Aging populations and multimorbidity have contributed to widespread increases in polypharmacy, or the concurrent use of several (e.g. five or more) chronic medications (Wastesson et al., Reference Wastesson, Morin, Tan and Johnell2018). Older adults with dementia are particularly vulnerable to polypharmacy given dementia’s heterogeneous clinical profile, lack of a single efficacious treatment, and high rates of multimorbidity (Tonelli et al., Reference Tonelli2017; Leelakanok and D’Cunha, Reference Leelakanok and D’cunha2019). Psychotropic medication use and psychotropic polypharmacy (i.e. the concurrent use of two or three-or-more psychotropic medications) has been a focus of public health and clinical research over the past several decades. Despite worrisome safety profiles and limited effectiveness, psychotropic medications like antidepressants and antipsychotics are often used to treat dementia’s neuropsychiatric symptoms (e.g. anxiety, depression, agitation, sleep disturbances) (Watt et al., Reference Watt2020; Watt et al., Reference Watt2019). In the long-term care setting, where dementia is common, psychotropic polypharmacy is also common (Jester et al., Reference Jester, Molinari, Zgibor and Volicer2020; Iaboni et al., Reference Iaboni, Bronskill, Reynolds, Wang, Rochon, Herrmann and Alastair2016).
There are significant concerns regarding the appropriateness of psychotropic polypharmacy in older adults with dementia. Current evidence and guidelines call for the prioritization of non-pharmacological strategies as a first-line treatment (Watt et al., Reference Watt2020; Watt et al., Reference Watt2019; American Geriatrics Society Beers Criteria Update Expert Panel, 2019), but resources for the implementation of these strategies in the long-term care is limited. The evidence for the use of individual psychotropics in dementia is modest, and their prescription must be weighed with the potential for significant side effects (Watt et al., Reference Watt2020). Importantly, no evidence supports combining multiple psychotropics in people with dementia, outside of the treatment of mental health disorders such as psychotic depression or bipolar disorder. In contrast, there is ample evidence of the additive risks of psychotropic polypharmacy. Pharmacokinetic and pharmacodynamic drug interactions are amplified by aging and frailty, and psychotropic polypharmacy has been shown to increase the rate of unplanned hospitalizations and premature mortality in older adults (Huang et al., Reference Huang, Wen, Shur-Fen Gau, Chen and Hsiao2019). These concerns are reflected in practice guidelines such as the Beer’s criteria, which explicitly warn against prescribing multiple central nervous system (CNS)-acting medications in frail older adults (American Geriatrics Society Beers Criteria Update Expert Panel, 2019).
Despite these warnings, the evidence points to increasing psychotropic polypharmacy in long-term care over the past decade (Iaboni et al., Reference Iaboni, Bronskill, Reynolds, Wang, Rochon, Herrmann and Alastair2016). To date, several studies have estimated the prevalence of psychotropic polypharmacy among long-term care residents with dementia (Iaboni et al., Reference Iaboni, Bronskill, Reynolds, Wang, Rochon, Herrmann and Alastair2016; Norgaard et al., Reference Norgaard, Jensen-Dahm, Gasse, Hansen and Waldemar2017), but substantial geographic variation and heterogeneity in the prevalence estimates have made it challenging to define a benchmark and characterize the scope of the problem. In this issue, Jester et al. present a meta-analysis that helps to address these gaps (Jester et al., Reference Jester, Molinari, Zgibor and Volicer2020).
The authors analyzed 25 unique studies, comprised of over 92,000 long-term care residents with dementia, and found that 33% (95% CI: 28%–39%) received 2-or-more psychotropic medications and 13% (95% CI: 10%–17%) received 3-or-more psychotropic medications. Given the high prevalence of dementia in long-term care and the historical preference for psychotropic prescribing in this population, it is unsurprising (albeit still concerning) to see that one-third of long-term care residents receiving two-or-more psychotropic medications. Psychotropic polypharmacy continues to be an issue despite well-established prescribing guidelines and a substantial evidence base indicating the associated risks.
