Drug use, potentially inappropriate medication and polypharmacy
In line with previous studies researched on this topic, we found the vast majority of PWAD were treated with more than one drug and polypharmacy was common with half of the PWAD receiving five or more drugs. Out of the 20 most frequently administered drugs, eight were PDs. Three drugs were preventive (acetylsalicylic acid, cholecalciferol, and simvastatine). According to Beers Criteria, 39% received PIM.
Unsurprisingly, older PWAD – who usually suffer from more physical illnesses [25] - received significantly more drugs than younger PWAD. Further, PWAD in LTC facilities received more drugs than those living at home. Similar results have been found in cohorts of older people (with and without dementia) [11]: Polypharmacy was common in older adults with the highest number of drugs taken by those residing in LTC facilities. A recent Italian study evaluated drug use in LTC facilities and reported the number of drugs prescribed were higher in residents without dementia than in those with dementia, the latter receiving 5.1 to 9.3 drugs per day [36].
The higher prevalence of drugs in LTC facilities as compared to home care, might be explained by the more comprehensive medical treatment in LTC facilities. In this type of care, a physician usually visits the PWAD at least once every three months, a higher frequency than those not in LTC facilities. Alternatively, PWAD may be admitted to LTC, when BPSD management at home becomes more difficult [37]. However, the study cannot answer if more intensive drug regimens in LTC actually are associated with better mental and physical health.
Lastly, there is a direct link between the number of drugs prescribed and the potential for dangerous drug-drug interactions, side effects and prescribing cascades. In Germany, specialized pharmacists infrequently are consulted for the treatment of people with dementia, to mitigate the chances of the unwanted consequences. We did not investigate, if prescribing physicians were aware of potential interactions or regularly checked for them in interaction databases .
Psychotropic drug use
79% of PWAD in our study received PDs. This is similar to a study from the Netherlands [38] that reported a PD prevalence of 87% in people with YOD living in LTC facilities. Another Dutch study found a 52% prevalence of PDU in YOD living at home [39]. Van der Spek et al. reported a 60% prevalence rate in LTC residents with dementia [40].
The differences in terms of prevalence might be explained, by the different study populations (YOD vs LOD, home care vs LTC, people older than 70, etc.). Another important consideration is the definition of PD. This definition ranges from “nervous system drugs” (according to ATC classification) to indication reason. An example to illustrate this point is our decision to exclude antiepileptic drugs from the logistic regression model because the indication - sedation vs. anticonvulsion vs. both - could not be verified with certainty.
APs were the PDs that were most frequently prescribed in almost 40% of PWAD. As discussed above, the range of prevalences in APs found in other studies is comparable to differences in PDU. The atypical APs, risperidone and quetiapine, were the most frequent APs. Typical APs, like haloperidol, were rarely used, which indicates prescribing physicians were probably aware of their negative side effects, particularly parkinsonism. With 39% the point prevalence of APs in our study was relatively high. It is worthy to point out that even though these drugs have been shown to not only increase morbidity and mortality, but also have significant side effects like sedation and cognitive deterioration, are still prescribed so frequently. Although some PWAD can experience a relieve of burdening symptoms, such as anxiety or restlessness, when treated with APs, there is a risk in using them as AP treatment can reduce quality of life [25]. Alternatively, Mirtazapin and selective serotonin reuptake inhibitors (SSRI) were the most commonly prescribed antidepressants. Tricyclic antidepressants with their anticholinergic side effects, particularly on cognition, are often avoided, as recommended by several treatment guidelines [19, 21]. Although donepezile and rivastigmine are approved for the treatment of mild to moderate dementia in Germany, 15% of people with severe dementia received an cholinesterase inhibitor (CHE-I). The question of, if the prescribing physician hoped the CHE-I could have a positive effect on the patient even in advanced dementia or if the CHE-I were not deprescribed inadvertently remains open.
Associations with psychotropic drug use
No associations were identified between the use of PD (antipsychotics, antidepressants, sedatives, and pain medication), and sex, symptom onset, severity of dementia, quality of life, pain, and impairment of basal activities of daily living.
A diagnosis of dementia due to FTLD was negatively associated with the use of APs and sedative substances. This is counterintuitive since BPSD are core features of behavioral variant frontotemporal dementia, the most common dementia in the FTLD spectrum. While BPSD could decrease in the advanced stages of frontotemporal dementia, BPSD in AD tends to increase in advanced dementia stages. Our analyses showed that “other” causes of dementia that mainly included vascular dementia and Lewy body dementia were positively associated with the use of antidepressants. It is challenging to compare our findings to other studies, mainly because the study design and the cohort differ considerably. In the aforementioned study of Koopmans et al. only people with YOD who were cared for at home were investigated [39]. PDU in total, defined as APs (N05A) + anxiolytics (N05B) + hypnotics (N05C) + antidepressants (N06A) were investigated. PDU was associated with age and depressive symptoms. Mulders et al. [38] who investigate YOD in LTC found that PDU in total (defined as in [39]) was associated with the male gender. This study also examined the PD subgroups and found an association between anxiolytics use and a measure of dementia severity. Specifically, anxiolytics were less frequently prescribed in less affected YOD. They also found a positive association between the administration of APs and non-Alzheimer's type dementia.
Bargagli et al. [41] addressed the question of predictors for AP treatment in dementia patients ≥65 years-old using a population-based approach. They found that people who were also treated with antidepressants or antidementia drugs were more likely to receive APs. PWD who received polypharmacy were treated with APs less likely.
Further, our data showed that being cared for in a LTC facility was positively associated with the use of analgesics suggesting that pain medications were better available, and the barrier to administer them were lower in the institutionalized setting than at home.
We found, that more BPSD, as measured with the NPI, were associated with a higher prevalence of APs. In particular, anxiety and nighttime behavior were associated with more AP treatment. This finding is difficult to interpret. It could mean BPSD are a consequence of AP treatment, or the AP treatment is not suitable or sufficient enough to alleviate the respective symptoms. Interestingly, inconspicuous nighttime behavior was associated with a decreased use of pain medication, which leads us to question if pain as a result from uncontrolled and negative nighttime behavior may have been overlooked, and therefore left untreated.
A limitation to our study is PRN drug use was not considered. PRN drugs could not be reliably assessed, as they were hardly traceable or not reliably documented in patient charts. The impression during most patient visits, however, was, that most LTC facilities were rather restrictive regarding PRN use, as were family caregivers of PWAD who lived at home. Another limitation to our study is the relatively low number of patients included. Many similar studies analyse large databases to come to their conclusion, however often lack a thorough characterization of the patients treated. With this in mind, the low sample size we used allowed us to carefully and meticulously analyse all parties involved.
