Enhancing Behavioral Health for Dementia Care: A Multi-Modal Approach to Neuropsychiatric Symptoms

Illustration of healthcare providers working with older adult patients.

Primary care and mental health providers are the frontline for managing the complex interplay between physical health and neuropsychiatric symptoms (NPS). Whether it is the subtle onset of depression in an older adult or the disruptive agitation of a patient with advancing dementia, the burden on the patient, their caregivers, and the healthcare system is profound. This article provides a concise guide to non-pharmacologic strategies, medication safety, and recent therapeutic updates to help streamline your psychiatric consultations for the care of those with dementia.

1. The Foundation: Non-Pharmacologic Management

Before reaching for the prescription pad, non-pharmacologic interventions should be the first-line approach, particularly for depression, anxiety, and agitation. These strategies are not only evidence-based but also avoid the polypharmacy risks inherent in psychiatric medications.

For Depression: Focus on Behavioral Activation. Encourage patients and caregivers to schedule small, manageable activities that once brought them joy. Even a 10-minute daily walk can significantly impact mood. Walking outside in the morning can also provide light exposure which can help with circadian rythms which can help promote regular sleep-wake cycles. Where and when available, engaging in adult day programs or senior centers that provide dementia support groups or programming can be helpful for structure.   Socialization is one of the main pillars of care for those with dementia.

For Anxiety: Implement Structured Relaxation. Teach simple diaphragmatic breathing or “box breathing” during the visit and provide written instructions/online resources to practice/review. Caregivers may need to cue them to do the breathing or suggest “let’s do some breathing together.” Referral to Cognitive Behavioral Therapy (CBT) remains the gold standard for long-term anxiety management but may need to be modified for those with cognitive impairment and also may not be readily available to all patients. Where cognitive impairment is still mild, this can still be effective with modifications.  Identify other calming environmental changes (check temperature, use of white noise or calming music, or distracting with a conversation or activity can be helpful).  What is calming should be individualized to that specific person.

For Agitation/Aggression: Use Environmental Modification. Identify triggers—such as loud noises, poor lighting, or “sundowning” patterns. Use nightlights to help with sundowning. Maintain a consistent daily routine. Using “validation therapy” (acknowledging the patient’s feelings rather than correcting their reality) can de-escalate aggressive outbursts. Avoid confrontation. Avoid overscheduling and allow adequate rest between activities. Acknowledge and respond to requests. Educate caregivers about dementia by providing resources for education and support. Identify sources of pain, constipation, need to use the bathroom, hunger, or thirst. Urinary retention and constipation from medications and dental issues are common underrecognized contributors to behavior.

2. Medication Review: Protecting Cognition

Polypharmacy is a quiet thief of cognitive function. Many common medications possess anticholinergic properties that can induce or worsen “pseudo-dementia.” A partial list of common contributors:

Drug ClassExamples to ReviewImpact on Cognition
Antihistaminesdiphenhydramine, hydroxyzineConfusion, sedation, increased fall risk.
TCAsamitriptyline, nortriptylineHigh anticholinergic burden; worsens memory.
Benzodiazepines And “Z drugs:lorazepam, alprazolam, zolpidem, zaleplon, eszopicloneParadoxical agitation, amnesia, and gait instability.
GI Agentshyoscyamine, dicyclomineMay cause acute delirium in the elderly.

The American Geriatrics Society’s has a list of medications (the Beers list) that can impact cognition and contribute to things like falls.  These medications are recommended not to be used in geriatric patients.  Remember that it’s not always a single agent causing the issue but rather the synergy of multiple agents with cognitive side effects.  Never abruptly stop medications; provide instructions for taper and discontinuation.  Regularly review and encourage patients and families to keep an updated list of all medications they take, who prescribes them, and include supplements and over the counter medications.  It is especially important to carefully review lists during transitions like a move or discharge from a hospitalization. For those in facilities, regularly review the Medication Administration Record (MAR) not just the orders list; the MAR documents scheduled medications but also how often as needed medications are being given and efficacy, which is especially important if as needed psychotropic medications are being prescribed.  Assessing from documentation whether a specific target symptom is improved with as needed medication administration is paramount so that ineffective medications are not given indefinitely.

