The research, led by investigators at Virginia Commonwealth University and published in the journal Dystonia, mined the TriNetX database platform to identify 27,339 patients diagnosed with blepharospasm or Meige syndrome over a 20-year index period. Of these, 20,485 carried a diagnosis of blepharospasm and 6,854 had Meige syndrome. The team, including first author Rachel J. Heo and senior author Brian D. Berman, grouped 42 oral medications into nine pharmacological classes—anticholinergics, GABA agonists, benzodiazepines, muscle relaxants, gabapentinoids, sodium channel blockers, dopaminergics, antidopaminergics, and stimulants—and analyzed prescription prevalence, documented prescription intervals, and patterns of polypharmacy across the cohort.

The headline finding is stark: only 46.7 percent of patients were prescribed at least one oral medication from any of the nine classes, meaning more than half received none at all. Treatment rates were modestly higher in the Meige syndrome group (52.7 percent) than in the blepharospasm group (46.8 percent). Benzodiazepines emerged as the most frequently prescribed class, given to 27.6 percent of all patients, followed by muscle relaxants (24.4 percent), gabapentinoids (20.2 percent), and anticholinergics (16.9 percent). Within the benzodiazepine class, clonazepam was the most common choice, while cyclobenzaprine dominated the muscle relaxant category.

The documented prescription intervals tell their own story about drug tolerability. Benzodiazepines showed the longest median documented prescription duration at 15.8 months, suggesting patients stayed on them longer than any other class. By contrast, anticholinergic medications—the class with the strongest evidence base for dystonia motor symptoms—had a median documented prescription duration of just 0.1 months, indicating most patients abandoned them almost immediately. The authors attribute this to the notorious side effect profile of anticholinergics, which include cognitive impairment, dry mouth, constipation, and urinary retention, particularly problematic in the older populations that tend to develop these cranial dystonias.

Polypharmacy patterns proved especially revealing. Among patients who received any oral medication, 35.0 percent were prescribed drugs from only one class, while 38.3 percent were prescribed medications from three or more different classes. Nearly 10 percent were treated with five or more classes simultaneously. The authors interpret this as strong evidence that current oral options are simply insufficient—when one drug class fails to control symptoms adequately, clinicians layer on additional classes in a trial-and-error effort to find relief. This pattern is consistent with the known limitations of botulinum neurotoxin injections, the standard of care, which provide only partial and transient symptom relief, can be painful, and wear off weeks before the next scheduled injection.

Multivariate logistic regression models uncovered significant demographic predictors of oral medication receipt. Male patients had lower odds of being prescribed any oral dystonia medication compared to females (odds ratio 0.788). Asian patients were less likely to receive treatment (odds ratio 0.687), while Black patients were more likely (odds ratio 1.103). Geographically, patients living in the Southern United States had significantly lower odds of receiving oral medications compared to those in the Midwest, Northeast, or West. The authors suggest these disparities may reflect cultural differences in attitudes toward oral medication, as well as regional variation in access to neurology specialists—only 3.1 percent of U.S. neurologists practice in rural counties, and the South has fewer urban medical centers relative to its population.

Psychiatric comorbidity adds another layer of complexity to the prescription data. Anxiety was diagnosed in 21.9 percent of the cohort and depression in 9.3 percent, rates consistent with prior studies linking cranial dystonias to mood disorders. Among patients prescribed benzodiazepines, 34.3 percent carried an anxiety diagnosis—but notably, 65.7 percent did not, suggesting these drugs are being prescribed primarily for dystonia symptoms rather than psychiatric comorbidity. Similar patterns held across other medication classes, indicating that oral prescriptions in this population are largely driven by the movement disorder itself.

The study has important limitations that the authors acknowledge candidly. TriNetX does not capture botulinum neurotoxin treatment data, so the team could not directly assess how oral medications function as adjuncts to injections, though prior research indicates roughly 60 to 75 percent of patients continue receiving injections with good response for 15 to 20 years. The database also lacks clinical severity measures, cannot confirm the indication for a given prescription, and relies on diagnostic codes that may miss cases or include acquired dystonias. The team mitigated these risks by excluding patients with confounding diagnoses such as Parkinson disease, hemifacial spasm, and drug-induced dystonia, and by examining medication history across a 20-year window to capture prescriptions even before formal diagnosis.

What emerges from this analysis is a portrait of a therapeutic landscape in urgent need of expansion. No oral medication is FDA-approved for blepharospasm or Meige syndrome, and the off-label options clinicians reach for—benzodiazepines, muscle relaxants, gabapentinoids—offer modest benefit at best, with tolerability problems that drive rapid discontinuation. The high rates of polypharmacy, the demographic disparities in access, and the fact that more than half of patients receive no oral medication at all all point toward the same conclusion: current oral treatment options for these disabling dystonias are inadequate, and a personalized, evidence-based approach to drug selection is needed to replace the standardized trial-and-error paradigm that currently dominates clinical practice.

Subject of Research: Neurology

Article Title: Oral medication treatment patterns in blepharospasm and Meige syndrome: a multi-institutional TriNetX study

Article References: Heo, R. J., Mukhopadhyay, N., Dintino, C., Negida, A., Barrett, M. J., & Berman, B. D. (2025). Oral medication treatment patterns in blepharospasm and Meige syndrome: a multi-institutional TriNetX study. Dystonia, 4, Article 15368. https://doi.org/10.3389/dyst.2025.15368

Image Credits: AI Generated

DOI: 10.3389/dyst.2025.15368

Keywords: blepharospasm, Meige syndrome, dystonia, oral medications, TriNetX, botulinum neurotoxin, polypharmacy, health disparities, Oral, medication, treatment, patterns