GHENT UNIVERSITY
FACULTY OF PHARMACEUTICAL SCIENCES
ACADEMIC YEAR 2016 - 2017
DEPRESCRIBING OF PSYCHOTROPIC DRUGS IN PATIENTS ADMITTED TO ORTHOGERIATRIC AND GERIATRIC WARDS
Saïn VANDEPOELE
INTERUNIVERSITY PROGRAMME: MASTER OF SCIENCE IN HOSPITAL PHARMACY
SUPERVISOR
KATY VERHELLE, PharmD
ANNE VERHAEGHE, PharmD
ACADEMIC PROMOTER
PROF. ANNEMIE SOMERS, PharmD, PhD
GHENT UNIVERSITY
FACULTY OF PHARMACEUTICAL SCIENCES
ACADEMIC YEAR 2016 - 2017
DEPRESCRIBING OF PSYCHOTROPIC DRUGS IN PATIENTS ADMITTED TO ORTHOGERIATRIC AND GERIATRIC WARDS
Saïn VANDEPOELE
INTERUNIVERSITY PROGRAMME: MASTER OF SCIENCE IN HOSPITAL PHARMACY
SUPERVISOR
KATY VERHELLE, PharmD
ANNE VERHAEGHE, PharmD
ACADEMIC PROMOTER
PROF. ANNEMIE SOMERS, PharmD, PhD
I
WORDS OF THANKS
_______________________________________________________________________________________
Without the support and contribution of many people, this work would not have become what it is
today. Therefore I would like to take the opportunity to thank some people for their help and
inspiration.
First of all, I am very grateful to Katy, head of pharmacy, and the rest of the hospital pharmacy team
for the fascinating internship in the ‘Groeninge’ hospital in which I got excellent guidance and was
offered exciting opportunities.
In particular, I would like to thank my internal supervisor Anne for her enthusiastic guidance in which
she taught a lot of clinical pharmacy knowledge.
I also want to thank Annemie Somers for the follow-up of my research and the detailed and extensive
readings of my study despite her many other work.
I would like to thank my closest colleague Eva who accompanied me during the whole internship, for
sharing the moments of happiness and frustration, for her support and help.
A special word of thanks to Tom who always believed in me, who helped me with reasoning questions
or layout issues and who gave me advice when I was stuck.
Thanks to my parents and sisters for giving me the opportunity to graduate as a hospital pharmacist
and to support this choice in all areas.
II
III
COPYRIGHT _______________________________________________________________________________________
"The author and the promoters give the authorization to consult and to copy parts of this thesis for
personal use only. Any other use is limited by the laws of copyright, especially concerning the obligation
to refer to the source whenever results from this thesis are cited."
May 31, 2017
Supervisor
Anne Verhaeghe, PharmD
Academic promoter
Prof. Annemie Somers, PharmD, PhD
Author
Saïn Vandepoele
IV
V
SUMMARY _______________________________________________________________________________________
Elderly have a great potential to benefit from their medication, but are also more vulnerable to
adverse drug reactions. Especially the use of psychotropic medications can increase the risk on
confusion, falls and cognitive impairment. Age related changing pharmacokinetics, polypharmacy and
presence of multiple comorbidities, noncompliance and reduced capabilities for safe and appropriate
handling of drugs are risk factors for drug related problems with adverse outcomes.
Deprescribing may be one way to reduce the number of medicines, to improve appropriate
prescriptions and to avoid adverse drug reactions. Deprescribing is the act of tapering, reducing or
stopping medication supervised by a health care professional with the goal to improve outcomes. In
this study, one of the main objectives was to determine the prevalence of potentially inappropriate
prescriptions in a geriatric population. In addition, the acceptation rates of the recommendations,
suggested by the pharmacist, were determined and the added value of multidisciplinary communication
with healthcare providers was investigated.
Patients, aged over 75 with a minimum intake of 5 drugs, were screened at the geriatric and
orthogeriatric ward of the ‘Groeninge’ Hospital in Kortrijk for inclusion in this deprescribing study.
Different tools are available to support health professionals for deprescribing, including implicit and
explicit tools. In this research inappropriate prescriptions were identified by using chapter ‘D’ of the
STOPP criteria. In addition, standardized tapering schemes were introduced and applied in practice.
These schemes could be adapted according to the needs of the patient. Patients, eligible for a
withdrawal scheme, were approached by the clinical pharmacist in training. They were informed about
the potential risks and long-term side effects. Afterwards their willingness to reduce psychotropic drugs
was questioned. Also geriatricians and general practitioners were involved. Their shared-decision
determined if a recommendation could be implemented for a patient. Deprescribing is a process that
needs a close follow-up and careful data collection. In this study, a follow-up call after discharge was
conducted by the clinical pharmacist to detect problems with withdrawal schemes.
In this study, 398 of the 470 screened patients were included. At least one intervention was
suggested by the clinical pharmacist in 89.7% of the included patients. The overall acceptation rate of
the geriatricians was 80.4%. After counseling by the pharmacist, still 20.9% patients were unwilling to
discontinue their psychotropic drugs. Deprescribing was refused because of fear for return of their
disease or fear for withdrawal effects. In this study, 145 general practitioners and 104 community
pharmacists were contacted to give their approval on the tapering schedule and follow-up.
After discharge, 59 patients were called by the pharmacist to detect possible problems with
withdrawal schedules. These schedules were interrupted by 31.1% of this patients. Lack of motivation
of the patient and insufficient follow-up by the first line caregivers were the main reasons for
discontinuation.
There is growing evidence that indicates that deprescribing for older people is safe and feasible.
Deprescribing can improve optimal and appropriate medication use for elderly patients. However, a
frequent medication review should be conducted in the older patient to detect inappropriate prescriptions
and to maintain the motivation of the patients. In addition, multidisciplinary cooperation between all
healthcare providers is necessary for seamless pharmaceutical care and a proper follow-up after
discharge.
VI
VII
SAMENVATTING _______________________________________________________________________________________
Ouderen hebben een groot potentieel om positieve effecten van hun medicijnen te ervaren,
maar zijn ook kwetsbaarder voor bijwerkingen. Vooral het gebruik van psychofarmaca kan het risico op
verwardheid, valincidenten en cognitieve achteruitgang verhogen. Risicofactoren voor deze slechte
gevolgen zijn onder andere leeftijdsgerelateerde veranderingen in de farmacokinetiek, polyfarmacie, de
aanwezigheid van comorbiditeiten, therapieontrouw en verminderde vaardigheden om medicatie correct
in te nemen.
Deprescribing kan het aantal geneesmiddelen doen dalen, het geschikt voorschrijven
verbeteren en bijwerkingen voorkomen. Deprescribing is een proces van afbouwen, verminderen of
stoppen van geneesmiddelen onder toezicht van een zorgverlener met als doel de eindpunten te
verbeteren. In deze studie was een van de hoofddoelstellingen om de prevalentie van potentieel
ongeschikt voorschrijven in een geriatrische populatie te bepalen. Daarnaast werd het
aanvaardingspercentage van de aanbevelingen, voorgesteld door de apotheker, nagegaan en werd de
meerwaarde van de transmurale communicatie met zorgverleners onderzocht.
Patiënten ouder dan 75 jaar die minstens 5 geneesmiddelen innamen werden gescreend op
geriatrie en orthogeriatrie in AZ Groeninge in Kortrijk voor inclusie in deze afbouwstudie. Verschillende
‘deprescribing’ hulpmiddelen zijn beschikbaar om gezondheidsverstrekkers te helpen, inclusief
impliciete en expliciete hulpmiddelen. In dit onderzoek werden ongeschikte voorschriften geïdentificeerd
aan de hand van hoofdstuk D van de STOPP criteria. Daarnaast werden standaard afbouwschema's
toegepast in de praktijk. Deze schema's kunnen aangepast worden naargelang de noden van de patiënt.
Patiënten die in aanmerking komen voor een afbouwschema werden benaderd door de klinisch
apotheker in opleiding. Ze werden geïnformeerd over de potentiële risico's en langdurige bijwerkingen
en hun bereidheid tot afbouw van psychofarmaca werd bevraagd. Ook de geriaters en huisartsen waren
betrokken en hun gezamenlijke beslissing bepaalde of het advies van de apotheker werd opgevolgd.
Deprescribing is een proces dat een nauwgezette follow-up en gegevensverzameling vereist. In deze
masterproef werd de patiënt opgebeld na ontslag door de klinisch apotheker om mogelijke problemen
rond afbouwschema’s op te sporen.
In totaal werden 398 van de 470 gescreende patiënten in deze studie geïncludeerd. Bij 89,7%
van de geïncludeerde patiënten werd minstens één interventie voorgesteld door de klinisch apotheker.
Hiervan werden 80,4% adviezen aanvaard door de geriaters. Toch waren 20,9% van de patiënten niet
bereid om hun psychofarmaca af te bouwen na advies door de apotheker. Afbouw werd geweigerd uit
angst voor het terugkeren van de aandoening of uit angst voor ontwenningsverschijnselen. In deze
studie werden 145 huisartsen en 104 officina- apothekers gecontacteerd met de vraag of ze akkoord
gingen met het afbouwschema en of ze wilden instaan voor verdere opvolging.
Na ontslag werden 59 patiënten gecontacteerd door de klinisch apotheker om problemen met
afbouwschema’s op te sporen. De afbouwschema's werden onderbroken bij 31,1% van de patiënten.
Gebrek aan motivatie van de patiënt en onvoldoende follow-up door zorgverstrekkers uit 1e lijn waren
redenen voor stopzetting.
Er is steeds meer evidentie dat ‘deprescribing’ in de oudere populatie veilig en haalbaar is.
‘Deprescribing’ kan het optimaal en geschikt geneesmiddelengebruik verbeteren. Toch is een nazicht
van het medicatieschema op regelmatige basis nodig om ongeschikt voorschrijven te detecteren en de
motivatie van de patiënten te behouden. Daarnaast is multidisciplinaire samenwerking tussen alle
VIII
zorgverleners noodzakelijk voor een duidelijke overdracht van informatie en een goede follow-up na
ontslag.
IX
ABBREVIATIONS
_______________________________________________________________________________________
ACE Angiotensin Converting Enzyme
ADME Absorption Distribution Metabolisation Excretion
ADR Adverse Drug Reaction
ACB Anticholinergic Cognitive Burden
ARS Anticholinergic Risk Scale
ATC Anatomical Therapeutic Chemical Classification System
BCFI Belgisch Centrum voor Farmacotherapeutische Informatie
BDZ Benzodiazepine
CHF Congestive Heart Failure
COPD Chronic Obstructive Pulmonary Disease
CP Community Pharmacist
DDD Defined Daily Dose
DRP Drug Related Problem
EHR Electronic Health Record
EMR Electronic Medical Record
EPR Electronic Patient Record
Etc. Et Cetera
FOD Federale OverheidsDienst (in Belgium)
FPS Federal Public Service
GFR Glomerular Filtration Rate
GP General Practitioner
HARM Hospital Admissions Related to Medication
i.e. id est
INCB International Narcotics Control Board
LOS Length Of Stay
MAI Medication Appropriateness Index
MMSE Mini Mental State Examination
X
NHG Nederlandse HuisartsenGenootschap
NIHDI National Institute for Health and Disability Insurance
PIP Potentially Inappropriate Prescribing
PPI Proton Pomp Inhibitor
RCT Randomized Controlled Trial
SD Standard Deviation
START Screening Tool to Alert doctors to the Right Treatment
STOPP Screening Tool of Older Person’s Prescriptions
SIMPATHY Stimulating Innovation Management of Polypharmacy and Adherence in the Elderly
SPC Summary of Product Characteristics
SSRI Serotonin Receptor Antagonist
STRIP Systematic Tool to Reduce Inappropriate Prescribing
TCA Tricyclic Antidepressant
XI
TABLE OF CONTENTS
_______________________________________________________________________________________
1. INTRODUCTION ............................................................................................................................... 1
1.1. Identification of drug related problems (DRP) in the elderly ...................................................... 1
1.2. Deprescribing, a must ? ............................................................................................................... 2
1.3. Medication review ....................................................................................................................... 4
1.3.1. Medication reconciliation ....................................................................................................... 4
1.3.2. Identify potentially inappropriate prescribing (PIP) ................................................................ 4
1.4. A step-wise approach to deprescribing ....................................................................................... 8
1.4.1. Discontinuing medication ........................................................................................................ 8
1.4.2. Monitoring and follow-up ..................................................................................................... 10
1.5. Which drugs to taper? ............................................................................................................... 10
1.6. A clinical pharmacist in geriatrics, an added value? ................................................................. 12
1.7. Barriers to routine deprescribing .............................................................................................. 13
2. OBJECTIVES .................................................................................................................................... 15
3. METHODS ...................................................................................................................................... 17
3.1. General study description ......................................................................................................... 17
3.2. Workflow ................................................................................................................................... 17
3.3. Deprescribing protocol .............................................................................................................. 19
3.3.1. Diazepam equivalents ........................................................................................................... 19
3.3.2. Deprescribing of hypnosedatives ......................................................................................... 21
3.3.3. Deprescribing of antidepressants and antipsychotics........................................................... 22
3.4. Data collection ........................................................................................................................... 23
3.5. Data analysis .............................................................................................................................. 23
4. RESULTS ......................................................................................................................................... 27
4.1. Study group ............................................................................................................................... 27
4.2. Patient characteristics ............................................................................................................... 28
4.3. Drug use at admission ............................................................................................................... 28
4.3.1. Number of drugs ................................................................................................................... 28
4.3.2. Use of (psychotropic) drugs .................................................................................................. 29
4.3.3. Types of drugs ....................................................................................................................... 31
4.3.4. Prevalence of PIPs according to STOPP D ............................................................................. 32
4.4. Drug use at discharge ................................................................................................................ 34
4.4.1. Number of drugs ................................................................................................................... 34
XII
4.4.2. Types of drugs ....................................................................................................................... 34
4.5. Deprescribing ............................................................................................................................ 37
4.6. Follow-up ................................................................................................................................... 38
5. DISCUSSION ................................................................................................................................... 39
5.1. Drug use..................................................................................................................................... 39
5.1.1. Number of drugs ................................................................................................................... 39
5.1.2. Use of (psychotropic) drugs .................................................................................................. 39
5.1.3. Types of drugs ....................................................................................................................... 42
5.1.4. Prevalence of PIPs according to STOPP D ............................................................................. 44
5.2. Deprescribing ............................................................................................................................ 45
5.3. Follow-up ................................................................................................................................... 46
5.4. Strengths and limitations of the project and future perspectives ............................................ 47
6. CONCLUSION ................................................................................................................................. 49
7. REFERENCES .................................................................................................................................. 51
8. APPENDICES ................................................................................................................................... 57
8.1. FARMAKA – REVISED STOPP CRITERIA 2016 ............................................................................. 57
8.2. ANTICHOLINERGIC COGNITIVE BURDEN SCORE........................................................................ 66
8.3. BENZODIAZEPINE AND Z-DRUG DEPRESCRIBING ALGORITHM ................................................. 67
8.4. ETHICS COMMITTEE APROVAL .................................................................................................. 69
8.5. TEMPLATE INFORMED CONSENT .............................................................................................. 71
8.6. POSTER OF THE ‘DEPRESCRIBING PROJECT’ .............................................................................. 72
8.7. PHARMACEUTICAL REPORT ....................................................................................................... 73
8.8. LETTER ....................................................................................................................................... 75
8.9. EQUIVALENCE TABLE OF DIAZEPAM ......................................................................................... 76
8.10. STOPP – CRITERIA REVISED DUTCH VERSION (2015) ............................................................ 77
1 | INTRODUCTION
1. INTRODUCTION _______________________________________________________________________________________
1.1. Identification of drug related problems (DRP) in the elderly
Increasing age is associated with a higher incidence of adverse drug reactions (ADR) and a higher
prevalence of polypharmacy. Elderly are more sensitive to the development of drug related problems
which is based on several contributing factors.
A first factor is the age-related changing pharmacokinetics which comprises four steps i.e. absorption,
distribution, metabolism and excretion (ADME). These changes may have an impact on drug
concentration and therefore on drug activity. Concerning the absorption, the intestinal motility and gastric
emptying can be delayed in older patients (1), in comparison with the younger healthy population (2).
