**1.2 Preliminary study of antipsychotic medication and mortality in older people**

When Sarah Worobetz, a doctoral student at Lakehead University, wanted to research relationships between antipsychotic medication and mortality in older people, after control for a wide range of variables we describe subsequently, faculty members Michael Stones and Peter Brink were happy to oblige. These researchers had a working familiarity with the RAI 2.0. They hoped to obtain census level data, with linkages to other mortality relevant datasets, to provide Sarah with the means to conduct her research. Peter Brink successfully submitted a proposal to CIHI for access to access these data.

The RAI 2.0 is a standardized assessment tool used routinely in LTCH and CCC facilities in Ontario and other settings across the world. The tool contains over 350 items relevant to medical diagnoses; physical, cognitive, social, and emotional functioning; and treatment categories that include medication use. It also indexes mortality within the relevant facilities. The trained health care professionals responsible for RAI 2.0 assessments obtain that information from multiple sources, such as direct observation, medical records, and communication with family members and other health care professionals. Objective scales on the RAI 2.0 consist of sets of items selected for relevance to a given construct. Evaluation of such scales may be against "gold standard" measures of the constructs (e.g., measures of activities of daily living, cognitive status, depression, aggression, and pain) or relevant outcomes (e.g., mortality risk). From a measurement perspective, previous findings on data quality and the reliability and validity of RAI 2.0 measures are positive [8–10].

The antipsychotic medication item on the RAI 2.0 falls within a psychotropic category that also contains items on antidepressant, analgesic, anxiolytic, and hypnotic medications. The wording of each of these items asks for the number of days during the past week that the resident received the medication. This form of measurement differs from that common to previous studies of psychotropic medication and mortality, which invariably report specific medications and dosages but not frequency of medication use.

The other databases provided by CIHI are the Discharge Abstract Database (DAD) and the National Ambulatory Care Reporting System (NACRS). The DAD contains demographic, administrative, and clinical data for hospital discharges (inpatient acute, chronic, and rehabilitation) and day surgeries. The NACRS contains data for hospital-based and community-based emergency and ambulatory care (e.g., day surgery and outpatient clinics). Both datasets contain mortality data pertaining to their respective contexts. CIHI encrypted the personal and facility identifiers across

datasets to ensure anonymity of residents. Brink merged these three datasets for purposes of analysis. Consequently, the merged file contains mortality data both within LTCH and CCC facilities and for those discharged to other health care settings.

The dataset analyzed by Worobetz includes all admission, quarterly and annual RAI 2.0 assessment for residents aged over 65 years in all LTCH and CCC facilities in Ontario during the financial years 2010–2011 and 2011–2012. The data are from 102,658 residents of approximately 760 facilities with a mean of 5.83 assessments per resident. Approximately 70% of residents are female and 30% male, with a mean age over all assessments of approximately 84 years. Approximately 86% of residents live in LTCH and 14% in CCC facilities. The mean length of stay prior to the first assessment was approximately 20 months, with the age at entry approximately 82 years. The distribution of antipsychotic prescriptions shows that approximately 69% of residents are without medication, 29% have daily prescriptions, and 2% have prescriptions of 1–6 days per week, which for purposes of this research we describe as PRN prescriptions. The total mortality rate during the 2-year period of data collection is approximately 32%.

The initial findings by Worobetz on relationships between mortality and type of antipsychotic prescription came as a big surprise. Her analysis by generalized linear mixed modeling (GLMM) appointed LTCH as a random effect variable (i.e., independent entities) with residents clustered (i.e., showing covariation) within their respective facilities. Such modeling is appropriate because of differences among facilities with respect to admission criteria, population size, staffing levels, types of programming, treatment protocols, etc., with localized interpersonal exchanges within facilities that foster covariation among residents. Compared to residents with no prescription for antipsychotic medication, her findings show attenuated mortality for those with daily prescription, but augmented mortality for those with PRN prescription. A possible interpretation is that these findings are consistent with earlier evidence of a protective effect of antipsychotics after 6 months but an increased mortality risk for residents prescribed antipsychotics on a PRN basis because they began to exhibit relevant symptoms.

Subsequent GLMM analyses by Worobetz included all residents, only those from LTCH, only those from CCC, new admissions, residents with dementia, and combinations of the preceding. The fixed effect variables in such analyses included not just prescriptions for antipsychotic medication but multivariate control for confounding variables such as demographics, scores on RAI 2.0 scales (e.g., activity limitation, cognitive status, aggression, depression, and mortality risk), temporal changes on those scales, and medical diagnoses (e.g., cancer, dementia, maniac depression, and schizophrenia [11]). The findings from all these analyses consistently show highest mortality among residents with PRN prescriptions on the final assessment.

### **1.3 Studies of other psychotropic medications and mortality in older people**

The preceding findings provide reasons to broaden the scope of investigation to encompass mortality in relation to prescriptions of other types of psychotropic medication. We begin this section with brief discussion of prescribing practices and mortality associated with analgesics, antidepressants, anxiolytics and hypnotics, which in the RAI 2.0 fall within an item-set of psychotropic medications. Then follows discussion of problems associated with PRN prescribing practices. Finally, we report findings from separate analyses of mortality against these types of psychotropic medications.

