Can long-term use of antipsychotics cause dementia? The evidence reviewed

October 9, 2025 •

5 min read

A large-scale UK Biobank cohort study found that exposure to any antipsychotic medication was associated with a 33% increased risk of all-cause dementia and a 90% increase in vascular dementia risk. This discovery highlights the complex question: Can long-term use of antipsychotics cause dementia? while underscoring the need for careful consideration of medication risks.

Quick Summary

Long-term antipsychotic use is associated with a higher risk of cognitive decline and dementia, with studies showing a dose-dependent relationship in older adults, though confounding factors complicate the causal link.

Key Points

Antipsychotic Use Linked to Higher Dementia Risk: Observational studies, including a large UK Biobank cohort study, have found an association between antipsychotic exposure and an increased risk of all-cause and vascular dementia.
Dose-Response Relationship Exists: Research suggests that higher cumulative doses of oral antipsychotics are linked to an increased risk of dementia, highlighting the importance of using the lowest effective dose for the shortest necessary duration.
Mechanisms Include Dopamine and Cholinergic Effects: Antipsychotics can cause cognitive impairment by blocking dopamine D2 receptors and, in some cases, muscarinic cholinergic receptors, the latter of which increases anticholinergic burden linked to dementia.
Serious Risks for Dementia Patients: In individuals already diagnosed with dementia, antipsychotic use carries additional serious risks, including higher rates of stroke, infections like pneumonia, and mortality.
Deprescribing is a Viable Strategy: Managed discontinuation of long-term antipsychotics is often feasible and may lead to improved cognitive function in some patients, though it requires careful monitoring and often support from non-pharmacological interventions.
Individualized Risk-Benefit Analysis is Crucial: The decision to use long-term antipsychotics must carefully weigh the benefits of managing severe, distressing symptoms against the significant and well-documented risks, especially in vulnerable older adult populations.
Non-Pharmacological Treatments are First-Line: Guidelines recommend exploring non-drug options first for behavioral and psychological symptoms of dementia before initiating or continuing antipsychotic therapy.

The Complex Link Between Antipsychotics and Dementia

Scientific evidence strongly indicates an association between the long-term use of antipsychotic medications and an increased risk of developing dementia or experiencing accelerated cognitive decline. While observational studies, such as the large 2024 UK Biobank cohort study, cannot prove direct causation, they reveal a significant correlation between exposure to these drugs and an elevated risk of all-cause and vascular dementia. The analysis found a dose-response relationship, meaning higher cumulative doses were linked to a greater risk.

This correlation is particularly concerning for older adults, who are more susceptible to cognitive issues and often prescribed antipsychotics for neuropsychiatric symptoms related to dementia, such as agitation or psychosis. The challenge for clinicians is differentiating the cognitive effects of the underlying psychiatric illness from the potential iatrogenic effects of the medication itself. For example, the very symptoms that lead to an antipsychotic prescription might also be markers for a more aggressive disease course, potentially confounding the results.

How Antipsychotics May Impact Cognitive Function

Multiple biological mechanisms are proposed to explain how antipsychotics might contribute to cognitive decline and dementia risk, reflecting the drugs' complex effects on brain chemistry and structure.

Neurochemical Modulation and Impairment

Dopamine Antagonism: All antipsychotics block dopamine D2 receptors. While this is the primary mechanism for treating psychosis, it can also impair cognitive functions regulated by the dopaminergic system, such as executive function, processing speed, and memory. Dopamine blockade in the nigrostriatal pathway, for instance, can cause motor side effects that impact physical and cognitive performance.
Anticholinergic Burden: Many antipsychotics, particularly some older agents, have anticholinergic effects, blocking muscarinic receptors. A higher anticholinergic burden is independently associated with cognitive impairment, especially affecting attention and memory, and an increased risk for dementia. This effect is a significant concern in geriatric patients, whose brains are more sensitive to these anticholinergic effects.

Brain Volume and Inflammation

Brain Tissue Loss: Some research indicates that long-term use of antipsychotics, especially at high doses, may be linked to a reduction in brain volume. The clinical implications of this are not fully understood, but it raises questions about the long-term morphological impact of these drugs on the brain.
Neuroinflammation: Growing evidence points to a complex interplay between inflammation, oxidative stress, and cognitive dysfunction. Antipsychotics can influence inflammatory processes in the brain, and while some studies suggest a reduction in proinflammatory cytokines, more research is needed to fully understand how these inflammatory effects relate to cognitive outcomes.

Comparing Antipsychotic Classes and Dementia Risk

Historically, newer second-generation (atypical) antipsychotics were thought to be safer than first-generation (typical) agents, especially regarding side effects like tardive dyskinesia. However, for the geriatric population with dementia, this distinction is less clear, and both classes carry significant risks.