Assuming that elderly take several drugs, effects of coprescribed drugs should be taken into
consideration (1). The absorption of iron decreases in the absence of acidic environment, for example
as a result of PPI-use.
The second step of ADME is distribution. An increased body fat and decreased total body water have a
significant impact on the drug distribution. This changed body composition provides a larger distribution
of fat-soluble drugs (such as benzodiazepines (BDZ)) resulting in a prolonged drug effect and an
increased risk of accumulation. On the other hand, drug concentration of water-soluble drugs (such as
digoxin, theofyllin) increases. (2; 1). A dose reduction may be required when these medicines are
prescribed for elderly. Also the protein binding has an effect on the distribution. However lower protein
levels are usually due to poor nutrition status and chronic illness, rather than increasing age. A clinical
significant change in distribution due to this protein binding is only shown in strongly bound drugs such
as warfarin, phenytoin for which the drug concentration can be increased.
In the third step, the impact of aging on metabolism is mainly on phase 1 reactions or the first pass
metabolism due to decreased hepatic blood flow and reduced liver mass. For example, an increased
bioavailability is seen with drugs such as ACE inhibitors or opioids that are strongly subjected to first-
pass metabolism.
The last step of ADME is excretion. Renal function and mainly the glomerular filtration rate (GFR)
decreases with age. As a result, there is a reduced clearance of drugs that are primarily excreted by the
kidney, such as digoxin, lithium, penicillin (3).
A second contributing factor for drug related problems in elderly patients is the high incidence of
comorbidities and the related high drug use. 84% of the patients older than 65 years have 2 or more
chronic conditions as compared to 35% of the patients between 45 and 65 years. The most common
comorbidities are hypertension, Chronic Obstructive Pulmonary Disease (COPD), diabetes mellitus,
heart failure, electrolyte disorders, and iron deficiency. Each comorbidity is associated with certain
medications which increases the total number of drugs, but also the number of different prescribers (4).
2 | INTRODUCTION
The third factor is the absence of geriatric patients in randomized controlled trials (RCTs) that can
contribute to inappropriate prescribing. Due to this underrepresentation there is lacking evidence about
the efficacy, safety and doses of several drugs. Involving this population in RCTs is challenging since
they are often excluded because of age, concomitant medications and co-morbidities. In addition, the
screening takes a lot of time and the risk of drop-outs is high. The number of RCTs of drugs, that are
taken frequently by older people, can lead to an increase if more incentives are taken (5).
A fourth important factor that affects the elderly is the compliance, which is poor and can be a potential
source of adverse drug reactions and therapeutic failure. Examples of nonadherence in geriatric patients
could be overuse, abuse, forgetting, alteration of schedules and doses after a consultation, change in
care or discharge from the hospital (6; 3). The underlying factors of nonadherence could be a decreasing
mental score and a reduced vision. According to Hughes et al. polypharmacy is the most contributing
factor which is proved by the risk of errors that increased a 15-fold when the number of drugs was raised
from one to four (1).
1.2. Deprescribing, a must ?
Polypharmacy can be defined as the regular consumption of 5 or more drugs. Excessive polypharmacy
is the regular consumption of 10 drugs or more. In a prospective, observational population-based cohort
of Belgian community-dwelling patients, it was found that 57,7% was exposed to polypharmacy and
even 9,1% to excessive polypharmacy (7).
In a study of Wastesson et al., it can be expected that individuals at the age of 65 years spent 8 of the
20 remaining years with polypharmacy. In addition, the question can be asked why patients are given a
therapy in which the time required to experience the positive benefits is longer than the life expectancy
(8). For patients with a low life expectancy a conservative therapy is justified and medication reduction
may be appropriate (9).
Polypharmacy can give rise to adverse drug reactions (ADR), drug-interactions, lower adherence to
drug regimens, a higher risk of falls, cognitive impairment, hospital admissions and a higher healthcare
cost. These effects are described in detail below.
The first effect is that approximately 30% of community-dwelling older patients taking more than five
medications perceived an ADR such as immobility, hypotension, fall accidents, delirium. The risk of an
ADR is 38% when taking four drugs and even 82% when taking 7 drugs or more (10). 25% of the adverse
drug reactions is estimated preventable (11).
A second result of polypharmacy is that 40% of the patients fail to comply with their treatment often due
to misunderstanding, forgetting, incorrectly performing or ignoring the doctor’s recommendation.
Depression, a low level of education, lack of confidence in the treating physician and a poor attitude of
the patient contributes to lower adherence. There is no single strategy to improve the compliance in
every patient. It is the art of the physician and pharmacist to empathize with the situation of the patient
so that the patients adherence can be guided in the right direction (12; 13).
3 | INTRODUCTION
A third observation related to polypharmacy are fall incidents. One third of the community-dwelling
patients older than 65 years fall at least once a year. The incidence for nursing home patients is even
higher and can approach 50%. The most important causes are poor visibility, depression, impaired
cognition, aging and syncope but none of these risk factors is as potentially avoidable as medication
use (14; 15). Leipzig et al. demonstrated a positive correlation between the use of psychotropic and
cardiac drugs and the risk of falling. In patients on psychotropic medication the incidence of fall accidents
within 6 months is 58% (15). Counseling of patients by exercising skills and behavior and monitoring
medications have found to reduce the risk of fall accidents. For example the withdrawal of psychotropic
medications such as benzodiazepines, antidepressants, hypnotics and neuroleptics can decrease the
fall risk in 66% of the cases. However almost half of the intervention group restarted these psychotropic
medications within the month (14).
Another consequence of polypharmacy is associated with a decline in cognitive ability. A cognitive
impairment was found in 22% of the patients taking 5 drugs, in 33% of the patients taking 6 to 9
medications and even 54% of the patients taking 10 or more (13). Drug classes such as
benzodiazepines, opioids and anticholinergics can contribute to the deterioration in cognitive function
(16).
The last discussed effect due to polymedication is the higher risk on hospitalization. These admissions
can be due to drug related problems (DRPs) or called drug related hospitalized admission (DRHA). In a
study of Somers et al., in which the contribution of DRPs to hospital admissions in the elderly is
investigated, a distinction is made between adverse drug reactions (ADRs) and drug therapy failure
(DTFs). An ADR is defined according to WHO as “a response to a drug that is noxious and unintended
and occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for
modification of physiological function”. An example of an ADR due to unintentional Absence of
therapeutic effect due to non-compliance, underdosing or drug-drug interactions is described as drug
therapy failure. In this latter study, 23 of 110 patients (or 20.9%) were admitted due to a drug-related
problem, in which 14 patients due to an ADR and 9 patients due to DTF. In the literature, the link between
DRP and hospitalization is proved by percentages between 4 and 30%. Of these hospitalizations, 50 to
97% was estimated avoidable (17).
As a result of these unnecessary hospitalizations and prescribed inappropriate medications the
healthcare cost increases. For example in Ireland 9 % of the overall expenses on pharmaceuticals in
people older than 70 was related to polypharmacy. In the Netherlands, the cost of hospitalizations due
to ADE was 355 million in 2009. It is obvious that polypharmacy increases burden to health economies.
Therefore appropriate prescribing should be stimulated by using different tools (3).
Efforts should be done to avoid this negative health outcomes associated with polypharmacy.
Deprescribing, the act of tapering, reducing or stopping medications, can be one way to improve the
use of medicines in geriatric patients (18; 19). Stopping of some classes of medications such as
diuretics, antihypertensives and psychotropic medication in older patients has proven to be feasible and
does not worsen clinical outcomes such as withdrawal symptoms (20). Moreover, the 12 month mortality
has improved and the long-term adverse consequences are reduced (11).
4 | INTRODUCTION
It has been suggested to step out of the traditional quantitative-based polypharmacy, in which the
number of drugs being taken into account, but to evolve from inappropriate polypharmacy (inappropriate
prescribing) to qualitative-based polypharmacy (appropriate prescribing) (21).
Several guidelines to help practitioners with drug deprescribing are discussed further.
1.3. Medication review
1.3.1. Medication reconciliation We should be able to rely on an accurate and complete patients medication schedule prior to optimize
medication use. An extensive medication reconciliation should be performed by a clinical pharmacist or
a pharmacist assistant for each older hospitalized patient. The goal of medication reconciliation is to
identify an accurate list of all medications that the patient is taking, including name, dosage, frequency,
and route, by comparing the medical record to an external list of medications obtained from a patient,
hospital, or other provider (22; 10).
In more than half of the elderly admitted to hospital, medication discrepancies are found between the
patient’s usual drug therapy and the therapy known in the hospital (23). It is suggested that bringing the
medication physically to the hospital gives the best result for the reconciliation (‘brown paper bag’
medication reconciliation) (11).
1.3.2. Identify potentially inappropriate prescribing (PIP)
High drug use frequently leads to prescription of inappropriate drugs. Potentially inappropriate
prescribing (PIP) is defined as the use of medicines whose harmful outcomes may outweigh the benefits
and contributes to a higher morbidity and mortality (24).
S. Cullinan et al. reported a PIP incidence of 20 to 40% in primary care (including GPs, community
pharmacists, home care nurses, ..) and 33 to 58% in the 2nd line (i.e. general hospitals). There is an
awareness among doctors about the problematic PIPs, however changing the patients prescription is
feared because of insufficient geriatric knowledge, a lack of time for medication surveillance or due to a
high workload (25).
PIPs can be defined by using an indicator, such as a frailty index (25), the STOPP/START or the Beers
criteria (24). A positive relationship between the frailty status and the appropriateness of the patient’s
medications and the development of ADRs has been shown. By using these indicators health care
providers gain insight into the problematic PIPs and can be motivated to review patients medications.
Also factors as life expectancy, care goals and comorbidities should be taken into consideration (25).
Several tools have been developed to detect inappropriate prescribing. PIP can be classified as
underprescribing, misprescribing and overprescribing. Underprescribing is the omission of an indicated
drug to treat a specific disease. In 22% of community-dwelling older adults and in 58 to 66% of
hospitalized older patients underprescribing, based on the START-criteria, was detected (26). An
unfavorable choice of medicine (for example a contra-indication), dose, or duration is called
misprescribing. Overprescribing is the presence of a drug which is not indicated for a particular treatment
or in the absence of a medical reason. In 21–36% of community-dwelling older adults and in 35–77% of
hospitalized older patients inappropriate prescribing, based on the STOPP-criteria, was identified (26).
5 | INTRODUCTION
The appropriateness of prescriptions can be assessed by computerized digital tools or by a patient
centred approach. The criteria of these patient centered tools can be based on clinical judgment , also
called the implicit criteria or based on standardized guidelines, also known as the explicit criteria (27;
10).
Computer assisted digital tools
Several hospitals already implemented an Electronic Patient Record (EPR) with computerized decision
support. This supportive tools are interaction checkers which can generate alerts for certain drug
combinations. There is sufficient evidence that this tool decreases the number of prescribing errors and
inappropriate prescriptions with a significant effect on the intermediate endpoints. However, limited
information is available on improvements in primary outcomes such as mortality, morbidity, functional
and cognitive status and costs. Besides, these computer programs do not reveal every possible drug
interaction and take no account of the age related illnesses or complications and other patient-related
characteristics (3). Also a lot of inaccurate or unimportant issues are mentioned which leads to
frustration and so called ‘alert fatigue’ (ignoring the alerts without reading them carefully) (28).
Implicit criteria
Implicit criteria focus on all aspects of the patient, including the EPR and the clinical circumstances,
rather than drugs or diseases.
One of the methods is the Medication Appropriateness Index (MAI) where each prescribed drug is
assessed using ten different criteria. Each of the elements including indication, effectiveness,
appropriate dosing, contraindications, side-effects, drug-drug interactions, drug-disease interactions,
correct directions, lack of duplication, duration and cost is accompanied with a certain weight (a number
between 1 and 3). By using the patients antecedents and medication list, a score can be assigned which
is multiplied by the weight of this criterion. The higher the score, the less appropriate the prescribed
drug.
These methods are time consuming, only reliable when the evaluator has substantial clinical knowledge
and are not detecting underuse. Although the sensitivity is high, this tool is not frequently used in various
settings (10; 3).
Explicit criteria
Explicit criteria on the other hand are evidence-based, reliable and require little clinical expertise. These
tools are more regularly used to detect inappropriate prescribing but also have some disadvantages.
The Beers list, the STOPP/START-criteria and the drug burden index are discussed below.
The Beers list is an example of a ‘drugs to avoid’-list and was originally developed in 1991 for use in
nursing home residents. This list has been revised 4 times already in 1997, 2003, 2012 and 2015 and
can be applied for all patients over 65 years now. The last update added two key areas : drug-drug
reactions and drugs in which dosage adjustment is necessary in case of renal insufficiency, but also a
summary of drugs with strong anticholinergic properties is included.
6 | INTRODUCTION
The drugs contained in the list are divided into 3 groups: drugs which must always be avoided, drugs
that must be avoided in certain diseases and drugs that should be used with caution. However, the
application of the Beers list did not reduce the number of hospitalizations, costs, morbidity and mortality
(3). In addition, often a drug is indicated as inappropriate while this is less important compared to other
inappropriate prescribing such as drug-drug interactions, under- or overuse. Also the evidence grade
may be low and the drug related problems may be underestimated since the elderly are
underrepresented in studies.
The list may be attractive because it is easy to use, is not time-consuming and requires little
individualization (29; 30).
The second discussed explicit approach are the STOPP/START (Screening Tool of Older Persons’
Prescriptions/Screening Tool to Alert doctors to Right Treatment) criteria which were developed in 2008
by Gallagher et al. to exceed the limitations of the Beers list. Comparative studies of the STOPP/START
criteria and the Beers list described the STOPP/START criteria as more accurate and more sensitive,
and drugs listed in the STOPP criteria are more strongly associated with adverse events (31; 3). It has
been suggested that screening of the PIP using the STOPP-START criteria should be repeated every
six months or systematically during each consultation since a gradual increase in PIP has been
observed after this period if not re-evaluated (26).
The aimed objectives of the START/STOPP-criteria are to improve medication appropriateness, to
reduce drug costs and to avoid adverse drug reactions (31). The different criteria are classified according
to the physiological system and for each STOPP criteria is argued why the drug is considered unsuitable.
In 2014 the criteria have been updated by expanding the Delphi panel of United Kingdom and Ireland
with experts (i.e. geriatricians, psychiatrists, clinical pharmacologists, hospital pharmacists and primary
care physicians) from 12 other European countries. In total, 80 STOPP and 34 START-criteria were
defined, an increase of 31% compared to the first version.
In 2012 a translation of the STOPP/START criteria, adapted to the Dutch situation, was published to
simplify the application in practice .The translated version excluded medicines which are not registered
in the Netherlands, used Dutch guidelines (such as the ‘Nederlandse Huisartsen Genootschap’ (NHG)
standards) and added or omitted some criteria. The reviewed Dutch version includes 72 STOPP criteria,
8 less compared to the international criteria and 36 START criteria.
Although the excluded medicines from the international guidelines are also in Belgium not available, it
is not possible to simply apply the Dutch guideline in Belgium. For example, some drugs that were listed
in the adapted Dutch guideline, are not on the Belgian market, e.g. calcium carbasalate, oxprenolol,
chlordiazepoxide, chlorpromazine, etc. (28).
Farmaka, a Belgian organization that focuses on evidence-based medicine and responsible drug use,
has also analyzed the STOPP criteria and compared these with the reference ‘Formularium
ouderenzorg’. This reference, prepared by Farmaka, gives guidance to all providers in the prescription
of drugs to elderly patients and was drafted by general practitioners and pharmacists (see Appendix
8.1).
7 | INTRODUCTION
Farmaka has commented on each criterion of the STOPP criteria using the literature, Belgian guidelines
and summaries of product characteristics (SPC). Finally, Farmaka assessed whether the criterion was
consistent with good medical practice or should be revised.
For example, in Section D, the criterion ‘Neuroleptics used as hypnotics, unless the sleep disorder is
due to psychosis or dementia: risk of confusion, hypotension, extrapyramidal adverse effects of falls’
was reviewed by Farmaka. It was concluded that this criterion was invalid and incomplete. Since this
indication was not included into guidelines, it was considered that the use of a neuroleptic for sleep-
inducing treatment is an off-label use.
