Caps project

ORIGINAL RESEARCH ARTICLE

Psychotropic Drug-Related Fall Incidents in Nursing Home Residents Living in the Eastern Part of The Netherlands

Sarah I. M. Janus1 • Gezinus H. Reinders1 • Jeannette G. van Manen1 •

Sytse U. Zuidema2 • Maarten J. IJzerman1

Published online: 8 April 2017

� The Author(s) 2017. This article is an open access publication

Abstract

Background Older people are more susceptible to falls

than younger people. Therefore, as the Dutch population

ages, the total number of falls and costs associated with

them will rise. The use of psychotropic drugs is associated

with an increased risk of falling. To create tailored fall-

prevention programmes, information on the magnitude of

the association between fall incidents and specific psy-

chotropic drugs or drug classes is needed.

Objective The goal of this study was to delineate the

associations between fall incidents and specific psy-

chotropic drugs or drug classes.

Methods In this retrospective cohort study, electronic

patient records, medication records and fall incident reports

were collected for 1415 residents receiving somatic or

psychogeriatric care in 22 nursing homes in the eastern part

of the Netherlands from May 2012 until March 2015.

Using a Cox proportional hazards model, we analysed the

magnitude of the association between psychotropic drugs

and the risk of falling for users and non-users of the psy-

chotropic drugs or drug classes.

Results Antipsychotics (adjusted hazard ratio [aHR] 1.49;

95% confidence interval [CI] 1.12–2.00) and hypnotics and

sedatives (aHR 1.51; 95% CI 1.13–2.02) increase the risk

of falling. There was no difference between the risk

incurred by typical and atypical antipsychotics. However,

within these groups, there were differences between the

most commonly prescribed drugs: haloperidol and queti-

apine were seen to have an association with falls, whereas

pipamperone and risperidone were not.

Conclusions The results suggest falls may be associated

with individual drugs rather than drug classes. Within the

drug classes, clear differences are evident between indi-

vidual drugs. Future fall-prevention programmes should

highlight the differential risks involved with the use of

specific psychotropic drugs, and doctors should take the

fall risk into account when choosing specific drugs.

Key Points

Falls within the nursing home population may be

associated with individual drugs rather than drug

classes.

Differences exist between individual drugs within

drug classes.

1 Introduction

Over 40% of nursing home residents experience a least one

fall each year [1]. A fall is hereby defined as ‘an event that

leads to a person coming to rest on the ground or other

lower level’ [2]. Because the population is aging, and older

people have a higher risk of falling, the number of falls is

likely to increase. Injuries resulting from falls are promi-

nent among the causes of disability in older people [3].

With an expected increase in age-related incidents such as

falls, a rise in associated costs can also be expected [3].

& Sarah I. M. Janus [email protected]

1 Department of Health Technology and Services Research,

University of Twente, Enschede, The Netherlands

2 Department of General Practice and Elderly Care Medicine,

University of Groningen, University Medical Centre

Groningen, Groningen, The Netherlands

Drugs R D (2017) 17:321–328

DOI 10.1007/s40268-017-0181-0

While falls are often considered accidents, it has been

shown that the incidence of falls significantly differs from a

Poisson distribution, implying that falls are causally con-

nected with external factors [5].

Factors that influence the risk of falling (besides age)

include state of health [4, 5] and drug use. The former is

difficult to influence, whereas the latter can be influenced

by changing medication prescriptions. For instance,

polypharmacy, defined as the simultaneous use of more

than five drugs, increases the risk of adverse events such as

falls [4, 6, 7]. In the Netherlands, people aged [75 years use five times as many prescription drugs as the average

citizen, and they use these drugs predominantly chronically

[8].

Some drugs are more harmful than others when included

in polypharmacy. The Screening Tool of Older Person’s

Prescriptions (STOPP) lists the potentially inappropriate

medications (PIMs) for older people [9], including several

classes of psychotropic drugs. In several studies, these

drugs were the most prevalent PIMs.

An association between the increased risk of falling in

older people and the use of psychotropic drugs was pre-

viously reported in the meta-analysis of three systematic

reviews of the literature between 1966 and 2007 [10, 11].

