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ABSTRACT: Factors that influence the variation in occurrence of antipsychotic-related parkinsonism in elderly have not been well elucidated. The aim of this study was to investigate whether previous identified and studied genetic polymorphisms at DRD2, ANKK1, DRD3, HTR2A, HTR2C, RGS2, COMT, and BDNF genes are associated with antipsychotic-related parkinsonism in elderly patients.This cross-sectional study included 150 inpatients aged 65 years and older who were treated with haloperidol. Parkinsonism assessed by the Simpson Angus Scale was present in 46% of the included patients. The investigated predictors were polymorphisms in DRD2 (141CIns/Del and C957T), ANNK1 (TaqIA), DRD3 (Ser9Gly), HTR2A (-1438G>A and His452Tyr), HTR2C (Cys23Ser and -759C/T), RGS2 (+2971C>G), COMT (G158A), and BDNF (Val66Met). Frequencies of the -759 T allele of the HTR2C gene and the 158A allele of the COMT gene were significantly higher in patients without antipsychotic-induced parkinsonism (AIP) (nominal P = 0.03 and P = 0.02, respectively). -759 T allele carriership in females was associated with a lower risk of AIP (adjusted odds ratio, 0.31; 95% confidence interval, 0.11-0.85). The decrease in risk of AIP in carriers of the COMT 158A allele did not reach statistical significance. No significant associations were found between AIP and the remaining selected polymorphisms.Although validation is needed, this study suggests that carriership of the -759 T allele of the HTR2C gene in females may be protective against development of parkinsonism in elderly patients during treatment with haloperidol.
Journal of clinical psychopharmacology 04/2013; · 5.09 Impact Factor
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Journal of the American Geriatrics Society 03/2013; 61(3):456-8. · 3.74 Impact Factor
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ABSTRACT: OBJECTIVES: Falls in the elderly are common and often serious. The aim of this study was to examine the association between the use of different classes of psychotropic medications, especially short acting benzodiazepines, and the frequency of falling in elderly. Study design This retrospective cohort study was performed with patients who visited the day clinic of the department of geriatric medicine of the University Medical Center Utrecht in the Netherlands between 1 January 2011 and 1 April 2012. Measurements Frequencies of falling in the past year and medication use were recorded. Logistic regression analysis was performed to assess the relationship between the frequency of falling in the past year and the use of psychotropic medications. RESULTS: During this period 404 patients were included and 238 (58.9%) of them had experienced one or more falls in the past year. After multivariate adjustment, frequent falls remained significantly associated with exposure to psychotropic medications (odds ratio [OR] 1.96; 95% confidence interval [CI] 1.17-3.28), antipsychotics (OR 3.62; 95% CI 1.27-10.33), hypnotics and anxiolytics (OR 1.81; 95% CI 1.05-3.11), short-acting benzodiazepines or Z-drugs (OR 1.94; 95% CI 1.10-3.42) and antidepressants (OR 2.35; 95% CI 1.33-4.16). CONCLUSIONS: This study confirms that taking psychotropic medication, including short-acting benzodiazepines, strongly increases the frequency of falls in elderly. This relation should be explicitly recognized by doctors prescribing for older people, and by older people themselves. If possible such medication should be avoided for elderly patients especially with other risk factors for falling.
Maturitas 01/2013; · 2.77 Impact Factor
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ABSTRACT: BACKGROUND: Earlier studies have shown poor documentation of the reasons for medication discontinuation during hospitalization. Communication of reasons for discontinuation, e.g. adverse drug reactions (ADRs), to general practitioners and pharmacists was also found to be insufficient, leading to a rate of represcription after an ADR of 27 % during the first 6 months after discharge. OBJECTIVE: The aim of this study was to develop and implement a user-friendly electronic clinical decision support system to document reasons for medication discontinuation in hospitalized geriatric patients and to flag potentially undesirable represcriptions. METHODS: The electronic clinical decision support module was developed using the Gaston framework. Pop-up windows force physicians to document reasons for medication discontinuation, and the system alerts physicians to the represcription of drugs withdrawn because of an ADR. We interviewed users regarding the acceptability of the system. RESULTS: On a 20-bed geriatric ward, the electronic system documented 2,228 medication discontinuations and the reasons for them over 11.4 months and alerted physicians to represcription of drugs associated with an ADR 20 times. The system was considered to be user-friendly. CONCLUSIONS: This clinical decision support system fulfilled its aims of documenting the reasons for medication discontinuation and alerting physicians to potentially undesirable represcription of previously withdrawn drugs. It was found to be user-friendly.