The focus of this research was on the section D (central nervous system and psychotropic drugs) and
a part of section F (gastrointestinal tract) of the STOPP-criteria.
Another major challenge is to identify the PIPs retrospectively using health administrative data (HAD) to
improve quality of prescribing. These data are collected in a standardized way so that computer
programs could be developed to assess the criteria appropriateness. It is assumed that data-health
administrative-tools will underestimate the prevalence of PIP in a population due to the incomplete
clinical information necessary for the determination of the appropriateness. However, no studies of the
most promising HAD-based tools are performed yet (26). Also, in a Belgian national report using the
NIHDI (National Institute for Health and Disability Insurance) data from 2013 on the Belgian geriatric
wards, it appeared that results were underrated (32).
Another discussed explicit criterion is the drug burden index. A lot of drugs listed in explicit lists are
anticholinergic and sedative and are individually identified in other tools. The cumulative effect of several
anticholinergics is called anticholinergic burden and can be calculated using an anticholinergic risk
scale. There are several risk scales to calculate anticholinergic burden. The Anticholinergic Cognitive
Burden (ACB) scale by Boustani et al. (see Appendix 8.2) is one of the most frequently used and
validated scale on adverse outcomes. Anticholinergics have been correlated with a decline in cognition,
a higher risk of fall accidents and mortality.
However, these risk scales tend to simplify the complex pharmacological mechanisms and take no
account of dose dependency, possible development of tolerances and the eventual synergistic or
antagonistic properties of the drugs (33).
Finally, also combinations of explicit and implicit criteria were designed. A systematic tool to reduce
inappropriate prescribing (STRIP) is a Dutch guideline that combines an implicit assessment method
with the modified Dutch method of the explicit STOPP-START criteria. The tool is a stepwise process to
deal with polypharmacy in the elderly. The five steps include a pharmacotherapeutic anamnesis, a
pharmacological analysis, a consultation between doctor and pharmacist (drafting of a
pharmacotherapeutic treatment), a consultation with the patient (determining the pharmacotherapeutic
treatment) and follow-up and monitoring.
The main obstacles in the Dutch implementation research are the large investment of time and the need
for further digitization and automatization of certain steps in the process.
In addition, the application of this guideline in the Belgian practice is complicated by the absent
consultative culture between GPs and pharmacists and the inadequate compatibility of computer
systems of general practitioners and pharmacists (28).
8 | INTRODUCTION
1.4. A step-wise approach to deprescribing
1.4.1. Discontinuing medication Benzodiazepines, antidepressants, antipsychotics, PPI, and opioids are examples of drugs that have to
be tapered off gradually to minimize the risk of withdrawal symptoms. Some practical reduction tools for
certain drug classes were developed and are discussed below.
The first example is Psychiatrienet.nl, a website which contains switching tables and reduction
schedules of antidepressants and antipsychotics. The withdrawal scheme of Amitriptyline until stop is
illustrated in Figure 1.
In each case two reduction methods are suggested. In the slow reduction method the dose is decreased
with 25% every 4 to 6 weeks. Another more risky reduction method makes use of the commercially
available doses with every week another reduction step.
Figure 1 : Withdrawal scheme of amitripty l ine according to psychiatr ienet.nl (34)
Another practical tool is the deprescribing.org website in which deprescribing algorithms for PPIs,
benzodiazepines, antipsychotics and antihyperglycemics can be found. An example of the
benzodiazepine and Z-drug deprescribing algorithm is illustrated in Appendix 8.3.
Medstopper.com is a third example. It is a website where the medication list of the patient can be added.
For each drug, the treated condition has to be filled in using several options. This webpage contains
approximately 400 medications, divided into 80 medication categories (e.g. statins, diuretics,
antipsychotics,..).
These medication categories are extended to 125 potential indications (blood pressure, heart failure,
depression) and were evaluated by a team of experts in gerontology, polypharmacy, pharmacology,
pharmacy.
After analysis of the medication list by Medstopper.com (Figure 2), the drugs are ranked from more likely
to stop (colored red and to the top) down to less likely to stop (colored yellow/orange and closer to the
bottom). This ranking is based on 3 criteria : 1) the potential of the drug to improve symptoms, 2) the
potential of the drug to induce future illness, 3) the risk of HARM. Advices for how to taper the drugs and
possible consequences are mentioned. This website provides a visual representation of opinions in
9 | INTRODUCTION
which the doctor can decide which action can be taken, the tool is easy to use and is proved to be time-
saving (35).
Figure 2 : Analys is of medicat ion l is t on Medstopper.com (36)
Deprescribing is a popular changing topic in the pharmacotherapy and knowledge should be shared. An
example of these committed projects is the SIMPATHY (‘Stimulating Innovation Management of
Polypharmacy and Adherence in the Elderly’) project, which runs from the beginning of June 2015 till
the end of May 2017. The SIMPATHY consortium is funded by the European Commission and the
review of appropriate polypharmacy in hospitals is carried out in 10 institutions from 8 European
countries in which Scotland plays the key role.
The aim is to support innovation in the management of polypharmacy and adherence in elderly patients
in Europe and to help different groups (caregivers, patients’ associations, policymakers) to implement
the best practices. Series of activities will be performed such as publishing case studies on the evolution
of polypharmacy and compliance in different European countries of the consortium, comparing current
healthcare models, developing networks to share information between health providers and identifying
the potential difficulties (21).
10 | INTRODUCTION
1.4.2. Monitoring and follow-up
Only 10% of the patients are discharged with the same medications as at admission. 60% of patients
have three or more drug changes during hospitalization. 28 to 40% of medicines are stopped within the
hospital and 45% of the drugs were initiated (37). These medication changes make the situation very
complicated for an older patient who was just discharged from the hospital with a lot of information about
follow-up appointments, post-discharge information and medication management.
It has been described that a multidisciplinary discharge planning team can improve the communication
with the patient about his most important interest including major diagnoses, medication changes, follow-
up appointments, self-care instructions and who to contact if problems would arise. This multidisciplinary
team can include a nurse, a social worker, a physical therapist, a pharmacist (38).
In a systematic review of Nazar et al., it can be concluded that the community pharmacist (CP) can play
an important role for the patient in identifying drug errors when transiting between care providers. But
the contribution of the CP to the medication adherence of the patient is rather limited (37). However a
discharge counseling session by a hospital pharmacist was found effective and helped patients with
tools for compliance, with an overview of the discharge medication and with an explanation of the new
started drugs. A few days after discharge, the patient was called by a study coordinator with pharmacist
follow-up if needed. Nevertheless, there was no decrease in medication errors demonstrated after the
pharmacist intervention. This makes clear that improving medication safety when changing care is not
evident. Involvement of the 1st line caregivers is recommended. In practice, CPs receive information
through a discharge letter or medication scheme at discharge or through a telephone call by the hospital
pharmacist (37; 39; 40).
A fully digital platform for exchanging medical information is one of the biggest opportunities to improve
the communication between healthcare providers and to reduce medication errors. However, this
digitization is still in progress in Belgium.
A digital platform in Belgium, called ‘Vitalink’, allows exchanging medication information between
medicinal professionals. Currently, second line care only has read permission (41).
1.5. Which drugs to taper?
A Delphi expert panel, composed of experts from medicine, pharmacy and nursing, rated 29 drug
classes using four criteria with the aim to identify priority drug classes for which evidence-based
deprescribing guidelines would be beneficial. These four criteria included the benefit versus harms of
the drug therapy, certainty of the estimated effects, patient preference and feasibility and costs. In
addition, the need for a guideline to stop the drug and the impact of stopping was questioned. The five
priority drug classes for which experts claimed that a guideline for deprescribing is required were
benzodiazepines, atypical antipsychotics, statins, tricyclic antidepressants and proton pump inhibitors.
It is remarkable that 3 of the 5 priorities have to do with mental health (19).
Reasons why experts find benzodiazepines a priority for deprescribing is because of the risk for
withdrawal symptoms, the difficulty to convince the patient to reduce the use of these drugs and the risk
11 | INTRODUCTION
of adverse drug reactions such as falls and reduced cognition. In a meta-analysis of 40 studies, it was
found that each of the studied psychotropic drug classes contributed to falling, without dependency on
other fall risk factors (19).
Benzodiazepines are primarily used to treat anxiety and sleep disorders. Use in the elderly is not
appropriate and is only recommended for short-terms. Gradually reducing the dose is therefore
recommended. Minimal interventions such as a personalized letter, a psychotherapeutic intervention or
a conversation with the doctor or pharmacist seemed effective. In a follow-up study of patients with an
average age of 70 years, the majority of patients sustained the discontinuation of the benzodiazepine
after 10 years (42).
In addition, the chronic use of antidepressants in the elderly is high and is therefore one of the priorities
to reduce. This drug class can have a great potential to interact with other drugs, can affect the QT
interval, can have anticholinergic side effects or side effects such as increased bleeding risk and
hyponatremia. The limited effectiveness of these drugs has always been weighed against the side
effects.
Furthermore, the PHEBE-study showed that 11% of the elderly in residential care took antipsychotics.
These drugs can also effect the QT-interval and can have strong anticholinergic properties. This low
effectiveness of antipsychotics for neuropsychiatric symptoms in dementia and the adverse effects can
explain the high need for deprescribing of antipsychotics (43).
Another important class to focus on are drugs with anticholinergic properties. These drugs can give rise
to a higher rate of ADR in older people. In particular, these ADRs are impaired physical function, decline
in cognition and function and moreover this drug class has been associated with falls and frailty. In a
study of Best et al., the drug burden index (DBI) which measured the total exposure to medicines with
anticholinergic and sedative effects, was used. It was concluded that 49% (n=163) of the patients were
exposed to DBI-contributing drugs of which antidepressants, opioids and antipsychotics were the most
contributing medicines. A higher DBI was associated with a delirium related admission (44) and in a
study of Wilson et al. with a higher risk of falls (45).
It was also decided to include the proton pump inhibitors (PPI) having regard to the high current
consumption and the often irresponsible chronic intake. This choice is not immediately linked with the
previous psychotropic medication at first sight, but can be supported by means of literature research in
the past.
PPI are very effective in certain gastrointestinal disorders. Overconsumption is frequent due to
inappropriate indications for an indefinite period. Long-term PPI can sometimes be required for
prevention of reflux esophagitis, Barrett esophagitis or for prevention of ulcer due to long-term NSAID
use. However, in most indications such as ulcer, reflux, Helicobacter pylori eradication a therapy of
longer than 8 weeks in maximal dose is not necessary. Chronic PPI use on the other hand can even
increase the risk of Clostridium difficile infections, pneumonia, malabsorption of iron, vitamin B12,
magnesium and calcium.
In addition, in a meta-analysis of 11 studies an increased risk of hip fracture was found under PPI users
compared to non-users. One possible explanation is the blocking mechanism of the PPI on the H+-K+
12 | INTRODUCTION
ATPase pump in the parietal cells that affects the osteoclasts resulting in an inhibition of the bone
resorption. Another mechanism can be explained by the pH-dependent absorption of calcium. The
absorption and dissolution of calcium decreases as a result of a rising pH with the use of PPI (46).
Prevention actions seem necessary due to the high prevalence of hip fractures (up to 1 in 3 women),
the functional consequences and the costs of these osteoporotic fractures. One possible prevention
strategy can be the intake of calcium vitamin D which is low in cost and well tolerated.
In a meta-analysis of 12 studies, the effectiveness of vitamin D supplementation in preventing hip and
nonvertebral fractures in older persons was investigated. It was concluded that an oral vitamin D
supplementation of 800 units cholecalciferol reduced the risk of hip and any nonvertebral fractures in
the elderly (47).
However, vitamin D supplementation should be restricted to older patients or those at risk of deficiency.
Most people can achieve adequate levels of vitamin D through sufficient exposure to the sun and
besides, unnecessary vitamin D supplementation increases the risk of renal tract stones (48).
The added value of the association with calcium could not be distracted. However a calcium intake of
more than 700 mg/day should be necessary for the prevention of non-vertebral fractures (47).
1.6. A clinical pharmacist in geriatrics, an added value?
Whether a clinical pharmacist has an added value depends on the proposed outcomes and the
corresponding conclusions. A frequently used surrogate or intermediate outcome is for example the
number of medicines. Although, this number is an inappropriate result since it reflects the quantity and
not the quality of the prescription and the need for clinical indications. However, the interventions of
clinical pharmacists in patients who are at high risk of harm due to polypharmacy has been proven
effective in reducing number of (inappropriate) prescriptions and medication costs. In addition, the
decrease in number of drugs improves the long-term adherence. In a prospective study on the Dutch
intensive care unit, the impact on prescribing errors of a clinical pharmacist in an ICU team was
evaluated. Preventable ADEs were reduced from 4 per 1000 monitored patient-days during the baseline
period to 1 per 1000 during the intervention period (49). This study reflects a decrease in prescription
errors and ADRs and this with an acceptable cost per occupied day by the clinical pharmacist.
Secondly, the outcome can be a hard end point such as hospitalizations, fall accidents and mortality.
Several RCTs, reviewed by Gnjidic et al., involving medication reviews by pharmacists could not
demonstrate a significant difference in GP visits, hospital readmissions and mortality. However
interventions through safety assessment and adjustment of medication, could reduce the risk of falling.
It can be concluded that the impact of clinical pharmacist-based interventions on clinical outcome has
mainly proven to affect intermediate outcomes, e.g. the decrease of the number of drugs and the costs
and the increase in appropriateness of prescribing (20; 26).
13 | INTRODUCTION
1.7. Barriers to routine deprescribing
A lot of barriers can prevent routine deprescribing. The decision for deprescribing is complicated by
pharmaceutical companies who put pressure on doctors on the one hand and make patients believe
that every ailment needs a cure and drug.
In the first place, patients who believe they are taking too many drugs, are afraid of the reaction of the
doctor when asking for deprescribing. They fear for relapse and fear that there is no possibility to restart
the medication.
Secondly, it is not surprising that when a doctor proposes to stop or reduce drugs in the patients therapy,
many of them are unwilling to stop. Doctors fear the reactions of family or patient by stopping a drug
that was initiated by a specialist. They fear an increased workload and are often not certain why a drug
is prescribed for a patient.
The lack of practical, applicable and successful guidelines to reduce polypharmacy and the little
awareness of the prevalence of HARMs brings routine deprescribing at a low level (10). Unfortunately,
the impact on health outcomes and health care costs has not been evaluated thoroughly.
Finally, two important concerns should be mentioned. First, not only inappropriate drugs must be
avoided, but also the appropriate and beneficial drugs should be motivated. Second, the responsibility
for appropriate prescribing should not only be given to the physician but this should be shared with every
other care provider and the family. Two reviews showed that the lack of consultation time is a major
obstacle for as well the patient and the physician. This confirms the necessity and the importance of
communication with health care providers and the follow-up at regular intervals (43).
14 | INTRODUCTION
15 | OBJECTIVES
2. OBJECTIVES __________________________________________________________________________________
This study focused on hospitalized patients at the geriatric and orthogeriatric wards in the ‘Groeninge’
hospital in Kortrijk. Patients with polypharmacy taking psychotropic drugs were approached for
deprescribing, during two similar periods of four months.
The main objectives of this study research were :
- To determine the prevalence of potentially inappropriate prescribing (PIPs) based on the
STOPP-criteria for the central nervous system (category D) and for high PPI dose both at
admission and discharge;
- To measure the vitamin D content and to estimate the underuse of vitamin D supplements;
- To compare the number and type of drugs at admission and at discharge;
- To identify the number and type of drug related problems (DRP);
- To give recommendations for deprescribing of psychotropic medication to health care providers
such as geriatricians, general practitioners (GPs), community pharmacists (CPs) and to analyze
the number of accepted recommendations by the geriatrician and the patient;
- To determine the success rate of withdrawal schemes and the importance of post-
hospitalization follow-up.
16 | OBJECTIVES
17 | METHODS
3. METHODS _______________________________________________________________________________________
3.1. General study description
This was a single center pharmacist driven intervention study for deprescribing of hypnosedatives,
antidepressants and antipsychotics for older (> 75) hospitalized patients.
