Barriers and facilitators to return to work in young and middle-aged patients after PCI: a qualitative study based on the COM-B model.

Tardive dyskinesia (TD) belongs to the spectrum of extrapyramidal symptoms (EPS) that may emerge following exposure to dopamine receptor‐blocking agents (DRBAs), particularly antipsychotics. Unlike acute EPSs such as drug‐induced Parkinsonism or acute dystonia, TD is considered a tardive syndrome characterized by delayed onset and potentially persistent abnormal movements. TD usually develops after at least 3 months of DRBA exposure, though in vulnerable populations such as older adults, symptoms may appear earlier. TD is typically characterized by the insidious onset of involuntary rhythmic, repetitive, stereotypic movements of the face, mouth, and tongue, which may extend to the trunk and extremities. Although the precise mechanisms underlying TD remain unclear, several hypotheses have been proposed. Dopamine receptor hypersensitivity is the most widely cited, suggesting that chronic DRBA exposure leads to compensatory upregulation of striatal D2 receptors. Additional mechanisms include GABAergic neuronal dysfunction within the basal ganglia, oxidative stress‐related striatal neurodegeneration, and maladaptive cortical–striatal plasticity contributing to abnormal motor encoding. A meta‐analytic work (41 studies, 11,493 participants) reported that the global mean prevalence of TD was 25.3% among patients receiving antipsychotics. Given its chronic course, TD may persist even after discontinuation of antipsychotics, causing significant impairment in daily functioning and quality of life., Anticholinergic drugs have traditionally been prescribed to manage EPSs, particularly drug‐induced Parkinsonism and acute dystonia. Importantly, anticholinergics are not considered evidence‐based treatments for TD and may even worsen tardive symptoms in some cases. A 2018 Cochrane review concluded that there is insufficient evidence to support the use of anticholinergics in the management of TD., Although treatment guidelines advise against their use in patients with TD, anticholinergic drugs are still frequently prescribed in practice. This is often because reducing or switching antipsychotics is not always feasible for maintaining psychiatric stability, and anticholinergics may already be co‐prescribed for other EPSs. In recent years, vesicular monoamine transporter 2 (VMAT2) inhibitors have emerged as the first evidence‐based pharmacological options for TD. Valbenazine and deutetrabenazine, a deuterated tetrabenazine analogue requiring dose titration, have both demonstrated efficacy in randomized controlled trials., , These agents represent a major advance in TD treatment; however, their use may still be restricted by cost and access, including limited insurance coverage, prior authorization requirements, specialty pharmacy distribution restrictions, and variability in prescriber familiarity or availability. Such access‐related barriers may influence real‐world treatment allocation and could introduce potential selection bias in observational studies. Both anticholinergic drugs and VMAT2 inhibitors are associated with adverse effects that require careful monitoring. Anticholinergic burden is particularly concerning in vulnerable populations, as it has been linked to falls, delirium, and cognitive decline. Similarly, VMAT2 inhibitors carry risks such as somnolence, depression, and drug‐induced parkinsonism. These safety concerns underscore the importance of judicious prescribing and highlight the need to understand comparative safety in real‐world practice. To address this issue, we conducted a real‐world cohort study using the TriNetX US collaborative network, a target trial emulation framework to compare several safety outcomes, including incidence of fall, injury, fracture, and mortality of VMAT2 inhibitors anticholinergic drugs in patients with TD.