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Majda Azermai Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium Abstract: Dealing with the behavioral and psychological symptoms of dementia (BPSD) is often complex. Given the controversy with regard to antipsychotics for behavioral problems in people with dementia, there has been a renewed emphasis on nonpharmacological interventions, with progress in the design of the relevant studies. Potential nonpharmacological interventions for BPSD are: cognitive training/stimulation, rehabilitative care, activities of daily living, music therapy, massage/touch, physical activity, education/training of professionals, and education and psychosocial support of informal caregivers. Use of antipsychotics in the management of BPSD is controversial due to limited efficacy and the risk of serious adverse effects, but credible alternatives remain scarce. The problem of chronic use of antipsychotics in nursing homes should be tackled. Discontinuation of antipsychotic medication in older individuals with BPSD appears to be feasible. Discontinuation efforts are needed to differentiate between patients for whom antipsychotics have no added value and patients for whom the benefits outweigh the risks. Keywords: behavioral symptoms, psychological symptoms, dementia, interventions, nonpharmacological intervention

Background: Although guidelines put forward non-pharmacological therapies and advise against the chronic use of psychotropic drugs, these are still being prescribed regularly in Belgian nursing homes., Goal: To explore the reasons for initiation, continuation and cessation of psychotropic drug treatment of elderly with dementia and behavioral problems, residing in the nursing home., Method: Twenty-seven interviews from an earlier project were used, in which a semi-structured interview was conducted with the nursing staff, the physicians and the caretakers of eleven randomly selected residents from three nursing homes. A qualitative analysis was performed by three independent researchers according to 'The Qualitative Analysis Guide of Leuven (QUAGOL)'. A first analysis focused on the process of initiation, continuation and cessation of medication. A second analysis compared the different participants of each interview and looked for similarities and differences., Results: Seventeen codes were developed for four themes: (1) To initiate, to continue or to cease?; (2) Behavior; (3) Therapy; and (4) Alternatives. The reasons for initiating psychotropic drugs were reducing disruptive behavior and improving the quality of life of the resident. A comparison between the interviewed showed that psychotropic drugs were initiated at the request of the nursing staff. Neither doctors nor nurses considered the monitoring of the drug therapy their task, and tended to pass on this responsibility. Once psychotropic drugs were started, the treatment was chronic but remained part of a dynamic process in which a balance was sought between benefits and adverse effects. More insights into the behavior of the resident led to a better treatment of the behavioral problems., Conclusion: Nurses play an important role in the initiation and continuation of psychotropic drugs. Physicians should take a more active role in the process of indication and monitoring of psychopharmaceuticals. Discontinuation of psychotropic drugs and the use of non-pharmacological alternatives are important bottlenecks in nursing homes. Education and training, updated practice guidelines, appropriate research, professionalization and management elements can, in a complex interaction, change this situation for the better.

Anticholinergics are frequently prescribed for older adults and can lead to adverse drug events. The novel MARANTE (Muscarinic Acetylcholinergic Receptor ANTagonist Exposure) scale measures the anticholinergic exposure by incorporating potency and dosages of each medication into its calculations. The aims were to assess prevalence and intensity of the anticholinergic exposure in a longitudinal cohort study of community-dwelling patients aged 80 years and over (n = 503) and to study the impact on mortality and hospitalization. Chronic medication use at baseline (November 2008-September 2009) was entered and codified with the Anatomical Therapeutic Chemical classification. Time-to-event analysis until first hospitalization or death was performed at 18 months after inclusion, using Kaplan-Meier curves. Cox regression was performed to control for covariates. Mean age was 84 years (range 80-102), and mean number of medications was 5 (range 0-16). Prevalence of anticholinergic use was 31.8%, with 9% taking ≥2 anticholinergics (range 0-4). Main indications for anticholinergics were depression, pain and gastric dysfunction. Female gender, the level of multi-morbidity and the number of medications were associated with anticholinergic use. Mortality and hospitalization rate were 8.9% and 31.0%, respectively. After adjustment for the level of multi-morbidity and medication intake, multi-variable analysis showed increased risks of mortality (HR 2.3, 95% CI: 1.07-4.78) and hospitalization (HR 1.7; 95% CI: 1.13-2.59) in those with high anticholinergic exposure. The longitudinal study among Belgian community-dwelling oldest old demonstrated great anticholinergic exposure, which was associated with increased risk of mortality and hospitalization after 18 months., (© 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Introduction: Government-funded quality improvement projects aimed to reduce the high psychotropic medication use in Belgian long-term care settings., Design: A pilot project (2013-2014) with a pre-post and follow-up intervention design., Methods: Two nursing homes received three educational courses. In the intervention nursing home (INH) additionally, a transition towards person-centred care through professional support was applied. Drug use was recorded at baseline, after 10 months (post) and after 22 months (follow-up), and coded into the Anatomical Therapeutic Chemical classification., Results: At baseline, the INH residents' (n = 118) mean age at baseline was 82 years, with 71% females. The control nursing home residents' (CNH, n = 275) mean age was 82.7 years, with 75% females. At baseline, mean drug use was 9 (range 1-21) and 8 (range 0-20), predominantly with a high proportion of psychotropic drug users of 73 and 65%, in INH and CNH respectively. At the time of post-measurement, only the proportion of hypno-sedative users decreased significantly in the INH (by 13%, p = 0.048). No significant changes were found in the CNH. At time of the follow-up, the proportion of hypno-sedative (51% vs. 31%; p = 0.005) and antidepressant users (42% vs. 25%, p = 0.007) decreased significantly in the INH. The decrease of antipsychotic drug users was less distinct. In the CNH, the proportion of hypno-sedative, antidepressant and overall psychotropic drug users did not change significantly., Conclusion: This quality improvement initiative led to a significant decrease in the use of psychotropic drugs in the INH, even after 1-year follow-up. Education only had a limited effect.