Approval was obtained from the medical ethics committee at the general hospital Groeninge in Kortrijk
(study number AZG2016140). This approval can be found in appendix 8.4. Informed consent was
submitted to all participants. The consent template is added to appendix 8.5.
3.2. Workflow
3.2.1. Selection of patients
Patients hospitalized at the orthogeriatric ward and at one geriatric ward (approximately 30 beds per
ward) were considered for inclusion in the study according to the availability of a clinical pharmacist.
Patients on the other geriatric wards were screened if the geriatrician requested an electronic
consultation. It was decided to include only one of the three geriatric wards in our hospital, due to time
constraints. Orthogeriatrics focuses on patients with a fracture, which involves a close cooperation
between geriatrics and orthopedics. The other ward is a typical geriatric ward with different pathologies.
About 5 geriatricians are switching between all the acute geriatric wards every 3 months. The clinical
pharmacist attended the wards approximately 3 days per week during the period April to July 2016 and
January to April 2017.
The workflow was described by means of different stages (Appendix 8.6) and is a continuation of a
project started in 2015 by a colleague-pharmacist in training.
During the first step the patients were screened and enrolled if they met all of the following requirements:
1) length of stay (LOS) of at least 3 days, 2) age of 75 years or older, 3) minimum intake of 5 drugs and
one of the following inclusion criteria: (1) a contra-indication for benzodiazepines (myasthenia gravis,
sleep apnea syndrome or severe respiratory insufficiency such as COPD or asthma), (2) a
pharmacodynamic synergistic interaction (antidepressants, antipsychotics, anticholinergics, sedative
antihistamines and opioids) or (3) a minimal dose equivalent of 20 mg diazepam. The calculation of the
diazepam equivalence is explained in section 3.3.1.
Psychiatric or palliative patients were excluded from the project and were not eligible for a withdrawal
scheme.
18 | METHODS
3.2.2. Counseling of patients
The patients eligible for a tapering scheme of one or more psychotropic drugs were approached by the
clinical pharmacist in training. In case the electronic medical record revealed that the patient was
cognitively weak (mini-mental state examination (MMSE) < 24), the conversation was performed with
the family when present or only with the geriatrician.
The clinical pharmacist took along an informed consent, the medication schedule at admission and a
leaflet about fall prevention when visiting the patient. Before counseling started, the patient or caregiver
was asked to sign the informed consent.
The patient was informed about the potential risks and long-term side effects and was encouraged to
reduce these psychotropic drugs. If the patient agreed, the patients therapy was discussed with the
geriatrician and the pharmacist. If the patient did not agree, cessation was not attempted.
The clinical pharmacist reviewed the therapy, focusing on the psychotropic medication, and made
recommendations in an electronic pharmaceutical report in the EMR (Appendix 8.7), including the dose
changes, withdrawal schemes and expected cessation date. This report can be read by the geriatrician
in the EMR and was sent electronically via e-health to the GP.
If the geriatrician had accepted one or more recommendations, the withdrawal scheme or another
recommendation was implemented (in hospital setting or at home). In addition, the 1st line caregivers
were involved if it concerned a withdrawal scheme. The clinical pharmacist informed the GP and the CP
by a telephone call. If it appeared that the 1st line had not accepted the advice, the withdrawal scheme
was not started. This also happened when the patient refused a tapering schedule. In addition this
refusal was reported to the geriatrician.
At discharge, the pharmaceutical discharge letter and the medication schedule was printed from the
EMR (after validation of the geriatrician). If a psychotropic drug was tapered in the patients therapy, a
leaflet with the reduction steps was added. Figure 3 shows an example of the leaflet with the withdrawal
scheme of zolpidem.
Figure 3 : Leaflet of the withdrawal schemee of zolp idem
Three copies of the medication scheme at discharge (plus corresponding leaflet) were provided to
the patient. One copy was for the patient /nursing/family, one copy for the general practitioner and
one copy for the community pharmacist.
19 | METHODS
A pharmaceutical discharge letter was added for the GP and CP. If the patient was discharged to a
nursing home an accompanying letter was added. This letter highlighted the importance of the
follow-up of the reduction of psychotropic medication. An example of this letter is shown in Appendix
8.8.
3.2.3. Follow-up
Patients who were discharged with a tapering scheme of psychotropic drugs were contacted by
phone by the clinical pharmacist in training about 10 days after discharge If the patient could not
be reached, one of the family members was interviewed. For nursing home residents, the
responsible nurse was contacted by phone about one week after discharge .
The patient or the responsible caregiver was asked if she/he managed to apply the tapering scheme
and in case of failure the possible causes were asked for. The pharmacist searched for solutions in
case of difficulties and if necessary the GP was contacted.
3.3. Deprescribing protocol
3.3.1. Diazepam equivalents
Before tapering these benzodiazepines and Z-drugs, we should have an idea of the strength of
the(se) benzodiazepine(s) which the patient is taking. This strength can be determined by converting
the benzo (type and strength) in an equivalent dose of diazepam. Therefore a diazepam dose
equivalence table for benzodiazepines is used (Table 1 or appendix 8.9) This table is composed
based on the book published by the Belgian Center of Pharmacotherapeutic Information (BCFI)
(50).
As is clear from the table, a dose of a certain benzodiazepine cannot be linked to a fixed dose of
diazepam; there is a range of doses between a minimum and maximum limit. This large range is
attributable to interindividual variability. In this project, a team of geriatricians and hospital
pharmacists decided to apply the minimum limit for the conversion, which is also the most stringent
limit. For example: when handling the lower limit, 4.5 mg bromazepam is equivalent to 10 mg of
diazepam or in practice: Lexotan® 3 mg corresponds to 7 mg of diazepam. But when using the upper
limit, 9 mg of bromazepam is equivalent to 10 mg of diazepam or in practice: Lexotan® 3 mg
corresponds to 3.5 mg of diazepam. Thus, the use of the minimum limit is a more strict measure.
Table 1: Diazepam equiva lence of the commercia lized benzodiazepines
Duration of action Generic name Brand name Dose(mg) Diazepam
equivalence(1)
(mg)
Limit values on equivalence of 10 mg
diazepam
Short-acting Triazolam Halcion®
0.125 5 0.25 – 0.5 mg 0.25 10
( 1 ) corresponding to the lower l imit value on diazepam equivalenc e
20 | METHODS
Continuat ion Table 1: Diazepam equivalence of the commercial ized benzodiazepines
Duration of action Generic name Brand name Dose(mg) Diazepam
equivalence(1) (mg)
Limit values on equivalence of 10 mg
diazepam
Intermediate-acting
Alprazolam
Alpratop® 0.25 5
0.5 - 1 mg Alpraz® 0.5 10
Xanax®
1 2
20 40
Bromazepam
Bromatop® 3 7
4.5 - 9 mg Lexotan® 6 14 12 28 Brotizolam Lendormin® 0.25 10 0.25 – 0.5 mg
Clotiazepam Clozan®
5 10 5 - 10 mg 10 20
Loprazolam
Dormonoct® 1 20 0.5 - 2 mg 2 40
Lorazepam
Lorazetop® 1.0 5
2 - 8 mg Temesta® 2.5 12.5 Serenase®
Lormetazepam
Loramet® 1 10
1 - 2 mg
Loranka® 2 20
Metatop®
Noctamid®
Stilaze®
Oxazepam Oxazepam EG® 15 10 15 - 100 mg
Long-acting Clobazam Frisium®
10 10 10 - 30 mg 20 20
Clonazepam Rivotril®
0.5 5.0 1 - 4 mg 2 20.0
Clorazepaat
Tranxene®
Uni-Tranxene®
5 10 50 15
5.0 10.0 50.0 15.0
10 - 30 mg
Cloxazolam Akton® 1 10 1 - 2 mg 2 20
Diazepam Valium®
2 2
10 mg 5 5 10 10 Ethylloflazepaat Victan® 2 20 1 - 3 mg
Flunitrazepam Flunitrazepam EG® 1 20 0.5 - 2 mg
Flurazepam Staurodorm® 27 18 15 - 60 mg
Nitrazepam Mogadon® 5 10 5 - 10 mg Nordazepam Calmday® 5 20 2.5 - 10 mg
Prazepam Lysanxia® 10 3 30 - 60 mg 20 6
Z-drugs
Zolpidem
Zolpeduar® 5 2.5
20 mg Stilnoct® 10 5.0 Zolpitop®
Zoplicone Imovane® 7.5 5 15 mg
21 | METHODS
3.3.2. Deprescribing of hypnosedatives
The discontinuation of chronic intake of hypnosedatives including benzodiazepines and Z-products
have to be done step by step and in every step the dose should be gradually decreased. In the
literature, a reduction of 10 to 20% of the initial dose for one to two weeks is described (51; 52; 50).
In this study, the commercialized doses of drugs available in the pharmaceutical sector are used,
without having to rely on individually compounded preparations. These preparations are often
expensive and would bring an additional workload especially in hospitals and besides not all doctors
are familiar with the prescription of these pharmaceutical compoundings.
For deprescription, a distinction between short- and intermediate-acting benzodiazepines and long-
acting benzodiazepines was made. At first, short- and intermediate-acting benzodiazepines were
reduced in steps corresponding to (half of) the lowest available commercial dose. Each step was
held 2 weeks giving the body the time to adapt to the revised dose. Examples of withdrawal schemes
are shown in Table 2.
Table 2: Withdrawal schemes of short-and intermediate-act ing benzodiazepines
Benzodiazepine Withdrawal scheme
Alprazolam 2mg Step 1 2 weeks 1.5 mg Step 2 2 weeks 1 mg Step 3 2 weeks 0.5 mg Step 4 2 weeks 0.25 mg Step 5 2 weeks 0.125 mg Step 6 2 weeks 0.125 mg every 2 days Step 7 Stop
Benzodiazepine Withdrawal scheme
Bromazepam 12mg
Step 1 2 weeks 9 mg
Step 2 2 weeks 6 mg
Step 3 2 weeks 4.5mg
Step 4 2 weeks 3 mg
Step 5 2 weeks 1.5 mg
Step 6 2 weeks 1.5 mg every 2 days
Step 7 Stop
Benzodiazepine Withdrawal scheme
Lorazepam 2.5 mg Step 1 2 weeks lorazepam 2 mg
Step 2 2 weeks lorazepam 1.5 mg
Step 3 2 weeks lorazepam 1 mg
Step 4 2 weeks lorazepam 0.5 mg
Step 5 2 weeks lorazepam 0.5 mg every 2 days
Step 6 Stop
22 | METHODS
Secondly, long-acting benzodiazepines for which commercially low doses were available, were
reduced using the withdrawal scheme as described above. The other long-acting molecules
(clobazam, clorazepate, flurazepam, nitrazepam and nordazepam) with only a few commercially
doses available were recommended to switch to diazepam in order to enable gradually tapering. A
general rule used was to initiate the first step with a dose of diazepam 25% lower than the equivalent
dose. Alternatively, such as in patients with very high doses of benzodiazepines, it may be
recommended to reduce first the originally benzodiazepine to an equivalent dose of 20 mg of
diazepam before switching to diazepam. Examples are shown in Table 3.
Table 3: Withdrawal scheme of long-act ing benzodiazepines
If the patient indicated that the reduction steps were going too fast and he would not sustain it, the
schedule was adjusted according to the profile of the patient and their compliance. If necessary, a
reduction step was maintained longer in agreement with the GP. This was mentioned in the
discharge letter and on the sticker with the withdrawal scheme.
Given the risk of relapse and withdrawal symptoms, it is essential to monitor the patient in order to
encourage them and help them with any misunderstandings. The hospital pharmacist and the
community pharmacist can play an important role in this follow-up (see section 1.4.2).
It is clear that a withdrawal schedule is not a strict protocol, but a guideline that has to be adapted
to the needs of the patient. This means that in our study, the dosage tapering was individualized by
discussion with the geriatrician, doctor and the community pharmacist.
3.3.3. Deprescribing of antidepressants and antipsychotics
For the discontinuation of antidepressants and antipsychotics, the withdrawal schedules on the
website of ‘Psychiatrienet’ were adopted. These withdrawal schedules are described more in detail
in section 1.4.1. Assuming a geriatric study population, it is not surprising that the dosages of most
tricyclic antidepressants and SSRIs are usually low so that in many cases these drugs can be
stopped immediately. Exceptions include paroxetine, nortriptyline and trazodone, the dosage of
these molecules are reduced to a lower dose than the lowest commercially available dose before
being stopped.
Benzodiazepine Withdrawal scheme
flunitrazepam 1 mg (= 20 mg diazepam)
or flurazepam 27 mg
(= 18 mg diazepam)
Step 1 2 weeks switch to diazepam 15 mg
Step 2 2 weeks diazepam 10 mg
Step 3 2 weeks diazepam 7.5 mg
Step 4 2 weeks diazepam 5 mg
Step 5 2 weeks diazepam 2.5 mg
Step 6 2 weeks diazepam 2.5 mg every 2 days
Step 7 Stop
23 | METHODS
3.4. Data collection
Patient characteristics such as sex, age, admission at geriatric or orthogeriatric ward and the number of
drugs taken were collected for all patients.
For all included patients also following patient characteristics were collected at admission: reason for
PPI intake, natrium blood level, reason for admission, drug related problems (DRPs), diazepam-
equivalence, anticholinergic burden score, vitamin D blood level, intake of vitamin D supplement,
MMSE-score and social living situation.
The reason for admission was considered as dominantly, partly or not contributing to drug related
problems1. The determination of DRPs was assessed by the clinical pharmacist and was not discussed
with other healthcare providers. Considerations were taken based on the emergency report written by
the emergency doctor. No causality of DRPs was evaluated.
The ACB-score was calculated using the anticholinergic burden scale tool which can be found in
Appendix 8.2.
The number and type of drugs taken at admission and discharge were registered. Drug use at admission
was found in the medication module of the EMR and drug use at discharge was registered based on
medication schedules at discharge or on discharge letters.
The follow-up calls with patients discharged on a withdrawal scheme were performed by the hospital
pharmacist about 10 days after discharge. These findings were documented and marked as either a
problem or no problem. No standard questionnaire was used. Reasons of failed withdrawal attempts
and types of actions that were taken, were documented.
3.5. Data analysis
For the processing of the data, Microsoft Excel 2013 was used.
All drugs at admission and at discharge were coded according to the Anatomical Therapeutic Chemical
(ATC) classification system.
The statistical significance difference in the number of drugs at admission and at discharge was
subjected to a paired t-test using SPSS version 24. A p-value of less than 0.05 was considered
statistically significant.
In addition, all drugs of included patients were subjected to a quality assessment to identify potentially
inappropriate prescriptions. This assessment was performed using selected STOPP criteria of the
revised Dutch version (2015) (Appendix 8.10). This selection included section D (central nervous system
and psychotropic drugs) and a part of section F (gastrointestinal system) which is illustrated in Table 4.
1 ‘dominant’: drug-related symptoms are the main reason for admission and no other symptoms contribute significantly
‘partly contributing’: drug-related symptoms are a substantial reason for admission, but other factors are also present
‘not contributing’: symptoms other than the drug-related symptoms are the main reasons for admission (17)
24 | METHODS
Table 4: Summary of selected STOP P-criter ia
STOPP
criterion
Description
D1
Tricyclic antidepressants (TCAs) with dementia, narrow angle glaucoma,
cardiac conduction abnormalities, prostatism, or prior history of urinary
retention
D2
Initiation of tricyclic antidepressants (TCAs) as first-line antidepressant
treatment
D3
Neuroleptics with moderate-marked antimuscarinic/anticholinergic effect
(chlorpromazine, clozapine, flupenthixol, fluphenzine, pipothiazine, promazine,
zuclopenthixol) with a history of prostatism or previous urinary retention
D4 Selective serotonin re-uptake inhibitors (SSRI’s) with current or recent
significant hyponatremia i.e. serum Na+ < 130 mmol/l
D5 Benzodiazepines for ≥ 4 weeks
D6 Antipsychotics (i.e. other than quetiapine or clozapine) in those with
parkinsonism or Lewy Body Disease
D7 Anticholinergics/antimuscarinics to treat extra-pyramidal side-effects of
neuroleptic medications
D8 Anticholinergics/antimuscarinics in patients with delirium or dementia
D9 Neuroleptic antipsychotic in patients with behavioral and psychological
symptoms of dementia (BPSD) unless symptoms are severe and other non-
pharmacological treatments have failed
D10 Neuroleptics as hypnotics, unless sleep disorder is due to psychosis or
dementia
D11 Acetylcholinesterase inhibitors with a known history of persistent bradycardia
(< 60 beats/min.), heart block or recurrent unexplained syncope or concurrent
treatment with drugs that reduce heart rate such as beta-blockers, digoxin,
diltiazem, verapamil
D12 Phenothiazines as first-line treatment, since safer and more efficacious
alternatives exist, with the exception of prochlorperazine for
nausea/vomiting/vertigo, chlorpromazine for relief of persistent hiccoughs and
levomepromazine as an anti-emetic in palliative care.