One factor that may be contributing to increases in psychotropic polypharmacy is an epidemic of antidepressant prescribing in this population. Among long-term care residents in Alberta, Canada, 48% received an antidepressant (Stock et al., Reference Stock, Amuah, Lapane, Hogan and Maxwell2017), with another Canadian study showing increasing use of trazodone over time in long-term care (Iaboni et al., Reference Iaboni, Bronskill, Reynolds, Wang, Rochon, Herrmann and Alastair2016). A recent preprint investigating the impact of the COVID-19 pandemic on prescribing in long-term care showed both an exceptionally high prevalence of antidepressant use (>50%) and a significant increase in antidepressant and antipsychotic use during the pandemic (Stall et al., Reference Stall2020). Extending beyond Canada, a recent study of seven European countries estimated that 36% of long-term care residents were using an antidepressant, ranging from 28% (Czech Republic) to 42% (France) (Giovannini et al., Reference Giovannini2020). Jester et al. found that antidepressants are commonly co-prescribed with sedative hypnotics and with antipsychotics. In Moyle et al., combination therapy with an atypical antipsychotic and selective serotonin reuptake inhibitor (SSRI) antidepressant accounted for 7% of the severe and 26% of the moderate drug–drug interactions (Moyle et al., Reference Moyle2017). Although the clinical significance of these potential interactions is unclear, the high and increasing utilization of antidepressants in long-term care requires closer attention.
Psychotropic polypharmacy is also suspected to be associated with antipsychotic reduction and deprescribing efforts (Maust et al., Reference Maust, Kim, Chiang and Kales2018). For example, increasing use of combinations of antidepressants, anticonvulsants, and other psychotropic drugs have been observed during periods of antipsychotic reduction (Maust et al., Reference Maust, Kim, Chiang and Kales2018; Iaboni et al., Reference Iaboni, Bronskill, Reynolds, Wang, Rochon, Herrmann and Alastair2016). Treatment substitutions in long-term care have been observed in the past, namely with the reporting of physical restraints lending to compensatory increases in antipsychotic use (Konetzka et al., Reference Konetzka, Brauner, Shega and Werner2014). As such, it is plausible for other psychotropic and CNS-acting medications to be used in place of antipsychotics for the treatment of neuropsychiatric symptoms, especially when a necessary shift to non-pharmacological interventions requires resources that long-term care homes may not have. Whether residents of long-term care are better served by these medication substitutions remains an important clinical and public health question. To help answer this question, we will need to identify methodological strategies for measuring psychotropic medication substitution and outcomes related to these changes using large pharmacy claims databases. A major strength of population-based pharmacy claims databases is their breadth, or their potential to characterize large populations of medication users over extended periods of time. However, their lack of depth can make it challenging to tease out prescribing decisions that are being made at the resident level. In order to better understand the potential unintended consequences of antipsychotic deprescribing initiatives such as medication substitution, it will be important to develop a measure for medication switching that ties basic dispensation data to the various and intricate strategies used to switch psychotropic medications (e.g. cross-tapering).
There are several notable limitations of the current meta-analysis. First, many studies included small samples of long-term care residents, with a median of 312 residents (range=55–59,785) across the 25 included studies. Such small numbers of residents are prone to facility- and physician-level prescribing idiosyncrasies, thereby complicating our understanding of the true prevalence of psychotropic polypharmacy. As such, there is a need for population-based studies to estimate the prevalence and incidence of psychotropic polypharmacy and characterize how the prevalence and the incidence change over time. As Jester et al. note, these meta-analytic estimates were derived from a single cross-section in time, and thus do not capture prescribing changes over time. Further, country-specific policies and regulations related to prescribing in long-term care and different prescribing guidelines make it challenging to pool prevalence estimates. These challenges are further complicated by the substantial variation in how studies define psychotropic medications, with some studies including anti-dementia, anti-Parkinson’s, opioids, and other CNS-acting medications. As such, it seems prudent for future studies in this area to identify and use a unified definition of psychotropic medications, perhaps leveraging existing classification systems (e.g. Anatomical Therapeutic Chemical Classification System [second level: psycholeptics and psychoanaleptics]).