Quantification of the anticholinergic exposure insufficiently or imprecisely incorporates dosage information, leading to inaccurate estimations. The aim was to construct a novel scale, including potency and dosage for the quantification of the anticholinergic exposure in older adults. Potency information was retrieved from a previous systematic review. The dosage range for each drug was delineated in minimal, maintenance and maximal dosage for adults and older adults. Dosage information was collected from authoritative sources and reviewed in an expert panel. The Muscarinic Acetylcholinergic Receptor ANTagonist Exposure (MARANTE) scale was tested for clinimetric properties using cohorts of community-dwelling older adults and nursing home residents. After three data collection rounds, data for the dosage ranges remained incomplete for 32 active substances. Remaining gaps were filled in, and 11 dosage adjustments were proposed during the expert panel meeting. We chose the values {0; 1; 2) for the categories of potency and {0; 0.5; 1; 1.5; 2) for the levels of dosage ranges, showing good clinimetric properties. Forty-one anticholinergic drugs were prescribed in the two cohorts. Most (61%) were low potency anticholinergics and used for depression (19%, e.g. citalopram). There were 31.8% (median MARANTE 1.5, IQR 1.5-2.5) and 37.6% (median 2, IQR 1.5-2.5) anticholinergic users in the community-dwelling cohort and nursing home cohort, respectively. The MARANTE scale combines potency with the dosage spectrum, to quantify the anticholinergic exposure in older adults. An open feedback system on the list of anticholinergic and proposed anticholinergic potency and dosage values is advised., (© 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Objectives: The psychotropic education and knowledge test for nurses in acute geriatric care (PEAK-AC) measures knowledge of psychotropic indications, doses and adverse drug reactions in older inpatients. Given the low internal consistency and poor discrimination of certain items, this study aims to adapt the PEAK-AC, validate it in the nursing home setting and identify factors related to nurses' knowledge of psychotropics., Method: This study included nurses and nurse assistants employed by nursing homes (n = 13) and nursing students at educational institutions (n = 5) in Belgium. A Delphi technique was used to establish content validity, the known groups technique for construct validity (n respondents = 550) and the test-retest procedure for reliability (n respondents = 42). Internal consistency and item analysis were determined., Results: The psychotropic education and knowledge test for nurses in nursing homes (PEAK-NH) (n items = 19) demonstrated reliability (κ = 0.641) and internal consistency (Cronbach's α = 0.773). Significant differences between-group median scores were observed by function (p < 0.001), gender (p = 0.019), educational background (p < 0.001), work experience (p = 0.008) and continuing education (p < 0.001) for depression, delirium and pharmacotherapy topics. Items were acceptably difficult (n items = 15) and well-functioning discriminators (n items = 17). Median PEAK-NH score was 9/19 points (interquartile range 6-11 points). Respondents' own estimated knowledge was related to their PEAK-NH performance (p < 0.001)., Conclusion: The PEAK-NH is a valid and reliable instrument to measure nurses' knowledge of psychotropics. These results suggest that nurses have limited knowledge of psychotropic use in nursing homes and are aware of their knowledge deficits. The PEAK-NH enables educational initiatives to be targeted and their impact on nurses' knowledge to be tracked.

