First-Line Approach: Non-Pharmacological Interventions
Before considering medication, healthcare professionals and caregivers should always prioritize non-drug approaches to manage agitation. These strategies focus on identifying and addressing the underlying causes of the behavior, such as discomfort, fear, confusion, or unmet needs. Effective management begins with a comprehensive assessment to rule out physical causes like pain, infection, or medication side effects.
Creating a Calm and Predictable Environment
- Maintain a routine: Keep daily schedules for activities, meals, and sleep consistent to reduce confusion and anxiety.
- Reduce overstimulation: Minimize clutter, harsh lighting, and loud noises, especially during periods of 'sundowning' (late afternoon/evening agitation).
- Use calming sensory input: Introduce soothing music, aromatherapy, or therapeutic touch to help reduce distress.
Using Distraction and Redirection Techniques
- Engage in favorite activities: Redirect the person's attention with a preferred hobby, music, or a familiar household task.
- Use validation therapy: Acknowledge the person's feelings and concerns without correcting their perceptions, which can build trust and reduce stress.
The Role of Medication: A Last Resort
When non-pharmacological methods are insufficient, or when behavior poses a risk of harm to the patient or others, medication may be considered. The following medications have been used, but their use must be carefully weighed against significant risks and side effects, especially in the elderly.
The Only FDA-Approved Medication: Brexpiprazole (Rexulti)
In 2023, brexpiprazole (Rexulti), an atypical antipsychotic, received FDA approval specifically for agitation associated with dementia due to Alzheimer's disease. The approval came with a boxed warning, the FDA's most serious type, noting an increased risk of death in elderly patients with dementia-related psychosis treated with antipsychotics. Brexpiprazole acts on serotonin and dopamine pathways in the brain to help reduce agitation. Its prescribing requires a careful benefit-risk discussion with the healthcare team and family.
Other Medications Used Off-Label
Several other drug classes are used off-label to manage agitation, though often with less evidence of efficacy and significant side effect profiles.
Antidepressants
Selective Serotonin Reuptake Inhibitors (SSRIs) like sertraline (Zoloft) and citalopram (Celexa) are sometimes prescribed, particularly if agitation is accompanied by depression or anxiety. While some studies show benefit, others highlight potential risks such as falls and an irregular heartbeat, especially with higher doses. Trazodone is another antidepressant sometimes used for its sedating properties to manage sleep disturbances related to agitation.
Antipsychotics (Off-Label Use)
Prior to brexpiprazole, other atypical antipsychotics like risperidone (Risperdal), olanzapine (Zyprexa), and quetiapine (Seroquel) were the most common drug class used off-label for severe agitation. However, significant safety concerns, including a black-box warning from the FDA, detail an increased risk of cerebrovascular events (like stroke) and mortality in elderly dementia patients. These are considered a last resort when behavior poses a danger.
Other Options
Some mood stabilizers or anticonvulsants, such as carbamazepine (Tegretol), have shown mixed results and carry a risk of side effects. Dextromethorphan/quinidine (Nuedexta) has also shown promise in clinical trials for treating agitation but requires more extensive research.
Comparison of Pharmacological Interventions for Agitation in Dementia
| Medication Class | Examples | FDA-Approved for Agitation? | Common Risks/Side Effects | Use Considerations |
|---|---|---|---|---|
| Atypical Antipsychotic | Brexpiprazole (Rexulti) | Yes (specifically for agitation due to Alzheimer's dementia) | Increased risk of death, stroke, weight gain, metabolic changes | Careful consideration of risks vs. benefits; black-box warning from FDA |
| Atypical Antipsychotics | Risperidone, olanzapine, quetiapine | No (used off-label) | Increased risk of death, stroke, sedation, falls | Generally used as a last resort for severe, dangerous behaviors |
| SSRIs (Antidepressants) | Citalopram, sertraline, trazodone | No (used off-label) | Drowsiness, dry mouth, risk of falls, irregular heartbeat with high dose citalopram | May help when agitation is linked to underlying mood issues |
| Dextromethorphan/Quinidine | Nuedexta | No (investigational) | Falls, dizziness, diarrhea, QT prolongation risk with quinidine | Based on limited evidence; not widely used for this indication |
Conclusion
Managing agitation in elderly dementia patients is a complex process that demands a personalized, stepwise approach. The first and most critical steps involve identifying and addressing potential triggers through non-pharmacological methods like creating a calm routine, redirection, and validation therapy. These methods are safer and have shown significant effectiveness.
For severe, persistent, or dangerous agitation unresponsive to these interventions, pharmacological options may be necessary. Brexpiprazole (Rexulti) is the only FDA-approved medication for agitation associated with Alzheimer's disease, but it carries a serious boxed warning about increased mortality in this population. Other medications like off-label antipsychotics, antidepressants, and mood stabilizers also present risks and are used cautiously. Any decision to use medication must involve a thorough risk-benefit analysis and be made in close consultation with a healthcare provider.
How to get help
If you or someone you know is struggling with dementia-related agitation, consult a healthcare provider or a geriatric specialist for a comprehensive assessment. You can also find valuable resources and support from organizations like the Alzheimer's Association, which offers online communities and helplines.
