Antipsychotics for Dementia: More damage and risks than previously assumed

English study warns of massive side effects and calls for reduced use

Antipsychotics are regularly used to treat the behavioral and psychological symptoms of dementia (BPSD) that occur in many patients. However, there have long been concerns about the side effects of the most commonly used drugs of this type, particularly in elderly people with dementia. Known risks include an increased likelihood of falls, cardiovascular problems, venous thromboembolism, stroke, pneumonia, acute kidney disease and increased mortality.

In a new study just published in the British Medical Journal, UK researchers investigated the side effects associated with the use of antipsychotics in people with dementia in a large cohort and subsequently call for urgent new regulatory decisions on the use of antipsychotics for the treatment of dementia.

Role of antipsychotics in the treatment of dementia

Around forty percent of all nursing home residents in Germany who suffer from dementia are treated with tranquilizers, with sedating antipsychotics being the main drugs used. However, these drugs, originally developed for the treatment of delusions and hallucinations, are also used in people with dementia for symptoms such as agitation, anxiety, irritability, aggression, disinhibition and sleep disorders – and the trend is increasing.

In particular, risperidone, quetiapine and pipamperone are frequently and “quite generously” prescribed for dementia patients and are often used for longer than necessary. The EPYLOGE study by the Technical University of Munich came to this conclusion some time ago and warned of “significant side effects such as increased cardiovascular mortality, Parkinson’s symptoms, movement disorders, low blood pressure, orthostasis problems and falls.”

Cohort study shows that side effects of antipsychotics are higher than assumed

The situation is similar in the UK, where only risperidone and haloperidol can be used to treat dementia patients. A large cohort study by the University of Manchester has now examined the benefits and side effects of antipsychotics more extensively: the study used data from over 173,000 dementia patients, of whom 35,339 were prescribed antipsychotics, over a period of 10 years. The initial conclusion: the range of adverse effects was greater than previously highlighted in regulatory warnings.

All relevant data was obtained from the electronic health records of the Clinical Practice Research Datalink (CPRD), which covers more than 2,000 GP practices in the UK. The CPRD consists of the Aurum and GOLD databases, which are considered broadly representative of the UK population. The study included people over the age of 50 who had been diagnosed with dementia. An important point was that none of the participants had received antipsychotic treatment within the year prior to their diagnosis.

The researchers used a matched cohort design in which each patient who received antipsychotics after their first dementia diagnosis was assigned to a group. The incidence density sampling method was used, in which up to 15 randomly selected patients who received a dementia diagnosis on the same day but were not prescribed antipsychotics served as a comparison group.

The average time between the first dementia diagnosis and the date of the first antipsychotic prescription was 693.8 days for Aurum and 576.6 days for GOLD. The most commonly prescribed antipsychotics included risperidone, haloperidol, olanzapine and quetiapine.

Increased risk of various secondary disorders

The current population-based study found that adults with dementia who were prescribed antipsychotics had an increased risk of venous thromboembolism, myocardial infarction, stroke, heart failure, pneumonia, fractures and acute kidney injury compared to those not taking antipsychotics.

A particularly high risk of adverse events was observed at the beginning of treatment in people taking antipsychotics. After taking antipsychotics for 90 days, the risk of venous thromboembolism, pneumonia, acute kidney damage and strokes was significantly higher than in people who did not take antipsychotics. Compared to non-use, the risk of venous thromboembolism was 1.5 times higher and the risk of pneumonia up to 2 times higher. However, the antipsychotics did not appear to have any influence on the risk of ventricular arrhythmias, appendicitis and cholecystitis.

The researchers estimate that the use of antipsychotics in the first six months of treatment could lead to one additional case of pneumonia for every nine patients treated and one additional heart attack for every 167 patients treated. If treatment continues for two years, there could be one additional case of pneumonia for every 15 patients treated and one additional myocardial infarction for every 254 patients treated.

Study authors: “Antipsychotic treatments need to be better balanced.

In summary, the study authors conclude that the use of antipsychotics in people with dementia entails a considerably wider range of harms than previously investigated. Any potential benefit of antipsychotic treatment must therefore be weighed against the risk of serious harm on multiple outcomes:

The use of antipsychotics in people with dementia is associated with a wide range of serious adverse outcomes, with a relatively high absolute risk of harm for some outcomes. These risks should be considered in future regulatory decisions alongside cerebrovascular events and mortality. Any potential benefit of antipsychotic treatment must be weighed against the risk of serious harm, and treatment plans should be reviewed regularly. The effect of antipsychotics on behavioral and psychological symptoms of dementia is modest at best, but the proportion of people with dementia who are prescribed antipsychotics has increased in recent years. Our finding that antipsychotics are associated with a wider range of risks than previously known is therefore of direct relevance to guideline developers, regulators and clinicians considering the appropriateness of prescribing antipsychotics for behavioral and psychological symptoms of dementia.”