Aims: Little is known about the impact of inappropriate prescribing (IP) in community-dwelling adults, aged 80 years and older. The prevalence at baseline (November 2008September 2009) and impact of IP (misuse and underuse) after 18 months on mortality and hospitalization in a cohort of community-dwelling adults, aged 80 years and older (n = 503) was studied., Methods: Screening Tool of Older People's Prescriptions (STOPP-2, misuse) and Screening Tool to Alert to Right Treatment (START-2, underuse) criteria were cross-referenced and linked to the medication use (in Anatomical Therapeutic Chemical coding) and clinical problems. Survival analysis until death or first hospitalization was performed at 18 months after inclusion using Kaplan-Meier, with Cox regression to control for covariates., Results: Mean age was 84.4 (range 80-102) years. Mean number of medications prescribed was 5 (range 0-16). Polypharmacy (≥5 medications, 58%), underuse (67%) and misuse (56%) were high. Underuse and misuse coexisted in 40% and were absent in 17% of the population. A higher number of prescribed medications was correlated with more misused medications (r s  = .51, P < 0.001) and underused medications (r s  = .26, P < 0.001). Mortality and hospitalization rate were 8.9%, and 31.0%, respectively. After adjustment for number of medications and misused medications, there was an increased risk of mortality (HR 1.39, 95% CI 1.10, 1.76) and hospitalization (HR 1.26, 95% CI 1.10, 1.45) for every additional underused medication. Associations with misuse were less clear., Conclusion: IP (polypharmacy, underuse and misuse) was highly prevalent in adults, aged 80 years and older. Surprisingly, underuse and not misuse had strong associations with mortality and hospitalization., (© 2016 The British Pharmacological Society.)

Background: High drug use and associated adverse outcomes are common in older adults. This study investigates association of medication use with mortality, hospitalisation, and institutionalisation in a cohort of community-dwelling oldest old (aged 80 and over)., Methods: Baseline data included socio-demographic, clinical, and functional characteristics, and prescribed medications. Medications were coded by the Anatomic Therapeutic Chemical classification. Survival analysis was performed at 18 months after inclusion using Kaplan-Meier, and multivariate analysis with Cox regression to control for covariates., Results: Patients' (n=503) mean age was 84.4 years (range 80-102), and 61.2% was female. The median medication use was 5 (0-16). The mortality, hospitalisation, and institutionalisation rate were 8.9%, 31.0%, and 6.4% respectively. The mortality and hospitalisation group had a higher level of multimorbidity and weaker functional profile. Adjusted multivariate models showed an 11% increased hospitalisation rate for every additional medication taken. No association was found between high medication use and mortality, nor with institutionalisation. A higher association for mortality was observed among verapamil/diltiazem users, hospitalisation was higher among users of verapamil/diltiazem, loop diuretics and respiratory agents. Institutionalisation was higher among benzodiazepines users., Conclusion: In the community-dwelling oldest old (aged 80 and over), high medication was clearly associated with hospitalisation, independent of multimorbidity. The association with mortality was clear in univariate, but not in multivariate analysis. No association with institutionalisation was found. The appropriateness of the high medication use should be further studied in relation to mortality, hospitalisation, and institutionalisation for this specific age group., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Polypharmacy is highly prevalent among older people (65+), but little is known on the medication use of the oldest old (80+). This study explores the medication use of the Belgian community-dwelling oldest old in relation to their demographic, clinical and functional characteristics., Methods: Baseline data was used from the BELFRAIL study; a prospective, observational population-based cohort of Belgian community-dwelling patients (80+). General practitioners recorded clinical problems and medications. Medications were coded by the Anatomic Therapeutic Chemical classification., Results: Participants' (n = 503) mean age was 84.4 years (range 80-102) and 61.2% was female. Median chronic medication use was 5 (range 0-16). Polypharmacy (≥5 medications) was high (57.7%), with excessive polypharmacy (≥10 medications) in 9.1%. Most commonly used medication group were antithrombotics, but also benzodiazepines and antidepressants were frequently consumed. Demographics related to polypharmacy (univariate analysis) were female gender, low education and moderate alcohol use. Age, care dependency and cognitive impairment showed no association with polypharmacy. In multivariate analysis, the predominant association with polypharmacy was found for multimorbidity (OR 1.78, 95% CI 1.5-2.1), followed by depression (OR 3.7, 95% CI 4.4-9.7) and physical activity (OR 0.8, 95% CI 0.7-0.9)., Conclusions: Polypharmacy was high among Belgian community-dwelling oldest old (80+). Determinants of polypharmacy were interrelated, but dominated by multimorbidity. On top of the burden of multimorbidity, polypharmacy was independently associated with less physical activity, and with depressive symptoms.

