Deadly Prescriptions: New Study Links Antipsychotics to Life-Threatening Risks in Dementia Patients

A new study published in BMJ has found that antipsychotic use is associated with severe, life-threatening conditions in people with dementia. The research, led by Pearl L. H. Mok of the University of Manchester, highlights an increased risk of stroke, pneumonia, acute kidney injury, heart failure, myocardial infarction, and other serious outcomes. These risks are highest immediately after starting the medication, particularly within the first week of use.

The study found that typical antipsychotics, such as haloperidol, were linked to a higher risk of adverse effects than atypical antipsychotics, such as risperidone and quetiapine. While quetiapine was associated with a lower risk of certain conditions, including stroke and pneumonia, it was not free from harmful effects.

Despite longstanding regulatory warnings against prescribing antipsychotics for behavioral and psychological symptoms of dementia, these drugs continue to be widely used. The authors of the study caution that risks beyond mortality—including the development of acute and chronic conditions—should be carefully considered before prescribing. They write:

“In this population based cohort study of adults (≥50 years) with dementia, use of antipsychotics compared with non-use was associated with increased risks for stroke, venous thromboembolism, myocardial infarction, heart failure, fracture, pneumonia, and acute kidney injury. Increased risks were observed among current and recent users and were highest in the first week after initiation of treatment. In the 90 days after a prescription, relative hazards were highest for pneumonia, acute kidney injury, stroke, and venous thromboembolism, with increased risks ranging from 1.5-fold (for venous thromboembolism) to twofold (for pneumonia) compared with non-use.”

The aim of this study was to investigate possible links between eight adverse outcomes (stroke, venous thromboembolism, myocardial infarction, heart failure, ventricular arrhythmia, fracture, pneumonia, and acute kidney injury) and antipsychotic use in individuals with dementia.

The authors utilized anonymized data from the UK’s Clinical Practice Research Datalink (CPRD). The CPRD comprises data from over 2,000 general practices in the UK, representing roughly 20% of the population. This database includes information on diagnoses, prescriptions, lab results, healthcare contacts, and referrals. Additionally, this data can be linked to the UK’s Hospital Episode Statistics database and the Office for National Statistics, providing further details on hospital admissions and mortality. According to the authors, these databases are “broadly representative of the UK population.”

To be included in the current research, service users had to receive a dementia diagnosis between January 1, 1998, and May 31, 2018, be at least 50 years old when dementia was first diagnosed, and have no prescriptions for antipsychotics in the 365 days prior to their dementia diagnosis. Additionally, service users needed to be registered with the CPRD for at least one year and have records that could be linked to the UK’s Hospital Episodes Statistics data. The authors compared rates of stroke, venous thromboembolism, myocardial infarction, heart failure, ventricular arrhythmia, fracture, pneumonia, and acute kidney injury in service users prescribed antipsychotics versus those who were not. Service users with a history of each negative outcome investigated were excluded from the analysis of that outcome. For example, service users who had previously experienced a stroke were not considered in the comparison of stroke risk between antipsychotic users and non-users.

To facilitate comparison, antipsychotic users were matched with non-users based on several factors that may have contributed to negative outcomes, including personal characteristics, lifestyle, additional diagnoses, and other prescribed medications. In total, data from 173,910 service users with dementia were included in this study, among whom 35,339 had an antipsychotic prescription.

The majority of service users included in this research were white (approximately 75%) and women (63%). The average age of the included service users was 82.1 years. The average number of days between the first dementia diagnosis and the antipsychotic prescription was 693.8. Atypical antipsychotics accounted for 74.7% of the prescriptions, while typical antipsychotics made up 25.3%. Risperidone was the most frequently prescribed antipsychotic (29.8% of all prescriptions), followed by quetiapine (28.7%), haloperidol (10.5%), and olanzapine (8.8%). Service users prescribed antipsychotics were more likely to have a history of serious mental illness, as well as prescriptions for antidepressants and benzodiazepines.

Links Between Antipsychotic Use and Negative Outcomes

Any use of antipsychotics, whether current (within 90 days of prescription), recent (180 days since last use), or past (after recent use ended), was linked to a heightened risk of seven out of eight negative outcomes investigated compared to non-users. Those prescribed antipsychotics faced an increased risk of:

• stroke (1.54 times more likely)
• venous thromboembolism (1.52)
• myocardial infarction (1.22)
• heart failure (1.16)
• fracture (1.36)
• pneumonia (2.03)
• acute kidney failure (1.57)

The only investigated negative outcome not associated with antipsychotic use was ventricular arrhythmia.

