De-escalation of antipsychotic medications in an elderly patient with Alzheimer's dementia residing in an assisted living facility

BACKGROUND

It has been stated that almost 25 million individuals worldwide are affected by some form of dementia, with approximately 5 million of those thought to be affected with Alzheimer's dementia (AD) in the United States.¹² Psychotic symptoms, including hallucinations, delusions, and changes in cognition, may be experienced by approximately 30–50% of AD patients. Agitation and/or aggression may be observed in up to 70% of AD patients.³⁴ Both first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) are currently used to treat agitation or psychosis in patients with dementia. However, these agents are not Food and Drug Administration (FDA)-approved to treat these symptoms in the elderly. Furthermore, using SGAs in patients with dementia is associated with a significantly increased risk of mortality due to reports of strokes and sudden cardiac death in older patients.⁴ Historically, it was thought that only FGAs were associated with such dangers. However, the 2005 warnings from the FDA were placed on antipsychotic agents after the reports of death and stroke in the elderly were found to be caused by various combinations of FGAs and SGAs. Since the FDA's issue of the black box warnings, Desai and colleagues described the impact of these warnings resulting in a small reduction in antipsychotic agent use, and very importantly, cite a lack of any alternatives.⁵⁶

Following a request by an assisted living facility, a local family medicine practice assessed one of the facility's residents with AD taking multiple antipsychotics. A collaborative consultation between the family medicine practice's clinical pharmacist, the family medicine physician, and the health care providers at the assisted living facility resulted in the decision to gradually discontinue each antipsychotic agent at subsequent facility visits by the family medicine team. This case report describes the encounter between the various health care providers caring for the patient and focuses on the appropriate use of antipsychotic medications in this situation.

CASE REPORT

The clinical pharmacist of a family medicine practice associated with a large, tertiary, academic medical center was consulted by one of the practice's physicians regarding an 80-year-old female with severe AD, who resided in a local assisted living facility. The family medicine physicians and medical residents have an agreement with the assisted living facility to make monthly visits to assess residents by request. This patient was new to the practice and available medical records were limited, but the team was able to establish that in addition to AD, the past medical history also included hypertension and vitamin D deficiency. Medications prescribed for the treatment of AD and neuropsychiatric symptoms at the time of consultation were memantine 10 mg by mouth twice daily, quetiapine 50 mg by mouth at bedtime, risperidone 0.5 mg by mouth twice daily, and haloperidol 0.5 mg by mouth up to three times daily as needed for agitation. The other medications the patient was receiving at that time included irbesartan/HCTZ 150/12.5 mg by mouth daily and amlodipine 10 mg daily by mouth daily for hypertension, as well as ergocalciferol 8000 IU by mouth weekly for vitamin D supplementation. The consultation focused on the evaluation of the use of three antipsychotic medications to treat this patient.

Evaluation of the patient's records revealed that in April of 2010, numerous behavioral disturbances, (e.g., spitting out food, resisting care) were reported and quetiapine 25 mg nightly was started in June 2010 secondary to the behavioral disturbances and increased agitation. Soon after, the patient moved into assisted living and risperidone 0.5 mg by mouth twice daily was added without clear documentation of an indication. The patient adjusted well to her new living situation and became cooperative with care. Over the following months, the patient developed increasing behavioral symptoms manifested by agitation and outbursts. These symptoms were isolated to trips outside of the facility and haloperidol 0.5 mg as needed was added to the patient's regimen in September 2011. The patient tolerated the medication change without complications.