Background: Little is known about the prevalence and clinical importance of potentially inappropriate prescribing instances (PIPs) in the very old (>80 years). The main objective was to describe the prevalence of PIPs according to START (Screening Tool to Alert doctors to Right Treatment; omissions) and,STOPP (Screening Tool of Older Person's Prescriptions; over/misuse) and the Beers list (over/misuse). Secondary objectives were to identify determinants if PIPs and to assess the clinical importance to modify the treatment in case of PIPs., Methods: Cross-sectional analysis of baseline data of the BELFRAIL cohort, which included 567 Belgian patients aged 80 and older in primary care. Two independent researchers applied the screening tools to the study population to detect PIPs. Next, a multidisciplinary panel of experts rated the clinical importance of the PIPs on a subsample of 50 patients., Results: In this very old population (median age 84 years, 63 % female), the screening detected START-PIPs in 59 % of patients, STOPP-PIPs in 41 % and Beers-PIPs in 32 %. Assessment of the clinical importance revealed that the most frequent PIPs were of moderate or major importance. In 28 % of the subsample, the relevance of the PIP was challenged by the global medical, functional and social background of the patient hence the validity of some criteria was questioned., Conclusion: Potentially inappropriate prescribing is highly prevalent in the very old. A good understanding of the patients' medical, functional and social context is crucial to assess the actual appropriateness of drug treatment.

In normal-tension glaucoma (NTG), optic nerve damage occurs despite a normal intraocular pressure. Studies implicating systemic blood pressure or, more recently, arterial stiffness in the pathophysiology of NTG have produced conflicting results. Our aim was to investigate whether NTG is associated with alterations in the macrocirculation or microcirculation, cardiac function, and peripheral and central hemodynamics. Thirty patients with NTG (mean age 65 years, range 46-79) and 33 healthy subjects (mean age 67 years, range 42-79) matched for age and sex were included in the study. Exclusion criteria (for both cases and controls) were history of cardiovascular disease, diabetes mellitus, severe hypertension, and hypercholesterolemia. Aortic stiffness was measured using carotid-femoral pulse wave velocity (PWV), central hemodynamics using carotid artery applanation tonometry, and diameter, stiffness, and intima-media thickness (IMT) of the carotid and femoral artery using echo-tracking. Total peripheral resistance index (TPRI) was derived from mean arterial pressure and cardiac index, measured using ultrasound. There were no statistically significant differences in arterial structure nor function between NTG patients and age and sex-matched controls. NTG versus controls, respectively: brachial blood pressure 126 ± 15/77 ± 8 versus 127 ± 16/76 ± 7 mm Hg, P = 0.81; carotid-femoral PWV 9.8 ± 2.1 versus 10.1 ± 1.9 m/s, P = 0.60; TPRI 1833 ± 609 versus 1779 ± 602 dyne.s/cm5/m2, P = 0.79; and carotid IMT 0.65 ± 0.14 versus 0.68 ± 0.13 mm, P = 0.39. This study could not show an association of NTG with altered IMT, arterial stiffness, total peripheral resistance, cardiac output, and peripheral or central hemodynamics at rest. Although the majority of these NTG patients do exhibit symptoms of vascular dysregulation, in the present study this was not translated into alterations in the microcirculation or macrocirculation at rest.

