Antipsychotics for dementia are associated with an increased risk of serious adverse outcomes

Antipsychotics for dementia are associated with an increased risk of serious adverse outcomes

According to a published study, the use of antipsychotics in people with dementia is associated with an increased risk of a variety of serious adverse outcomes compared to non-use, including stroke, blood clots, heart attack, heart failure, bone fractures, pneumonia and acute kidney injuryThe BMJToday.

These results show that there is a significantly wider range of harm associated with the use of antipsychotics in people with dementia than has previously been acknowledged in regulatory warnings, with risks peaking shortly after starting the medication, highlighting the need for increased caution in the early stages of treatment.

Despite safety concerns, antipsychotics continue to be widely prescribed to treat behavioral and psychological symptoms of dementia such as apathy, depression, aggression, anxiety, irritability, delirium, and psychosis.

Previous regulatory warnings about prescribing antipsychotics for these symptoms were based on evidence of an increased risk of stroke and death. However, in people with dementia, evidence of other adverse outcomes is less conclusive.

To address this uncertainty, researchers set out to examine the risks of several adverse outcomes that may be associated with the use of antipsychotics in people with dementia.

The outcomes of interest were stroke, severe blood clots (venous thromboembolism), heart attack (myocardial infarction), heart failure, irregular heart rhythm (ventricular arrhythmia), fractures, pneumonia, and acute kidney injury.

Using linked primary care, hospital and mortality data in England, they identified 173,910 people (63% women) who were diagnosed with dementia between January 1998 and May 2018, at an average age of 82, and who had not been prescribed an antipsychotic in the year before their diagnosis.

Each of the 35,339 patients who were prescribed an antipsychotic on or after the date of dementia diagnosis was then matched with up to 15 randomly selected patients who were not taking antipsychotics.

Patients in whom the specific outcome studied occurred before diagnosis were excluded from the analysis of that outcome.

The most commonly prescribed antipsychotics were risperidone, quetiapine, haloperidol, and olanzapine, which together accounted for nearly 80% of all prescriptions.

Potentially influential factors such as personal patient characteristics, lifestyle, pre-existing medical conditions and prescribed medications were also taken into account.

Compared with nonuse, antipsychotic use was associated with an increased risk of all outcomes except ventricular arrhythmia. For example, the rate of pneumonia in the first three months of treatment among antipsychotic drug users was 4.48% versus 1.49% among nonusers. After one year, this value increased to 10.41% among antipsychotic drug users compared to 5.63% among non-users.

Antipsychotic drug users were also at high risk of acute kidney injury (1.7-fold increased risk) as well as stroke and venous thromboembolism (1.6-fold increased risk) compared to non-users.

For almost all outcomes, risks were highest in the first week of antipsychotic treatment, particularly pneumonia.

The researchers estimate that antipsychotic use in the first six months of treatment could be associated with one additional case of pneumonia per nine patients treated and one additional heart attack per 167 patients treated. After two years, there could be one additional case of pneumonia for every 15 patients treated and one additional heart attack for every 254 patients treated.

Because this is an observational study, no firm conclusions can be drawn about cause and effect. The researchers also warned that misclassification of antipsychotic drug use may have occurred. And although they took a number of factors into account, they cannot rule out the possibility that other unmeasured variables could have influenced their results.

However, this was a comprehensive analysis based on reliable health data and examined a wide range of adverse events and reported both relative and absolute risks over multiple time periods.

Therefore, the researchers say antipsychotics are associated with a significantly wider range of serious adverse outcomes than has previously been highlighted in regulatory warnings, with the highest risks occurring soon after starting treatment and therefore of direct relevance to guideline developers, regulators, clinicians, patients, etc., and their caregivers.

Any potential benefit of antipsychotic treatment must be weighed against the risk of serious harm, and treatment plans should be reviewed regularly, they add.

The results of this study will provide healthcare professionals with more nuanced data to help them make personalized treatment decisions, US researchers say in a linked editorial.

They explain that international guidelines advise limiting use to adults with severe behavioral and psychological symptoms of dementia, but prescription rates have increased in recent years, in part due to the relative scarcity of effective non-drug alternatives and the significant resources required to implement them.

“It is overdue to place greater priority on more patient-centered care, tailored care plans, regular reassessment of treatment options, and a move away from the overprescription of antipsychotics,” they conclude.

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