Dementia-Related Results of “Costs of Medication in Older Patients: Before and After Comprehensive Geriatric Assessment”

Abstract

Changes in the pharmacokinetics and pharmacodynamics of drugs in the presence of certain comorbidities and geriatric syndromes and reduced tolerability of potential drug side effects due to physiological changes with aging lead to difficulties in planning treatments in elderly adults, especially patients with dementia. The Comprehensive Geriatric Assessment has an important role in assessing polypharmacy and optimizing potentially inappropriate medications and potentially prescribing omissions in these patients. For this reason, we intend to reexamine our new study titled “Costs of medication in older patients: before and after comprehensive geriatric assessment,” because most of these results are also very important for dementia practice.

Polypharmacy and the use of inappropriate medication have been associated with various adverse outcomes such as frailty, urinary incontinence, depression, malnutrition, falls, decreased functional capacity, and hospitalization and mortality in older adults. ¹ Therefore, in our recent study by Unutmaz et al, we aimed to elaborate patients who applied to our geriatric clinic; to determine the impact of Comprehensive Geriatric Assessment (CGA) on polypharmacy, potentially unsuitable drugs (PIMs), and potentially prescribing deficiencies (PPOs); to detect the inclusion and exclusion of drug groups by CGA; and to evaluate the economic implications of these changes in treatment. Although all of the results have been already reported, we wanted to reemphasize them for dementia practice.

Firstly, polypharmacy, a risk factor for dementia, is quite common in older adults and 2 times higher in patients with dementia than nondemented ones, which means that patients with dementia are more likely to have all negative polypharmacy results. ² A recent study has demonstrated that hospitalization and mortality risks are significantly associated with polypharmacy after adjustment for potentially hazardous drugs in patients with dementia, indicating that polypharmacy itself is an independent risk factor for many complications. ²

Secondly, it has been found that the most frequent PIMs were proton pump inhibitors (PPIs), anti-dementia drugs, and antipsychotics. ³ Of these PIMs, PPIs are quite common and likely associated with an increased risk for brain dysfunction and dementia, although possible deleterious effects on cognitive function are unknown. ⁴ Given the debate between the use of PPI and the risk of dementia in the current literature, it is clear that the deprescribing of PPIs as a PIM may be an important strategy to prevent a potential risk factor for dementia. ⁴ This strategy is also important to prevent side effects associated with the use of long-term PPI such as Clostridium difficile-associated colitis, community-acquired pneumonia, acute interstitial nephritis, vitamin B₁₂ deficiency, and hip fracture risk.

The main reason for using antidementia drugs as second PIM in this study is that about 5% to 20% of patients with memory impairment in geriatric clinics have treatable causes such as hypothyroidism and vitamin B₁₂ deficiency, depression, normal pressure hydrocephalus, folic acid deficiency, and drugs. ⁵ In addition, this result from our reference center of dementia is very important in showing that many elderly patients are receiving antidementia drugs who are overdiagnosed in clinics; previously, subjective memory complaints may have been made and they may have been exposed to side effects. Given the potential side effects of acetylcholinesterase inhibitors and memantine, the N-Methyl-D-aspartate (NMDA) receptor inhibitor, and their costs, the implications of our results will be better understood. ⁶

Antipsychotics were the third most common PIMs in our study because it is well known that the long-term use of high-dose antipsychotics may cause side effects such as cardiovascular, metabolic, cognitive, and extrapyramidal. ⁷ This can be attributed to the off-label use of antipsychotics, particularly in the treatment of behavioral and psychological symptoms of dementia and in the treatment of sleep disorders in geriatric patients, even when appropriate, without nonpharmacological interventions. ^7,8 Due to potentially undesirable events, antipsychotics carry black box stimulation (1.6-1.7 times greater than placebo) for increased risk of death in patients with dementia and have been included in the American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. ⁹ Nevertheless, recent guidelines suggested that low-dose antipsychotics should be used in geriatric patients with dementia behavioral symptoms for less than 16 weeks when the nonpharmacological interventions are inadequate. Another important issue related to the antipsychotics is the adverse effect of antipsychotics on the course of illness as well as side effects, such as increased dependency and progressive severity of the disease, diminished daily functioning, vein thrombosis, metabolic changes, and cardiac arrhythmia in the patients with dementia. ^7,8 Furthermore, it is well known that anticholinergic medicines, such as antipsychotics, are associated with an increased risk of cognitive impairment, stroke, and death in people with dementia. ⁹ The cumulative effect of taking anticholinergic medications is described as the anticholinergic burden, and clinicians prescribe these drugs for their therapeutic effects, but they often do not take into consideration the cumulative effect due to anticholinergic drug burden in older adults. ^10,11 Comprehensive Geriatric Assessment may have an impact on predicting anticholinergic burden-related outcomes. As a consequence, the results can help clinicians recognize the importance of protecting these drugs from inappropriate use in dementia practice.

Thirdly, vitamin supplements, such as vitamin D and vitamin B₁₂, and folic acid preparations, trazodone, and other antidepressants are the leading drugs among PPOs initiated after the CGA. ³ Deficiency of micronutrients, such as vitamin D and vitamin B₁₂, and folic acid is common in older adults and each may be associated with various comorbidities, such as frailty, falls, depression, and orthostatic hypotension, particularly cognitive impairment in patients with or without dementia. ¹² For this reason, it is important that the older adults are routinely be evaluated for these vitamin deficiencies and those who have such deficiencies, for the appropriate micronutrient supplement. Additionally, it should also be kept in mind that diagnosis treatment of depression and insomnia is crucial in dementia practice because it can easily be overlooked in older patients with pain, frailty, cognitive impairment, and numerous comorbidities. Likewise, it is also important that trazodone and other antidepressants are also among such drugs, in our study. ³

Changes in the pharmacokinetics and pharmacodynamics of drugs in the presence of certain comorbidities and geriatric syndromes and reduced tolerability of potential drug side effects due to physiological changes with aging lead to difficulties in planning treatments in elderly adults, especially patients with dementia. As a result, long-term complications with CGA can be avoided by preventing PIMs and polypharmacy and allowing the use of appropriate agents identified by PPOs in elderly patients with or without dementia.