The most recent review [12] provided the most extensive

overview. The three systematic reviews found that all

psychotropic drug classes were associated with an

increased risk of falling. The pooled odds ratios (ORs)

ranged between 1.37 and 1.71 for antipsychotics, between

1.31 and 1.54 for sedatives and hypnotics and between 1.59

and 1.72 for antidepressants. It should be noted that these

studies present the drugs by classes, whereas the specific

drugs within these classes may have different chemical

properties and may thus have different effects on the risk of

falling.

Literature on the contribution of specific psychotropic

drugs to fall frequency in older people is inconsistent. Only

a few studies have investigated the fall risk of specific

drugs. Two studies showed that the use of the sedative drug

zolpidem is associated with an increased risk of falling,

with an OR of between 2.51 and 4.37 [13, 14], which are

both higher than the pooled estimates for the whole drug

class of sedatives. An increased fall risk for individual

drugs has been found for haloperidol (OR 6.09) [15]. Some

studies did not show an increased risk of falling for the

atypical antipsychotic drugs quetiapine and risperidone

[16], and no significant fall risk was found for temazepam

[17]. Given the lack of evidence of fall risks for specific

drugs, treatment guidelines often report only those risks

associated with the classes of psychotropic drugs and not

possible differences between the drugs within these classes.

Insight into the differences between specific drugs could

raise awareness among physicians and contribute to

decisions regarding the prescription of certain drugs.

Moreover, we expect our exploratory analyses could lead

to more focused follow-up studies with clear hypotheses to

be tested. Therefore, this study examines the association

between specific psychotropic drugs and fall incidents in

nursing home residents.

2 Methods

2.1 Study Design

This was a retrospective cohort study. The cohort was

identified using electronic pharmacy records from May

2012 until March 2015 and included somatic (n = 467)

and psychogeriatric (n = 948) residents and former resi-

dents of long-stay wards in 22 nursing homes in the eastern

part of the Netherlands. Short-stay residents (\60 days) and physical rehabilitation residents were excluded from

this study.

2.2 Data Collection

Medication records collected from the electronic pre-

scription system included all prescribed drugs, their names

and the start and stop dates as well as the sex and date of

birth of each resident. Drugs prescribed on a pro re nata

basis were excluded from analyses.

Electronic patient records provided patient admission

and, if applicable, discharge dates. The incident report

system provided records of all falls and other types of

incidents. We did not use this system to retrieve informa-

tion on the fall incidents, the patient’s medical condition or

the drug prescribed, because data are entered into this

system as free text and were neither coded nor consistent.

2.3 Data Analysis

All collected data were anonymised by removing names

and birthdates. All prescribed drugs were classified

according to the anatomical therapeutic chemical (ATC)

classification system [33]. Residents’ prescriptions for

identical drugs, and with adjacent stop and start dates, were

combined into one prescription period.

A Cox proportional hazards model was used to inves-

tigate the magnitude of the association between the use of

psychotropic drugs and the risk of falling during the first

60 days after the prescription start date [34]. Outcomes

were calculated with a 95% confidence interval (CI). Crude

hazard ratios (HRs) and adjusted hazard ratios (aHR) were

calculated, with the age, sex, type of department (somatic

or psychogeriatric), polypharmacy, and the use of other

psychotropic drugs as covariates. The use of drugs from

322 S. I. M. Janus et al.

ATC classes N05A (antipsychotics), N05B (anxiolytics),

N05C (hypnotics and sedatives), N06A (antidepressants)

and N06D (anti-dementia drugs) were entered as separate

covariates. The time to fall (60-day period) was compared

between users and non-users of a specific drug or drug

class. Users were entered into the survival analysis on the

prescription start date. Non-users were entered into the

reference group using a random date from their admission

period. Additionally, possible differences in the effects of

psychotropic drugs on fall incidents were also analysed for

residents receiving psychogeriatric care and residents

receiving somatic care by analysing the two groups sepa-

rately. The model was adjusted for age, sex, polypharmacy,

and the use of other psychotropic drugs as covariates.

All data were processed and analysed with Microsoft �

Excel 2010, MySQL Workbench 6.2 and IBM SPSS

Statistics 21.0.

3 Results

A total of 1415 residents were included, with a combined

number of 698,567 patient-days and 3879 fall incidents.

Within this cohort, 795 residents (56.2%) experienced at

least one fall during residence at the nursing home. This

equated to 9.2 falls per 1000 patient-days for this subgroup

and 5.6 falls per 1000 patient-days for the whole cohort.