An important next step is to develop a better understanding of prescribing practices that contribute to the layering of psychotropic therapies. Prescribing cascades are one factor, where the side effects of one psychotropic are treated by the addition of a second psychotropic (e.g. akathisia treated with the addition of a benzodiazepine) (Piggott et al., Reference Piggott, Mehta, Wong and Rochon2020). Another common scenario is the addition of a second or third medication rather than the substitution of the previous inefficacious treatment(s). Poor communication and continuity of care, in particular the failure to track and document treatment response, are important factors here. Given the widespread overreliance on psychotropic medications to manage behavioral symptoms in dementia, deprescribing of psychotropic medications is a process with many barriers in the long-term care setting (Harrison et al., Reference Harrison, Cations, Jessop, Hilmer, Sawan and Brodaty2019). Beyond fears of exacerbating symptoms, there is also a lack of time and resources to devote to a careful deprescribing plan. Finally, the adverse effects of polypharmacy can be easily missed in frail long-term care residents, with a decline in cognition, mobility, and falls misattributed to geriatric syndromes or progression of the underlying dementia (Hilmer et al., Reference Hilmer, Gnjidic and Le Couteur2012). Further research is needed to support the role of deprescribing as a routine part of clinical practice in long-term care (Kua et al., Reference Kua, Mak and Huey Lee2019).
In summary, psychotropic medication use in long-term care residents with dementia is constantly evolving, sensitive to changing resident demographics, facility- and physician-level characteristics, prescribing guidelines, and policies and regulations. Research informing the appropriate use of psychotropic polypharmacy is needed alongside strategies to guide psychotropic deprescribing. There is also a need to understand how policies shape prescribing decisions and lend to unintended consequences, such as psychotropic polypharmacy and treatment substitution. Lastly, it is critical to consider how the resources within a long-term care home are related to prescribing and deprescribing practices. Identifying which structural correlates are related to prescribing and ways to feasibly address them is likely to have a positive impact on reducing inappropriate psychotropic polypharmacy among older adults with dementia.
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Aging populations and multimorbidity have contributed to widespread increases in polypharmacy, or the concurrent use of several (e.g. five or more) chronic medications (Wastesson et al., Reference Wastesson, Morin, Tan and Johnell2018). Older adults with dementia are particularly vulnerable to polypharmacy given dementia’s heterogeneous clinical profile, lack of a single efficacious treatment, and high rates of multimorbidity (Tonelli et al., Reference Tonelli2017; Leelakanok and D’Cunha, Reference Leelakanok and D’cunha2019). Psychotropic medication use and psychotropic polypharmacy (i.e. the concurrent use of two or three-or-more psychotropic medications) has been a focus of public health and clinical research over the past several decades. Despite worrisome safety profiles and limited effectiveness, psychotropic medications like antidepressants and antipsychotics are often used to treat dementia’s neuropsychiatric symptoms (e.g. anxiety, depression, agitation, sleep disturbances) (Watt et al., Reference Watt2020; Watt et al., Reference Watt2019). In the long-term care setting, where dementia is common, psychotropic polypharmacy is also common (Jester et al., Reference Jester, Molinari, Zgibor and Volicer2020; Iaboni et al., Reference Iaboni, Bronskill, Reynolds, Wang, Rochon, Herrmann and Alastair2016).
There are significant concerns regarding the appropriateness of psychotropic polypharmacy in older adults with dementia. Current evidence and guidelines call for the prioritization of non-pharmacological strategies as a first-line treatment (Watt et al., Reference Watt2020; Watt et al., Reference Watt2019; American Geriatrics Society Beers Criteria Update Expert Panel, 2019), but resources for the implementation of these strategies in the long-term care is limited. The evidence for the use of individual psychotropics in dementia is modest, and their prescription must be weighed with the potential for significant side effects (Watt et al., Reference Watt2020). Importantly, no evidence supports combining multiple psychotropics in people with dementia, outside of the treatment of mental health disorders such as psychotic depression or bipolar disorder. In contrast, there is ample evidence of the additive risks of psychotropic polypharmacy. Pharmacokinetic and pharmacodynamic drug interactions are amplified by aging and frailty, and psychotropic polypharmacy has been shown to increase the rate of unplanned hospitalizations and premature mortality in older adults (Huang et al., Reference Huang, Wen, Shur-Fen Gau, Chen and Hsiao2019). These concerns are reflected in practice guidelines such as the Beer’s criteria, which explicitly warn against prescribing multiple central nervous system (CNS)-acting medications in frail older adults (American Geriatrics Society Beers Criteria Update Expert Panel, 2019).