Background: Drug-related problems are common in older people. Often they are related to low estimated glomerular filtration rate (eGFR), which has a high prevalence among older adults., Objectives: The aim of this study was to investigate inappropriate drug prescriptions and dose adaptations in a very old population and their relationship with the eGFR., Design: A cross-sectional study within a Belgian prospective population-based cohort study (the BELFRAIL study) of 539 participants aged 80 years and older (mean age 85 years). Drug prescriptions at inclusion were reported by the participant's responsible general practitioner. The eGFR was estimated using the MDRD equation. Based on their eGFR, the participants were divided in three groups: > 50, 30-50 and < 30 ml/min/1.73 m², respectively. Drug prescriptions were analysed in different eGFR groups. The prevalence and odds ratios of inappropriate drugs and the unadjusted defined daily doses (DDD) of the participant eGFRs were calculated., Results: Thirty-six (of 111) and eight (of 31) of the participants with an eGFR between 30-50 and < 30 ml/min/1.73 m², respectively, had at least one inappropriate drug prescribed. No decrease in mean DDD, was observed in any prescribed drug in both lower eGFR groups. Participants with a lower eGFR were at higher risk of receiving gliclazide (OR: 4.51; 95% CI: 1.45-14.02) or unadjusted doses of allopurinol (OR: 3.48; 95% CI: 1.26-9.61)., Conclusion: Drug prescriptions inappropriate for patient eGFR are common in subjects aged 80 years and older, despite automatic eGFR reporting.

Objective(s): Atherosclerotic disease is caused by a combination of systemic and local factors (e.g. geometry) affecting local flow conditions. In contrast to the carotid artery, at the iliac-femoral artery region, a large degree of bilateral asymmetry exists. Therefore, we aimed to determine the influence of body side on the prevalence of atherosclerosis (i.e. plaque and intima-media thickness; IMT) at the carotid and femoral arteries., Methods: Data were used from the ASKLEPIOS study, including 2524 apparently healthy individuals with a mean age of 46 years (range 35-55 years). Echographic images were obtained bilaterally of the carotid and femoral arteries. A single observer approach was used for the acquisition and quantification of plaques and IMT., Results: The carotid artery displays no significant left-right difference in IMT values nor plaque prevalence (right: 12.0 vs. left 13.3%; P = 0.18). In contrast, for the femoral artery, the IMT distribution at the right common femoral artery is more skewed (P90 right: 1.11 mm, left 1.01 mm; P < 0.001), which is mirrored by a significantly higher plaque prevalence (right: 21.9 vs. left: 15.7%; P < 0.001)., Conclusion: In the present study, atherosclerotic lesions are more prevalent at the right than at the left femoral artery. This finding highlights the possible role of local arterial geometry in the development of atherosclerosis and underscores the importance of the choice of body side when assessing vascular health.

Objectives: Despite safety warnings on serious adverse effects and guidance advising discontinuation, antipsychotic use in nursing homes remains high. Studies documenting the barriers experienced to antipsychotic discontinuation are rare. This exploratory study investigates the willingness of nurses and general practitioners (GPs) as well as the barriers to undertake antipsychotic discontinuation., Design and Setting: A mixed-method study involving an expert meeting, followed by a survey using structured questionnaires distributed to responsible nurses (primary caregivers) and treating GPs on selected nursing home residents in Belgian nursing homes to generate case-specific information., Results: Antipsychotic users (n = 113) had a mean age of 81 years (range 57-97); 62% were female and 81% had moderate to severe cognitive impairment. Nurses and GPs indicated a willingness for antipsychotic discontinuation in a small proportion of residents, 13.8% and 12.2%, respectively, with a shared willingness in only 4.2%. Residents for whom there was a higher willingness to try antipsychotic discontinuation were generally older (mean age 84.6 vs. 80.3, p = 0.07), had high physical dependency (ADL > 14, 93.3% vs. 60.9%, p = 0.01) and resided on a ward with controlled access (80.0% vs. 45.7%, p = 0.02). In contrast, residents for whom there was a significant lower willingness for discontinuation already had a previously failed discontinuation effort, and may present risk of harm to themselves or to others. Nurses working longer on the ward, with lower education, presented higher barriers to discontinuation of antipsychotics., Conclusion: Nurses and GPs share a very low willingness and high barriers to antipsychotic discontinuation. To implement discontinuation programs, complex multidisciplinary interventions should be offered taking existing barriers into account.