Table 1 presents the characteristics of the residents and the

number of prescribed psychotropic drugs and fall incidents.

With an average use of 7.9 (±3.7) drugs, polypharmacy

was highly prevalent among the cohort of 1415 residents.

Antipsychotic drugs were prescribed to 42% of all residents

at some point in the study period, and almost half of the

residents (47%) received at least one prescription for a

sedative or hypnotic drug. The most commonly prescribed

psychotropic drugs were temazepam (29%), oxazepam

(20%) and haloperidol (19%). On average, antidepressant

drugs were used for 361 days (standard deviation [SD]

298), which was longer than any other psychotropic drug.

The shortest intake duration was found for hypnotics and

sedatives (average 175 days [SD 228]). Table 2 shows the

magnitude of the association between the use of psy-

chotropic drugs and fall incidents as analysed by the Cox

proportional hazards model.

Looking at the five ATC classes of psychotropic drugs,

an association was seen between fall incidents and the use

of antipsychotics (aHR 1.49; 95% CI 1.12–2.00), hypnotics

and sedatives (aHR 1.51; 95% CI 1.13–2.02), antidepres-

sants (aHR 1.40; 95% CI 1.02–1.85) and anxiolytics (aHR

1.39; 95% CI 1.04–1.86). No association was found for

anti-dementia drugs (aHR 1.32; 95% CI 0.85–2.05).

Typical (aHR 1.40; 95% CI 1.05–1.86) and atypical

antipsychotics (aHR 1.73; 95% CI 1.27–2.36) were both

associated with fall incidents. However, differences were

observed between drugs within these categories. The two

most used typical antipsychotics were haloperidol and

pipamperone; while haloperidol had an aHR of 1.54 (95%

CI 1.13–2.10), no clear association between the use of

pipamperone and fall incidents was found (aHR 1.38; 95%

CI 0.91–2.10). Similar differences within drug categories

were also visible for the two most used atypical antipsy-

chotics, quetiapine (aHR 1.99; 95% CI 1.39–2.85) and

risperidone (aHR 1.31; 95% CI 0.81–2.12). Within hyp-

notics and sedatives, an increased risk of falling was found

for temazepam, zopiclone, zolpidem and melatonin but not

for midazolam: the number of falls (n = 7) in midazolam

users (n = 158) was lower than that for users of other

drugs from this group.

As shown in Table 1, the incidence of falls for residents

in psychogeriatric wards was higher than for those in

somatic wards: 25 versus 5%, respectively, fell more than

four times during their admission. We performed additional

analyses to investigate a possible difference in the magni-

tude of the risk of falling and the use of psychotropic drugs

in somatic and psychogeriatric residents; the results are

shown in Table 3.

Table 3 shows a correlation between the use of

antipsychotics (both typical and atypical) and hypnotics

and sedatives and fall incidents in psychogeriatric resi-

dents. No clear association between the use of any type of

psychotropic drugs and fall incidents was found for somatic

care residents.

4 Discussion

This study reports on the association between falls and

several specific psychotropic drugs and psychotropic drug

classes that are commonly prescribed for nursing home

residents. The risk of falling appeared to increase with the

use of both typical and atypical antipsychotics, hypnotics

and sedatives, antidepressants and anxiolytics, with aHRs

varying between 1.39 and 1.73. A link to falls was found

with the use of the following specific drugs: zolpidem

(aHR 2.35), melatonin (aHR 1.97), quetiapine (aHR 1.99),

temazepam (aHR 1.96), zopiclone (aHR 1.81) and

haloperidol (aHR 1.54). Other specific drugs, such as

pipamperone, risperidone, midazolam, amitriptyline and

citalopram did not show a clear association with falls. Anti-

dementia drugs as a group also did not show any associa-

tion with falls. The increased risks were especially

observed in residents receiving psychogeriatric care, and

falling is also much more prevalent among this group of

residents than among somatic residents.

For the drug classes and three specific drugs (haloperi-

dol, temazepam and zolpidem) that have been investigated

Drug-Related Fall Incidents in the Elderly 323

previously, the results of this study are mostly in line with

other research. We confirmed an increased risk of falling

for residents who received antipsychotics [12]. The most

recent meta-analysis [12] found increased risks for both the

hypnotic and sedative and the antidepressant drug classes,

which we also observed.

