Polypharmacy in Schizophrenia May Have Adverse Effect on Cognition

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Scientists researched the association between multiple drug treatments for psychotic disorders and anticholinergic burden.
Scientists researched the association between multiple drug treatments for psychotic disorders and anticholinergic burden.

Researchers identified an adverse effect threshold of anticholinergic burden on cognition in clinically stable patients with schizophrenia, according to a study published in Schizophrenia Research.

Since medications with high anticholinergic activity may adversely affect cognition and quality of life, Seenae Eum, PharmD, and colleagues from the department of experimental and clinical pharmacology at the College of Pharmacy, University of Minnesota, Minneapolis, researched the cognitive effects of multiple drug treatments on patients with psychotic disorders.

"To our knowledge, this is the first study to identify a potential threshold effect of cumulative anticholinergic burden on neuropsychological performance using medication regimen data from clinically stable patients with schizophrenia," Ms Eum said.

Using participants selected from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium, the researchers designed a study to examine cognition across psychotic disorders analyzed clinically stable patients (206 with schizophrenia, 131 with schizoaffective disorder, and 146 patients with psychotic bipolar disorder). They selected patients taking at least 1 antipsychotic medication and whose antipsychotic exposure could be consistently measured across diagnoses in the analysis.

The researchers quantified the anticholinergic properties of the prescribed medications using the Anticholinergic Drug Scale (ADS). Additionally, a chlorpromazine dose equivalent was calculated using the Andreasen method. They summed ADS scores 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. Patients with ADS scores ≥4 had lower composite BACS scores compared with patients with ADS <4

(P =0.004). Among BACS subtests, verbal memory was the most adversely affected by a 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. There was a significant association between lower token motor and symbol coding performance and high anticholinergic burden; researchers also associated token motor performance with higher antipsychotic doses in all diagnostic groups.

"We identified an adverse effect threshold of anticholinergic burden on cognition in clinically stable participants with schizophrenia," Ms Eum said. "However, the mechanisms underlying this effect require further investigation."

"While it is difficult to dissociate illness severity and [a] different baseline of cognitive impairment from pharmacologic effects in the current study, our findings support the hypothesis that patients with schizophrenia may have increased cognitive sensitivity to anticholinergic medications and that the aggregate effects of one's anticholinergic medication regimen on cognition is sufficiently robust to be important to consider in clinical practice."

Reference

Eum S, Hill SK, Rubin LH, et al. Cognitive burden of anticholinergic medications in psychotic disorders [published online April 5, 2017]. Schizophr Res. doi:10.1016/j.schres.2017.03.034 

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