3. Updates in Pharmacotherapy: Brexpiprazole and Pimavanserin

In 2026, the landscape for managing agitation associated with dementia shifted toward more targeted agents with improved safety profiles compared to traditional antipsychotics.

  • Brexpiprazole: Originally an adjunct for MDD and schizophrenia, brexpiprazole is now FDA-approved for agitation associated with Alzheimer’s dementia. It acts as a partial agonist at D2 and 5-HT1A receptors. Unlike older agents, it has lower intrinsic activity at dopamine receptors, which may reduce the risk of extrapyramidal symptoms (EPS).
  • Pimavanserin: This is a selective serotonin inverse agonist (SSIA) targeting 5-HT2A receptors. It is notably the only medication FDA-approved for Parkinson’s disease psychosis. Its lack of dopamine D2 blockade is critical because it treats hallucinations and delusions without worsening motor function.
  • Both medications are new and therefore can be quite expensive, often necessitating prior authorization/review of prior failed medications or justification for use.

The Role of Medications for the Treatment of Dementia

While not primary treatments for agitation, Acetylcholinesterase Inhibitors (AChEIs) like donepezil and NMDA receptor antagonists like memantine should be optimized. AChEIs can subtly improve apathy and anxiety, while memantine may help reduce the “overflow” of glutamate that contributes to irritability and aggression in moderate-to-severe cases.

4. Other antipsychotics: Considerations for Use and the “Black Box”

Antipsychotics (e.g., quetiapine, risperidone, haloperidol, aripiprazole) are frequently used off-label in primary care and in psychiatry for management of neuropsychiatric symptoms in dementia. Common reasons for use include:

  1. Acute Safety: When a patient is a danger to themselves or others.
  2. Severe Psychosis: Distressing hallucinations or paranoid delusions.
  3. Refractory Agitation, Inconsolable or persistent distress, or difficulty receiving care: When non-pharmacologic and first-line agents fail

FDA Black Box Warning: All antipsychotics (both typical and atypical) carry a “Black Box” warning regarding an increased risk of death in elderly patients with dementia-related psychosis. Most deaths are cardiovascular (heart failure, sudden death) or infectious (pneumonia) in nature. Informed consent with family and caregivers is mandatory before initiation.

Be aware of the particular risks of using many antipsychotic medications in those with dementia with Lewy bodies or dementia due to Parkinson’s disease as they can be exquisitely sensitive to extrapyramidal side effects. Quetiapine, pimsvanserin, or sometimes clozapine are first line agents where antipsychotic medications are needed. Brexpiprazole may be another option given its potentially lower propensity for EPS.

5. Supporting the “Invisible Patient”: The Caregiver

Caregiver stress is often an underrecognized contributor to symptoms in patients with dementia.  When a caregiver’s mental health fails, the patient’s institutionalization can become imminent and crisis-driven so it’s important to check in regularly.

  • Screening: Use the Zarit Burden Interview or simply ask: “How are you holding up?”
  • Depression in Caregivers: Caregivers have significantly higher rates of clinical depression than the general population. PCPs should treat the caregiver as an essential component of the patient’s “care ecosystem.”
  • Resources: Emphasize respite care. Encourage them to utilize local Area Agency on Aging resources to prevent burnout.

Managing psychiatric symptoms in dementia requires a delicate balance between behavioral interventions and careful medication management. Prioritizing non-pharmacologic strategies, reviewing cognitive-impairing drugs, and staying updated on new developments in pharmacotherapy are central management strategies for individualized dementia care.

Resources:

UW Medicine Project ECHO Dementia (virtual)
Free case-based learning for primary care providers hosted by dementia specialists at the UW; meets every other Friday; CME/CNE credit available.

Dementia Road Map
The DSHS Health Care Providers and Community Organizations page hosts clinical tools from the Dementia Action Collaborative, including the Dementia Road Map, a free guide for newly diagnosed patients and families.

Washington Association of Area Agencies on Aging
Connects adults with dementia and their families with local long-term care, community resources, and specialized caregiver support.

The Memory Hub, UW Medicine Memory and Brain Wellness Center
Offers education, support groups, and resources for patients and their care partners, including virtual or phone appointments with a Memory Navigator.