In contrast with other studies [17], we found temaze-

pam, the most commonly used hypnotic, to be associated

Table 1 Characteristics of 1415 residents, their falling incidents and their drug prescription data from a total of 1912.6 patient years, observed between May 2012 and March 2015

Characteristics Total (N = 1415) Psychogeriatric residents

(n = 948 [67%])

Somatic residents

(n = 467 [33%])

Age a

83.5 (± 8.8)

Sex

Female 1000 (71) 687 (72) 313 (67)

Male 415 (29) 261 (28) 154 (33)

Number of drugs used simultaneously 7.9 (3.7) 7.2 (3.4) 9.1 (3.8)

Number of residents who received psychotropic drugs at least once in the study period

Antipsychotics 594 (42) 480 (51) 114 (25)

Typical antipsychotics 409 (29) 339 (36) 70 (15)

Haloperidol 276 (20) 216 (23) 60 (13)

Pipamperone 131 (9) 124 (13) 7 (2)

Atypical antipsychotics 281 (20) 221 (23) 60 (13)

Quetiapine 141 (10) 114 (12) 27 (6)

Risperidone 93 (7) 79 (8) 14 (3)

Anxiolytics 438 (31) 330 (35) 108 (23)

Oxazepam 281 (20) 223 (24) 58 (13)

Lorazepam 150 (11) 117 (12) 33 (7)

Hypnotics and sedatives 664 (47) 443 (47) 221 (47)

Temazepam 416 (29) 262 (28) 154 (33)

Midazolam 158 (11) 116 (12) 42 (9)

Zopiclone 121 (9) 90 (10) 31 (7)

Zolpidem 94 (7) 70 (7) 24 (5)

Melatonin 102 (7) 76 (8) 26 (6)

Antidepressants 502 (36) 339 (36) 163 (35)

Amitriptyline 108 (8) 68 (7) 40 (9)

Citalopram 177 (13) 135 (14) 42 (9)

Anti-dementia drugs 110 (8) 97 (10) 13 (3)

Average number of days used

Antipsychotics 227 ± 255 230 ± 256 211 ± 247

Anxiolytics 216 ± 259 217 ± 258 206 ± 270

Hypnotics and sedatives 175 ± 228 174 ± 227 183 ± 231

Antidepressants 361 ± 298 371 ± 297 303 ± 295

Anti-dementia drugs 340 ± 286 346 ± 286 225 ± 224

Fall characteristics

No falls 618 (44) 314 (33) 304 (66)

One fall 255 (18) 187 (20) 68 (15)

Two falls 131 (9) 98 (10) 33 (7)

Three falls 83 (6) 68 (7) 15 (3)

Four falls 65 (5) 44 (5) 21 (5)

More than four falls 259 (18) 236 (25) 23 (5)

Falls/1000 patient-days 5.6 6.7 2.7

Data are presented as mean ± SD or N (%) a Average age is calculated using the study inclusion date for those using antipsychotics

324 S. I. M. Janus et al.

with an increased risk of falling. These different results

might be because other research was conducted in different

health contexts, such as in hospital patients or community-

dwelling subjects, whereas our study was conducted solely

in nursing home residents. Additionally, an adjusted OR of

4.37 (95% CI 3.34–5.76) was previously reported for

zolpidem [14], which suggests a strong association

between this drug and subsequent falling incidents; we

found an increased risk (HR 2.35). Costa-Dias et al. [15]

found an association between haloperidol and falls, with a

reported OR of 6.09; we also found an increased risk, albeit

smaller (aHR 1.54), for haloperidol. The difference might

be due to adjusting for other drugs in variables in the

current study and including nursing home residents instead

of hospitalized patients. Furthermore, we calculated HRs

instead of ORs, which might contribute to these quantita-

tive differences. The advantage of HRs is that they repre-

sent an instantaneous risk rather than a cumulative risk and,

as such, do not depend on the time period investigated.

