Medical Bulletin 19/ April/ 2024

Antipsychotics for dementia causes more harm, finds study

A study published in the journal The BMJ found that antipsychotic use in people with dementia is associated with elevated risks of a wide range of serious adverse outcomes including stroke, blood clots, heart attack, heart failure, fracture, pneumonia, and acute kidney injury when compared with non-use.

Antipsychotic use in dementia carries a wider range of risks than previously recognized, especially in the early stages of treatment, emphasizing the need for caution. Despite safety concerns, they are commonly prescribed for behavioral and psychological symptoms such as apathy, depression, aggression, and anxiety. Regulatory warnings highlight increased risks of stroke and death, but evidence of other adverse outcomes is less clear.

In the study, researchers examined potential adverse outcomes linked to antipsychotic use in individuals with dementia. They analyzed data from 173,910 dementia patients, of whom 35,339 were prescribed antipsychotics after diagnosis. The study looked at outcomes including stroke, blood clots, heart attack, heart failure, irregular heart rhythm, fractures, pneumonia, and acute kidney injury. The most commonly prescribed antipsychotics were risperidone, haloperidol, and olanzapine, which accounted for almost 80% of all prescriptions.

The results showed that compared to non-use, antipsychotic use was linked to higher risks for all outcomes except ventricular arrhythmia. For instance, within the first three months of treatment, antipsychotic users had higher rates of pneumonia (4.48% vs. 1.49% for non-users), which increased to 10.41% vs. 5.63% at one year. Antipsychotic users also faced increased risks of acute kidney injury (1.7-fold), stroke, and venous thromboembolism (1.6-fold) compared to non-users. Risks were highest during the first week of treatment, especially for pneumonia.

“Antipsychotics are associated with a considerably wider range of serious adverse outcomes than previously highlighted in regulatory alerts, with the highest risks soon after starting treatment, and are therefore of direct relevance to guideline developers, regulators, clinicians, patients and their carers. Any potential benefits of antipsychotic treatment need to be weighed against risk of serious harm and treatment plans should be reviewed regularly, they add. The findings of this study will equip healthcare professionals with more nuanced data to help guide personalised treatment decisions,” said the study authors.

Reference: Pearl L H Mok, Matthew J Carr, Bruce Guthrie, et al; Multiple adverse outcomes associated with antipsychotic use in people with dementia: population based matched cohort study; The BMJ; https://doi.org/10.1136/bmj-2023-076268

Do sugary beverages elevate the risk of atrial fibrillation?

In a recent study published in the European Journal of Clinical Nutrition, researchers used Mendelian randomization (MR) to explore the associations between the intake of pure fruit juices (PFJ) and sugar-sweetened beverages (SSBs) with cardiovascular disease (CVD).

CVD, a global health issue, relates to factors like high BMI, alcohol, and smoking. While sugar-sweetened beverages and fruit juices are linked to CVD, the causal relationship is uncertain. Cutting back on sugary drinks may reduce CVD risk, but fruit juice intake may still be a predictor. Despite nutrient benefits, limiting fruit juice intake is advised due to its high sugar content.

In the study, researchers investigated whether sugar-sweetened beverages and pure fruit juices consumption increased CVD risk by assessing genetically estimated causal relationships between sugar-sweetened beverages, pure fruit juices and six CVDs using mendelian randomization. The team obtained dietary intake data of 85,852 individuals by conducting a genome-wide association study.

The analysis showed genetically, sugar-sweetened beverages are causally associated with atrial fibrillation, but not with other cardiovascular disease risks. Pure fruit juices lack such associations. Sugar-sweetened beverages contain additives like sodium citrate, potentially raising atrial fibrillation risk. Meanwhile, pure fruit juices' anti-inflammatory properties may lower CVD incidence by preventing plaque development and platelet aggregation.

The findings highlighted the impact of long-term sugar-sweetened beverages/pure fruit juice intake on cardiovascular disease (CVD) and recommended dietary choices for people who are at risk. Patients with atrial fibrillation should limit their sugar-sweetened beverage consumption to prevent potential pathogenic hazards, whereas individuals may incorporate pure fruit juice into their diet as a protective factor against CVD.

Reference: Xie, H., Liu, Y., Gu, X., et al., (2024) Association between sugar-sweetened beverages and pure fruit juice with risk of six cardiovascular diseases: a Mendelian randomization study. Eur J Clin Nutr. doi:https://doi.org/10.1038/s41430-024-01441-9. https://www.nature.com/articles/s41430-024-01441-9

Does a father's diet have an impact on the health of offspring?

A new research, published in Nature Communications, found that the macronutrient balance in the diet of male mice affected the level of anxiety-like behaviour of sons and the metabolic health of daughters.

Previous studies have discovered that a mouse father’s diet can have an impact not only on his reproductive health but on that of his offspring. Over- or under-feeding male mice can affect their offspring’s metabolism and behaviour, as well as their risk of cancer. However, the various health impacts on offspring, depending on the type and composition of the diet of male mice before conception, are not well understood.

In the study, researchers from the University of Sydney’s Charles Perkins Centre in Australia fed male mice one of ten diets differing in the proportions of protein, fats, and carbohydrates, then allowed them to mate with females reared on the standard diet. The behaviour and physiology of the offspring were then studied.

Researchers discovered that male mice who were fed low protein and high carbohydrate diets were more likely to have male offspring with higher levels of anxiety. They also found that male mice who were fed high-fat diets were more likely to have daughters with higher levels of body fat and markers of metabolic disease. The team also observed that males on a low-protein diet consumed more food overall.

“Our study shows that the type of diet eaten before conception can program specific characteristics of the next generation. It is extraordinary that by titrating mixtures of protein, fat and carbs in the father’s diet, we could influence specific features of his sons and daughters health and behaviour. Further, our study showed that it’s not just eating too much or too little, but the composition of the diet that can have an impact on future children,” said the study authors.

Reference: Crean, A.J., Senior, A.M., Freire, T. et al. Paternal dietary macronutrient balance and energy intake drive metabolic and behavioral differences among offspring. Nat Commun 15, 2982 (2024). https://doi.org/10.1038/s41467-024-46782-y