Alzheimer’s Association Washington State Chapter, Education and Resources
Free on-demand webinars and live programs on Alzheimer’s and dementia and a 24/7 Helpline for patients and families.

American Geriatrics Society Beers Criteria® Alternatives Panel, & Steinman, M. A. (2025). Alternative treatments to selected medications in the 2023 American Geriatrics Society Beers Criteria®. Journal of the American Geriatrics Society, 73(9), 2657–2677. https://doi.org/10.1111/jgs.19500

Brody, H., & Heath, A. (2023, July). Nonpharmacologic approaches to adverse behaviors associated with dementia. Practical Neurology. https://practicalneurology.com/diseases-diagnoses/alzheimer-disease-dementias/nonpharmacologic-approaches-to-adverse-behaviors-associated-with-dementia/32015/

Imbimbo, C., Cotta Ramusino, M., Leone, S., et al. (2025). Emerging pharmacological approaches for psychosis and agitation in Alzheimer’s disease. CNS Drugs, 39(2), 143–160. https://doi.org/10.1007/s40263-024-01133-9

Whitney Carlson, MD

Dr. Carlson is a board-certified psychiatrist and geriatric psychiatrist in the UW Medicine Department of Psychiatry and Behavioral Sciences. She graduated from the University of Iowa College of Medicine, completed her Psychiatry Residency at the University of Michigan and a Geriatric Psychiatry Fellowship at the University of Washington. Dr. Carlson is the medical director of the Geriatric Psychiatry Services Clinic at Harborview Medical Center and is one of the primary faculty on the Psychiatry Consultation Line (PCL). Her clinical interests include aging in chronic mental illness, mood disorders, nursing home psychiatry/consult liaison psychiatry, ethics, and palliative care.

Back to Basics: A Refresher on Treating Major Depressive Disorder

A blue graphic illustration shows a heart and brain divided, with medical icons symbolizing health and well-being.

Major Depressive Disorder (MDD) remains one of the most common and impactful conditions seen in primary care. While many of us treat depression daily, it is valuable to periodically revisit the foundational principles of diagnosis and initial treatment to ensure we are offering the best possible care.

This article highlights key takeaways and “clinical pearls” from a recent presentation on the initial treatment of MDD. For those interested in a deeper dive, a link to the full transcript is provided at the end of this article.

Diagnosis: Beyond the Checklist

The DSM-5 criteria for a Major Depressive Episode are familiar to most: five or more symptoms present for at least two weeks, representing a change from previous functioning. One of the symptoms must be either depressed mood or loss of interest/pleasure (anhedonia).

However, beyond the checklist, pay attention to functional impairment. Is the patient calling in sick to work? Withdrawing socially? Spending excessive time in bed? These behavioral changes are often the most reliable indicators of severity.

The PHQ-9 as a Clinical Tool The PHQ-9 is not just a screener; it maps directly to DSM-5 criteria and can support your diagnosis. It is also the standard for measurement-based care to track symptoms and response to treatment over time. Initially, the total score helps stratify severity and guide treatment selection:

  • 5-9 (Mild): Consider psychotherapy or behavioral activation first.
  • 10-14 (Moderate): Psychotherapy, medication, or both are reasonable initial options based on patient preference.
  • 15-19 (Moderately Severe) & 20+ (Severe): Combination treatment (medication + psychotherapy) is often the gold standard.

Don’t Forget the Differential Before initiating treatment, rule out common mimics:

  • Medical causes: Hypothyroidism (TSH), anemia (CBC), vitamin deficiencies (B12, Folate, Vitamin D), and obstructive sleep apnea (OSA). Treating OSA can often resolve depressive symptoms entirely.
  • Substance use: Alcohol and cannabis are frequent contributors.
  • Bipolar Disorder: Screening for mania/hypomania is critical before starting an antidepressant. Use the Mood Disorder Questionnaire (MDQ) to reduce the likelihood of triggering a manic episode. The MDQ can be self-administered or administered with a provider. If the MDQ is negative, you can feel reassured that the likelihood of triggering a manic episode is unlikely. However, if it is positive, you will need to review the results to clarify the diagnosis as false positives are common.