When interpreting the results, one must consider that, in

some instances, the association between a drug and falling

could be due to a baseline difference in the risk of falling

between users and non-users of the drug rather than the

effect of the drug itself. For example, haloperidol is the

most widely used neuroleptic for the treatment of acute

delirium [18], and delirium itself is associated with a

higher rate of falls. Data on the medical condition of res-

idents in this study were unavailable, so we cannot com-

pletely rule out confounding by indication. Studies that did

take this into account found an increased unadjusted risk

for psychotropic drugs [19, 20] that declined after adjusting

for comorbidities and health status. According to the

STOPP criteria [9], quetiapine is an antipsychotic that can

be prescribed for patients with parkinsonism since it is

regarded as having fewer negative effects on motor control

[21]. Therefore, the results for quetiapine might be con-

founded because physicians may prescribe it for residents

who are already prone to falling. The relatively high aHR

Table 2 Magnitude of the association between commonly prescribed psychotropic drugs, or drug classes, and falls among nursing home residents

ATC code a

Number of users (falls) b

Reference group (falls) b

HR (95% CI) aHR c (95% CI)

Antipsychotics N05A 594 (110) 821 (89) 1.79 (1.35–2.37) 1.49 (1.12–2.00)

Typical antipsychotics 412 (82) 1003 (126) 1.68 (1.27–2.22) 1.40 (1.05–1.8 6)

Haloperidol N05AD01 275 (57) 1140 (153) 1.64 (1.21–2.22) 1.54 (1.13–2.10)

Pipamperone N05AD05 131 (27) 1284 (184) 1.51 (1.01–2.26) 1.38 (0.91–2.10)

Atypical antipsychotics 281 (60) 1134 (141) 1.82 (1.35–2.46) 1.73 (1.27–2.36)

Quetiapine N05AH04 141 (39) 1274 (167) 2.35 (1.66–3.33) 1.99 (1.39–2.85)

Risperidone N05AX08 93 (19) 1322 (185) 1.49 (0.93–2.39) 1.31 (0.81–2.12)

Anxiolytics N05B 438 (85) 977 (121) 1.64 (1.24–2.17) 1.39 (1.04–1.86)

Oxazepam N05BA04 282 (55) 1133 (153) 1.49 (1.10–2.04) 1.41 (1.03–1.92)

Lorazepam N05BA06 150 (39) 1265 (178) 2.02 (1.43–2.87) 1.53 (1.07–2.20)

Hypnotics and sedatives N05C 664 (111) 751 (82) 1.59 (1.20–2.12) 1.51 (1.13–2.02)

Temazepam N05CD07 416 (90) 999 (127) 1.86 (1.42–2.43) 1.96 (1.49–2.58)

Midazolam N05CD08 158 (7) 1257 (183) 1.47 (0.68–3.16) 1.08 (0.49–2.36)

Zopiclone N05CF01 121 (33) 1294 (181) 2.21 (1.54–3.19) 1.81 (1.24–2.64)

Zolpidem N05CF02 94 (32) 1321 (186) 2.79 (1.92–4.07) 2.35 (1.61–3.44)

Melatonin N05CH01 102 (31) 1313 (184) 2.45 (1.68–3.59) 1.97 (1.33–2.90)

Antidepressants N06A 502 (89) 913 (126) 1.33 (1.01–1.74) 1.40 (1.06–1.85)

Amitriptyline N06AA09 108 (20) 1307 (188) 1.35 (0.85–2.13) 1.49 (0.93–2.38)

Citalopram N06AB04 177 (37) 1238 (182) 1.47 (1.04–2.10) 1.29 (0.89–1.85)

Anti-dementia drugs N06D 110 (23) 1305 (190) 1.42 (0.92–2.18) 1.32 (0.85–2.05)

Analyses based on a Cox proportional hazards model. Reference group: residents who have never used the investigated drug or drug class during

the study period (May 2012–March 2015); the size of each reference group is 1415—number of users

aHR adjusted hazard ratio, ATC anatomical therapeutic chemical, CI confidence interval, HR hazard ratio a See the main text for the class indicated by each ATC code

b Number of residents who fell within 60 days of their inclusion date

c Adjusted for age, sex, polypharmacy, type of care and the use of other drugs from ATC classes N05A, N05B, N05C, N06A or N06D