D13 Levodopa or dopamine agonists for benign essential tremor
D14 First-generation antihistamines
F2
PPI for uncomplicated peptic ulcer disease or erosive peptic esophagitis at full
therapeutic dosage for > 8 weeks
When at least one drug in the medication scheme of the patient met the STOPP criterion, this criterion
was documented. A STOPP criterion was not documented if the drug was stopped or tapered.
The difference in prevalence at admission and discharge of each STOPP criterion was assessed using
a Mc Nemar test in SPSS version 24.
The START criterion ‘vitamin D deficiency in patients with a fracture or osteoporosis’ was not assessed
in this study. Not all fall incidents and diagnoses of osteoporosis have been documented. Conclusions
were taken based on the documentation of the intake of vitamin D supplements and vitamin D blood
levels.
25 | METHODS
Associations were investigated by dividing patients into different groups.
At first, patients were classified into 2 groups in which patients took benzodiazepines or not. The
Pearson chi squared test was performed to determine differences between variables such as sex,
residence in nursing home and fall incidents. Differences in number of drugs between both groups were
tested by using the Mann-Whitney U-test.
On the other hand, patients were divided into groups depending on whether the admission was due to
a drug-related problem (dominant or partially contributing) or not. Different variables in these groups
were statistically tested to detect risk factors for hospitalized admissions related to medications. The
Pearson chi squared test was used for assessing differences in sex and residence in nursing home.
Furthermore, the Mann-Whitney U-test was conducted to detect differences in age between the study
groups.
26 | METHODS
27 | RESULTS
4. RESULTS _______________________________________________________________________________________
4.1. Study group In total 470 patients were approached, namely 270 patients during the first period (April - July 2016) and
200 patients during the second period (January - April 2017).
In total 398 of the 470 patients were included in the study (Figure 4). For 72 patients the inclusion criteria
were not met. At first, the age of the patients and number of drugs was considered in which 9.7% was
younger than 75 years and 40.3% patients had an intake of less than 5 drugs. Furthermore, in 45.8% of
patients a pharmacodynamic synergistic interaction was absent and 4.2% patients were excluded due
to a LOS less than 3 days. In total 203 (51%) patients were admitted to geriatric wards and 195 (49%)
patients to orthogeriatrics.
Since 18 patients died during the hospitalization, 380 of 398 included patients were discharged from the
hospital.
Figure 4: Summary of study group
All results are discussed for the patients included in the two study periods (n = 398), except for the
distribution of drugs at admission and discharge (section 4.3.3 and 4.4.2) and the follow-up of withdrawal
schedules after hospitalization (section 4.6). These data were documented only for patients included in
the second study period.
28 | RESULTS
4.2. Patient characteristics
The population (n=398) consisted of 309 (77.6%) women and 89 (22.4%) men. The mean age was 84.7
(75-98) ± 5.5 years. For women and men the age was respectively 85.0 ± 5.4 and 83.6 ± 5.8 years
(Table 5).
Table 5: Age characterist ics by sex (n=398)
Female (n=309) Male (n=89) Total (n=398)
Mean age (years ± SD) 85.0 ± 5.4 83.6 ± 5.8 84.7 ± 5.5
Maximum age (years) 98 98 98
Regarding the patient origin, 75.9% of the included patients lived at home, 17.6% lived at a nursing
home, 5% in a service flat and 1.5% lived with family.
The MMSE-score was determined during hospitalization for 264 patients. 63 patients achieved a score
equal or more than 24 and 201 patients had a score less than 24. A score less than 24 was defined as
cognitive impairment (45). The mean MMSE-score was 20.3 ± 5.5 (Table 6).
Table 6: Orig in and MMSE -scores (n=398 )
Patient origin N (n = 398) Total (%)
Community 302 75.9
Service flat 20 5
Nursing home 70 17.6
With family 6 1.5
MMSE N (n = 398) Total (%)
Mean MMSE-score 20.3 ± 5.5
MMSE-score ≥ 24 63 15.8
MMSE-score < 24 201 50.5
No data 134 33.7
4.3. Drug use at admission
4.3.1. Number of drugs
The mean number of drugs was calculated for all patients (n=398) and was 10.7(5-22) ± 3.8 at
admission. For women and men respectively the number of drugs was 10.9 ± 3.9 and 10.2 ± 3.3.
Excessive polypharmacy was present (≥ 10 drugs) in 232 patients or in 58.3% of the total study
population (Table 7).
29 | RESULTS
Table 7: Number of drugs by sex at admiss ion (n=398)
Women (n= 309) Men (n= 89) Total (n= 398)
Mean number of drugs (±SD) 10.9 ± 3.9 10.2 ± 3.3 10.7 ± 3.8
Excessive polypharmacy
(≥ 10 drugs)
185 47 232 (58.3%)
Maximum number of drugs 22 21 22
4.3.2. Use of (psychotropic) drugs
The average ACB-score was 1.3 per patient (n = 398) and 107 (26.9%) patients had an ACB-score
higher than 3.
The vitamin D level was determined for 265 patients in which 217 patients (81.9%) had inadequate
vitamin D levels (<30 µg/L) and 18.1% had sufficient levels (>30 µg/L). In the 217 patients with
inadequate vitamin D levels, 167 patients had a vitamin D deficiency (< 20 µg/L) and 50 patients had an
insufficiency (20-30 µg/L). 72.8% of them did not take a vitamin D supplement at admission despite their
deficit. In total, 33.2% of the included patients (n=398) took a vitamin D supplement at admission.
80.4% of the included patients (n=398) were benzodiazepine(BDZ) users. The mean diazepam
equivalence of the BDZ users was 13.5 mg. 38 patients of the BDZ users (n=320) had a contraindication
for benzodiazepines in which COPD was the most frequent indication (n=28) (Table 8).
Table 8: Drugs characterist ics of th e BDZ users
N %
BDZ users (n=398) 320 80.4
Mean diazepam equivalence (mg) (n=320) 13.5
Contra-indication for benzo-use (n=320) 38 11.9
COPD as contra-indication (n=38) 28 73.7
A distribution of the diazepam equivalence of the benzodiazepine users (n=320) is shown in Figure 5.
A large part of the benzodiazepine users (n = 77) had a diazepam equivalent between 0 and 5mg, the
second largest group had a diazepam equivalent between 15 and 20 mg (n = 71).
30 | RESULTS
F igure 5 : Distribut ion of d iazepam equiva len ce (mg) of the benzo users (n=320)
In this study, the most common benzodiazepines used were lorazepam (32.5%), lormetazepam (29.1%)
and the benzodiazepine related z-drug zolpidem (15.9%) (Table 9).
Table 9: Summary of most common benzodiazepines among BDZ users (n=320 )
ATC-code Benzodiazepine N % (n=320)
N05BA06 lorazepam 104 32.5
N05BA08 bromazepam 35 10.9
N05BA12 alprazolam 29 9.1
N05CD06 lormetazepam 93 29.1
N05CF02 zolpidem 51 15.9
The differences between the variables fall incidents, sex, residence in nursing home and number of
drugs between benzodiazepine users and non-users were determined and are shown in Table 10.
As can concluded from the table, female patients were more likely to take benzodiazepines than males
(p-value = < 0.001). In addition, BDZ users took a significantly higher number of drugs at admission
compared to non-benzo users (p-value= 0.013).
However no relationship between the intake of benzodiazepines and fall incidents (p-value = 0.411) or
coming from a nursing home (p-value = 0.643) was found.
77
5863
71
16 14
5 4 4 50 2 1
0
10
20
30
40
50
60
70
80
90
0-5 6-10 11-15 15-20 21-25 26-30 15-20 21-25 26-30 46-50 51-55 56-60 60-65
Be
nzo
-use
rs (
n=3
20
)
Diazepam equivalence (mg)
31 | RESULTS
Table 10: Benzodiazepine use in relation to fal l inc idents and sex and or ig in .
N (n=398) BDZ user
(n=320)
Non BDZ user
(n=78)
p-value
Fall incidents 168 138 30 0.411
Female 310 262 48 < 0.001
Coming from a nursing home 70 57 13 0.643
Number of drugs (±SD) 10.7 ± 3.8 11.0 ± 3.8 9.8 ± 3.6 0.013
Hospital admission was dominantly or partly drug related for 164 patients (41.2%). In 11 of the 164
patients (2.8 %), a drug was considered to be the dominant reason for hospital admission and in 153 of
the patients (38.4 %), a drug was found to partly contribute to admission. These considerations were
assessed by the clinical pharmacist and were not discussed with a panel of healthcare providers.
Drugs which attributed to hospital admissions concerned central nervous system drugs, drugs for the
musculoskeletal system medication and cardiovascular drugs.
The differences between the variables age, sex and residence in nursing home between patients
admitted due to a DRP and due to no DRP were determined and are shown in Table 11.
Female patients were more frequently admitted because of a drug related problem compared to males
(p-value = 0.003). However, no relationship was found between drug related hospitalization and age (p-
value = 0.880) or coming from a nursing home (p-value= 0.226).
Table 11: Drug related problems in re lation to age, sex and orig in.
DRP (n=164) No DRP (n=234) p-value
Mean age (years) 84.8 84.9 0.880
Female (# patients) 140 169 0.003
Coming from a nursing home (# patients) 36 54 0.226
4.3.3. Types of drugs
Types of drugs at admission were assessed for all patients (n=200) of the second study period and are
shown in Figure 6. This distribution is a representation of all (both included and excluded) patients.
Three major drug classes dominated the distribution. Of all documented drugs 27.5% were drugs that
acted on the nervous system (N), 26.7% were drugs of the cardiovascular system (C) and 21.1% were
drugs of the alimentary tract and metabolism (A).
32 | RESULTS
Figure 6 : Distribut ion of drug classes at admiss ion
The drug classes according to the ATC c lassi f ication system are drugs for (A) Al imentary tract and metabol ism,
(B) Blood and blood forming organs, (C ) Cardiovascular system, (D) Dermatological drugs , (G) Genitourinary
system and reproductive hormones, (H) Systemic hormonal preparations, excluding reproduct ive hormones
and insul ins, ( J) Ant i infectives for systemic use, (L) Antineoplast ic and immunomo dulating agents, (M)
Musculoskeletal system, (N) Nervous system, (P) Ant iparasit ic products, insecticides and repel lents, (R)
Respiratory system, (S ) Sensory organs, (V) Var ious ATC structures.
4.3.4. Prevalence of PIPs according to STOPP D
The frequency of potentially inappropriate prescriptions at admission and discharge (n=398) as
determined by the STOPP criteria is shown in Table 12. The prevalence of PIPs, reported as the
percentage of prescriptions with at least one PIP, was 94.0% at admission and 66.8% at discharge.
698 PIPs were registered at admission and 359 PIPs at discharge. The number of PIPs decreased with
48.6%, however still in 66.8% patients, at least 1 PIP was present at discharge.
In general, it can be considered that for each PIP criterion the prevalence was decreased when
comparing admission and discharge. Except for patients with parkinsonism or Lewy Body Disease that
took antipsychotics (D6) and patients that took levodopa or dopamine agonists for benign essential
tremor (D13), the number of PIPs did not change at discharge.
The most frequently involved drugs in PIPs at admission were long term use of antidepressants (7%),
long term use of benzodiazepines (80.4%), anticholinergics (11.8%) and high dose of PPIs (49.2%).
The Mc Nemar test found a significant difference in prevalence of the STOPP indicators D1, D2, D5,
D8, D14 and F2 between admission and discharge. The prevalence of the STOPP indicators D2, D5
and F2 was almost halved at discharge.
21.1
10.4
26.7
0.21.5
2.9
0.7 0.5
3.2
27.5
0.1
4.5
0.6 0.00.0
5.0
10.0
15.0
20.0
25.0
30.0
A B C D G H J L M N P R S V
Nu
mb
er
of
dru
gs (
%)
Drug classes
33 | RESULTS
Table 12: Number of PIPs per pat ient at admiss ion and discharge
STOPP indicator At admission
At discharge p- value
N (n=398) % N (n=380) %
D1
Tricyclic antidepressants (TCAs) with dementia, narrow angle glaucoma,
cardiac conduction abnormalities, prostatism, or prior history of urinary
retention
19 4.8 8 2.1 < 0.001
D2
Initiation of tricyclic antidepressants (TCAs) as first-line antidepressant
treatment
21 5.3 13 3.4 0.008
D3
Neuroleptics with moderate-marked antimuscarinic/anticholinergic
effect (chlorpromazine, clozapine, flupenthixol, fluphenzine,
pipothiazine, promazine, zuclopenthixol) with a history of prostatism or
previous urinary retention
8 2.0 4 1.1 0.125
D4
Selective serotonin re-uptake inhibitors (SSRI’s) with current or recent
significant hyponatremia i.e. serum Na+ < 130 mmol/l
6 1.5 5 1.3 1.0
D5
Benzodiazepines for ≥ 4 weeks
320 80.4 163 42.9 < 0.001
D6
Antipsychotics (i.e. other than quetiapine or clozapine) in those with
parkinsonism or Lewy Body Disease
6 1.5 6 1.5 1.0
D7
Anticholinergics/antimuscarinics to treat extra-pyramidal side-effects
of neuroleptic medications
2 0.5 1 0.3 1.0
D8
Anticholinergics/antimuscarinics in patients with delirium or dementia
46 11.6 25 6.6
< 0.001
D9
Neuroleptic antipsychotic in patients with behavioral and psychological
symptoms of dementia (BPSD) unless symptoms are severe and other
non-pharmacological treatments have failed
14 3.5 9 2.4 0.125
D10
Neuroleptics as hypnotics, unless sleep disorder is due to psychosis or
dementia
15 3.8 10 2.6 0.063
D11
Acetylcholinesterase inhibitors with a known history of persistent
bradycardia (< 60 beats/min.), heart block or recurrent unexplained
syncope or concurrent treatment with drugs that reduce heart rate
such as beta-blockers, digoxin, diltiazem, verapamil
11 2.8 8 2.0 0.250
D12
Phenothiazines as first-line treatment, since safer and more efficacious
alternatives exist, with the exception of prochlorperazine for
nausea/vomiting/vertigo, chlorpromazine for relief of persistent
hiccoughs and levomepromazine as an anti-emetic in palliative care.
5 1.3 1 0.3 0.125
D13
Levodopa or dopamine agonists for benign essential tremor
1 0.3 1 0.3 1.0
D14
First-generation antihistamines
22 5.5 8 2.1 < 0.001
F2
PPI for uncomplicated peptic ulcer disease or erosive peptic esophagitis
at full therapeutic dosage for > 8 weeks
196 49.2 97 25.5 < 0.001
34 | RESULTS
4.4. Drug use at discharge
4.4.1. Number of drugs
The mean number of drugs was calculated for 380 patients. 18 patients died during the hospitalization,
including 10 women and 8 men.
At discharge the mean number of drugs was 11.5 ± 3.6. The number of drugs was higher than at
admission and was found to be statistically significant (p-value = < 0.001).
The number of drugs for women and men was respectively 11.7 ± 3.6 and 10.9 ± 3.4 (Table 13).
