Abstract
BACKGROUND AND HYPOTHESIS: Drug-induced dystonia and dyskinesia are associated with increased all-cause mortality, with limited data on cause-specific mortality. We aim to confirm mortality risk and cause-specific mortality in drug-induced acute dystonia or tardive dyskinesia. STUDY DESIGN: From Taiwan's National Health Insurance Database (2015-2021), we identified adults with ≥2 psychiatrist- or neurologist-confirmed diagnoses of drug-induced acute dystonia or tardive dyskinesia, and created 1:4 age- and sex-matched population controls and an unaffected sibling cohort. Outcomes included all-cause, natural-cause, and unnatural-cause mortality expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). Multivariable Cox models were adjusted for sex, age, urbanization, socioeconomic status, and comorbidities. STUDY RESULTS: A total of 2862 patients and 11 448 matched controls were identified. Mean age was 64.6 years, 67.2% female, mean follow-up duration was 4.5 years. Drug-induced acute dystonia or tardive dyskinesia was associated with significant excess risk of all-cause (HR = 1.51, 95% CI 1.36-1.67), natural-cause (1.39, 1.25-1.55), and unnatural-cause (3.67, 2.42-5.54) mortality. For natural-cause mortality, mortality risk was elevated for endocrine, nutritional, and metabolic diseases; mental and behavioral disorders; nervous, circulatory, and respiratory system diseases; but reduced for neoplasms. For unnatural-cause mortality, both accidents and suicides revealed higher mortality risks. Results were similar across age groups and ten psychiatric comorbidities. Sex subgroup analysis revealed higher suicide mortality risk in females than males. CONCLUSIONS: Drug-induced acute dystonia and tardive dyskinesia are associated with elevated all-cause, natural-cause, unnatural-cause, and cause-specific mortalities, highlighting the need for targeted interventions to prevent these specific causes of deaths.