Purpose: The aim is to describe the process, principles and results of the International Nonproprietary Name (INN) prescribing project in Belgium. The purpose of this project was to operationalize electronic INN prescribing for outpatient care in daily medical practice and to develop a factual database which can be used in electronic INN prescribing applications., Methods: The operationalization process consisted of three phases: (1) expert consultation, (2) review by regulatory authorities and (3) test phase with stakeholders and end-users., Results: The INN prescribing project resulted into (1) operational rules for electronic INN prescribing and (2) a reference database to be implemented in commercial medical software. The operational rules for electronic INN prescribing define valid INN groups as sets of equivalent medicinal products, described by three elements: the therapeutic moiety (the active part of the therapeutic ingredient) or combination of therapeutic moieties, the strength (with standardized denominators), and the method of administration (with simplified but standardized options). The operational rules also define two categories of exemptions for INN prescribing: INN groups where the first choice of treatment should be continued throughout the therapy period (NO SWITCH) and medicinal product groups not suitable for INN prescribing (NO INN). The reference database is the result of the virtual classification of the Belgian therapeutic arsenal into INN groups, according to the operational rules., Conclusions: Defining the operational rules for INN prescribing for and with different stakeholders was a difficult yet feasible assignment. The INN prescribing project resulted into explicit operational rules and a reference database. The Belgian experience may provide important information for other countries planning to operationalize or refine electronic INN prescribing. It can also be used for a thorough evaluation of the impact of the new concept of INN prescribing on daily practice and on medical education., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Recently, an expert group advised to measure carotid-femoral (cf) pulse wave velocity (PWV) on the right side of the body, and to use a sliding caliper when tape measure distance cannot be obtained in a straight line. The present study investigates the evidence for this advice by comparing the real travelled cf path lengths (RTPLs) at both body sides and comparing the straight distance (as can be obtained with a sliding caliper) with the tape measure distance., Methods: RTPLs were measured with MRI in 98 individuals (49 men, age 21-76 years). Path lengths from the aortic arch to the carotid (AA-CA) and femoral (AA-FA) sites were determined. RTPL was calculated as (AA-FA) - (AA-CA) and compared between both sides. RTPLs were compared with 80% of the direct cf distance using a tape measure and the straight cf distance obtained from MRI images., Results: RTPL was slightly longer [11 mm (12), P < 0.001] at the right side. The 80%-rule overestimated RTPLs with 0.5% at the right and 2.7% at the left side. Straight MRI distance tended (P = 0.09) to perform slightly better than tape measure distance., Conclusion: The travelled cf path is slightly longer at the right than at the left body side and the straight MRI distance tends to perform better than tape measure distance. The present study supports the advice of the expert consensus group to measure cf-PWV at the right body side using a sliding caliper when tape measure distance cannot be obtained in a straight line.