Table 13: Number of drugs by sex at discharge
Drug characteristic Women (n= 299) Men (n= 81) Total (n= 380)
Mean number of drugs (±SD) 11.7 ± 3.6 10.9 ± 3.4 11.5 ± 3.6
Excessive polypharmacy
(≥ 10 drugs)
221 55 276 (72.6%)
Maximum number of drugs 24 19 24
4.4.2. Types of drugs
The distribution of drug classes at discharge was calculated for all patients (n=188) of the second study
period. 12 (included or excluded) patients died during this hospitalization period. The percentage change
on discharge per drug class in relation to the distribution at admission is shown in Figure 7.
The largest change was seen in drugs of the alimentary tract and metabolism. This drug class increased
from 21.1% to 28.1%. In addition, a decrease of 4.8% was found in the cardiovascular drugs. The
proportion of the nervous system drugs, on the other hand, was slightly reduced (1.1%) compared to
admission. The shift of these drug classes at discharge is discussed in more detail below.
Figure 7 : D istribution of drug classes at discharge
The drug classes according to the ATC c lassi f ication system are drugs for (A) Al imentary tract and metabol ism,
(B) Blood and blood forming organs, (C ) Cardiovascular system, (D) Dermatologica l drugs, (G) Genitour inary
21.1
10.4
26.7 27.5
4.5
+7.0
+0.7
-4.8-1.1 -1.5
-10.0
-5.0
0.0
5.0
10.0
15.0
20.0
25.0
30.0
A B C D G H J L M N P R S V
Nu
mb
er
of
dru
gs (
%)
Drug classes
Drug classes at admission % change on discharge
35 | RESULTS
system and reproductive hormones, (H) Systemic hormonal preparations, excluding reproduct ive hormones
and insul ins, (J ) Anti- infectives for systemic use, (L) Antineoplast ic and immunomodulating agents, (M)
Musculoskeletal system, (N) Nervous system, (P) Ant iparasit ic products, insecticides and repel lents, (R)
Respiratory system, (S ) Sensory organs, (V) Var ious ATC structures.
The distribution of the subclasses of the ATC class A at admission and discharge is shown in Figure 8.
The increase of drug class A with 7% could be attributed to the increase of drugs for constipation (A06),
vitamins (A11) in which mainly vitamin D and minerals (A12) in which mainly calcium.
Figure 8 : Number of drugs at admiss ion and discharge pe r subclass of A
Drug c lass A is subdivided into fol lowing subclasses ( A01) : Stomatologica l preparat ions , (A02) : Drugs
for acid related d isorders , (A03) Drugs for funct ional gastrointest ina l d isorders , (A04) Antiemetics and
ant inauseants , (A05) Bi le and l iver therapy, (A06) Drugs for constipat ion , (A07) Antid iarrheals, intest ina l
ant i- inflammatory/anti - infective agents , (A08) Antiobesity preparations , (A09) Digest ives, including
enzymes, (A10) : Drugs used in d iabetes , (A11) Vitamins, (A12) : Minera l supplements, (A14) Anabolic
agents for systemic use , (A15) Appetite st imulants , (A16) : Other a l imentary tract and metabolism
products
The proportion of cardiovascular drugs decreased from 26.7 to 21.9% at discharge. This change was
due to a decrease of lipid modifying agents(C10) from 92 drugs at admission to 77 at discharge. In
addition, there was a decrease of agents acting on the renin angiotensin system (C09) from 65 drugs to
52 and a reduction of cardiac drugs (C01) (i.e. antiarrhythmic drugs, cardiac glycosides,..) from 46 drugs
to 29.
The distribution of the subclasses of ATC class C at admission and discharge is shown in Figure 9.
99 96
4131
95
152
113
75
0
20
40
60
80
100
120
140
160
A01 A02 A03 A04 A05 A06 A07 A08 A09 A10 A11 A12 A14 A15 A16
Nu
mb
er
of
dru
gs
Subclassification of drug class AAdmission Discharge
36 | RESULTS
F igure 9 : Number of drugs at admiss ion and discharge per subclass of C
Drug c lass C is subdivided into fo llowing subcla sses : (C01) Cardiac therapy, (C02) Ant ihypertensive drugs,
(C03) Diuretic drugs, (C04) Periphera l vasodi lators, (C05) Vasoprotect ive drugs, (C07) Beta b locking
agents, (C08) Calcium channel blockers, (C09) Agents acting on the renin -angiotensin system, (C 10)Lipid
modifying agents
Although only a small decrease (1.1%) was reported in drug class N, still a major shift took place
between the subclasses. The proportion of subclass N02 (analgesic drugs) increased from 126 drugs
at admission to 184 drugs at discharge. The proportion of subclasses N05 (psycholeptic drugs) and N06
(psychoanaleptics) decreased from 191 drugs to 162 and from 108 drugs to 96 respectively.
The distribution of subclasses N at admission and discharge is shown in Figure 10 .
Figure 10 : Number of drugs at admission and discharge per subclass of N
Drug c lass N is subdivided into fo llowing subclasses : (N01) Anesthetic drugs, (N02) Analges ic drugs, (N03)
Antiepi lept ic drugs, (N04) Antiparkinson drugs, (N05) Psycholeptic drugs, (N06) Psychoanalept ics and (N07) Other
nervous system drugs
46
119
65
92
29
124
52
77
0
20
40
60
80
100
120
140
C01 C02 C03 C04 C05 C06 C07 C08 C09 C10
Nu
mb
er
of
dru
gs
Subclassification of drug class C
Admission Discharge
126
191
108
184
162
96
0
50
100
150
200
250
N01 N02 N03 N04 N05 N06 N07
Nu
mb
er
of
dru
gs
Subclassification of drug class NAdmission Discharge
37 | RESULTS
4.5. Deprescribing
The clinical pharmacist in training made 357 different reports in the EMR of the patients which contained
847 recommendations. For 89.7% of the included patients (n=398) at least one intervention was
suggested. Minimum 1 recommendation was accepted in 80.4% of the reports and in 75.6% minimum
1 recommendation was implemented.
A total of 4298 drugs were taken at admission. The clinical pharmacist in training proposed to reduce
656 drugs in which 379 drugs were deprescribed effectively. Overall, 15.3% of all drugs at admission
were reduced.
At first, 228 withdrawal schemes for benzodiazepines were proposed. The geriatrician accepted 209
schemes (91.7%) but unfortunately only 134 schemes (58.8%) were implemented by the geriatrician
due to negligence, forgetting or reviewed opinion. For the 209 accepted withdrawal schemes, a
counseling was considered by the pharmacist. 148 patients were questioned about their willingness to
withdraw these drugs. 79.1 % of the interviewed patients were motivated for cessation and 20.9% were
unwilling. Although 61 of 209 patients were eligible for a tapering scheme, they were not approached
for an interview due to time shortage or because of weak mental status of the patient. However, in some
of these patients a withdrawal scheme was initiated when discussed with the geriatrician and GP.
Apart from the BDZ, for 59 patients the reduction of antidepressants was suggested. Dose reduction or
complete stopping was implemented in 35 patients.
For 18 patients deprescribing of antipsychotics was suggested and in 8 patients the reduction was
started.
In addition, in 12 patients the reduction of antihistamines was suggested and in 9 patients the reduction
was accepted and implemented. Also reduction of anticholinergics was accepted in 9 patients.
Dose reduction or stopping of PPI use was suggested in 322 patients. 59.3% of the recommended
reductions was accepted by the geriatrician.
Prescribing of vitamin D was suggested for 120 patients and was accepted in 63.3% of the patients.
A summary of the suggested, accepted and implemented recommendations can be found in Table 14.
Table 14: Summary of the suggested, accepted and implemented interventions
Number of suggested
interventions (%)
Number of accepted
interventions (%)
Number of implemented
interventions (%)
Total interventions 357 287 (80.4) 270 (75.6)
(De)prescribing of
benzodiazepines 228 209 (91.7) 134 (58.8)
antidepressants 59 38 (64.4) 35 (59.3)
antipsychotics 18 10 (55.6) 8 (44.4)
antihistamines 12 9 (75.0) 9 (75.0)
anticholinergics 13 10 (76.9) 9 (69.2)
PPI 322 191 (59.3) 181 (56.2)
vitamin D 120 76 (63.3) 70 (58.3)
38 | RESULTS
In addition, the first line caregivers were contacted as part of the follow-up. In this study, 145 general
practitioners and 104 community pharmacists were informed about withdrawal schemes.
Communication with the first line occurred through a discharge letter and medication scheme, either by
a telephone call or both.
A summary of the communication with the first line caregivers is shown in Table 15.
Table 15: Communication with the fi rst l ine careg ivers
Number of contacts
with GP (%) (n=145)
Number of contacts with
CP (%) (n=104)
discharge letter + medication scheme
(written)
26 (17.9) 13 (12.5)
Telephone call (orally) 16 (11.0) 15 (14.4)
Written and orally 103 (71.0) 76 (73.1)
4.6. Follow-up
A follow-up call was performed after discharge by the hospital pharmacist for patients included in the
second study period. During this period, 59 patients were eligible to be called after hospitalization
regarding the implemented withdrawal schemes. 45 (76.3%) of them could be reached. 8 patients were
still on the ward and had not been discharged yet and 6 patients were lost of follow-up.
45 persons were contacted from which 12 patients, 14 family members, 16 nursing home nurses and 3
GPs.
For 68.9% of the patients (n=45) no problems were observed and the withdrawal scheme was
maintained. However, in 14 (31.1%) of the contacted patients problems were detected. 7 patients were
no longer motivated and so the withdrawal attempt failed. But in 3 of the patients sensitization was
successful and the withdrawal scheme would be reconsidered with the GP. In 3 patients the withdrawal
scheme was stopped due to insufficient follow-up by the first line caregivers. Another explanation of the
failure, which occurred in 2 patients, was due to discharge with the wrong medication schedule in which
the withdrawal was not clear. And finally for 2 patients the drug was discontinued but another drug was
restarted.
39 | DISCUSSION
5. DISCUSSION ______________________________________________________________________________________
5.1. Drug use
5.1.1. Number of drugs
In this research, the mean number of drugs taken at admission was 10.7± 3.8. The number of drugs in
community dwelling persons with an age over 80 years, reported in a Belgian study of Wauters et al.,
was 5.4 (7) and the presence of polypharmacy and excessive polypharmacy was 57.7% and 9.1%
respectively. Our observation was that 58.3% of the patients took 10 drugs or more which is higher
compared to findings of Wauters et al. A retrospective analysis of patients at geriatric wards in Sydney
observed polypharmacy for 60% of the patients and excessive polypharmacy for 11% of the patients
(44). Another study of Somers et al. which was performed at the geriatric wards of the Ghent university
hospital found an average of 5.9 drugs at admission (17).
It is clear that the number of drugs at admission, revealed in this study, was higher compared to findings
in the literature. This can be explained by several reasons. First, one of the requirements for inclusion
was the minimum intake of 5 drugs. In fact, the complete population of this research was dealing with
‘polypharmacy’ (intake of ≥ 5 drugs). Further, not only regular or chronic medications were taken into
account but also acute and temporary drugs (topical, dermatological, ophthalmological, supplements).
However, some studies reported higher number of drugs. In a study of Page et al., residents of
residential age care facilities were taking an average of 9.3 medicines (18) and in a RCT of Potter et al.
an average of 9.6 regular medicines per patient was found. This may be due to the origin of the patient
(nursing home resident) and the fact that the majority of the patients lived with dementia which can
contribute to a higher number of drugs. In a study of Perehudoff et al. 80% of the patients took 5
medicines or more which is a similar result compared to the findings in this study. The high presence of
polypharmacy could be due to the selection method of the patients. Patients for whom a consultation
with the geriatric liaison team was requested, were included (53).
From our study it can be concluded that the mean number of drugs was higher in women than men.
This result was confirmed by a study in the US in which the number of medications increased with age
and female gender (54).
The mean number of drugs taken at discharge was 11.5 ± 3.6. There was an increase in medicines of
0.8 from admission to discharge. Similar findings were reported in other studies. A study in the US found
an increase of 2.9 drugs on an acute medical service. An increase of 6.0 to 6.2 was reported in an older
population of a Slovakian study and an increase of 4.1 to 4.7 in an older Australian population at
admission (54).
5.1.2. Use of (psychotropic) drugs
The mean ACB score, calculated by the anticholinergic cognitive burden scale by Boustani et al., was
1.3. 26.7% of the included patients had an ACB-score higher than 3. A Belgian health survey of 2013
reported that 7% of the patients, aged over 75 and hospitalized in geriatric departments, had an ACB
score higher than 3 (32). Since it is not clear from this latter survey which anticholinergic rating scale
was used, comparisons are difficult to make. In a similar research, a prevalence of 17.9% was detected
40 | DISCUSSION
when the anticholinergic risk scale (ARS) was used (23). However, it is difficult to extrapolate these
results. The ARS listed only 49 medicines compared to 88 medicines listed in the ACB scale and the
rating score of certain drugs (i.e. quetiapine) was different between the rating scales.
In our study, medicines contributing to anticholinergic burden were not registered. According to Best et
al. patients are most exposed to SSRIs, antipsychotics, opioid receptor agonists, anticonvulsants (44).
Wilson et al. reported similar drug classes which attributed to anticholinergic burden (45).
It was shown that a higher anticholinergic burden was associated with cognitive impairment in older
people (33), with delirium related hospital admission (44) and fall incidents (45).
However, is it useful to calculate anticholinergic burden knowing that risk scales seem to simplify
pharmacological mechanisms and do not take into account dose-dependency of anticholinergic adverse
effects and possible synergic and antagonistic effects of medicines (33)?
This study showed a mean vitamin D level in serum of 18.4 µg/L. In a research of Broe et al., the effect
of vitamin D supplement doses in elderly nursing home residents on fall risk was determined. The mean
vitamin D level was similar for this population: 19.5 µg/L. A higher dose of vitamin D was not associated
with a lower risk of falls. However, it was shown that patients taking 800IU cholecalciferol per day had
fewer fall incidents compared to the placebo group. Similar findings were reported in a Swiss and
Australian randomized trial (55). In a meta-analysis of RCTs, it was concluded that a supplementation
of 800 IU vitamin D per day reduced the risk of hip and nonvertebral fractures both for ambulatory and
institutionalized elderly persons. The importance of vitamin D in elderly with bone loss, was attributed
to the beneficial effect on muscle strength and balance (47).
Nevertheless, a British clinical trial found no association between the vitamin D level and the risk on
falls. The explanation was that serum concentrations of vitamin D were higher in healthy patients, which
resulted in fewer falls (55).
In this study, the prevalence of the START criterion ‘vitamin D deficiency in patients with a fracture or
osteoporosis’ had not been documented. Knowing that 72.8% of the patients with inadequate vitamin D
levels (< 30 µg/l) took no vitamin D supplements at admission, the measurement of the prevalence of
this START criterion would be beneficial. In a study of Wauters et al. the absence of vitamin D and
calcium supplements in patients with known osteoporosis or fragility fractures was 9.1% (56) and
according to Dalleur et al. 13.9% (57). This percentages proved the importance of applying the START-
criterion in daily practice.
However, for 120 patients prescribing of vitamin D was suggested by the clinical pharmacist in training.
The effect of this proposed intervention was clear by the shift of drug class with ATC code A on discharge
(Figure 7). The drug distribution at discharge showed an increase of 7% in drugs of the alimentary tract
and metabolism, which contained vitamins such as vitamin D supplements. The high level of acceptance
by the geriatricians was partly due to results revealed by the Belgian health care report. It was revealed
that only 16.2% of geriatric patients in AZ Groeninge stayed with vitamin D during hospitalization. This
was a poor result compared to the national mean of this report in which 50% of the patients stayed with
vitamin D (32). This has convinced the geriatricians to monitor the vitamin D content closely.
In this research 80.4% of the patients were benzodiazepine users. This high percentage may be due to
the predetermined inclusion criteria. Based on the distribution of drug classes by ATC code the
proportion of nervous system drugs was 27.5%. This latter percentage represented a part of all
41 | DISCUSSION
consumed drugs and did not represent the intake per patient. In addition, this distribution was plotted
for all patients during the second study period, including those who did not meet the inclusion criteria.
