Anticholinergic Medication Burden–Associated Cognitive Impairment in Schizophrenia

Joshi, Yash B.; Michael, Thomas; Braff, David L.; Green, Michael F.; Gur, Ruben C.; Gur, Raquel E.; Nuechterlein, Keith H.; Stone, William S.; Greenwood, Tiffany A.; Lazzeroni, Laura C.; MacDonald, Laura; Molina, Juan L.; Nungaray, John; Radant, Allen D.; Silverman, Jeremy M.; Sprock, Joyce; Sugar, Catherine A.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Swerdlow, Neal R.; Light, Gregory A.

doi:10.1176/appi.ajp.2020.20081212

Cited by 116 publications

(73 citation statements)

References 37 publications

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“…Although the explanatory power decreased after adjusted analysis, anticholinergic load continued to have a statistically negative impact on the MCCB composite score ( p = 0.013). The recent study of Joshi et al with a large sample size ( 47 ) was also in agreement with these findings using a different intervention and outcome assessment method. Specifically, patients with higher scores based on Anticholinergic Cognitive Burden (ACB) scale demonstrated worse cognitive performance across all cognitive domains assessed with Penn Computerized Neurocognitive Battery (PCNB) compared to patients with low ACB scores.…”

Section: Resultssupporting

confidence: 83%

“…Most of the studies included, recruited clinically stable adults in inpatient setting, with no history of pre-existing organic impairment, unstable medical or neurological conditions, or prohibited drug abuse. As regards to the study design, the majority were cross-sectional studies (38)(39)(40)(41)(42)(43)(44)(45)(46)(47). Additionally, one retrospective (19), four prospective cohort studies (48)(49)(50)(51), and two randomized clinical trials (52,53) were included.…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

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Anticholinergic Burden and Cognitive Performance in Patients With Schizophrenia: A Systematic Literature Review

2021

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Objective: Cognitive impairment in schizophrenia forms the key cause of the disease's disability, leading to serious functional, and socioeconomic implications. Dopaminergic-cholinergic balance is considered essential to cognitive performance in schizophrenia and patients are often treated with many drugs with anticholinergic properties. This study aims to examine the cognitive impact of anticholinergic burden in patients with schizophrenia.Methods: A systematic literature review was performed on English-language studies published on PubMed, Embase, and Web of Science, from inception to June 2021, to identify research studies that examined the effect of anticholinergic load on cognition in clinically stable patients with schizophrenia. No restrictions on study design, age of participants, or geographical distribution were applied. Two researchers performed independently the screening and shortlisting of the eligible articles. A narrative synthesis of the main characteristics and findings of studies included was reported.Results: In total, 17 articles of varying methodological design met the inclusion criteria. Three of them found statistically significant improvement in cognition after anticholinergic tapering without adverse effects. Thirteen studies found a statistically significant association between high anticholinergic burden and cognitive impairment (neurocognitive composite scores and individual cognitive domains such as learning and memory, executive function, processing speed), apart from a study, related to the specific characteristics of clozapine.Conclusions: Medication with increased anticholinergic load has been found in most of the studies to negatively affect neurocognitive performance of patients with schizophrenia. However, the clinical and methodological heterogeneity of studies included limit our interpretation and conclusions.

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Section: Resultssupporting

confidence: 83%

Section: Study Selection and Characteristicsmentioning

confidence: 99%

Anticholinergic Burden and Cognitive Performance in Patients With Schizophrenia: A Systematic Literature Review

2021

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“…These findings are particularly interesting considering that several pharmacological therapies used to treat schizophrenia are characterized by significant anticholinergic properties ( Kaar et al, 2020 ). Data in the literature highlighted that AB was associated with impaired cognitive ability and functioning ( Eum et al, 2017 , Eum et al, 2021 ; Joshi et al, 2021 ) as well as negative impact on the outcome of psychosocial treatment in people with schizophrenia ( O'Reilly et al, 2016 ). In this view, clarifying the impact of cognitive impairment attributable to anticholinergic medication the burden may help optimize cognitive outcomes in psychosis.…”

Section: Treatment Of Cognitionmentioning

confidence: 99%

Cognitive dysfunction in schizophrenia: An expert group paper on the current state of the art

Harvey

Bosia

Cavallaro

et al. 2022

Schizophrenia Research: Cognition

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“…Future antipsychotic medication studies should include genetic and non-genetic biomarkers for the potential to develop antipsychotic-induced dopamine supersensitivity psychosis, aiDSP and treatment resistance, and various forms of oxidative stress and genetic metabolic responses, which may affect dropout rates, side effect profiles, and outcomes more generally. It is now possible to track longterm antipsychotic side effects such as cognitive decline and metabolic syndrome more precisely (Bar-Yosef et al, 2020;Cem Atbaşoglu, Schultz, & Andreasen, 2001;Joshi et al, 2021;Scaini et al, 2018). We, therefore, recommend that researchers follow biomarker adaptive antipsychotic medication clinical trial designs, in order to control for a myriad of molecular confounders and long-term side effects (Perkovic et al, 2017).…”

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confidence: 99%

Long-term effectiveness of antipsychotics

2021

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We welcome the comments by Drs Pierre et al. and Aftab regarding the Chicago Follow-up Study, especially in relation to our most recent publication in Psychological Medicine, 'Twenty-year effects of antipsychotics in schizophrenia and affective psychosis' (Harrow, Jobe, & Tong, 2021). By way of introduction we should provide some background regarding our study, which is a prospective naturalistic observational study of 20 years duration that includes six follow-up evaluations, having been funded almost continuously for over a 35 year period, 25 of those years by the National Institute of Mental Health, NIMH, in addition to 5 years of funding by the MacArthur Foundation and 4 years by the Center of Excellence in Mental Health. Our findings bring into question the current standard of practice that emphasizes long-term maintenance treatment with antipsychotic medication in patients with schizophrenia as the optimal strategy in all cases (American Psychiatric Association, 2020).First with reference to Dr Pierre et al.'s comments regarding the problem of reverse association, the proverbial chicken and egg question, we would point out that this kind of confound is difficult to control because the relevant variables are unanticipated and often discovered long after a study is completed (Carvalho et al., 2020;Marquis, Habicht, Lanata, Black, & Rasmussen, 1997). As a prospective long-term naturalistic study over 20 years, the Chicago Follow-up Study has made extraordinary efforts to sufficiently consider patients' heterogeneity and minimize biases.

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Anticholinergic Medication Burden–Associated Cognitive Impairment in Schizophrenia

Cited by 116 publications

References 37 publications

Anticholinergic Burden and Cognitive Performance in Patients With Schizophrenia: A Systematic Literature Review

Anticholinergic Burden and Cognitive Performance in Patients With Schizophrenia: A Systematic Literature Review

Cognitive dysfunction in schizophrenia: An expert group paper on the current state of the art

Long-term effectiveness of antipsychotics

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