Drugs & Aging 11/2012; · 2.67 Impact Factor
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ABSTRACT: Factors that influence the variation in occurrence of antipsychotic-induced parkinsonism (AIP) in the elderly have not been well elucidated. The aim of this study was to investigate the association between parkinsonism in elderly users of haloperidol and prescribed dose, plasma concentration, and duration of use of haloperidol in a cross-sectional design. This study included 150 inpatients aged 65 years and older who were treated with haloperidol. Parkinsonism assessed by the Simpson Angus Scale was present in 46% of the included patients. Prescribed haloperidol dose varied from 0.3 to 5 mg/d. Plasma concentration ranged from 0.13 to 4.11 μg/L, with one outlying measurement (21.43 μg/L). Dose is moderate but significantly associated with haloperidol plasma concentration (weighted R = 0.32; P < 0.001). Variability in the total score on the Simpson Angus Scale could not be explained by the variability in dose, concentration (respectively R = 0.003 and 0.001) nor duration of use of haloperidol. Smoking showed to be not significantly protective in the development of AIP (crude odds ratio, 0.39; 95% confidence interval, 0.15-0.997; and adjusted odds ratio, 0.44; 95% confidence interval, 0.17-1.17). In a clinical practice-setting dose, neither plasma concentration nor duration of use of haloperidol is associated with an increased occurrence of AIP. This study does not support the hypothesis of the peripheral pharmacokinetic explanation for the high prevalence of AIP and differences in AIP sensitivity in the elderly during treatment with haloperidol.
Journal of clinical psychopharmacology 08/2012; 32(5):688-693. · 5.09 Impact Factor
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ABSTRACT: To examine the association between antipsychotic use and the risk of acute coronary syndrome (ACS) in elderly de novo users of antipsychotics.
A community-based nested case-control study.
Pharmacy dispensing records from community pharmacies in The Netherlands were linked to hospital discharge records of 950,000 community-dwelling residents from 1998 to 2008.
Cases were 2803 patients aged 60 years or older, with a first hospital admission for ACS identified within a cohort of 26,157 elderly persons with at least one antipsychotic prescription (de novo users). For each case, four controls with no hospitalisation for ACS (n=11,024) were randomly selected from the same cohort, matched by age, gender and duration of registration in the database.
Relative risks, expressed as ORs, for ACS associated with antipsychotic drug use adjusted for comorbidity.
Current exposure to antipsychotics was associated with a decreased risk of hospitalisation for ACS compared with past users (adjusted OR 0.5, 95% CI 0.5 to 0.6). Cumulative use up to 100 Defined Daily Doses was also associated with a decreased risk of hospitalisation (OR 0.7, CI 0.6 to 0.8). No differences in risk were found between typical and atypical antipsychotics, current dosage or different degrees of serotonergic, histaminergic or adrenergic affinity of the antipsychotic.
A decreased risk of hospitalisation for ACS in elderly patients currently using antipsychotics was found. Further research is needed to confirm our results and to determine whether there is a cardioprotective effect or a high non-referral rate in elderly antipsychotic users with ACS.
Heart (British Cardiac Society) 06/2012; 98(15):1166-71. · 4.22 Impact Factor
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ABSTRACT: Aim of the study was to analyze temporal trends in prevalence of hyponatremia over four decades in different settings. A systematic review of the literature from 1966 to 2009 yielded prevalences of hyponatremia, with standard errors (SE) and pooled estimated means (PEM), calculated by year and setting (geriatric, ICU, other hospital wards, psychiatric hospitals, nursing homes, outpatients). 53 studies were included. Prevalence of hyponatremia was stable from 1976 to 2006, and higher on geriatric wards accept for ICU: e.g. PEM prevalence of mild hyponatremia (serum sodium <135mM) was 22.2% (95%CI 20.2-24.3) on geriatric wards, 6.0% (95%CI 5.9-6.1) on other hospital wards and 17.2% (SE 7.0) in one ICU-study; for severe hyponatremia (serum sodium<125mM) these figures were 4.5% (95%CI 3.0-6.1), 0.8% (95%CI 0.7-0.8) and 10.3% (SE 5.6). In nursing homes PEM prevalence of mild hyponatremia was 18.8% (95%CI 15.6-22.2). The higher prevalence on geriatric wards could partly be explained by age-related changes in the regulation of serum sodium. Other underlying factors can be the presence of multiple diagnoses and the use of polypharmacy.