Feature	First-Generation (Typical) Antipsychotics	Second-Generation (Atypical) Antipsychotics	Assessment in Dementia
Mechanism of Action	Primarily strong dopamine D2 receptor antagonism.	Modulates multiple receptors (D2, serotonin 5-HT2A, histamine, muscarinic).	Both block dopamine pathways involved in cognition.
Anticholinergic Effects	Some, especially low-potency agents, have high anticholinergic burden.	Varies by drug; some (e.g., quetiapine, olanzapine) have significant anticholinergic effects.	Anticholinergic burden increases cognitive risk in both classes.
Mortality Risk	Significant risk, possibly higher than atypicals, though some studies suggest comparable risks.	Significant risk, noted with a FDA black box warning; often cited at 1.5-1.7 times the mortality risk of placebo.	Both classes are associated with increased mortality in dementia patients.
Cerebrovascular Risk	Associated with increased risk of cerebrovascular events (CVA) like stroke.	Also associated with increased CVA risk, prompting FDA warnings.	Both typical and atypical agents increase CVA risk in dementia.
Metabolic Risk	Generally lower metabolic risk compared to most atypicals.	Associated with cardiometabolic side effects like weight gain and diabetes.	Metabolic issues, particularly insulin resistance, can exacerbate cognitive decline.

Special Considerations for Patients with Dementia

When managing symptoms in patients with pre-existing dementia, the risks associated with antipsychotic use are particularly acute.

Increased Risks: In addition to cognitive issues, use in this population is associated with elevated risks for stroke, heart failure, pneumonia, acute kidney injury, and higher all-cause mortality, especially in the early stages of treatment.
Cognitive Worsening: Even atypical antipsychotics, which are sometimes seen as having a lower cognitive impact, can worsen cognition in patients with dementia. The CATIE-AD study found atypical antipsychotic treatment was associated with a cognitive decline equivalent to a year's natural deterioration over just 36 weeks.
Deprescribing: Current guidelines for managing neuropsychiatric symptoms of dementia often recommend non-pharmacological interventions first and advise caution with antipsychotic use. For patients on long-term antipsychotics, deprescribing—the planned and supervised reduction or discontinuation of medication—can be considered. Studies suggest that many patients can safely have their antipsychotics reduced or stopped, with some experiencing improved cognition. However, this must be done carefully, as abrupt withdrawal can carry its own risks.

Managing Behavioral Symptoms: Beyond Medication

For both psychiatric disorders and dementia, non-pharmacological strategies are often the first and safest approach to managing behavioral symptoms and improving cognitive function. These strategies include:

Environmental Adjustments: Modifying the patient's environment to reduce triggers for agitation or distress, and creating a calming, structured routine.
Psychosocial Interventions: Using techniques like reassurance, redirection, validation therapy, and increased social activities can help address underlying needs and improve mood.
Addressing Comorbidities: Pain, infection, and other medical issues can exacerbate behavioral symptoms. A thorough medical evaluation is essential before resorting to medication.
Caregiver Education: Providing caregivers with training and support can equip them with effective communication and de-escalation techniques.

Conclusion

While antipsychotic medications are essential for managing severe psychiatric symptoms, the available evidence indicates a concerning link between their long-term use and an increased risk of dementia and accelerated cognitive decline, especially in older adults. Multiple potential mechanisms, including dopamine blockade and anticholinergic effects, contribute to this risk. The decision to prescribe long-term antipsychotics must involve a careful and balanced evaluation of the potential benefits for managing severe behavioral issues versus the known risks, which include serious adverse events like stroke and increased mortality. For many patients, particularly those with dementia, non-pharmacological approaches should be the preferred first-line treatment. When medication is necessary, ongoing reassessment and consideration of safe deprescribing strategies are critical to minimizing long-term harm.

For more detailed information, consult authoritative sources such as the American Academy of Family Physicians guidelines on deprescribing antipsychotics in elderly patients with dementia.

Frequently Asked Questions

No, taking antipsychotics does not guarantee you will get dementia. The relationship is one of association, not proven causation. The risk is influenced by many factors, including age, genetics, underlying medical conditions, and the specific medication and dosage used.

While atypical (second-generation) antipsychotics often have a better side effect profile for extrapyramidal symptoms, studies show that in older people with dementia, both typical and atypical agents carry significant risks, including higher mortality rates and cerebrovascular events. Regulatory agencies have issued warnings for both classes.

Early signs can be subtle and might include slowed thinking, difficulty with memory or concentration, confusion, and worsened executive functions like planning or decision-making. Patients or caregivers may notice a worsening of cognitive performance that is not consistent with the underlying disease progression alone.

Yes, carefully managed discontinuation, or 'deprescribing,' is often possible and recommended for many patients, especially older adults with dementia. However, it must be done under strict medical supervision and with a gradual taper to minimize withdrawal symptoms or symptom relapse.

Yes, non-drug treatments are the recommended first-line approach for behavioral and psychological symptoms of dementia. These include personalized social activities, environmental adjustments, validation therapy, and addressing any underlying medical issues like pain or infection.

Antipsychotics can impact cognition through several mechanisms, including blocking dopamine receptors crucial for executive function, increasing the anticholinergic burden that impairs memory, and potentially contributing to brain volume loss and neuroinflammation with long-term use.

The decision should be a collaborative one involving the prescribing clinician, the patient, and their caregivers or family members. It is crucial to have an open discussion about the risks of the medication versus the risks associated with the untreated psychiatric or behavioral symptoms.