The First Week: A Period of Extreme Risk

The most striking finding of the study was the significantly increased risk of life-threatening conditions immediately after starting antipsychotics. Within the first seven days of use, patients faced dramatically heightened risks:

• Stroke (3.75 times more likely)
• Venous thromboembolism (2.05 times more likely)
• Myocardial infarction (2.33 times more likely)
• Heart failure (2.85 times more likely)
• Fracture (2.22 times more likely)
• Pneumonia (9.99 times more likely)
• Acute kidney injury (3.79 times more likely)

Even beyond this initial period, the risks remained elevated for at least 90 days after starting treatment.

Comparing Antipsychotic Types

The study found that typical antipsychotics (e.g., haloperidol) were associated with a greater risk of adverse outcomes than atypical antipsychotics (e.g., risperidone and quetiapine). Those taking typical antipsychotics were at higher risk of:

• Stroke (1.23 times more likely)
• Heart failure (1.18 times more likely)
• Fracture (1.22 times more likely)
• Pneumonia (1.92 times more likely)
• Acute kidney injury (1.22 times more likely)

While atypical antipsychotics were linked to slightly lower risks, they were still associated with severe adverse outcomes.

There were no significant differences between these groups for risk of myocardial infarction or venous thromboembolism.

Compared to the non-use of antipsychotics, the current use of risperidone and haloperidol was linked to an increased risk of all the adverse outcomes investigated, except for ventricular arrhythmia. The current use of quetiapine was associated with a higher risk of fractures, pneumonia, and acute kidney injury when compared to the non-use of antipsychotics. Furthermore, the current use of haloperidol was associated with an increased risk of fractures, pneumonia, and acute kidney injury compared to the current use of risperidone. Haloperidol use was also linked to a greater risk of stroke, venous thromboembolism, heart failure, fractures, pneumonia, and acute kidney injury in comparison to quetiapine use. Additionally, the current use of risperidone was associated with a greater risk of stroke, venous thromboembolism, pneumonia, and acute kidney injury compared to quetiapine use.

The authors acknowledge several limitations of the current work. Other variables besides antipsychotic use may have contributed to the observed negative outcomes. For instance, the use of multiple prescription drugs, which is common for the age group examined in this study, could have influenced some of the negative outcomes. The authors did not have data on the reasons for antipsychotic treatments. Dosage information was not consistently recorded in the CPRD records. While CPRD records accurately document antipsychotic prescriptions, there is no data on adherence to these prescriptions. It is likely that some service users who were prescribed antipsychotics did not actually take them. Electronic health data collected for administrative purposes can occasionally be unreliable.

The authors conclude:

“Antipsychotic use is associated with a wide range of serious adverse outcomes in people with dementia, with relatively large absolute risks of harm for some outcomes. These risks should be considered in future regulatory decisions, alongside cerebrovascular events and mortality. Any potential benefits of antipsychotic treatment need to be weighed against risk of serious harm, and treatment plans should be reviewed regularly.”

A Growing Body of Evidence Against Antipsychotic Use in Dementia

Past research has linked antipsychotics to acute kidney injury, stroke, and death in elderly patients. A JAMA Psychiatry study found that the mortality risk associated with these drugs is likely underestimated and increases with dose.

Experts warn that the financial incentives of for-profit medicine may be driving overmedication of dementia patients. A Huffington Post exposé revealed that pharmaceutical companies have aggressively marketed antipsychotics to vulnerable populations, including the elderly, for off-label uses—despite evidence of serious harm.

Additionally, research has demonstrated that elderly service users with dementia can often withdraw from antipsychotics without worsening behavioral symptoms. The British Psychological Society has recommended non-drug interventions as a safer and more effective approach.

Regulatory Action and Clinical Implications

The authors of the BMJ study urge regulators and prescribers to reconsider the risks of antipsychotic use in dementia patients, emphasizing the need for routine reassessment of treatment plans.

The findings add to mounting concerns that psychiatry’s reliance on medication-based interventions often ignores safer alternatives. While antipsychotics may provide short-term sedation, their long-term risks raise fundamental ethical questions.

Dementia care demands a shift away from pharmaceutical quick-fixes toward evidence-based behavioral interventions. Without significant reform, the continued reliance on antipsychotics risks prioritizing convenience and profit over patient well-being.

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Mok, P. L., Carr, M. J., Guthrie, B., Morales, D. R., Sheikh, A., Elliott, R. A., Camacho, E. M., van Staa, T., Avery, A. J., & Ashcroft, D. M. (2024). Multiple adverse outcomes associated with antipsychotic use in people with dementia: Population-based matched cohort study. BMJ. (Link)