Ageing research reviews 05/2012; 12(1):165-173. · 5.62 Impact Factor
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ABSTRACT: Doelstelling: Hoewel antipsychotica veel worden voorgeschreven bij behandeling van gedragsproblemen bij dementie, zijn onderzoeken naar
het beloop van deze symptomen in verpleeghuizen schaars. Onze primaire doelstelling is het beloop van gedragsproblemen te
beschrijven tijdens de behandeling met antipsychotica in een grote steekproef van oudere verpleeghuispatiënten met dementie.
Methoden: Het beloop van gedragsproblemen tijdens de behandeling met antipsychotica werd bestudeerd door het vergelijken van de kenmerken
van de patiënten voor, tijdens en na de behandeling met antipsychotica. De studie werd uitgevoerd met behulp van de VURAIDB,
een database met meer dan 40.000 beoordelingen van meer dan 10.000 verpleeghuisbewoners in Nederland. We gebruikten de challenging
behaviour profile (CBP) als maat voor het probleemgedrag.
Resultaten: In totaal werden 556 patiënten die met antipsychotica begonnen, onderzocht. Van deze verbeterden 101 (18,2%) en verslechterden
260 patiënten (46,8%) na 3 maanden op de gedragscore, vergeleken met hun scores voor de therapie (z = −7,96, p < 0,0001). Patiënten met ernstig uitdagend gedrag lieten vaker verbetering zien dan patiënten met milde stoornissen. Het
beloop van gedragsproblemen na het staken van het antipsychoticagebruik werd geëvalueerd bij 520 patiënten. Van deze patiënten
bleven 352 (68%) stabiel of verbeterden na 3 maanden in vergelijking met hun scores vóór het staken (z = −0,70, p = 0,486), dit cijfer was 6 maanden na staken 58% (z = −2,77, p = 0,006).
Conclusie: Tijdens de behandeling van verpleeghuisbewoners met dementie met antipsychotica neemt de ernst van de meeste gedragsproblemen
toe bij de meeste patiënten. Bij slechts een op de zes patiënten is er een verbetering. Na het staken van antipsychotica bleven
de gedragsproblemen stabiel of verbeterden in 58% van de patiënten.
Background: Although antipsychotic treatment of behavioral problems in dementia is common, studies investigating the course of these
symptoms in nursing homes are scarce. Our primary objective is therefore to describe the course of behavioral problems during
antipsychotic treatment in a large sample of elderly nursing home patients with dementia.
Methods: The course of behavioral problems during antipsychotic treatment was studied by comparing the characteristics of patients
before, during and after antipsychotic treatment. The study was conducted using the VURAIDB, a database with over 40,000 assessments
of over 10,000 nursing home residents in the Netherlands. We used the Challenging Behavior Profile (CBP) to measure an overall
behavior score.
Results: In total, 556 patients starting with antipsychotics were studied. Of these, 101 (18.2%) improved and 260 (46.8%) deteriorated
at three months on the behavior score, compared with their scores before therapy (z = −7.955; p<0.0001). Patients with severe challenging behavior showed improvement more often than patients with mild disturbances. The
course of behavioral symptoms after withdrawal was evaluated in 520 patients. Of these patients, 352 (68%) remained stable
or improved at 3 months compared with their scores before withdrawal (z = −0.697; p = 0.486), this figure was 58% at 6 months after withdrawal (z = −2.77; p = 0.006).
Conclusions: During treatment of nursing home residents with dementia with antipsychotics the severity of most behavioral problems continues
to increase in most patients, with only one out of six patients showing improvement. After withdrawal of antipsychotics, behavioral
problems remained stable or improved in 58% of patients.
04/2012; 2010(2):70-79.
