What is the best medication for agitation in dementia?

October 11, 2025 •

4 min read

Agitation is an extremely common and challenging symptom, affecting up to 76% of people with Alzheimer's disease. When considering what is the best medication for agitation in dementia, it's crucial to understand that non-pharmacological interventions are the first-line approach, and any drug therapy must weigh potential benefits against serious risks.

Quick Summary

Brexpiprazole is the only FDA-approved medication for agitation in Alzheimer's dementia, but carries significant risks. Off-label use of other antipsychotics, antidepressants, or mood stabilizers is possible but requires careful consideration. Non-drug interventions are always recommended first before considering any pharmacological treatment.

Key Points

Start with Non-Pharmacological Interventions: The primary and safest approach to managing agitation in dementia involves non-drug strategies such as environmental modification, creating routines, music therapy, and addressing underlying physical discomforts.
Brexpiprazole is the only FDA-Approved Drug: Brexpiprazole (Rexulti) is specifically approved for agitation in Alzheimer's dementia, but it, like other antipsychotics, carries an FDA Black Box Warning for increased mortality risk in elderly patients with dementia-related psychosis.
Antipsychotics Are Used with Extreme Caution: Off-label atypical antipsychotics like risperidone are used for severe aggression but are associated with significant adverse effects, including a higher risk of stroke and falls.
Antidepressants Offer an Alternative: For agitation linked to anxiety or depression, off-label use of SSRIs like citalopram may be considered, although evidence for agitation is mixed and they carry side effect risks.
Dextromethorphan/Quinidine Shows Promise: An emerging combination drug, dextromethorphan/quinidine, has demonstrated efficacy in trials but needs more extensive research before widespread recommendation.
Treatment Must be Individualized: The most effective plan involves a patient-centered approach that carefully balances potential medication benefits against the risks, under the guidance of a healthcare professional.

Understanding Agitation in Dementia

Agitation in dementia is a complex and challenging behavioral symptom that can manifest in various ways, causing significant distress for both the person with dementia and their caregivers. It is often an expression of an unmet need or discomfort rather than an intentional act. Symptoms can be categorized into verbal and physical forms, including both aggressive and non-aggressive behaviors.

Aggressive Verbal: Screaming, yelling, cursing, or making threats.
Non-Aggressive Verbal: Repeating questions or phrases, unwarranted crying or laughter, or excessive complaining.
Aggressive Physical: Hitting, kicking, pushing, biting, or scratching.
Non-Aggressive Physical: Pacing, wandering, restlessness, or repetitive actions.

Agitation can be triggered by many factors, including physical discomfort (like pain, hunger, or constipation), environmental changes (such as noise or new surroundings), emotional distress (fear or anxiety), and side effects from other medications. Identifying and addressing these triggers is the first, most important step in management.

The First Line of Treatment: Non-Pharmacological Interventions

Healthcare guidelines and experts universally recommend prioritizing non-pharmacological interventions before considering medication. These methods focus on understanding the individual and their environment to reduce stressors and promote comfort and engagement.

Key non-pharmacological strategies include:

Behavioral Management: Adjusting daily routines to be simple and consistent, providing clear and calm communication, and offering reassurance.
Environmental Modification: Creating a calm, safe, and familiar environment by minimizing noise, clutter, and overstimulation. Ensuring comfort with temperature and familiar objects can also be helpful.
Engagement in Meaningful Activities: Redirecting attention with familiar and enjoyable activities, such as listening to personalized music, looking at photos, or performing simple household tasks.
Sensory Therapies: Music therapy, aromatherapy, and tailored light therapy have shown promise in reducing agitation and improving mood.
Addressing Physical Needs: Regularly checking for pain, hunger, thirst, or other physical discomforts that the person may not be able to express.

Pharmacological Options for Severe Cases

When non-pharmacological methods are insufficient, particularly if the behavior poses a safety risk, medication may be necessary. The decision to use medication must be made cautiously and in close consultation with a healthcare provider, weighing the benefits against significant potential risks.

FDA-Approved Medication

Brexpiprazole (Rexulti): This is the only medication specifically approved by the FDA for the treatment of agitation associated with dementia due to Alzheimer's disease. While it has shown dose-dependent benefits, it carries a Black Box Warning regarding an increased risk of death in older adults with dementia-related psychosis.

