Anticholinergics are related to poor cognition: It’s time to seriously consider our prescription
Mental ill people (such as bipolar with psychotic symptoms of schizophrenia or bipolar disorder) have a large symptom burden. Research focuses on helping symptoms such as sounds and delusions (called “positive” symptoms), which are the symptoms most antipsychotic drugs aim to improve.
However, we know from the research that psychopaths also suffer from negative symptoms (depressed mood, lack of motivation and enjoyment) and cognitive impairment. This means they may have problems with memory, learning, information processing and problem solving, which can have a huge impact on their lives. This is partly why many people with chronic mental illness need community support, which represents a large proportion of medical expenses.
Brain chemistry acetylcholine helps in learning and cognitive processes and has become an interesting goal for research. For example, in Alzheimer’s dementia, we use drugs to increase the amount of acetylcholine. However, some antipsychotics (such as clozapine and quetiapine) are used in the receptors of acetylcholine, and we usually assist anticholinergic drugs to reduce certain side effects of antipsychotics (such as stiffness or motor problems). This has the effect of reducing the amount of acetylcholine.
To sum up, one has to doubt that at least to some extent the drugs we prescribe are to help, at least to some extent, some cognitive problems seen in some degree.
Mancini et al. (2025) conducted a recent study published in the American Journal of Psychiatry to see if there is an association between cognitive impairment and anticholinergic drugs in psychiatric disorders.
People with psychiatric experience may have problems with memory, learning, information processing and problem solving
method
The researchers conducted a systematic review and meta-analysis of related research; this is a way for many smaller studies to gather. They searched three databases and used a wide range of search terms, including observational studies and clinical trials. These include studies involving adults over the age of 18 and diagnosis across the entire range of psychiatric disorders, including individuals at risk for mental illness. Researchers excluded studies of patients with primary diseases other than psychiatric disorders, such as anxiety, neurodevelopmental disorders, or nonpsychomotional disorders. Only when the study objective quantitative measurement of cognition and studies using self-report measurements were excluded.
Potential studies were screened for suitability by independent researchers and analyzed by random effects meta-analysis model. This is a statistical method that considers heterogeneity or variation between studies due to methodological differences.
result
40 studies were included in the meta-analysis. These are divided into three categories:
- Study on the use of clinical scales to evaluate cognitive function and anticholinergic burden,
- Study on the use of serological (laboratory) measures to evaluate cognitive function and anticholinergic burden
- Study on comparing cognitive functions before and after anticholinergic drugs.
The analysis included 5,188 people, most (87.6%) of whom were diagnosed with schizophrenia, while the rest were diagnosed with episode one psychosis. 64.5% of individuals were male, with an average age of 38.6.
The following statistically significant results were reported (key results are described in detail):
- Negative correlation between anticholinergic burden and cognition
- Domain: Global Cognition (R = -0.37, 95%CI -0.48 to -0.25, PCORR <0.001), Speech Learning, Visual Learning, Working Memory, Processing Speed, Attention, Attention, Executive Function, Executive Function, Executive Function, and Social Cognition
- 25 studies, n = 4,620
- Negative correlation between serum anticholinergic activity and cognition
- Domain: Speech Learning (R = -0.26, 95%CI -0.38 to -0.14, PCORR <0.001), Working Memory and Administrative Functions
- 6 studies, n = 382
- Gradually reducing anticholinergic drugs improve cognition
- Domain: Speech Learning, Working Memory (D = 0.94, 95% CI 0.63 to 1.26, PCORR = 0.001) and Executive Functions
- 9 studies, n = 186.
Negative correlations mean that anticholinergic burden and increased serum anticholinergic activity are associated with reduced cognition in specific areas described above.
As anticholinergic burden increases, global cognition decreases.
in conclusion
The author concluded:
In this systematic review and meta-analysis, we found that anticholinergic burden was associated with poor cognitive function in psychiatric patients and that reduced anticholinergic drugs effectively improve cognitive function. These findings highlight the negative effects of routinely used pharmacological interventions on cognitive function in psychiatric patients. From a clinical point of view, gradual reduction of anticholinergic drugs may be beneficial. However, further randomized clinical trials are needed to perform unbiased quantitative quantification of welfare.
Advantages and limitations
Overall, the study was well conducted and highly effective:
- The research question is well defined and appropriate search terms are used (including clinically high risk of psychiatric disorders as part of spectrum and mental mood disorders).
- The research identification was conducted by independent reviewers and described a method of adjudication that diverged from a clear Prisma flow chart, all of which increased internal validity, or studied the extent of the research question.
- Most of the studies included are of high quality and no publication bias was found.