Drug-Related Fall Incidents in the Elderly 325

(1.99) could be influenced by the patient group rather than

by the medicine. Depression is also known to increase the

risk of falls [22], and antidepressants have the potential to

impair gait, balance, and blood pressure regulation. How-

ever, the association between antidepressants and falls is

unclear [7]. The most commonly prescribed antidepressant

class in frail older adults is selective serotonin reuptake

inhibitors (SSRIs) because they lack the side effects of

traditional tricyclic antidepressants; however, this and

other studies [22, 23] have found SSRIs to be associated

with an increased risk of falling. Although a recent meta-

analysis found that many observational studies indicated an

association between SSRI use and falls, it also found that

the evidence for SSRIs causing impairments in postural

control in experimental studies such as RCTs was incon-

clusive [24, 25]. The STOPP criteria [9] recommend

amitriptyline not be used as an antidepressant because it is

associated with fall incidents. Therefore, the reason we did

not find an association between fall risk and the use of

amitriptylinemight be that it is prescribed in lower dosages

for neuropathic pain and not as an antidepressant. We

expect that confounding by indication also holds for the

risk associated with melatonin. Physicians might be

inclined to prescribe melatonin instead of hypnotic drugs

such as temazepam to patients with an increased baseline

fall risk, since melatonin is considered to have fewer side

effects. However, it has been associated with an increased

risk of fractures [26].

As expected, given the pharmacological properties, we

did not find an increased risk of falls with anti-dementia

drugs. These drugs are prescribed to prevent cognitive

decline, for aggression in moderate to severe Alzheimer’s

disease (memantine) and for psychosis in Lewy Body

dementia (cholinesterase inhibitors) [27]. The latter group

has an increased baseline risk of falls [28]. Evidently, the

potential risk of bias due to confounding by indication is

not large enough to lead to a positive association with falls.

Research indicates that differences exist within this drug

class [29]; however, we chose not to split the anti-dementia

drug group further because it was already small, and sep-

arate groups would have been too small for a regression

analysis.

Also relevant is that we did not account for dosage in

this study. However, other research suggests that the risk of

falls rises as the dose of antipsychotics, anxiolytics, hyp-

notics or sedatives, and antidepressants increases and with

the combined use of these drugs [30]. In our analysis, we

adjusted for polypharmacy but did not adjust specifically

for other drugs associated with an increased risk of falling.

Additionally, the records of the fall incidents were

dependent on nurses reporting the falls. Studies have

indicated that falls that did not result in injuries were more

often unreported than those that did [31]. This probably

does not affect the relative risks of falling but might result

in less accurate associations and larger confidence inter-

vals. This type of information bias is likely to be non-

differential (i.e. the underestimation of falls is equal for

users and nonusers of all drug classes), so this would not

influence the HRs we found. Our data only included

nursing home residents living in the eastern part of the

Table 3 Association between the use of psychotropic drugs and falls among somatic and psychogeriatric nursing home residents

ATC code Somatic residents Psychogeriatric residents

Number of users

(falls) a

Reference group

(falls) a

aHR b (95% CI) Number of users

(falls) a

Reference group

(falls) a

aHR b (95% CI)

Antipsychotics N05A 114 (11) 353 (27) 1.20 (0.59–2.46) 480 (99) 468 (62) 1.54 (1.11–2.13)

Typical

antipsychotics

71 (5) 396 (31) 0.79 (0.31–2.06) 341 (78) 607 (95) 1.49 (1.10–2.02)

Atypical

antipsychotics

60 (7) 407 (32) 1.65 (0.72–3.78) 221 (53) 727 (109) 1.73 (1.24–2.42)

Anxiolytics N05B 108 (13) 359 (26) 1.67 (0.83–3.36) 330 (72) 618 (95) 1.33 (0.97–1.83)

Hypnotics and

sedatives

N05C 221 (19) 246 (16) 1.40 (0.71–2.80) 443 (92) 505 (66) 1.60 (1.16–2.21)

Antidepressants N06A 163 (19) 304 (27) 1.51 (0.81–2.80) 339 (70) 609 (99) 1.40 (0.99–1.98)

Anti-Dementia

drugs

N06D 13 (2) 454 (40) 2.2 (0.51–9.73) 97 (21) 851 (150) 1.25 (0.79–2.00)

Analyses based on Cox proportional hazards model. Reference group: residents who have never used the investigated drug or drug class during

the study period (May 2012–March 2015) a Number of residents who fell who within 60 days after their analysis inclusion date

b Adjusted for age, sex, polypharmacy, type of care and the use of other drugs from ATC classes N05A, N05B, N05C, N06A or N06D (see the

main text for the class indicated by each ATC code)

326 S. I. M. Janus et al.

Netherlands. Patient characteristics and the numbers

receiving psychotropic drugs were comparable to other

studies from the Netherlands [32]. Therefore, we believe

our results are representative for the Netherlands.

