly higher Cs <i>C</i> _max compared to those without ADRs. The risk of ADRs rose with increasing Cs exposure, especially when <i>C</i> _max exceeded 30 mg/L. Receiver operating characteristic analysis demonstrated the strong predictive value of <i>C</i> _max for neuropsychiatric ADRs. Notably, the predictive efficacy of the logistic regression model significantly improved after incorporating drinking history as a covariate, achieving a final predictive accuracy of 87.6%. Cs <i>C</i> _max serves as a critical indicator for predicting Cs-related neuropsychiatric ADRs. Dynamic monitoring of Cs <i>C</i> _max combined with alcohol history assessment can enable accurate identification of high-risk populations for neuropsychiatric ADRs, thereby providing a scientific basis for developing individualized medication regimens and implementation of early interventions.IMPORTANCECycloserine (Cs) is a vital medication for treating multidrug-resistant tuberculosis (MDR-TB), but its use is often limited by severe neuropsychiatric side effects such as depression, anxiety, and seizures. This study highlights the critical role of monitoring Cs peak plasma concentration (<i>C</i> _max) to predict and mitigate these adverse reactions. By analyzing data from 136 patients, the researchers found that higher Cs <i>C</i> _max levels significantly increase the risk of neuropsychiatric toxicity, particularly when concentrations exceed 30 mg/L. Additionally, a history of alcohol consumption further elevates this risk. These findings provide a practical approach for clinicians: regular monitoring of Cs levels and assessing alcohol use can help identify high-risk patients early, enabling timely adjustments to treatment plans. This work not only enhances patient safety but also supports the broader goal of improving MDR-TB treatment outcomes by minimizing harmful side effects.