34% of the patients took psychotropic medications in a retrospective study cohort of patients staying at
the day clinic of geriatrics in Utrecht (58). On the other hand, the Belgian health care report 2013
mentioned a national average of BDZ use of 18% (32). This report seems to underestimate the BDZ use
in the geriatric population compared to other findings.
In this study research, no relationship between the intake of benzodiazepines and fall incidents (p-value
= 0.411) was found. This was against all expectations. The absence of statistical significance may be
due to the low number of non-BDZ users in the study. Secondly, it may be due to the selection of the
patients. 49% was admitted via orthogeriatrics in which the incidence of fall incidents and fractures is
high. Better results would be obtained if diazepam equivalents were linked to fall incidents, rather than
the use of benzodiazepines.
Nevertheless, in a systematic review by Leipzig et al., the relation between fall risk and psychotropic
drugs was investigated. Several studies found an association between falls and the intake of
psychotropic medication such as antidepressants, neuroleptics and benzodiazepines (15; 59).
However, in a study of Van Strien et al. distinction was made between incidental falls and recurrent falls.
In this latter study, only an association between the intake of psychotropic medication and multiple falls
was found. The reason of a single fall was attributed to an underlying cause, but for patients with
recurrent falls the link with psychotropic medication was more obvious.
The effect of antipsychotics on falls was attributed to drug effects on gait and stability. Tapering
antipsychotic medication was found to improve the mobility of geriatric patients (58).
In addition, taking benzodiazepines, including short-and long-acting molecules, would contribute to more
fall incidents. However, it had been concluded that only long-acting benzodiazepines had a higher risk
on fall incidents. This effect can be explained because half-lives of benzodiazepines may seem longer
due to reduced hepatic drug clearance in the elderly (58).
Finally, the link of fall incidents with antidepressants, mainly SSRIs, was demonstrated. These drugs
were described as having a direct effect on fall incidents through their sedative and orthostatic effects.
Next, Strien et al. found significant differences in living situation and sex between psychotropic and non-
psychotropic users. The group of psychotropic users had more females and more patients lived in long
term care facilities or had professional help. A similar result was confirmed in this study, female patients
were more likely to take benzodiazepines (p < 0.001). However the link between benzodiazepine use
and residence in a nursing home could not be confirmed.
Moreover, Strien et al. found that psychotropic medication users took an average of 8.8 medications
compared to 5.1 medicines among non users (58).
In this research, the largest group of BDZ users had a diazepam equivalent between 0 and 5 or between
15 and 20 mg. The mean diazepam equivalent was 13.5 mg. No similar study reported consumption
data of diazepam equivalents in the elderly. However, in a study of Ray et al. an association between
diazepamequivalents and the rate of falls was reported. A higher risk of falls was associated with higher
diazepam doses (60). The link between diazepam doses and risk on falls was not investigated in this
research.
In this study the most common taken benzodiazepines among benzo-users were lorazepam (32.5%),
lormetazepam (29.1%) and zolpidem (15.9%). Also Wayne et al. observed that the most frequent
intermediate-acting benzodiazepine was lorazepam (64.7% of all benzodiazepine use) (60). The INCB
42 | DISCUSSION
reported a high manufacture of alprazolam, diazepam and lorazepam during the period 2006-2015
which followed the overall trend in consumption. According to a report of ‘The Order of Pharmacists’ in
France, the most consumed benzodiazepines were alprazolam, zolpidem and bromazepam.
In this study 41.2 % of the admissions were attributable to drug related problems, in which 2.8 % were
considered to be the dominant reason for hospital admission and 38.4% were found to partly contribute
to admission. This percentage was high compared to a study of Somers et al. in which 20.9% of the
patients presented with a drug related admission. Additionally, patients admitted due to a DRP took a
higher number of drugs compared to patients who were admitted because of other reasons. No
relationship between DRPs and residence in nursing home or sex was found according to Somers et al.
(17). No association between DRPs and nursing home residents was found (p-value = 0.226) according
to our study. However, female patients were found to be more admitted because of drug related
problems compared to men (p-value = 0.003).
In a review of Beijer et al, the prevalence of HARMs varied from 0.4 to 41.3%. This variation was
attributed to a large number of studies which reported a lower percentage of ADR related hospital
admissions compared to smaller studies. Moreover, it was shown that the percentage among elderly
was 4 times higher than in the younger population: 16.6% compared to 4.1%. And if hospitalizations
were prevented, 7 times more elderly could be kept out of hospital than non-elderly. A high amount of
money seems to be wasted, thinking of all these preventable hospitalizations (61).
In this study, no relationship between the prevalence of DRPs and age was found. However, patients
admitted due to a DRP were younger compared to patients admitted for another reason according to
Somers et al. Despite the large sample size, the method used to detect DRPs in our study was not well
substantiated. Considerations concerning DRPs were not discussed with other healthcare providers and
the causality of the DRP was not evaluated. Probably this attributed to a higher prevalence of DRPs and
insignificance between the variables.
5.1.3. Types of drugs
The main drug classes at admission were the nervous system drugs (27.5%), cardiovascular drugs
(26.7%) and drugs of the alimentary tract and metabolism (21.1%)
Compared to a study of Perehudoff et al., in which the relationship between discrepancies and potential
clinical outcomes was assessed for patients admitted to non-geriatric wards at the Ghent University
Hospital, the 3 main classes were identical. These consisted of 30% cardiovascular drugs, 19% central
nervous drugs and 16% alimentary tract drugs (53). In a study of Dalleur et al. at the University Hospital
St-Luc in Brussels, the most frequent drugs prescribed in community dwelling older patients were 38.8%
of psycholeptics (N05), 24.3% drugs for acid related disorders (ATC code A02), 23.1% of
psychoanaleptics (N06) and 20.3% of cardiac therapy (ATC code CO1) (57).
In this study, the ATC codes of drugs were not always documented at the time of discharge from the
hospital. For example, medication changes conducted on another ward than geriatric wards were not
documented when the patient was transferred before discharge.
Differences between ATC distribution at admission and discharge are discussed below. In this study the
increase of alimentary tract drugs was one of the largest differences between admission and discharge.
This increase may be due to prescribing of vitamin D and drugs for constipation during hospitalization.
In addition, considering the focus of this project, it is surprising that the subclass A02 only decreased
43 | DISCUSSION
from 99 to 95 drugs. This can be explained by the fact that mostly the dose was reduced (i.e. Pantomed®
40 mg to 20 mg) which had no effect on the ATC code. The ATC code is a classification system and
does not take into account the assumed average maintenance dose per day.
Another remarkable change was the decrease of the proportion of cardiovascular drugs. This reduction
was mainly due to a decrease of cardiac drugs (antiarrhythmics and cardiac glycosides) and a decrease
of lipid modifying agents. The latter drug class was probably stopped during hospitalization because
primary prevention did not benefit from life expectancy.
Although the slight decrease (1.1%) of ATC class N compared to admission, the shift of subclasses N
was an important observation in this study. The distribution of the subclasses showed that the proportion
of analgesic drugs had increased strongly (from 126 to 184 drugs). The increase of pain medication was
expected because many patients were recovering from a fall incident and underwent surgery of a knee
or hip replacement. In addition, the increase of oral laxatives could be attributed to the increased
prescription of opioid analgesics at discharge. Although, the association of laxatives with the regular use
of opioids was absent in 10.7% of the cases according to a study of Wauters et al (56). A measurement
of the prevalence of START criteria beyond the scope of this research.
The proportion of psycholeptics (N05) and psychoanaleptics (N06), on the other hand, had decreased
from 191 at admission to 162 drugs at discharge and from 108 to 96 respectively. It would have been
better to distinguish between patients in which only a dose reduction occurred compared to patients in
which a tapering schedule was initiated and the medication was ceased. The ATC code remained the
same for patients who were discharged with a reduced dose of a drug and the proportion of that drug
class did not decrease at discharge. A possibility in the future is to take into account the defined daily
dose (DDD). The defined daily dose is the considered average maintenance dose per day for a drug
used for its main indication in adults. In a study of Tjagvad et al., benzodiazepine prescriptions and
factors associated with increasing amounts of benzodiazepines were studied in patients aged between
18 and 67 years. For each prescription, the numbers of DDD dispensed were measured. In addition,
patients were classified into 2 groups depending on whether they took more (high dose) or less
(moderate dose) than 584 DDD per year. Tjagvad et al. concluded that 30% of the patients was
prescribed more than 365 DDD per year, which indicated a therapeutic amount of benzodiazepine in its
main indication per day or in other words 1 DDD per day. This number indicates an inappropriate use
of benzodiazepines (62). A DDD measurement can detect dose reductions and provides better insight
into drug changes at discharge.
The distribution of the ATC drug classes at discharge was similar to findings in the Belgian health report
2013. In this survey, the prevalence of patients, who had been discharged with psychotropic medication
and PPIs, was 26% and 21% respectively.
These results corresponded to findings reported in the study of Potter et al. in which the most commonly
prescribed new medications were laxatives, analgesics and vitamins in addition to eye drops and topical
antifungal agents (63). Also a study of Somers et al. (2010) showed a decrease in the use of
psychotropic medication and an increase in the use of laxatives (17).
44 | DISCUSSION
5.1.4. Prevalence of PIPs according to STOPP D
The PIP prevalence of the STOPP criteria category D, observed in this study, was very high: 94.0% at
admission and 66.8% at discharge. A limitation of the registration of PIPs at discharge was that PIPs
resolved without requirement of pharmacist involvement, may not have been documented.
The Mc Nemar test showed that the STOPP indicators D1, D2, D5, D8, D14 and F2 were significantly
different at discharge. The absence of statistical significance in the remaining documented STOPP
indicators may be due to the low incidence in patients.
In a systematic literature review of Tommelein et al. that aimed to determine the prevalence and type of
PIPs for community dwelling patients, the overall PIP prevalence was 22.6% (64). In an investigation of
older patients admitted to six European hospitals, the PIP prevalence was determined by using the
STOPP criteria and was 51.3% (65). The large difference in PIP prevalence could be attributed to
different living situations: community dwelling patients compared to acute sick patients in the hospital.
However, a cross sectional study of a cohort of older Belgian patients in primary care found a PIP
prevalence of 41% (57). Prevalences may vary depending on the selected STOPP criteria and the way
of applying and interpreting the tools by various healthcare providers. Recommendations to improve the
validity and applicability of explicit tools are suggested in the study of Dalleur et al. The validity of explicit
criteria could be improved by mentioning contraindications for criteria and by avoiding contradictions
and overlaps. The applicability of explicit criteria on the other hand, could be improved by clearly
describing the conditions, drug categories and diseases, by suggesting tips and possible alternatives
(57).
The high PIP prevalence of 94% in this study research is probably due to the high number of benzo
users (80.4%) at admission. The STOPP criterium D5 (use of benzodiazepines longer than 4 weeks)
was met for all benzo users and therefore a high overall prevalence was detected.
The most frequently drugs involved in PIPs were anxiolytics, antidepressants and NSAIDs according to
a study of Tommelein et al (64). In our study, the most common drugs involved at admission were
benzodiazepines (80.4%), PPIs (49.2%), anticholinergics (11.8%) and antidepressants (7%). The
prevalence of all these drugclasses was significantly reduced at discharge. A strong decrease of PPI
users and BDZ users took place, from 80.4% to 45.5% and from 49.2% to 25.0% respectively.
The most common contributing STOPP criteria were benzodiazepines and neuroleptic drugs in older
patients with recurrent fall incidents (15.2%) and prolonged prescription of high-dose proton pump
inhibitors (8.2%) according to Gallagher et al. (65). In a research of Wauters et al., in which the impact
of inappropriate prescribing in people aged over 80 years was studied, the most common criterion for
misuse was the intake of benzodiazepines for longer than 4 weeks (35%). In addition, the absence of
vitamin D and calcium supplements in patients with known osteoporosis was 9.1% (56).
A study of Dalleur et al. reported a PIP prevalence of 4.9% for long-acting benzodiazepines (57). The
large difference can be explained by the fact that every intake of a (short or long-acting) benzodiazepine
for more than 4 weeks was recorded in our study. The prevalence of benzodiazepines and neuroleptic
drugs in older patients with recurrent falls was not measured.
45 | DISCUSSION
5.2. Deprescribing
In this study 656 drugs or 15.2% of all drugs at admission (n= 4298) were suggested to deprescribe. In
a study of Page et al. even 271 drugs or 58% of all drugs (n=464) of the residents were targeted to
deprescribe (18). Page et al. performed a complete medication review for each resident and thus more
drugs were targeted to deprescribe.
For 75.6% of the patients in this study at least one recommendation was accepted, which is lower
compared to a randomized controlled trial of Potter et al. in which at least 1 drug was tapered in 89% of
the participants. Also in a RCT of Gallagher et al. the acceptance rate was high; 91% of STOPP
recommendations and 97% of START recommendations were accepted and implemented (26). In a
study of Klopotowska et al.in which the participation of a hospital pharmacist in reducing prescribing
errors and HARMs was investigated on ICU, 71% of the recommendations were accepted by the ICU
physicians.
The lower degree of acceptance in our study may be due to the drug classes that were targeted. On the
other hand, no complete appropriateness check of the medication scheme at admission was performed
and less drugs were proposed to deprescribe. Finally in 31 (20.9%) patients was no cessation attempted
since the willingness to cease a medication was absent. In a study of Reeve et al., the patients
willingness to stop medications was checked by administering questionnaires and was found to be 89%
in older patients. However, the real-life acceptance rate of this withdrawal attempt was expected to be
lower (66). In several studies, different acceptances rates are found. For example in a RCT of
community-dwelling older patients with polypharmacy, only 1.5 drugs of the 4.5 recommended drugs
were stopped (67). In a study of Garfinkel al. in which the Good Palliative-Geriatric Practice algorithm
was applied, the success rate for discontinuation was very high (82%) (68). Difference in populations
on the one hand (palliative versus community-dwelling patients) and the types of drug classes that were
targeted on the other hand, can explain the varied degrees of acceptance.
Similar findings were mentioned in a study of Potter et al. in which antidepressants, PPIs and
benzodiazepines had a lower withdrawal success rate compared to other classes such as
biphosphonates, aspirin and iron supplements. It can be concluded that risk-modifying drugs (statins,
aspirin, vitamins) were more successfully tapered than symptom-modifying drugs (analgesics,
antidepressant, hypnotics) (63). The focus of this study is on psychotropic medication and PPIs, which
can explain the lower withdrawal success rate.
In addition, several problems were recurring for certain BDZ users.
A first example was the almost impossible reduction of Flunitrazepam®, a long-acting benzodiazepine
that was equated to narcotic drugs by the Belgian government. Almost all users, included in this study,
refused the withdrawal of this drug. In the past, the addiction to Flunitrazepam®, was already recognized
by the International Narcotics Control Board (INCB). The INCB was concerned about the sale of this
molecule on the illicit market in frequent diversions (69). In this research, telephone conversations with
GPs revealed that this molecule is not frequently prescribed nowadays, only for elderly patients who
took it for years.
A second common problem is the intake of multiple benzodiazepines in alcohol addicts admitted to
hospital. When a patient with problematic alcohol use suddenly stops or reduces drinking, withdrawal
symptoms may occur. Benzodiazepines appear to be the most appropriate therapy to treat alcohol
withdrawal. They act on neurotransmission pathways and have cross-tolerance with ethanol. The
preference is given to long-acting benzodiazepines (Valium®, Tranxene®) because increased
46 | DISCUSSION
compliance and reduced morbidity (due to less pronounced withdrawal symptoms) is expected (70).
Kosten et al. referred to a study in which a significant reduction of withdrawal symptoms was found with
benzodiazepines compared to the placebo group (71). However, for patients with a problematic
benzodiazepine use in combination with a problematic alcohol use, the administration of long-acting
benzodiazepines is contraindicated because of risk on oversedation. But when do we speak of a
problematic benzodiazepine use? Should we substitute all benzodiazepines to an equivalent dose of
diazepam? And if we should add another benzodiazepine, do we run the risk that these patients will get
used to this higher dose? (70; 72). The article of Kosten et al. refers to studies in which carbamazepine
seemed effective in patients undergoing benzodiazepine withdrawal.
