{"doi":"10.1111/jgs.19107","title":"Selective serotonin/serotonin‐norepinephrine reuptake inhibitor serum concentrations' association with delirium duration","abstract":"Delirium is a form of acute brain failure that commonly afflicts older hospitalized patients.1 The association between delirium and benzodiazepines is well-documented,2 but the association with other psychotropic medication classes is less clear. Using a novel liquid chromatography-mass spectrometry (LC-MS) assay, we observed supratherapeutic psychotropic drug levels (SPDLs) occurred in 17% of delirium cases and were associated with prolonged delirium episodes. Over half of SPDLs were secondary to selective and serotonin-norepinephrine reuptake inhibitors (SSRI/SNRIs),3 which are not considered deliriogenic.2 Most studies examining SSRI/SNRIs and delirium relied on medication lists, which do not account for SPDLs.4, 5 They also did not account for preexisting dementia, which may increase vulnerability to developing delirium, even at nontoxic, therapeutic drug concentrations.4, 5 We sought to determine if serum SSRI/SNRI concentrations were associated with prolonged delirium duration in older hospitalized adults and examined if this association was modified by preexisting dementia. This was an exploratory analysis of a prospective cohort study.3, 6 Patients ≥65 years old who were admitted to the hospital, had serum available for LC-MS measurements, and enrolled within 4 h of emergency department presentation were included. All delirious and a random selection (~17%) of non-delirious patients were enrolled between March 2012 and November 2014. Delirium was assessed daily using the modified Brief Confusion Assessment Method (bCAM), which is 82% sensitive and 96% specific for delirium.7 Serum SSRI/SNRI drug levels were measured using a LC-MS assay that measured 30+ psychotropic medications (Precera Bioscience, Inc., Franklin, TN). Standardized serum SSRI/SNRI concentrations were calculated by dividing each measurement by the upper limit of normal published in the literature. To establish the validity of our standardization approach, we analyzed standardized serum benzodiazepine concentrations. A patient was considered to have pre-illness dementia if they had: (i) a pre-illness dementia assessment (IQCODE) greater than 3.38,8 (ii) documented dementia diagnosis in the medical record, or (iii) prescribed cholinesterase inhibitors prior to admission. To determine if standardized serum concentrations of SSRI/SNRIs or benzodiazepines were associated with delirium duration, proportional odds logistic regression was performed adjusting for age, pre-illness dementia, functional status, and depression, comorbidity burden, pre-illness severity, kidney/liver dysfunction, and central nervous system diagnosis.6 A standardized serum concentration*pre-illness dementia interaction was incorporated; effect modification was considered present if the p-value was <0.20. Adjusted odds ratios (aORs) with 95% confidence intervals (95% CI) are reported. Statistical analyses were performed on SAS version 9.3 (SAS Institute, Cary, NC). Patient characteristics for the 158 patients included in this analysis can be seen in Supplemental Table 1. The median (interquartile range) delirium duration was 3 (2, 5) days. SSRI/SNRIs and benzodiazepines were detected in the sera in 54 (34.2%) and 26 (16.5%) patients, respectively. Of note, five out of 56 (8.9%) had SSRI/SNRIs and eight out of 26 (30.8%) had benzodiazepines detected by LC-MS, but were not listed in the electronic health record. As standardized serum concentrations of SSRI/SNRI and benzodiazepines increased, delirium duration also increased (Figure 1). The aOR (95% CI) for the proportional odds logistic regression models evaluating the association between serum SSRI/SNRI and benzodiazepine concentrations and delirium duration are seen in Figure 2. In the adjusted analysis, standardized serum SSRI/SNRI concentrations were significantly associated with longer delirium duration in patients with preexisting dementia only (aOR = 2.4, 95% CI: 1.2, 4.7, p-value for interaction = 0.126). Standardized serum benzod","journal":"Journal of the American Geriatrics Society","year":2024,"id":462161,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.962,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":519212,"name":"Eduard E. Vasilevskis","orcid":"0000-0001-8165-5321","position":1,"is_corresponding":false},{"id":880803,"name":"Sandra F. Simmons","orcid":"0000-0002-2576-327X","position":2,"is_corresponding":false},{"id":415599,"name":"Warren D. Taylor","orcid":"0000-0002-9975-3082","position":3,"is_corresponding":false},{"id":11389,"name":"Andrew A. Monte","orcid":"0000-0002-6210-8418","position":4,"is_corresponding":false},{"id":1106000,"name":"Maria Duggan","orcid":"0000-0002-7979-8881","position":5,"is_corresponding":false},{"id":729984,"name":"Jin H. Han","orcid":"0000-0003-0384-210X","position":6,"is_corresponding":false},{"id":1105999,"name":"James O. Jordano","orcid":"0000-0003-1601-1022","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-19T02:04:20.631898Z","pmid":"39073750","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}