Despite these warnings, the evidence points to increasing psychotropic polypharmacy in long-term care over the past decade (Iaboni et al., Reference Iaboni, Bronskill, Reynolds, Wang, Rochon, Herrmann and Alastair2016). To date, several studies have estimated the prevalence of psychotropic polypharmacy among long-term care residents with dementia (Iaboni et al., Reference Iaboni, Bronskill, Reynolds, Wang, Rochon, Herrmann and Alastair2016; Norgaard et al., Reference Norgaard, Jensen-Dahm, Gasse, Hansen and Waldemar2017), but substantial geographic variation and heterogeneity in the prevalence estimates have made it challenging to define a benchmark and characterize the scope of the problem. In this issue, Jester et al. present a meta-analysis that helps to address these gaps (Jester et al., Reference Jester, Molinari, Zgibor and Volicer2020).
The authors analyzed 25 unique studies, comprised of over 92,000 long-term care residents with dementia, and found that 33% (95% CI: 28%–39%) received 2-or-more psychotropic medications and 13% (95% CI: 10%–17%) received 3-or-more psychotropic medications. Given the high prevalence of dementia in long-term care and the historical preference for psychotropic prescribing in this population, it is unsurprising (albeit still concerning) to see that one-third of long-term care residents receiving two-or-more psychotropic medications. Psychotropic polypharmacy continues to be an issue despite well-established prescribing guidelines and a substantial evidence base indicating the associated risks.
One factor that may be contributing to increases in psychotropic polypharmacy is an epidemic of antidepressant prescribing in this population. Among long-term care residents in Alberta, Canada, 48% received an antidepressant (Stock et al., Reference Stock, Amuah, Lapane, Hogan and Maxwell2017), with another Canadian study showing increasing use of trazodone over time in long-term care (Iaboni et al., Reference Iaboni, Bronskill, Reynolds, Wang, Rochon, Herrmann and Alastair2016). A recent preprint investigating the impact of the COVID-19 pandemic on prescribing in long-term care showed both an exceptionally high prevalence of antidepressant use (>50%) and a significant increase in antidepressant and antipsychotic use during the pandemic (Stall et al., Reference Stall2020). Extending beyond Canada, a recent study of seven European countries estimated that 36% of long-term care residents were using an antidepressant, ranging from 28% (Czech Republic) to 42% (France) (Giovannini et al., Reference Giovannini2020). Jester et al. found that antidepressants are commonly co-prescribed with sedative hypnotics and with antipsychotics. In Moyle et al., combination therapy with an atypical antipsychotic and selective serotonin reuptake inhibitor (SSRI) antidepressant accounted for 7% of the severe and 26% of the moderate drug–drug interactions (Moyle et al., Reference Moyle2017). Although the clinical significance of these potential interactions is unclear, the high and increasing utilization of antidepressants in long-term care requires closer attention.