A key advantage of this article is that the authors conducted four sensitivity analyses and a meta regression that addressed potential confounding problems in chronic or antipsychotic doses of disease:
- The negative correlation has a strong correlation for all sensitivity analyses, including episode 1 psychosis – meaning long-term psychosis patients or a single first event, both have the same association between cognitive impairment and anticholinergic ability.
- Metare regression found no statistically significant association between effect size and age, gender, or chlorpromazine-equivalent antipsychotic dose, suggesting that these factors cannot explain this association.
One of the main limit What this study is that it cannot include other variables such as negative symptoms, depression or severity of psychiatric symptoms, all of which may play an important role in cognitive impairment. The author points out the importance of future research on these studies and reports Potential confounders.
Furthermore, studies involving tapering of anticholinergic capacity do not include controls, so randomized controlled studies are needed to strengthen this finding.
Finally, despite the wide range of psychosis mentioned in the search terms, the papers included in this analysis include only diagnosing schizophrenia and first event psychosis, and therefore do not necessarily generalize the results to people with psychotic symptoms, or at an extremely high risk of psychosis.
Overall, this study was well conducted and has high effectiveness.
Impact on practice
This study has The clinical significance of potential large number of patients is very great. For decades, research on schizophrenia and psychiatric disorders has focused on targeting and alleviating “positive” symptoms, but slowly shifting attention to less appreciation, but significantly disabling areas of these diseases – negative and cognitive symptoms. Cognitive symptoms can have a wide range of impacts on people’s lives, leading to high levels of unemployment and community support.
The reading of this article is really exciting because its application is so direct and clinically relevant to daily exercises. Translation studies seem to be abstract and removed from clinical work, when I know there is no benefit in decades, but I have a patient I worry about. The patients I treat in South London are diverse and complex, and there are a lot of socio-economic stresses and deprivation that complicate any mental health manifestations. This study proposes a simple and safe way to improve someone’s life. Since the focus of the intervention is on reducing the burden of medication, it may be welcomed by patients and caregivers, although it is prudent to explore the patient’s perception of this.
In co-discussion with patients, all prescription decisions should be made after careful risk and welfare considerations. We don’t prescribe antipsychotics unless directed – in my experience, they are often transformative and life-saving. Additionally, anticholinergic drugs are essential to reduce uncomfortable and unpleasant side effects. However, This article prompts us to question the burden of these drugs and is crucial when it should be reviewed.
Review of anticholinergic drugs
Chengappa et al. has written an editorial on Mancini’s paper (Chengappa et al., 2025), which provides useful advice on how psychiatrists can review the burden of anticholinergic drugs (Chengappa et al., 2024). They suggest:
- Identify patients who are stable for at least six months and
- No extraconital side effects,
- Use a shared decision-making method.
Reduction should be gradually (i.e. within a few months), reviews are conducted regularly to monitor psychiatric symptoms, reappearing side effects, and changes to cognitive function. This is a pragmatic and achievable approach, some of which are practiced by conventional genital psychiatrists used to measuring anticholinergic affordability and reducing excess medications, which I believe can be accepted by adult colleagues in general and in the wider field of psychiatry.
While all this is very encouraging, it is important to consider important warnings. This article shows the correlation and In order to prove causality, further prospective controlled studies are needed. Other factors that may affect cognition need to be considered in future research, including the presence of negative symptoms and the severity of psychiatric symptoms.
This won’t be a panacea, and for some it’s impossible to reduce prescriptions, but emerging therapies like Karxt may provide alternatives to improve cognition.
Ultimately, I feel hopeful that cognitive impairment in chronic psychiatric disorders is gaining reasonable focus and action and that patients will see real benefits in the near future.
This article prompts us to question the burden of these drugs and is crucial when it should be reviewed.
Statement of interests
Dr. Dawkins has previously worked on the same research group with T Pillinger and R McCutcheon, but has not been involved in the paper.
Link
Main paper
Mancini V, Latreche C, Fanshawe JB, etc. (2025) Anticholinergic burden and cognitive function in psychiatric disorders: systematic review and meta-analysis. It’s J Psychiatry ; 182:349–359.
Other references
Chengappa Knr, Cotes RO (2024) The high incidence of clozapine and the high incidence of pneumonia are needed, and better clinical strategies are needed – how do we get there? I’m J Psychiatry 181:851–853. 10.1176/appi.ajp.2024077
Chengappa, Knr, Gannon, JM, and Joshi, YB (2025) calls on psychiatrists: The sort of unnecessary anticholinergic drugs in schizophrenia must now begin, the American Journal of Psychiatry. 2025/04/01, American Psychiatric Publishing (AJP), 182 (4), pp. 319–321. 10.1176/appi.ajp.20250124