Off-Label Options with Associated Risks

Antipsychotics: Many atypical antipsychotics, such as risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), and aripiprazole (Abilify), are used off-label. While they can be effective for severe aggression or psychosis, they all carry the FDA Black Box Warning for increased risk of death in elderly patients with dementia-related psychosis. They also pose risks of metabolic changes, sedation, and extrapyramidal symptoms. Risperidone is sometimes licensed for short-term aggression in moderate-to-severe Alzheimer's in some regions.
Antidepressants: Certain antidepressants, particularly Selective Serotonin Reuptake Inhibitors (SSRIs) like citalopram (Celexa) and sertraline (Zoloft), can be used, especially if agitation is linked to depression or anxiety. However, evidence for their efficacy in agitation is mixed, and they can increase the risk of falls. Trazodone is also sometimes used off-label, often for sleep-related agitation.
Mood Stabilizers/Anticonvulsants: Medications like carbamazepine or divalproex are occasionally used, but evidence for their efficacy in dementia agitation is mixed, and they have notable side effect profiles.
Cholinesterase Inhibitors and NMDA antagonists: Drugs like memantine and cholinesterase inhibitors, primarily used for cognitive symptoms, have shown variable and modest effectiveness for behavioral symptoms like agitation.

Emerging Treatments

Dextromethorphan/quinidine: This combination drug has shown evidence of efficacy in clinical trials for agitation in dementia, but more research is needed. Its use is currently limited due to restricted evidence and potential side effects.

Comparison of Common Agitation Medications


Medication/Class	FDA-Approved for Agitation in AAD	Common Side Effects	Key Considerations
Brexpiprazole (Rexulti)	Yes	Headache, dizziness, sleep disturbances, urinary tract infection	Only FDA-approved drug, but has a Black Box Warning for increased mortality risk in elderly patients with dementia-related psychosis.
Antipsychotics (Off-label)	No (except Brexpiprazole)	Stroke, sedation, risk of falls, extrapyramidal symptoms, metabolic changes, increased mortality	Used cautiously for severe symptoms. Significant risks and Black Box Warning apply to all antipsychotics in this population.
SSRIs (Off-label)	No	Increased fall risk, sexual dysfunction, sleep disturbances	Mixed efficacy for agitation, but may help with associated depression/anxiety. Risks must be weighed.
Trazodone (Off-label)	No	Sedation, dizziness, orthostatic hypotension	Often used to manage sleep issues related to agitation. Efficacy for agitation varies.
Dextromethorphan/Quinidine	No	Falls, diarrhea, dizziness, urinary tract infection	Promising trial results, but limited evidence and need for more research.

Conclusion: A Patient-Centered Approach

Ultimately, there is no single "best" medication for agitation in dementia. The most effective strategy is a personalized, comprehensive approach that prioritizes identifying and managing the underlying causes of the behavior through non-pharmacological interventions first. Medication should only be considered for severe, persistent, and dangerous agitation that does not respond to non-drug approaches, and it must be managed carefully by a specialist. Regular monitoring and periodic attempts to taper the medication are essential to minimize risks and ensure that benefits outweigh potential harm. Family caregivers play a vital role in reporting observations to the healthcare team to find the right balance for their loved one's care.

Frequently Asked Questions

The first step is always to investigate and address potential non-pharmacological triggers. This includes checking for physical discomforts like pain or hunger, simplifying the environment, maintaining routines, and using calming communication techniques.

Yes, brexpiprazole (Rexulti) is the only FDA-approved drug specifically for agitation associated with dementia due to Alzheimer's disease.

The Black Box Warning indicates that older adults with dementia-related psychosis who are treated with antipsychotic drugs have an increased risk of death. This warning applies to both FDA-approved and off-label antipsychotics used for this purpose.

Medications are typically considered only after non-pharmacological interventions have failed and the agitated behavior is severe, persistent, and poses a safety risk to the patient or others.

Studies have shown that non-drug interventions, such as music therapy, massage and touch therapy, and environmental modifications, can be more effective than medications in reducing agitation and aggression. Personalized and individualized approaches tend to yield better results.

Certain antidepressants, like SSRIs, may be used off-label, especially if agitation is thought to be related to depression or anxiety. However, the evidence for their effectiveness in treating agitation is mixed, and they carry risks such as increased fall risk.

Caregivers play a critical role by observing and reporting behavioral patterns, triggers, and medication side effects to the healthcare team. Their input is essential for developing a personalized care plan, monitoring the effectiveness of treatment, and weighing risks and benefits.