Initial Treatment Selection

For mild to moderate depression, psychotherapy (CBT, Behavioral Activation) is as effective as medication and has lasting benefits. For more severe cases, or when therapy is inaccessible, pharmacotherapy is indicated.

Choosing an Antidepressant Most first-line agents (SSRIs, SNRIs, Bupropion, Mirtazapine) have comparable efficacy across the population. Therefore, selection should be driven by:

  1. Side Effect Profile: Leverage side effects to the patient’s advantage.
    • Insomnia + Weight Loss? Consider Mirtazapine (sedating, increases appetite).
    • Low Energy + Smoking + No anxiety? Consider Bupropion (activating, helps cessation, may worsen anxiety).
    • Sexual Dysfunction Concern? Bupropion and mirtazapine have a lower risk than SSRIs and SNRIs
  2. Prior Response: If it worked before (for the patient or a family member), try it again.
  3. Comorbidities:
    • Chronic Pain? Duloxetine (SNRI) has an FDA indication for certain kinds of pain.
    • Anxiety? SSRIs are generally preferred.

Initiating and Monitoring Treatment

Start Low and Go Slow: Minimize initial side effects to improve adherence. Titrate every few weeks until you reach a therapeutic dose or see a response.

The 4-6 Week Rule: An adequate trial is typically 4-6 weeks at a therapeutic dose.

  • No response? Switch to a different medication (different SSRI or different class).
  • Partial response? Consider augmentation (e.g., adding Bupropion, Mirtazapine, or a second-generation antipsychotic like aripiprazole).

Duration of Treatment: For a first episode, continue treatment for 6-12 months after remission to prevent relapse. For recurrent or severe episodes, long-term maintenance may be necessary.

Clinical Pearls & FAQs

  • Anxiety Spike: Warn patients that anxiety may briefly worsen when starting an antidepressant. This prevents early discontinuation.
  • Sexual Side Effects: Patients rarely volunteer this information, but it is a common reason why patients stop the medication without telling their provider. Ask directly. If present, consider switching to Bupropion or adding it as an adjunct.
  • Pharmacogenomics: Tests like GeneSight are not a “magic bullet” for initial selection. They help guide dosing based on metabolism but do not predict efficacy. Reserve them for treatment-resistant cases or those with unusual side effects. Most insurances will not pay for gene-drug interaction tests unless the patient has failed at least two antidepressant trials.
  • Exercise as Medicine: For mild-moderate depression, exercise can be as effective as medication. Use behavioral activation (“Just walk to the mailbox today”) to help patients overcome the inertia of depression.
  • Cannabis Use: Daily cannabis use can mimic or worsen depression. While we can’t force patients to quit, encouraging a “tincture of time” off the substance can clarify the diagnosis. Note that substance-induced depression often resolves without antidepressants once substance use stops.

When to Refer to Psychiatry (if/when available) or call the UW Psychiatry Consultation Line (PCL)

Primary care is the ideal setting for uncomplicated depression. Consider referral if:

  1. Diagnosis is unclear (e.g., suspected bipolar or schizoaffective disorder).
  2. Treatment resistance (failed 2+ medication trials).
  3. High safety risk (active suicidal ideation, psychosis).
  4. Complex comorbidities (severe substance use, personality disorders).

If a referral to psychiatry is not possible, you can always call the PCL for free clinical advice about your adult patients with mental health and/or substance use conditions. Prescribing providers can call any time, 24/7, and non-prescribing providers can call Mon-Fri, 8 a.m. – 5 p.m. (excluding holidays). 877-WA-PSYCH/877-927-7924 We are here to help!

To see Dr. Duncan’s complete UW PACC presentation on this topic, click on this link: Initial Treatment of MDD

Mark Duncan, MD

Dr. Duncan, trained in both family medicine and addiction psychiatry, practices at the intersection of mental health and primary care. He is the co-medical director for the University of Washington Psychiatry and Addiction Case Conference (UW PACC), a weekly online learning collaborative to help community providers across the state improve their psychiatric and addiction clinical skills. Dr. Duncan is one of the PCL’s core weekday faculty where his unique expertise in primary care and psychiatry is available to healthcare providers across Washington.