Psychostimulant Use in Patients With Dementia and Apathy

An Expert Interview With Jena Ivey Burkhart, PharmD, BCPS, CPP

Steven Fox

November 06, 2012

HOLLYWOOD, Florida — Editor's note: Research has shown that up to 70% of patients with Alzheimer's dementia are affected by symptoms of apathy, defined as diminished motivation not attributable to a diminished level of consciousness, cognitive impairment, or emotional distress. Such symptoms can manifest as a lack of goal-directed behavior or decreased emotional responsiveness.

Although no uniformly effective approaches have been found for preventing or managing such symptoms, researchers have made some progress in recent years managing these challenging patients.

During a symposium on clinical challenges in geriatric medicine here at the American College of Clinical Pharmacy (ACCP) 2012 Annual Meeting, speakers highlighted some of that research. In particular, Jena Ivey Burkhart, PharmD, BCPS, CPP, provided attendees with useful tips on pharmacologic and nonpharmacologic strategies for managing patients with Alzheimer's-related apathy.

Dr. Burkhart earned her PharmD degree in 2004 and then went on to complete a 1-year Pharmacy Specialty Residency in Geriatrics. She is currently a clinical assistant professor at the University of North Carolina (UNC) Eshelman School of Pharmacy and a clinical pharmacist at the UNC Geriatric Specialty Clinic at UNC Hospitals and Clinics in Chapel Hill.

In an email interview with Medscape Medical News, Dr. Burkhart discussed some of the strategies to manage patients who are affected by symptoms of apathy.

Medscape: Is there any reliable way to identify which patients with dementia are most likely to develop symptoms of apathy?

Dr. Burkhart: Validated scales exist to identify and stage apathy (the Apathy Evaluation Scale developed by Marin, and the Apathy Scale developed by Starkstein), but it is unclear how often these tools are really being used in clinical practice.

Time constraints during office visits often limit practical use of these instruments. A lot of times practitioners rely on reports from caregivers or other informants on patients' day-to-day activities, routines, and behaviors.

Medscape: How do you distinguish between depression and apathy, and why is the distinction important?

Dr. Burkhart: Differentiating between depression and apathy is important because this will dictate the treatment plan. Establishing the right diagnosis is accomplished using those tools I mentioned earlier, as well as caregiver and informant reports, and monitoring the patient's mood and behavior over time.

Medscape: When is it appropriate to use stimulants to treat apathy in patients with dementia, and which drugs are the most effective?

Dr. Burkhart: Deciding when to institute pharmacological treatment needs to be based on frank, informed discussions between the patient, the family, and the provider.

There is not a "one size fits all" approach. First and foremost, other reversible medical causes should be ruled out, as should all medications that might be causative factors. If a possible cause is suspected, that should be investigated and addressed first.

Once that's done — and the patient/family feel that apathy symptoms are persisting and continuing to cause a significant burden — then pharmacological therapy can be considered.

As to which drugs have proven most effective, the evidence that exists is somewhat difficult to interpret because there is no consensus definition of apathy in the trials, and no consensus diagnostic scale has been demonstrated to be more effective than another.

Stimulants such as methylphenidate have garnered the most attention, given their mechanism of action involving the dopaminergic brain reward system. Cholinesterase inhibitors have been studied as well, given the possible association with impaired cholinergic transmission leading to apathy symptoms. Memantine, antipsychotics, antidepressants, and amantadine have also been studied but have not shown any benefit, and risks of therapy are likely to outweigh benefits.

My first-line preference for pharmacologic agents, given the data that exist, is a psychostimulant, particularly methylphenidate, in patients with no contraindications to therapy. Initiation of therapy must be approached with care, starting at low doses and titrating up slowly. We also monitor patients closely to see how they're tolerating the drug, and we continue tracking them to check for efficacy of therapy as we escalate the dosage.

Medscape: What else do you look for when initiating treatment?

Dr. Burkhart: It's essential that clinicians consider the safety of these agents before initiating therapy and avoid using them in patients with uncontrolled hypertension, structural cardiac problems, myocardial infarction in the previous 6 to 12 months, or a history of hypersensitivity to the drug.

If the decision is made to start the drug, start at low doses, such as immediate-release methylphenidate 5 mg every day or twice a day, increasing every 1 to 2 weeks until a maximum dose of 10 mg twice a day is reached, or as tolerated. Also, ensure that the second dose is given no later than 1 PM to 2 PM to avoid risk for insomnia. Be sure to monitor the patient's blood pressure and heart rate while they are on this therapy. Also, keep a close watch for other side effects, such as agitation, irritability, and psychosis.

Medscape: What tools do you use to monitor response to therapy?

Dr. Burkhart: As I alluded to earlier, probably one of the best and most reliable ways to monitor patients is to regularly obtain caregiver/informant reports detailing the patient's day-to-day behavior/activities.

If scales were used earlier in the course of treatment to diagnose apathy, repeating those instruments may be helpful in monitoring effect.

Medscape: Are there any effective nonpharmacologic approaches?

Dr. Burkhart: Many of these patients do very well in structured day programs where activities are set up for them and they are given attention and prompting to complete and stay on task.

Programs coordinated by occupational therapists, recreational therapists, and programs using music therapy, pet therapy, and reminiscence therapy can be very engaging and enjoyable. I would recommend providers look into programs such as these that may be offered by their local communities and/or in local institutionalized settings.

Medscape: Are there any other points you want to make or reinforce?

Dr. Burkhart: I would encourage providers to try nonpharmacological methods before initiating pharmacotherapy for apathy. Again, be sure to consider patient risk factors before initiating therapy, and use low doses with slow titration steps if stimulants are used.

Carefully monitor for side effects from therapy, and educate patients and caregivers on the benefits/risks of the drug therapy.

If no benefits from therapy are noted within a reasonable time frame (approximately 2 to 4 weeks), discontinuation of therapy would be warranted. Caregiver education and community resources and support programs for patients and caregivers are key in the comprehensive treatment approach.

Dr. Burkhart has disclosed no relevant financial relationships.

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