LITERATURE REVIEW

The use of multiple antipsychotics to treat psychiatric disorders and related symptoms is common in clinical practice, but does not always produce the desired therapeutic results. It also is not without serious risks and potential complications in the elderly, such as irreversible tardive dyskinesia and neuroleptic malignant syndrome, among others.⁷ Furthermore, attention to medication safety and tolerability is a constant concern due to the increased use of psychotropic combinations in the elderly, despite serious warnings that include an increased risk of adverse events and death,^8–11 and lack of efficacy of antipsychotics in the elderly when not used in tandem with non-pharmacological methods to mitigate behavioral disturbances and agitation.¹² Combinations of antipsychotics are often used clinically to limit exposure to high doses of one specific antipsychotic agent. Additionally, the co-administration of non-antipsychotic agents (e.g., memantine) with antipsychotic agents have been used to reduce the total exposure to antipsychotic agents.¹³ Such combinations, whether to reduce exposure to specific SGAs or take advantage of different pharmacological targets, have had inconsistent clinical results across various populations, including the elderly patients. In a review of the Agency for Health Research and Quality's (AHRQ) most recent summary on antipsychotics, Maher and Theodore concluded that agents such as aripiprazole, olanzapine, and risperidone had statistically significant but small benefits in the elderly. Furthermore, their review of the 2011 AHRQ summary was consistent with the FDA black box warnings of associated death, stroke and other adverse effects such as weight gain, extrapyramidal symptoms and urinary effects.¹⁴

In order to address the potential overuse of antipsychotic medications in the elderly, efforts have been made to encourage gradual dose reductions of these and other psychotropic medications and eventually discontinue them. Ballard and collaborators found that patients with AD had no significant adverse reactions or reduced cognitive function when withdrawing from neuroleptics, specifically thioridazine, chlorpromazine, haloperidol, trifluoperazine, or risperidone. This effort to withdraw potentially unnecessary psychotropic agents indicates that patients may do well without them and encourages clinicians to constantly reevaluate their effectiveness in elderly patients with AD. It also supports that antipsychotic agents may not need to be continued indefinitely.¹⁵¹⁶ While no there are no specific guidelines available regarding the most appropriate use of antipsychotic agents in the elderly, current literature continues to challenge clinicians to consider the risks and benefits of prolonged use of antipsychotics beyond the timeframe suggested for reevaluation and gradual dose reduction. Timelines for gradual dose reduction (GDR) of antipsychotic agents from the time of admission to long-term care facilities outline a trial dose reduction within two separate quarters, at least one month apart, during the first year. After the first year, GDR should be attempted annually in long-term care settings with pharmacist follow-up with residents at least monthly.¹⁷ In assisted living settings, state regulations differ and pharmacist follow-up with residents is done at least quarterly. During these visits, the same pharmacists that consult with long-term care firms will typically apply GDR to these residents, as they deem clinically appropriate. There is currently no established timeline for GDR in assisted living facilities and currently published methods of GDR are followed in settings outside of long-term care depending on patient-specific clinical information. The literature suggests that the use of these agents should be reevaluated and then reduced or eliminated if found to be unnecessary.^17–19

CONCLUSION AND CLINICAL RECOMMENDATION

When antipsychotic medications are prescribed for behavioral symptoms in patients with AD, they must be used cautiously and judiciously. The decision was made by the patient's providers and caregivers to discontinue quetiapine. This decision was based on available evidence and current recommendations regarding the use of antipsychotic medications in elderly patients with AD. Future management will include gradual tapering of risperidone and reserving either a dose of risperidone 0.25 mg or haloperidol 0.5 mg for severe behavioral symptoms on an as-needed basis. The patient had used both of these agents in the past at low doses with reduction of behaviors that were not amenable to non-pharmacological treatment and did not suffer any adverse effects.²⁰ Clinical considerations for the use of antipsychotics in the elderly should include periodic attempts at gradual dose reduction, re-evaluation of target symptoms and medication efficacy, and de-escalation if there is a suspected adverse event. Sharing cases describing the course of the use of antipsychotic agents in elderly patients are necessary to help guide clinicians on how to taper these medications in the safest manner possible. We recommend that future care for this patient would include the use of well-defined parameters that clearly describe the patient's target behaviors which require medication along with guidance to clinicians on the administration of only one “as needed” antipsychotic agent at the lowest dose possible (in this case, risperidone 0.25 mg). Additionally, staff administering the agent should be instructed to document the beneficial and adverse effects of each dose of risperidone. Clinicians working with the patient should be educated on what to expect in terms of adverse effects, and given instructions on how to manage them. The use FGAs or SGAs in the elderly is controversial because of the potential for adverse effects and increased mortality, but providing no medication may be detrimental to the individual patient's safety, as well as those around them. Using antipsychotic agents sparingly and according to patient-specific and well-defined behavioral parameters can optimize patient care and improve patient safety.