Background 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. Method 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). Results 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. Conclusion 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.
Bibliographical noteFunding Information:
C.A.T. has received support from Intracellular Therapies (ITI, Inc.), PureTech Ventrues, Eli Lilly Pharmaceuticals, Sunovion, Astellas, Merck (ad hoc consulting), International Congress on Schizophrenia Research (unpaid volunteer), NAMI (unpaid volunteer), American Psychiatric Association (Deputy Editor), and Finnegan Henderson Farabow Garrett & Dunner, LLP. J.L.R. has received investigator initiated support from Naurex, Inc. R.S.E.K. has received investigator initiated support from the Department of Veteran's Affair, Feinstein Institute for Medical Research, GlaxoSmithKline, National Institute of Mental Health, Novartis, Psychogenics, Research Foundation for Mental Hygiene, Inc., and the Singapore National Medical Research Council. R.S.E.K. has received honoraria, served as a consultant, or advisory board member for Abbvie, Akebia, Amgen, Astellas, Asubio, AviNeuro/ChemRar, BiolineRx, Biomarin, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, EnVivo, Helicon, Lundbeck, Merck, Mitsubishi, Otsuka, Pfizer, Roche, Shire, Sunovion, Takeda, Targacept. R.S.E.K. is a shareholder in Sengenix and NeuroCog Trials, Inc. and receives royalties from the BACS testing battery and the MATRICS Battery (BACS Symbol Coding). M.S.K. has received support from Forum Pharmaceuticals. J.A.S. has received support from Takeda, BMS, Roche, and Eli Lilly and research funding from Janssen. The other authors report no related conflict of interest.
This work was supported in part by funding from the National Institute of Mental Health ( MH083888 to J.R.B., MH072767 to S.K.H., MH083126 to J.L.R., MH077851 to C.A.T., MH078113 to M.S.K., MH077945 to G.P., MH077852 to G.T., MH077862 to J.A.S.).
- Anticholinergic medication burden
- Cognitive impairments
- Psychotic disorders