title: Cognitive burden of anticholinergic medications in psychotic disorders.
abstract: Patients with psychotic disorders are often treated with numerous medications, many of which have anticholinergic activity. We assessed cognition in relation to the cumulative anticholinergic burden of multiple drugs included in treatment regimens of participants from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study.
  
  
  
  Clinically stable participants with schizophrenia (n=206), schizoaffective disorder (n=131), and psychotic bipolar disorder (n=146) were examined. Anticholinergic properties of all scheduled drugs were quantified using the Anticholinergic Drug Scale (ADS). ADS scores were summed across individual drugs to create a total ADS burden score for each participant and examined in relation to the Brief Assessment of Cognition in Schizophrenia (BACS).
  
  
  
  Anticholinergic burden aggregated across all medications was inversely related to cognitive performance starting at ADS scores of 4 in participants with schizophrenia. Those with ADS scores ≥4 had lower composite BACS scores compared to those with ADS<4 (p=0.004). Among BACS subtests, Verbal Memory was the most adversely affected by high anticholinergic burden. Despite similar anticholinergic burden scores across groups, a significant threshold effect of anticholinergic burden was not detected in schizoaffective or psychotic bipolar disorder.
  
  
  
  We identified an adverse effect threshold of anticholinergic burden on cognition in clinically stable participants with schizophrenia. This relationship was not identified in affective psychoses. Examination of other medications, doses, and clinical measures did not account for these findings. Patients with schizophrenia may have increased cognitive susceptibility to anticholinergic medications and the aggregate effects of one's medication regimen may be important to consider in clinical practice.
authors.affiliation: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 308 Harvard St. S.E., Minneapolis, MN 55455, USA.
authors.forename: Seenae
authors.initials: S
authors.lastname: Eum
authors.affiliation: Department of Psychology, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA.
authors.forename: S Kristian
authors.initials: SK
authors.lastname: Hill
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, 912 S. Wood Street, Chicago, IL 60612, USA.
authors.forename: Leah H
authors.initials: LH
authors.lastname: Rubin
authors.affiliation: Department of Epidemiology, College of Public Health, University of Iowa, 145 N. Riverside Drive, Iowa City, IA 52242, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Carnahan
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, 710 N Lake Shore Drive, Chicago, IL 60611, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Reilly
authors.affiliation: Department of Psychiatry, University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
authors.forename: Elena I
authors.initials: EI
authors.lastname: Ivleva
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Keedy
authors.affiliation: Department of Psychiatry, University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Tamminga
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University, 300 George St., New Haven, CT 06511, USA.
authors.forename: Godfrey D
authors.initials: GD
authors.lastname: Pearlson
authors.affiliation: Department of Psychology, University of Georgia, 125 Baldwin St., Athens, GA 30602, USA.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Clementz
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA.
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Gershon
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Medical Center and Harvard Medical School, 401 Park Drive, Boston, MA 02215, USA.
authors.forename: Matcheri S
authors.initials: MS
authors.lastname: Keshavan
authors.affiliation: Department of Psychiatry, Duke University School of Medicine, 4080 Hosp South, Durham, NC 27710, USA.
authors.forename: Richard S E
authors.initials: RSE
authors.lastname: Keefe
authors.affiliation: Department of Psychiatry, University of Cincinnati, 3235 Eden Ave., Cincinnati, OH 45267, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Sweeney
authors.affiliation: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 308 Harvard St. S.E., Minneapolis, MN 55455, USA; Department of Psychiatry, College of Medicine, University of Minnesota, 2450 Riverside Ave. S., Minneapolis, MN 55454, USA. Electronic address: jrbishop@umn.edu.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Bishop
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D018680:Cholinergic Antagonists / Q000009:adverse effects* / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced; D005260:Female; D006801:Humans; D007406:Interview, Psychological; D008297:Male; D009299:Nasal Provocation Tests; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000523:psychology; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology
chemical_list: D018680:Cholinergic Antagonists
keywords: Anticholinergic medication burden; Cognitive impairments; Psychotic disorders