DIET & NUTRITION 
PATIENT EDUCATION 
OBESITY/WEIGHT MANAGEMENT 
EXERCISE/TRAINING 
LEGAL MATTERS 
GUIDELINES/RECOMMENDATIONS ℹ️ Observational Association Only Evidence
A retrospective cohort study published in Psychiatry and Clinical Neurosciences used the TriNetX network and target trial emulation to compare VMAT2 inhibitors against anticholinergic agents in 5,498 propensity-matched adults with TD between 2019 and 2025.
Clinical Considerations
- VMAT2 inhibitor use was associated with lower fall risk (HR 0.83), injuries (HR 0.77), fractures (HR 0.82), and all-cause mortality (HR 0.71) compared with anticholinergics.
- Secondary outcomes showed substantially lower delirium risk (HR 0.39) and dementia risk (HR 0.55), patterns consistent with anticholinergic burden literature.
- Subgroup analyses produced similar hazard ratios across age strata, with HRs for falls and injuries ranging 0.77-0.86 in patients under 65 and 0.78-0.80 in those 65 and older.
- Sensitivity analyses weakened mortality, fracture, and arrhythmia associations, signaling caution about causal interpretation despite directional consistency.
Practice Applications
- Recognize anticholinergic burden as a contributor to falls, cognitive impairment, and delirium in TD populations.
- Interpret findings as hypothesis-generating given residual confounding from smoking, activity, and diet.
- Consider VMAT2 inhibitors when guideline-supported and clinically appropriate for TD management.
- Avoid treating these data as a head-to-head efficacy comparison absent randomized evidence.