While our results are in line with those of others in terms

of the different drug classes, we cannot know whether the

drug classes studied in the literature comprise the same

drugs we studied. For example, while temazepam and

midazolam were the most frequently prescribed drugs, they

might not have been used as often in other studies per-

formed at another time or in another country [33, 34]. The

personal or guideline-based treatment preferences of

physicians may change over time, and new drugs may

become available on the market [35, 36]. Given the dif-

ferential prescription rates of individual drugs, a fair

comparison between the studies was difficult. This

demonstrates the flaws inherent in studying whole drug

classes and highlights the necessity of focusing on indi-

vidual drugs. In this retrospective study, we were only able

to adjust for a limited set of covariates (age, sex,

polypharmacy, and the use of other psychotropic drugs).

We were unable to adjust for comorbidity, functioning and

mobility or rule out indication or prescription bias.

This study also has strengths that must be highlighted.

The Cox model accounted for the type of care residents

received (psychogeriatric or somatic) and the other possi-

ble confounders, such as age, sex, polypharmacy and the

use of other psychotropic drugs. Furthermore, two of the

three meta-analyses included studies from different health

contexts, such as hospitals and nursing homes. The

heterogeneity of these groups might have influenced results

and increased variation. However, our results come from a

more homogenous group [37]. Whereas somatic residents

are usually characterized by serious physiological chronic

disorders, psychogeriatric residents are characterized by

serious mental or psychiatric disorders such as dementia.

Consequently, comorbidities and functional status differ

between these groups, and higher fall rates among psycho-

geriatric patients can also be attributed to the frequency of

cognitive problems, behavioral problems and additional

morbidity within this group. Therefore, we analyzed the

two groups separately and expect less confounding.

Furthermore, this study included data for 1415 residents,

with a combined 698,567 patient-days. The large amount

of available data enabled us to analyze not only drug

classes, such as antipsychotics, but also subclasses, such as

typical and atypical antipsychotics and the most commonly

used individual drugs.

Our study adds to the evidence regarding associations

between psychotropic drugs and falls. Several drugs, such as

haloperidol, quetiapine, temazepam, zolpidem and mela-

tonin, seem to increase the risk of falls. However, these

exploratory results should be further tested in a prospective

study focussing on each of these individual drugs while also

considering that fall incidents are multifactorial. Therefore,

further study should also account for all potential con-

founders such as medical conditions (comorbidities,

dementia severity, neuropsychiatric symptoms), mobility,

additional medications (e.g. to determine the Drug Burden

Index [38]) and indications for specific drugs.

Other commonly used antipsychotics, pipamperone and

risperidone, were not associated with falls and therefore

seem to be safe or at least prescribed safely. When we

analysed the data for somatic and psychogeriatric residents

separately, we found no clear association between psy-

chotropic drugs and falls in somatic residents. These results

suggest that assessing the risk of psychotropic drugs by

looking at the drug class alone is unjustified because the fall

risk may depend not only on the drug and dosage but also on

the severity of the disease (which influences overall risk of

fall). Further research focusing on the effects of the indi-

vidual drugs is needed to provide physicians with more data

that are applicable in practice. Current fall-prevention pro-

grammes consider entire drug classes to be a risk factor, but

our results suggest this needs to be reviewed. Additionally,

future studies should look at particular combinations of

psychotropic drugs associated with falls given that nursing

home residents often use several psychotropic drugs at once.

Compliance with Ethical Standards

Conflict of interest Sarah Janus, Gezinus Reinders, Jeannette van Manen, Sytse Zuidema, and Maarten IJzerman have no conflicts of

interest that may be directly relevant to the content of this article.

Funding No sources of funding were used to conduct this study or prepare this manuscript.

Open Access This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International

License (http://creativecommons.org/licenses/by-nc/4.0/), which per-

mits any noncommercial use, distribution, and reproduction in any

medium, provided you give appropriate credit to the original

author(s) and the source, provide a link to the Creative Commons

license, and indicate if changes were made.

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