Polypharmacy and Self-Reported Tooth Clenching: An Electronic Health Record Analysis

INTRODUCTION: Central nervous system (CNS) medications, particularly antidepressants (selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs]), stimulants for attention-deficit/hyperactivity disorder (ADHD), and antipsychotics, are commonly implicated in drug-induced bruxism, yet evidence derives predominantly from case reports. No large-scale studies have examined associations between CNS medication classes and bruxism while controlling for confounders, and potential effects of drug combinations remain unexplored. OBJECTIVES: This study aimed to investigate the associations between CNS medication use and self-reported tooth clenching, examining individual drugs, drug classes, and drug combinations. METHODS: This cross-sectional study analyzed electronic health records from 14,643 dental clinic patients at a university dental college. Medications were standardized using RxNorm and classified into 14 pharmacological classes. Multivariable logistic regression estimated adjusted odds ratios (aORs) for self-reported tooth clenching, controlling for age, sex, polypharmacy, respiratory conditions, and neurologic conditions. Missing data were handled using multiple imputation, and the Benjamini-Hochberg (BH) procedure controlled the false discovery rate for exploratory analyses. A total of 66 pairwise drug class combinations were evaluated. RESULTS: Overall self-reported clenching prevalence was 54.0%. Among 14 drug classes, SNRIs showed significantly elevated odds of clenching (aOR, 1.24; 95% CI, 1.08-1.43; BH-adjusted P = 0.036), whereas SSRIs showed no association. A graded association was observed with CNS polypharmacy: 2 drug classes (aOR, 1.26; 95% CI, 1.13-1.42) and 3 or more classes (aOR, 1.38; 95% CI, 1.20-1.59) showed progressively higher odds (P < 0.001). One of 66 drug combinations (SSRI plus SNRI) retained a significant association (aOR, 2.40; 95% CI, 1.51-3.83; BH-adjusted P = 0.015). CONCLUSIONS: In this exploratory analysis, SNRIs rather than SSRIs were associated with self-reported clenching, in contrast to the predominance of SSRIs in case-report literature. Greater CNS polypharmacy was associated with higher odds of self-reported clenching, and SSRI-SNRI coexposure emerged as a hypothesis-generating signal requiring confirmatory analysis.Knowledge Transfer Statement:Evidence linking specific central nervous system (CNS) medications to bruxism has relied predominantly on case reports. This cross-sectional study found that serotonin-norepinephrine reuptake inhibitors (SNRIs) and CNS polypharmacy, rather than selective serotonin reuptake inhibitors (SSRIs), were associated with self-reported clenching. These findings may prompt dental professionals to consider CNS medication profiles as one contextual factor when evaluating reported clenching or grinding, pending confirmation in studies with clinician-validated outcomes.