One last consideration is the position of alternative medication therapies in the treatment of sleeping
disorders. Considering the increase in the number of prescriptions for psychotropic drugs in Belgium,
we may ask questions about the adequacy of these prescriptions. A number of patients are prescribed
psychotropic drugs while an alternative is possible.
Fytotherapy could be one of the possible alternatives. Herbs such as Passiflora, Valerian and Kava
(pyrones) are often incorporated into plant preparations. The latter is an extract of a pepper plant, but
should cause liver failure and it is not permitted in Belgium. Passiflora preparations are commercialized
and are known under the brand names Sedinal®, Sedistress® and Valdispert®. Valerian is used in
Dormiplant®, Sedistress sleep®, Valdispert®,.. (73) Usually these phytopreparates are not included into
the hospital's formularium and thus alternatives are not systematically presented during the counseling
of the patient. However, the addition of these preparations to a withdrawal scheme of benzodiazepines
could be an option for patients who are convinced they need ‘a sleeping pill’.
Another possible alternative is the use of the hormone melatonin. In Belgium only 1 drug has been
registered, known under the brand name Circadin® at a dose of 2 mg melatonine (73). However,
variable ranges of doses are available in herb shops. The use of this agent was investigated for jet lag,
but according to the SPC this agent has only indications for short-term primary insomnia in people aged
over 55 (74).
And finally, the use of trazodone in low doses (between 25 and 100 mg) is common in the elderly.
Trazodone is used for its sedative side effects, but actually it is indicated for depression in doses
between 150 and 300 mg. The addition of Trazolan® to the patients therapy next to the use of
benzodiazepines is often seen in patients with complaints of insomnia.
5.3. Follow-up
In this study, the follow-up after hospitalization revealed that for 31.1% of the patients the withdrawal
attempt failed. In a review of Reeve et al., some approaches to optimize the patients’ willingness to
cease medications are represented. This includes: presenting deprescribing in a way that does not
provoke stress or fear and does not affect the relationship with the prescriber, by clarifying that the
advice is formulated to achieve therapeutic goals and by making clear the steps of the reduction process.
Furthermore, it is important to consider every adult individually for deprescribing and to mention that
deprescribing is a trial (75; 66).
In a systematic review of 31 studies was found that diuretics, antihypertensives and psychotropic
medication could be discontinued without problems. Especially psychotropic medication had a high risk
of relapse (63).
47 | DISCUSSION
In several articles, the need for follow-up after discharge was emphasized in which the patients
preference was a face-to-face conversation over a telephone call (75). However, in a study of Haynes
et al., which objective was to determine the role of a pharmacist in improving care transitions, also follow-
up calls were performed. These post-discharge calls were conducted by non-healthcare professionals,
making this follow-up less time-consuming and less expensive than when performed by a pharmacist.
However, some pharmacists preferred to conduct the follow-up call personally (39).
On the other hand, in a study of Gujral et al. the impact of CPs on discussing patients’ belief about their
myocard infarct drugs did not improve the medication adherence at 12 months. In this latter study, a
face-to-face conversation by the researcher 5 to 6 weeks after discharge preceded the telephone call
conducted by the CP 3 months after discharge (76). However according to a review by Nazar et al., in
which the contribution of CPs in improving transfer of care was studied, CPs could play a role in the
identification of DRPs. The interventions of CPs in the reviewed studies were characterized by home
visits within a certain period of time after discharge, reporting discrepancies in the prescribed drugs after
comparison with the medication schedule at discharge or by a medical review a few months post-
discharge (37). It is clear that in also in our study the follow-up after discharge was an added value.
However, the interviewer did not use a standardized questionnaire that determined sleep quality and
possible withdrawal symptoms. In a study of Baldwin et al. the association between sleeping disorders
and the effect on quality of life (QOL) was investigated by using the short form (SF) – 36 questionnaire.
This was a measurement for health-related quality of life including questions about physical and social
activities, pain, mental health, emotional problems, vitality and general health perceptions. Another
example of a questionnaire which focused specifically on sleep habits was the Sleep Habits
Questionnaire (SHQ) which was completed by patients in the study of Baldwin et al (77). There are
plenty of ways to measure sleep quality or quality of life, which is also recommended to be used in future
research when conducting a follow-up call post discharge.
5.4. Strengths and limitations of the project and future perspectives This was a single center observational prospective study. In ideal circumstances, a prospective
multicenter randomized controlled trial would have been performed. To determine if the results are
generalizable, this study should be performed in several care settings including those in primary care
and nursing home care. In addition, this study was only performed on geriatrics, while geriatric patients
were spread throughout the hospital. It would be an opportunity to extend this project hospital-wide with
the focus on non-psychiatric patients with long-term benzodiazepine use.
The full potential of interventions would be more appreciated if there was a comparison with a control
group rather than comparison with uncontrolled ‘usual care’. According to Thompson and Schoenfeld,
the use of a usual care-arm is appropriate in two-armed randomized controlled trials for drug and devices
and for non-pharmacological interventions lying well outside usual-care practices (37).
Medication reconciliation was found to be the key factor in improving care transitions according to
Haynes et al. Benefits that were cited were: clarifying certain drug therapies for the patient and enabling
communication with the doctors (39). Also in this study research, discrepancies or recent therapy
changes in the medication scheme were often revealed which took extra time when making
recommendations in the EMR. Medication reconciliation is certainly an added value but was beyond the
scope of this project, considering the amount of time required.
48 | DISCUSSION
Furthermore, factors as potential drug-drug or drug-disease interactions and adherence but also
outcome parameters such as life expectancy, future risk of ADRs and quality of life were not assessed
in this research and would be beneficial. The addition of a pharmaco economic analysis would be
opportune (75).
In future studies, deprescribing should be applied for all categories of the STOPP criteria when detecting
inappropriate prescriptions. In addition, also the START criteria should be screened because the effect
of misuse and underuse is often omitted. According to a study of Wauters et al., it was demonstrated
that patients with a high underuse (3 drugs or more) have a 3.3 fold higher risk of mortality and a 2.8
fold higher risk of hospitalization compared to patients without underuse. The effect of misuse was
associated with a higher risk for hospitalization, but not for mortality (56).
Another future perspective would be the counseling of patients at discharge. This session, led by a
clinical pharmacist, can help patients understand their new medication regimen and can anticipate
barriers to noncompliance. A teach-back method, which is mostly not performed by nurses due to lack
of time, could improve understanding medication related problems (39).
Finally, the information exchange should occur between all healthcare actors, with the necessary
information security and protection. An electronic platform of healthcare, called eHealth, was established
by the Belgian government in 2008. This allows an electronic exchange of health data through different
systems. One of the systems is called Vitalink; this platform includes a vaccination platform (Vaccinet),
an exchange platform for medication schemes and includes sumEHR (Summarized Electronic Health
Record). The latter is an encrypted and structured file which is accessible for GPs, for specialists in the
hospital and for the patient but not for (hospital) pharmacists. Nevertheless, these applications are still
in development and are faced with problems such as inadequate usability in software packages (41).
49 | CONCLUSION
6. CONCLUSION _______________________________________________________________________________________
This study aimed to evaluate the process of deprescribing on geriatric wards. This evaluation could be
organized thanks to the collaboration between the clinical pharmacist, the geriatricians, the general
practitioners, community pharmacists and the caregivers in nursing homes.
The study showed that the clinical pharmacist could provide at least 1 recommendation for 89.7% of the
398 included patients. These recommendations resulted in a decrease of the prevalence of PIPs with
48.6% at discharge. Moreover, 15.3% of all drugs at admission were deprescribed. This decline could
be mainly attributed to accepted interventions by the geriatrician for the reduction of benzodiazepines,
antidepressants and PPIs. Besides, the effect of deprescribing was clearly visible in the shift of ATC
classes at discharge. The proportion of ATC class A (drugs of the alimentary tract and metabolism)
increased with 7% mainly due the increased prescription of drugs for constipation, vitamin D and
minerals such as calcium. A favorable shift in the subclasses of the nervous system drugs (ATC class
N) took place. This trend showed an expected increase of the analgesic drugs, but also a desired
decrease of the proportion of psycholeptic and psychoanaleptic drugs.
The involvement of first-line healthcare providers seemed necessary to achieve a good follow-up. For
example, follow-up calls with discharged patients revealed that in some cases the tapering scheme was
interrupted due to incomplete follow-up. Nevertheless, 68.9% of patients completed the schedule
properly so we can conclude that the various contacts with the GP and community pharmacists were
beneficial.
Deprescribing is not easy and the algorithm should always be personalized. It provides guidance for
doctors, pharmacists and other healthcare providers on when and how to reduce or stop medications.
Moreover, deprescribing requires a centralized patient approach that takes into account the patients
preferences, expectations but also their medical history and medicines. Clinical pharmacists may have
an important role in counseling and monitoring the patient and in helping physicians to make decisions
regarding deprescription.
50 | CONCLUSION
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57 |
8. APPENDICES _______________________________________________________________________________________
8.1. FARMAKA – REVISED STOPP CRITERIA 2016
58 | APPENDICES
FARMAKA – REVISED STOPP CRITERIA 2016 (2)
59 | APPENDICES
FARMAKA – REVISED STOPP CRITERIA 2016 (3)
60 | APPENDICES
FARMAKA – REVISED STOPP CRITERIA 2016 (4)
61 | APPENDICES
FARMAKA – REVISED STOPP CRITERIA 2016 (5)
62 | APPENDICES
FARMAKA – REVISED STOPP CRITERIA 2016 (6)
63 | APPENDICES
FARMAKA – REVISED STOPP CRITERIA 2016 (7)
64 | APPENDICES
FARMAKA – REVISED STOPP CRITERIA 2016 (8)
65 | APPENDICES
FARMAKA – REVISED STOPP CRITERIA 2016 (9)
66 | APPENDICES
8.2. ANTICHOLINERGIC COGNITIVE BURDEN SCORE
67 | APPENDICES
8.3. BENZODIAZEPINE AND Z-DRUG DEPRESCRIBING ALGORITHM
68 | APPENDICES
BENZODIAZEPINE AND Z-DRUG DEPRESCRIBING ALGORITHM (2)
69 | APPENDICES
8.4. ETHICS COMMITTEE APROVAL
70 | APPENDICES
ETHICS COMMITTEE APROVAL (2)
71 | APPENDICES
8.5. TEMPLATE INFORMED CONSENT
72 | APPENDICES
8.6. POSTER OF THE ‘DEPRESCRIBING PROJECT’
73 | APPENDICES
8.7. PHARMACEUTICAL REPORT
74 | APPENDICES
PHARMACEUTICAL REPORT (2)
75 | APPENDICES
8.8. LETTER
Naam rusthuis
Adres
Postcode + stad
Kortrijk, datum
Betreft : ‘Deprescribing van psychofarmaca bij de geriatrische patiënt’
Beste
Uw patiënt, XXXXX (naam + geboortedatum), neemt al geruime tijd XXXX (GM), een geneesmiddel die behoort
tot de groep van de psychofarmaca.
Veel studies benadrukken de verhoogde incidentie van ernstige risico’s veroorzaakt door polymedicatie bij de
geriatrische patiënt. Voornamelijk het chronisch gebruik van benzodiazepines en/of de combinatie met andere
psychofarmaca verhogen het risico op verwardheid, duizeligheid, cognitieve stoornis, valaccidenten, verstoorde
coördinatie,….
Deze geneesmiddelen kunnen verslavend zijn waardoor mensen last krijgen van angst of slapeloosheid als zij
hun tabletten niet innemen. Dit zijn tijdelijke symptomen van ontwenning.
Het is daarom aangeraden om dit/deze geneesmiddel(en) geleidelijk aan te verminderen en zo mogelijk te
stoppen. De patiënt werd hiervoor geïncludeerd in het project ‘Deprescribing van psychofarmaca’ binnen
AZ Groeninge die als doelstelling heeft om het gebruik van psychofarmaca bij de geriatrische patiënt af te
bouwen. Hierbij wordt de medicatie bij opname, die mogelijks gerelateerd is aan de ziekenhuisopname,
geëvalueerd door een klinisch apotheker. In samenspraak met de geriater en huisarts kunnen één of meerdere
geneesmiddelen in het medicatieschema worden gereduceerd of zelfs worden gestopt. De patiënt wordt
hierover geïnformeerd en gestimuleerd. Ook de huisapotheker (indien van toepassing) wordt betrokken in dit
project.
Het voorstel is om elke 2 weken de dosis met een fractie te verlagen. Mocht blijken dat dit voor de patiënt te
snel gaat, kan in samenspraak met de huisarts beslist worden om het afbouwplan over langere termijn aan te
houden.
In bijlage kan je het medicatieschema met het afbouwschema van het/de desbetreffend geneesmiddel(en)
van deze patiënt terugvinden.
Binnen een periode van 1 à 2 weken zouden wij u graag opnieuw contacteren om de continuïteit van deze
afbouw te bekijken en eventuele onduidelijkheden op te helderen.
Alvast bedankt voor jullie opvolging en medewerking.
Met vriendelijke groeten
Saïn Vandepoele Anne Verhaeghe Veronique Ghekiere
Ziekenhuisapotheker Klinisch apotheker Medisch diensthoofd geriatrie
in opleiding
Saïn Vandepoele
Ziekenhuisapotheker in opleiding
t. 056/634966
campus vercruysselaan
Dr. Veronique Ghekiere
Medisch diensthoofd geriatrie
t. 056/633232
campus reepkaai
Anne Verhaeghe
Klinisch apotheker
t. 056/635080
campus vercruysselaan
76 | APPENDICES
8.9. EQUIVALENCE TABLE OF DIAZEPAM
Werkingsduur Benzodiazepine Specialiteit ATC code dosis(mg)
Diazepam
equivalentie
(mg)
Grenzen aan
equivalentie van 10 mg
diazepam
Kortwerkend 0,125 5
0,25 10
Intermediair Alpratop 0,25 5
Alpraz 0,5 10
Xanax 1 20
2 40
Bromatop 3 7,0
Lexotan 6 14,0
12 28,0
Brotizolam Lendormin N05CD09 0,25 10,0 0,25 - 0,5 mg
5 10,0
10 20,0
Dormonoct 1 20,0
2 40,0
Lorazetop 1,0 5,0
Temesta 2,5 12,5
Serenase
Loramet 1 10,0
Loranka 2 20,0
Metatop
Noctamid
Stilaze
Oxazepam N05BA04 15 10 15 - 100 mg
Langwerkend 10 10
20 20
0,5 5,0
2 20,0
5 5,0
10 10,0
50 50,0
Uni-Tranxene 15 15,0
1 10
2 20
2 2
5 5
10 10
Ethylloflazepaat Victan N05BA18 2 20 1 - 3 mg
Flunitrazepam N05CD03 1 20 0,5 - 2 mg
Flurazepam Staurodorm 27 18 15 - 60 mg
Nitrazepam Mogadon N05CD02 5 10 5 - 10 mg
Nordazepam Calmday N05BA16 5 20 2,5 - 10 mg
10 3
20 6
Z-drugs Zolpeduar 5 2,5
Stilnoct 10 5,0
Zolpitop
Zoplicone Imovane N05CF01 7,5 5 15 mg
N05BA06
N05BA11
N05CD05
N05CF02Zolpidem 20 mg
Diazepam Valium 10 mg
Prazepam Lysanxia 30 - 60 mg
N05BA01
ClorazepaatTranxene
10 - 30 mg
Cloxazolam Akton 1 - 2 mg
N05BA05
N05BA22
Lormetazepam 1 - 2 mg
Clobazam Frisium10 - 30 mg
Clonazepam Rivotril 1 - 4 mg
N05BA09
N03AE01
Clotiazepam Clozan 5 - 10 mg
Loprazolam 0,5 - 2 mg
Lorazepam 2 - 8 mgN05BA06
N05BA21
N05CD11
Triazolam Halcion 0,25 - 0,5 mg
Alprazolam 0,5 - 1 mg
Bromazepam 4,5 - 9 mg
N05BA12
N05BA08
77 | APPENDICES
8.10. STOPP – CRITERIA REVISED DUTCH VERSION (2015)
78 | APPENDICES
STOPP – CRITERIA REVISED DUTCH VERSION (2015) (2)
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