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Journal of the American Geriatrics Society 10/2011; 59(10):1976-7. · 3.74 Impact Factor
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Journal of the American Geriatrics Society 09/2011; 59(9):1750-2. · 3.74 Impact Factor
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Maarten M van Eijk,
Mark van den Boogaard, Rob J van Marum,
Paul Benner,
Piet Eikelenboom,
Marina L Honing,
Ben van der Hoven,
Janneke Horn,
Gerbrand J Izaks,
Annette Kalf, [......],
Michael A Kuiper,
Frank-Erik de Leeuw,
Tjarda de Man,
Roos C van der Mast,
Robert-Jan Osse,
Sophia E de Rooij,
Peter E Spronk,
Peter H van der Voort,
Willem A van Gool,
Arjen J Slooter
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ABSTRACT: Delirium is often unrecognized in ICU patients and associated with poor outcome. Screening for ICU delirium is recommended by several medical organizations to improve early diagnosis and treatment. The Confusion Assessment Method for the ICU (CAM-ICU) has high sensitivity and specificity for delirium when administered by research nurses. However, test characteristics of the CAM-ICU as performed in routine practice are unclear.
To investigate the diagnostic value of the CAM-ICU in daily practice.
Teams of three delirium experts including psychiatrists, geriatricians, and neurologists visited 10 ICUs twice. Based on cognitive examination, inspection of medical files, and Diagnostic and Statistic Manual of Mental Disorders, 4th edition, Text Revision criteria for delirium, the expert teams classified patients as awake and not delirious, delirious, or comatose. This served as a gold standard to which the CAM-ICU as performed by the bedside ICU-nurses was compared. Assessors were unaware of each other's conclusions.
Fifteen delirium experts assessed 282 patients of whom 101 (36%) were comatose and excluded. In the remaining 181 (64%) patients, the CAM-ICU had a sensitivity of 47% (95% confidence interval [CI], 35%-58%); specificity of 98% (95% CI, 93%-100%); positive predictive value of 95% (95% CI, 80%-99%); and negative predictive value of 72% (95% CI, 64%-79%). The positive likelihood ratio was 24.7 (95% CI, 6.1-100) and the negative likelihood ratio was 0.5 (95% CI, 0.4-0.8).
Specificity of the CAM-ICU as performed in routine practice seems to be high but sensitivity is low. This hampers early detection of delirium by the CAM-ICU.
American Journal of Respiratory and Critical Care Medicine 05/2011; 184(3):340-4. · 11.08 Impact Factor
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ABSTRACT: Elderly patients with multiple morbidities and polypharmacy are at an increased risk of adverse drug events (ADEs). Appropriate prescribing, preserving the balance between drug effectiveness and safety, and treatment adherence may prevent these ADEs. In this study, we investigated which drug properties, such as effectiveness, safety, clinical experience and convenience, are relevant to the choice of medicine most appropriate for frail elderly patients.
The primary aim of this study was to develop a set of criteria to assist in the selection of the most appropriate drug within a drug class for the treatment of frail elderly patients. A secondary goal was to test the usefulness of the set of criteria in the prescription of antipsychotics for delirium and behavioural and psychological symptoms of dementia (BPSD).
Thirty-one criteria potentially relevant to the choice of appropriate drugs for frail elderly patients were selected on the basis of a literature search in MEDLINE (1966-2008), EMBASE (1947-2008) and the Cochrane Library (1993-2008). This list was reviewed by 46 experts (24 physicians, 22 pharmacists), who scored each item for relevance in clinical practice on a scale from 1 to 10 (where 1 is not important and 10 is very important). By consensus, the authors selected the most relevant criteria for the final set of criteria. The usefulness of the final set of criteria was assessed with regard to the prescription of antipsychotics for delirium and BPSD.
The final set of 23 items consisted of 3 items on effectiveness, 14 on safety, including pharmacokinetic and pharmacodynamic criteria, 3 on clinical experience and 3 on convenience. Assessment using these criteria of the appropriateness of antipsychotics prescribed for delirium and BPSD revealed that certain drugs should be prescribed with caution to patients with Parkinson's disease and Lewy body dementia.
The criteria identified in this study, selected on the basis of a literature review and clinical expert opinion, represent a promising approach for determining the appropriateness of a drug for use in frail elderly individuals relative to alternative drugs for the same indication or from the same class.