Psychotropic polypharmacy is also suspected to be associated with antipsychotic reduction and deprescribing efforts (Maust et al., Reference Maust, Kim, Chiang and Kales2018). For example, increasing use of combinations of antidepressants, anticonvulsants, and other psychotropic drugs have been observed during periods of antipsychotic reduction (Maust et al., Reference Maust, Kim, Chiang and Kales2018; Iaboni et al., Reference Iaboni, Bronskill, Reynolds, Wang, Rochon, Herrmann and Alastair2016). Treatment substitutions in long-term care have been observed in the past, namely with the reporting of physical restraints lending to compensatory increases in antipsychotic use (Konetzka et al., Reference Konetzka, Brauner, Shega and Werner2014). As such, it is plausible for other psychotropic and CNS-acting medications to be used in place of antipsychotics for the treatment of neuropsychiatric symptoms, especially when a necessary shift to non-pharmacological interventions requires resources that long-term care homes may not have. Whether residents of long-term care are better served by these medication substitutions remains an important clinical and public health question. To help answer this question, we will need to identify methodological strategies for measuring psychotropic medication substitution and outcomes related to these changes using large pharmacy claims databases. A major strength of population-based pharmacy claims databases is their breadth, or their potential to characterize large populations of medication users over extended periods of time. However, their lack of depth can make it challenging to tease out prescribing decisions that are being made at the resident level. In order to better understand the potential unintended consequences of antipsychotic deprescribing initiatives such as medication substitution, it will be important to develop a measure for medication switching that ties basic dispensation data to the various and intricate strategies used to switch psychotropic medications (e.g. cross-tapering).
There are several notable limitations of the current meta-analysis. First, many studies included small samples of long-term care residents, with a median of 312 residents (range=55–59,785) across the 25 included studies. Such small numbers of residents are prone to facility- and physician-level prescribing idiosyncrasies, thereby complicating our understanding of the true prevalence of psychotropic polypharmacy. As such, there is a need for population-based studies to estimate the prevalence and incidence of psychotropic polypharmacy and characterize how the prevalence and the incidence change over time. As Jester et al. note, these meta-analytic estimates were derived from a single cross-section in time, and thus do not capture prescribing changes over time. Further, country-specific policies and regulations related to prescribing in long-term care and different prescribing guidelines make it challenging to pool prevalence estimates. These challenges are further complicated by the substantial variation in how studies define psychotropic medications, with some studies including anti-dementia, anti-Parkinson’s, opioids, and other CNS-acting medications. As such, it seems prudent for future studies in this area to identify and use a unified definition of psychotropic medications, perhaps leveraging existing classification systems (e.g. Anatomical Therapeutic Chemical Classification System [second level: psycholeptics and psychoanaleptics]).
An important next step is to develop a better understanding of prescribing practices that contribute to the layering of psychotropic therapies. Prescribing cascades are one factor, where the side effects of one psychotropic are treated by the addition of a second psychotropic (e.g. akathisia treated with the addition of a benzodiazepine) (Piggott et al., Reference Piggott, Mehta, Wong and Rochon2020). Another common scenario is the addition of a second or third medication rather than the substitution of the previous inefficacious treatment(s). Poor communication and continuity of care, in particular the failure to track and document treatment response, are important factors here. Given the widespread overreliance on psychotropic medications to manage behavioral symptoms in dementia, deprescribing of psychotropic medications is a process with many barriers in the long-term care setting (Harrison et al., Reference Harrison, Cations, Jessop, Hilmer, Sawan and Brodaty2019). Beyond fears of exacerbating symptoms, there is also a lack of time and resources to devote to a careful deprescribing plan. Finally, the adverse effects of polypharmacy can be easily missed in frail long-term care residents, with a decline in cognition, mobility, and falls misattributed to geriatric syndromes or progression of the underlying dementia (Hilmer et al., Reference Hilmer, Gnjidic and Le Couteur2012). Further research is needed to support the role of deprescribing as a routine part of clinical practice in long-term care (Kua et al., Reference Kua, Mak and Huey Lee2019).
In summary, psychotropic medication use in long-term care residents with dementia is constantly evolving, sensitive to changing resident demographics, facility- and physician-level characteristics, prescribing guidelines, and policies and regulations. Research informing the appropriate use of psychotropic polypharmacy is needed alongside strategies to guide psychotropic deprescribing. There is also a need to understand how policies shape prescribing decisions and lend to unintended consequences, such as psychotropic polypharmacy and treatment substitution. Lastly, it is critical to consider how the resources within a long-term care home are related to prescribing and deprescribing practices. Identifying which structural correlates are related to prescribing and ways to feasibly address them is likely to have a positive impact on reducing inappropriate psychotropic polypharmacy among older adults with dementia.