Background: Antipsychotic agents are often used to treat neuropsychiatric symptoms (NPS) in dementia, although the literature is sceptical about their long-term use for this indication. Their effectiveness is limited and there is concern about adverse effects, including higher mortality with long-term use. When behavioural strategies have failed and drug therapy is instituted, regular attempts to withdraw these drugs are recommended. Physicians, nurses and families of older people with dementia are often reluctant to try to stop antipsychotics, fearing deterioration of NPS. Strategies to reduce antipsychotic use have been proposed, but a systematic review of interventions aimed at withdrawal of antipsychotic agents in older people with dementia has not yet been performed., Objectives: To evaluate whether withdrawal of antipsychotic agents is successful in older people with dementia in community or nursing home settings, to list the different strategies for withdrawal of antipsychotic agents in older people with dementia and NPS, and to measure the effects of withdrawal of antipsychotic agents on behaviour., Search Methods: ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS, clinical trials registries and grey literature sources were searched on 23 November 2012. The search included the following terms: antipsychotic* or neuroleptic* or phenothiazines or butyrophenones or risperidone or olanzapine or haloperidol or prothipendyl or methotrimeprazine or clopenthixol or flupenthixol or clothiapine or metylperon or droperidol or pipamperone or benperidol or bromperidol or fluspirilene or pimozide or penfluridol or sulpiride or veralipride or levosulpiride or sultopride or aripiprazole or clozapine or quetiapine or thioridazine combined wither terms such as discontinu* or withdraw* or cessat* or reduce* or reducing or reduct* or taper* or stop*.ALOIS contains records from all major healthcare databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), as well as from many clinical trials registries and grey literature sources., Selection Criteria: Randomised, placebo-controlled trials comparing an antipsychotic withdrawal strategy to continuation of antipsychotics in people with dementia., Data Collection and Analysis: Review authors independently assessed trials for inclusion, rated their risk of bias and extracted data., Main Results: We included nine trials with 606 randomised participants. Seven trials were conducted in nursing homes, one trial in an outpatient setting and one in both settings. In these trials, different types of antipsychotics prescribed at different doses were withdrawn. Both abrupt and gradual withdrawal schedules were used. The risk of bias of the included studies was generally low regarding blinding and outcome reporting and unclear for randomisation procedures and recruitment of participants.There was a wide variety of outcome measures. Our primary efficacy outcomes were success of withdrawal (i.e. remaining in study off antipsychotics) and NPS. Eight of nine trials reported no overall significant difference between groups on the primary outcomes, although in one pilot study of people with psychosis and agitation that had responded to haloperidol, time to relapse was significantly shorter in the discontinuation group (Chi(2) = 4.1, P value = 0.04). The ninth trial included people with psychosis or agitation who had responded well to risperidone therapy for four to eight months and reported that discontinuation led to an increased risk of relapse, that is, increase in the Neuropsychiatric Inventory (NPI)-core score of 30% or greater (P value = 0.004, hazard ratio (HR) 1.94, 95% confidence interval (CI) 1.09 to 3.45 at four months). The only outcome that could be pooled was the full NPI-score, used in two studies. For this outcome there was no significant difference between people withdrawn from and those continuing on antipsychotics at three months (mean difference (MD) -1.49, 95% CI -5.39 to 2.40). These two studies reported subgroup analyses according to baseline NPI-score (14 or less versus > 14). In one study, those with milder symptoms at baseline were significantly less agitated at three months in the discontinuation group (NPI-agitation, Mann-Whitney U test z = 2.4, P value = 0.018). In both studies, there was evidence of significant behavioural deterioration in people with more severe baseline NPS who were withdrawn from antipsychotics (Chi(2) = 6.8; P value = 0.009 for the marked symptom score in one study).Individual studies did not report significant differences between groups on any other outcome except one trial that found a significant difference in a measure of verbal fluency, favouring discontinuation. Most trials lacked power to detect clinically important differences between groups.Adverse events were not systematically assessed. In one trial there was a non-significant increase in mortality in people who continued antipsychotic treatment (5% to 8% greater than placebo, depending on the population analysed, measured at 12 months). This trend became significant three years after randomisation, but due to dropout and uncertainty about the use of antipsychotics in this follow-up period this result should be interpreted with caution., Authors' Conclusions: Our findings suggest that many older people with Alzheimer's dementia and NPS can be withdrawn from chronic antipsychotic medication without detrimental effects on their behaviour. It remains uncertain whether withdrawal is beneficial for cognition or psychomotor status, but the results of this review suggest that discontinuation programmes could be incorporated into routine practice. However, two studies of people whose agitation or psychosis had previously responded well to antipsychotic treatment found an increased risk of relapse or shorter time to relapse after discontinuation. Two other studies suggest that people with more severe NPS at baseline could benefit from continuing their antipsychotic medication. In these people, withdrawal might not be recommended.

Aim: (1) To describe the prevalence of benzodiazepine use in Belgian nursing homes, with specific attention to indications and dosages. (2) To compare actual and recommended dosages of benzodiazepines for anxiety and insomnia. (3) To explore the risk profile for chronic benzodiazepine use in institutionalised older adults., Methods: Medication charts of 1,730 residents from 76 nursing homes in Belgium were collected and analysed, using the ATC classification. Drug name, indication and daily dosage were recorded. From authoritative international sources, we extracted for each drug and each indication a daily dosage recommended not to be exceeded in older adults for comparison with observed actual dosages., Results: Among the chronic benzodiazepine or z-drug (BZD/Z) users (50% of the residents), the leading indication was 'insomnia' (59% of the users) followed by 'anxiety' (17%) and 'unrest' (10%). In the chronic prescriptions of BZD/Zs indicated for insomnia, the actual daily dose exceeded the geriatric upper limit in 95% of lormetazepam prescriptions, 82% of zolpidem, 78% of zopiclone and 35% of lorazepam prescriptions. For anxiety, daily doses also exceeded the limit but not to the same extent. Multivariate analysis showed BZD/Z use was positively associated with pain (OR 1.58, 95% CI 1.27-1.97), constipation (OR 1.43, 95% CI 1.16-1.76) and depression (OR 1.68, 95% CI 1.35-2.08). Residents with dementia were less likely to receive a BZD/Z (OR 0.60, 95% CI 0.48-0.74)., Conclusion: Efforts to reduce the use of BZD/Zs in nursing homes should concentrate on insomnia, with interventions aimed at reducing too high prevalence of chronic use and too high daily dosages in this indication.