Drugs & Aging 05/2011; 28(5):391-402. · 2.67 Impact Factor
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Drug Safety 04/2011; 34(4):354-5. · 3.63 Impact Factor
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ABSTRACT: Antipsychotic-induced parkinsonism (AIP) is one of the most common adverse effects of haloperidol. The purpose of this study was to investigate the association between AIP and quality of life of elderly patients treated with haloperidol.
Cross-sectional study design.
Eleven nursing homes, geriatric departments of 2 hospitals, and 3 mental health care centers in the Netherlands.
Participants were 140 elderly patients aged 65 years and older treated for at least 5 days with haloperidol.
The presence of AIP was determined with the Simpson Angus Scale. Quality of life was scored with the QUALIDEM scale. Multivariate linear regression analysis was used to assess whether the presence of AIP and quality of life were correlated. The data of patients with advanced dementia were analyzed separately.
Of the 140 included patients, 65 (46%) were diagnosed with AIP. Patients with AIP scored lower than patients without AIP on the QUALIDEM subscales "positive affect," "negative affect," "social relations," "social isolation," and "having something to do." In patients with advanced dementia, quality of life was not significantly different in patients with or without AIP.
The presence of AIP is negatively associated with the quality of life of elderly patients treated with haloperidol.
Journal of the American Medical Directors Association 02/2011; 13(1):82.e1-5. · 4.64 Impact Factor
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ABSTRACT: Despite serious safety concerns, prescription rates of antipsychotics for the treatment of the behavioral and psychological symptoms of dementia remain high, especially in nursing homes. This high prevalence of antipsychotic use cannot be explained by the modest success rate reported in the literature. In this study, we aim at clarifying the reasons for prescribing an antipsychotic drug in behavioral and psychological symptoms of dementia and look at the role of nurses and family caregivers in the decision-making process that precedes the prescription of an antipsychotic drug.
Questionnaire used in a one-on-one interview with elderly care physicians, nurses, and family caregivers.
We conducted a survey in 23 nursing homes in the Netherlands.
On each dementia ward, the physician selected 1 or 2 patients who started antipsychotics most recently. An interviewer then held a structured questionnaire with the physician, the nurse, and the first relative of the patient. The first part of the interview consisted of questions about the general ideas of the physicians and the second part consisted of case-related questions to physicians, nurses, and family caregivers.
Physicians, nurses, and family caregivers generally consider the possible benefits of antipsychotics to outweigh the risk of side effects. The main reasons to start therapy are agitation and aggression. Physicians felt pressured by nurses to prescribe in 17% of cases. Physicians felt supported by the guideline of the Dutch Association of Elderly Care Physicians. The estimated average success rate in the discussed cases (the patient is expected to improve on the target behavior) among physicians was 50%, nurses reported 53%, and relatives 55%. The most frequently expected adverse reactions were increased fall risk, sedation, and parkinsonism. Nurses expected cognitive decline. The family felt insufficiently informed about the side effects in 44% of the cases.
The interviewed nursing home physicians and nurses expect almost half of their patients with dementia and behavioral disturbances to benefit from antipsychotic therapy. Serious side effects were expected to occur only sporadically. These expectations may contribute to the high rate of antipsychotic use among these patients.
Journal of the American Medical Directors Association 12/2010; 13(1):80.e1-6. · 4.64 Impact Factor
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ABSTRACT: Our aim was to investigate the relationship between exposure to antipsychotic drugs and the risk of venous thromboembolism (VTE) in elderly patients.
A time-matched case-control analysis nested within a cohort of 111,818 patients with at least 1 antipsychotic drug prescription during 1998 to 2008. Data were used from the PHARMO institute's database, which contains drug dispensing data from community pharmacies and hospital admission data. The index date was for the cases defined as the date of hospital admission for VTE (deep venous thrombosis [DVT] or pulmonary embolism) or, for outpatient cases, the start of therapeutic dose low-molecular weight heparin therapy. For each case, 4 controls matched by age and sex were randomly sampled from the cohort.
Two measures were used to evaluate the temporal relationship between antipsychotic drug use and the occurrence of VTE: being a current, recent, or past user and the duration of use up to the index date. The strength of the association was expressed as odds ratios with 95% confidence intervals, taking into account potential confounders.