Prescribing practices with analgesics show the following trends. Although rates for PRN prescription in elderly care services are generally low, some reports indicate highest levels for analgesics [12]. Worldwide, scheduled rates for analgesic use (that include acetaminophen and opioids) in LTCH show a historical increase, whereas

**5**

**and mortality**

*Psychotropic Medication Use and Mortality in Long-Term Care Residents*

rates for scheduled plus PRN rates show no such increase [13]. Recent findings from the Czech Republic suggest that a large proportion of LTCH residents with pain receive no analgesic medication and a moderate proportion of those that receive analgesic medication continue to report pain. These findings of analgesic underprescription are consistent with those from North America and elsewhere in Europe. The lowest frequency of reported pain and lowest prevalence of analgesic administration are for residents with moderate-to-severe dementia [14], which suggests this group's susceptibility to under-detection and under-prescribing of this medication. Anti-depressant medications find frequent use in older people, with average prevalence rates of approximately 25% [15, 16]. Recent evidence suggests no association between antidepressant prescriptions and augmented risk of all-cause mortality [17, 18]. However, best practice guidelines recommend caution when prescribing because low adherence may increase risks of fatal cardiovascular and cerebrovascular injuries [19]. On the other hand, high adherence appears to lower mortality risk [20]. The findings give rise to hypotheses that intermittent use of antidepressants (e.g., comparable to PRN prescribing) has unfavorable implications for mortality whereas regular use (e.g., associated with daily prescription) has favorable implica-

tions. However, we will discuss other interpretations later in the chapter.

7-year period, after adjusting for a range of potential confounders [23].

that relate mortality to PRN usage appear to be absent in the literature.

They provide the impetus for the new analyses that follow.

A recent review suggests that benzodiazepines are the most frequently prescribed anxiolytic medications for geriatric anxiety [21]. However, consensus is low about whether anxiolytic and hypnotic medications have unfavorable implications for mortality risk amongst older adults [22]. On the other hand, a large-scale retrospective cohort study of patients in UK primary care concluded that anxiolytic and hypnotic drugs were associated with significantly increased risk of mortality over a

A number of studies and reviews examined PRN prescription in psychiatric and LTCH settings [24–27]. Summary findings indicate higher PRN use for residents with lower care needs, frequent use alongside regularly scheduled medications, and recent entry into a facility. Contextual factors also have a strong influence on PRN prescribing. These include general levels of activity and disturbance on the ward, staffing level, perceived competence of staff, and familiarity of the staff with residents. The reports also indicate frequent omissions and errors in records of PRN usage. Findings

Following the thesis research by Worobetz, subsequent analyses of the same dataset examined relationships of mortality to prescriptions of anesthetics (Jason Randle), antidepressants (Carlina Marchese and Shauna Fossum), anxiolytics (Michael Stones), and hypnotics (Dane Ostrom). We describe the sampling procedure in the following section. The main findings show significantly higher mortality with PRN prescriptions for each type of psychotropic medication compared with daily or null prescription. These findings persist even after statistical control of relevant confounding variables.

**2. New analyses on relationships between psychotropic medication** 

We try here to expand the scope and level of precision beyond those present in previous analyses, each of which examined associations of mortality with a single psychotropic medication. First, we analyze the effects on mortality of all the psychotropic prescriptions within a series of multivariate analyses that includes the psychotropic medications. Second, we introduce a verified measure of mortality risk into the array of control variables. Third, we examine intervals for mortality of 90 days from the final RAI 2.0 assessment (i.e., the scheduled date of the next

*DOI: http://dx.doi.org/10.5772/intechopen.85971*

### *Psychotropic Medication Use and Mortality in Long-Term Care Residents DOI: http://dx.doi.org/10.5772/intechopen.85971*

*Aging - Life Span and Life Expectancy*

because they began to exhibit relevant symptoms.