Background: Within the treatment of dementia, management of behavioural and psychological symptoms (BPSD) is a complex component., Purpose: We wanted to offer a pragmatic synthesis of existing specific practice recommendations for managing BPSD, based on agreement among systematically appraised dementia guidelines., Data Sources: We conducted a systematic search in MEDLINE and guideline organisation databases, supplemented by a hand search of web sites., Study Selection: Fifteen retrieved guidelines were eligible for quality appraisal by the Appraisal of Guidelines Research and Evaluation instrument (AGREE), performed by 2 independent reviewers., Data Extraction: From the 5 included guidelines, 18 specific practice recommendations for BPSD were extracted and compared for their level of evidence and strength., Data Synthesis: No agreement was found among dementia guidelines for the majority of specific practice recommendations with regard to non-pharmacological interventions, although these were recommended as first-line treatment. Pharmacological specific practice recommendations were proposed as second-line treatment, with agreement for the use of a selection of antipsychotics based on strong supporting evidence, but with guidance for timely discontinuation., Limitations: The appraisal of the level of agreement between guidelines for each specific practice recommendation was complicated by variation in grading systems, and was performed with criteria developed a posteriori., Conclusion: Despite the limited number of recommendations for which agreement was found, guidelines did agree on careful antipsychotic use for BPSD. Adverse events might outweigh the supporting evidence of efficacy, weakening the recommendation. More pivotal trials on the effectiveness of non-pharmacological interventions, as well as guidelines specifically focusing on BPSD, are needed., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Given the potential adverse effects of antipsychotics, high use in nursing homes creates concern. Our study goal was to explore the use of antipsychotics in relation to resident characteristics, and to assess the appropriateness of antipsychotic prescribing in Belgian nursing homes., Methods: Data were used from a cross-sectional study (Prescribing in Homes for the Elderly; PHEBE) conducted in 76 nursing homes in Belgium. Antipsychotics were classified into typical and atypical, using the anatomical therapeutic and chemical classification. Ten inappropriate antipsychotic prescribing indicators were selected from the updated Beers criteria (2003), Bergen District Nursing Home Study (BEDNURS) indicators, and Screening Tool of Older People's Prescriptions criteria (STOPP)., Results: The residents' mean age was 84.8 years, 78.1% of whom were female. The prevalence of antipsychotic utilization was 32.9%. Antipsychotics were mainly indicated for dementia-related agitation, and psychosis with/without dementia. Higher use of antipsychotics was found for dementia (OR: 3.27; 95% CI: 2.61-4.09), insomnia (OR: 1.38; 95% CI: 1.10-1.73), depression (OR: 1.30; 95% CI: 1.03-1.65), and age <80 years (OR: 1.79; 95% CI: 1.38-2.33). Inappropriate antipsychotic prescribing indicators scoring the highest among users were: long-term use (92.6%), use despite risk of falling (45.6%), combined use with other psychotropics (31.8%), and duplicate use (15.1%). Inappropriate prescribing was associated with depression (OR: 3.41) and insomnia (OR: 2.17)., Conclusion: The indicator-driven analysis of antipsychotic prescribing quality revealed a need for improvement, with the main prescribing problems relating to duration and combination of therapies. Risks/benefits of off-label use need to be evaluated more consciously at the start of therapy, and at periodic re-evaluations.

Objective: To determine the prevalence of psychotropic drug use in Belgian nursing homes, in relation to residents' and institutional characteristics., Methods: The PHEBE project (Prescribing in Homes for the Elderly in Belgium, 2005) was a cross-sectional study, investigating drug use in 76 nursing homes. Psychotropics were categorised into antidepressants, antipsychotics, benzodiazepines and anti-dementia drugs using the ATC classification., Results: Residents' mean age (n=1730) was 85 (SD: 8) years and 78% were female. The overall prevalence of psychotropic drug use among nursing home residents was 79%. Benzodiazepines were used by 54% and antipsychotics by 33% of all residents. Residents received a higher number of antipsychotics ( p<0.001) but fewer antidepressants (and other medicines) with increasing severity of dementia. Antidepressants were prescribed in 40% of which 2/3 was indicated for depression and 1/3 for insomnia. Anti-dementia drugs were used by 8%. Institutional characteristics showed no relationship with psychotropic drug use, except for a lower use when medication was dispensed by a hospital pharmacist (p=0.001)., Conclusion: As in other European countries, the prevalence of psychotropic utilisation in Belgian nursing homes is exceedingly high, with excessive duplicate use. Guidelines, education and clinical practice recommendations focusing on initiation, reassessment and withdrawal of psychotropic therapy, are needed.