We identified 367 cases of hospital admission for DVT, 342 cases of hospital admission for PE, and 323 cases of outpatient treatment of DVT. Current exposure to antipsychotic drugs was not associated with an increased risk of VTE, compared with nonusers (odds ratio, 0.9; 95% confidence interval, 0.7-1.1). We found no association between dosage, the duration of use, or the type of antipsychotic drug and the risk of VTE.
We found no evidence of an increased risk of VTE in elderly patients using antipsychotic drugs.
Journal of clinical psychopharmacology 10/2010; 30(5):526-30. · 5.09 Impact Factor
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ABSTRACT: Adverse drug reactions (ADRs) are a common, and often preventable, cause of hospital admission, especially in the elderly, and can occur during hospitalization. In this current opinion article, we present three cases of recurrence of a serious ADR due to re-prescription of a withdrawn medication that highlight the need for a system to prevent the undesirable re-prescription of medications withdrawn because of an ADR. In addition, we describe an electronic system that could help prevent undesirable re-prescription following an ADR. Such a system should document ADRs systematically at the patient level, make this information available to relevant healthcare providers and the patient, and flag re-prescription of the offending drug. The effectiveness and cost effectiveness of such a system would need to be determined.
Drug Safety 07/2010; 33(7):535-8. · 3.63 Impact Factor
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ABSTRACT: Hyponatraemia due to antipsychotic use is a potentially serious problem; however, it is not known whether it is an adverse drug reaction (ADR) to antipsychotic use or is due to the underlying psychiatric disease.
To estimate the strength of the association between antipsychotics and hyponatraemia or syndrome of inappropriate antidiuretic hormone secretion (SIADH), using information reported to the WHO Collaborating Centre for International Drug Monitoring, the Uppsala Monitoring Centre (UMC).
The WHO global individual case safety report database system (VigiBase) maintained by the UMC.
Case-control study, with cases being reports of hyponatraemia/SIADH, and controls being reports of other ADRs. Each case was sampled with ten controls sequencing in time from the date the corresponding case was entered into the database. The potential contribution of the chemical structures and receptor affinity (dopaminergic and/or serotonergic) of the antipsychotics was studied, as was the influence of concomitant use of other medications known to cause hyponatraemia.
The strength of the association between antipsychotic use and hyponatraemia in comparison with other drugs was expressed as reporting odds ratio (ROR), a measure of disproportionality, with corresponding 95% CIs, adjusted for age, sex and concomitant medication associated with hyponatraemia. In addition, stratification by the presence or absence of concomitant medication was performed.
Up to August 2008, 3 881 518 suspected ADRs were reported and filed in VigiBase, with 912 reports on hyponatraemia related to antipsychotics. The adjusted ROR for the association between antipsychotic use and hyponatraemia was 1.58 (95% CI 1.46, 1.70). The adjusted RORs did not vary for the different chemical structures or dopamine D(2) and serotonin 5-HT(2A) receptor affinity profiles. The ROR was 3.00 (95% CI 2.65, 3.39) for the association between hyponatraemia and antipsychotic use in the absence of concomitant medication associated with hyponatraemia, and 1.16 (95% CI 1.06, 1.28) in the presence of concomitant medication associated with hyponatraemia.
Antipsychotic use may be associated with reporting of hyponatraemia. Moreover, the concomitant use of medication associated with hyponatraemia potentially leads to under-reporting of antipsychotic-associated hyponatraemia. We advise testing patients whose psychiatric and/or physical condition deteriorates while on antipsychotics for hyponatraemia.
Drug Safety 07/2010; 33(7):569-78. · 3.63 Impact Factor
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ABSTRACT: Adverse drug reactions (ADRs) are a common, and often preventable, cause of hospital admission, especially in the elderly, and can occur during hospitalization.In this current opinion article, we present three cases of recurrence of a serious ADR due to re-prescription of a withdrawn medication that highlight the need for a system to prevent the undesirable re-prescription of medications withdrawn because of an ADR. In addition, we describe an electronic system that could help prevent undesirable re-prescription following an ADR. Such a system should document ADRs systematically at the patient level, make this information available to relevant healthcare providers and the patient, and flag re-prescription of the offending drug. The effectiveness and cost effectiveness of such a system would need to be determined.
Drug Safety 06/2010; 33(7):535-538. · 3.63 Impact Factor
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Archives of internal medicine 06/2010; 170(12):1085-7. · 11.46 Impact Factor