datasets to ensure anonymity of residents. Brink merged these three datasets for purposes of analysis. Consequently, the merged file contains mortality data both within LTCH and CCC facilities and for those discharged to other health care settings. The dataset analyzed by Worobetz includes all admission, quarterly and annual RAI 2.0 assessment for residents aged over 65 years in all LTCH and CCC facilities in Ontario during the financial years 2010–2011 and 2011–2012. The data are from 102,658 residents of approximately 760 facilities with a mean of 5.83 assessments per resident. Approximately 70% of residents are female and 30% male, with a mean age over all assessments of approximately 84 years. Approximately 86% of residents live in LTCH and 14% in CCC facilities. The mean length of stay prior to the first assessment was approximately 20 months, with the age at entry approximately 82 years. The distribution of antipsychotic prescriptions shows that approximately 69% of residents are without medication, 29% have daily prescriptions, and 2% have prescriptions of 1–6 days per week, which for purposes of this research we describe as PRN prescriptions. The total mortality rate during the 2-year period of data collection is approximately 32%. The initial findings by Worobetz on relationships between mortality and type of antipsychotic prescription came as a big surprise. Her analysis by generalized linear mixed modeling (GLMM) appointed LTCH as a random effect variable (i.e., independent entities) with residents clustered (i.e., showing covariation) within their respective facilities. Such modeling is appropriate because of differences among facilities with respect to admission criteria, population size, staffing levels, types of programming, treatment protocols, etc., with localized interpersonal exchanges within facilities that foster covariation among residents. Compared to residents with no prescription for antipsychotic medication, her findings show attenuated mortality for those with daily prescription, but augmented mortality for those with PRN prescription. A possible interpretation is that these findings are consistent with earlier evidence of a protective effect of antipsychotics after 6 months but an increased mortality risk for residents prescribed antipsychotics on a PRN basis

Subsequent GLMM analyses by Worobetz included all residents, only those from LTCH, only those from CCC, new admissions, residents with dementia, and combinations of the preceding. The fixed effect variables in such analyses included not just prescriptions for antipsychotic medication but multivariate control for confounding variables such as demographics, scores on RAI 2.0 scales (e.g., activity limitation, cognitive status, aggression, depression, and mortality risk), temporal changes on those scales, and medical diagnoses (e.g., cancer, dementia, maniac depression, and schizophrenia [11]). The findings from all these analyses consistently show highest

mortality among residents with PRN prescriptions on the final assessment.

**1.3 Studies of other psychotropic medications and mortality in older people**

The preceding findings provide reasons to broaden the scope of investigation to encompass mortality in relation to prescriptions of other types of psychotropic medication. We begin this section with brief discussion of prescribing practices and mortality associated with analgesics, antidepressants, anxiolytics and hypnotics, which in the RAI 2.0 fall within an item-set of psychotropic medications. Then follows discussion of problems associated with PRN prescribing practices. Finally, we report findings from separate analyses of mortality against these types of psycho-

Prescribing practices with analgesics show the following trends. Although rates for PRN prescription in elderly care services are generally low, some reports indicate highest levels for analgesics [12]. Worldwide, scheduled rates for analgesic use (that include acetaminophen and opioids) in LTCH show a historical increase, whereas

**4**

tropic medications.

rates for scheduled plus PRN rates show no such increase [13]. Recent findings from the Czech Republic suggest that a large proportion of LTCH residents with pain receive no analgesic medication and a moderate proportion of those that receive analgesic medication continue to report pain. These findings of analgesic underprescription are consistent with those from North America and elsewhere in Europe. The lowest frequency of reported pain and lowest prevalence of analgesic administration are for residents with moderate-to-severe dementia [14], which suggests this group's susceptibility to under-detection and under-prescribing of this medication.

Anti-depressant medications find frequent use in older people, with average prevalence rates of approximately 25% [15, 16]. Recent evidence suggests no association between antidepressant prescriptions and augmented risk of all-cause mortality [17, 18]. However, best practice guidelines recommend caution when prescribing because low adherence may increase risks of fatal cardiovascular and cerebrovascular injuries [19]. On the other hand, high adherence appears to lower mortality risk [20]. The findings give rise to hypotheses that intermittent use of antidepressants (e.g., comparable to PRN prescribing) has unfavorable implications for mortality whereas regular use (e.g., associated with daily prescription) has favorable implications. However, we will discuss other interpretations later in the chapter.

A recent review suggests that benzodiazepines are the most frequently prescribed anxiolytic medications for geriatric anxiety [21]. However, consensus is low about whether anxiolytic and hypnotic medications have unfavorable implications for mortality risk amongst older adults [22]. On the other hand, a large-scale retrospective cohort study of patients in UK primary care concluded that anxiolytic and hypnotic drugs were associated with significantly increased risk of mortality over a 7-year period, after adjusting for a range of potential confounders [23].

A number of studies and reviews examined PRN prescription in psychiatric and LTCH settings [24–27]. Summary findings indicate higher PRN use for residents with lower care needs, frequent use alongside regularly scheduled medications, and recent entry into a facility. Contextual factors also have a strong influence on PRN prescribing. These include general levels of activity and disturbance on the ward, staffing level, perceived competence of staff, and familiarity of the staff with residents. The reports also indicate frequent omissions and errors in records of PRN usage. Findings that relate mortality to PRN usage appear to be absent in the literature.

Following the thesis research by Worobetz, subsequent analyses of the same dataset examined relationships of mortality to prescriptions of anesthetics (Jason Randle), antidepressants (Carlina Marchese and Shauna Fossum), anxiolytics (Michael Stones), and hypnotics (Dane Ostrom). We describe the sampling procedure in the following section. The main findings show significantly higher mortality with PRN prescriptions for each type of psychotropic medication compared with daily or null prescription. These findings persist even after statistical control of relevant confounding variables. They provide the impetus for the new analyses that follow.
