Wilma Knol

Antipsychotic Drug Use and Risk of Pneumonia in Elderly People

OBJECTIVES: To investigate the association between antipsychotic drug use and risk of pneumonia in elderly people.

Risk of cerebrovascular events in elderly users of antipsychotics.

It has been shown that elderly patients with dementia treated with atypical and conventional antipsychotics have a twofold increased risk of cerebrovascular adverse events (CVAEs). To investigate the temporal relationship between exposure to antipsychotics and the risk of CVAE, a case-control analysis nested within a cohort of 26,157 community-dwelling patients (mean age 76 ± 9.7) with at least one antipsychotic prescription was conducted. Data were used from Dutch community pharmacies and hospital discharge records. Five hundred and eighteen cases of hospital admission for CVAE were identified. For each case, four randomly selected controls matched by sex and age were sampled from the cohort. To evaluate the temporal relationship between antipsychotic use and the occurrence of CVAE, two measures were used: the first being a current, recent or past user, and the second for the current users, the duration of use up to the index date. In addition, the cumulative exposure was assessed. Current and recent exposure to antipsychotics were associated with an increased risk of CVAE compared with non-users (odds ratio [OR] 1.7, CI 1.4—2.2). A strong temporal relationship was found; the OR for a history of use less than a week is 9.9 (5.7—17.2). The risk decreases in time and is comparable to non-users after 3 months of use (OR 1.0, CI 0.7—1.3). Cumulative exposure was not associated with an increase in risk. The risk of CVAE in elderly patients associated with antipsychotics is elevated especially during the first weeks of treatment. This risk decreases over time and is back on base level after 3 months of treatment. Chronic use is not associated with CVAE.

Prescribing Optimization Method for Improving Prescribing in Elderly Patients Receiving Polypharmacy Results of Application to Case Histories by General Practitioners

BackgroundOptimizing polypharmacy is often difficult, and critical appraisal of medication use often leads to one or more changes. We developed the Prescribing Optimization Method (POM) to assist physicians, especially general practitioners (GPs), in their attempts to optimize polypharmacy in elderly patients. The POM is based on six questions: (i) is undertreatment present and addition of medication indicated; (ii) does the patient adhere to his/her medication schedule; (iii) which drug(s) can be withdrawn or which drugs(s) is/are inappropriate for the patient; (iv) which adverse effects are present; (v) which clinically relevant interactions are to be expected; and (vi) should the dose, dose frequency and/or form of the drug be adjusted?ObjectiveThe aim of this study was to evaluate the usefulness of the POM as a tool for improving appropriate prescribing of complex polypharmacy in the elderly.MethodsForty-five GPs were asked to optimize the medication of two case histories, randomly chosen from ten histories of geriatric patients admitted to a hospital geriatric outpatient clinic with a mean ± SD of 7.9±1.2 problems treated with 8.7±3.1 drugs. The first case was optimized without knowledge of the POM. After a 2-hour lecture on the POM, the GPs used the POM to optimize the medication of the second case history. The GPs were allowed 20 minutes for case optimization. Medication recommendations were compared with those made by an expert panel of four geriatricians specialized in clinical pharmacology. Data were analysed using a linear mixed effects model.ResultsOptimization was significantly better when GPs used the POM. The proportion of correct decisions increased from 34.7% without the POM to 48.1% with the POM (p=0.0037), and the number of potentially harmful decisions decreased from a mean ±SD of 3.3±1.8 without the POM to 2.4±1.4 with the POM (p=0.0046).ConclusionThe POM improves appropriate prescribing of complex polypharmacy in case histories.

Validity and reliability of the Simpson‐Angus Scale (SAS) in drug induced parkinsonism in the elderly

Quantification of drug induced parkinsonism (DIP) for study purposes is difficult. The most often used Simpson Angus Scale (SAS) lacks proper clinimetric evaluation. The newer Schedule for Assessment of Drug‐Induced Movement Disorders (SADIMoD) shows good clinimetric characteristics, but has not been used in published clinical studies, probably due to the complexity of the scale.

Parkinsonism in elderly users of haloperidol: associated with dose, plasma concentration, and duration of use.

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 &mgr;g/L, with one outlying measurement (21.43 &mgr;g/L). Dose is moderate but significantly associated with haloperidol plasma concentration (weighted R2 = 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 R2 = 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.

Efficiency of Clinical Decision Support Systems Improves with Experience

Efficiency, or the resources spent while performing a specific task, is widely regarded as one the determinants of usability. In this study, the authors hypothesize that having a group of users perform a similar task over a prolonged period of time will lead to improvements in efficiency of that task. This study was performed in the domain of decision-supported medication reviews. Data was gathered during a randomized controlled trial. Three expert teams consisting of an independent physician and an independent pharmacist conducted 150 computerized medication reviews on patients in 13 general practices located in Amsterdam, the Netherlands. Results were analyzed with a linear mixed model. A fixed effects test on the linear mixed model showed a significant difference in the time required to conduct medication reviews over time; F(31.145) = 14.043, p < .001. The average time in minutes required to conduct medication reviews up to the first quartile was M = 20.42 (SD = 9.00), while the time from the third quartile up was M = 9.81 (SD = 6.13). This leads the authors to conclude that the amount of time users needed to perform similar tasks decreased significantly as they gained experience over time.

Genetic variation and the risk of haloperidol-related parkinsonism in elderly patients: A candidate gene approach

AbstractFactors 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.

Development of a core outcome set for medication review in older patients with multimorbidity and polypharmacy: a study protocol

Background Medication review has been advocated to address the challenge of polypharmacy in older patients, yet there is no consensus on how best to evaluate its efficacy. Heterogeneity of outcomes reported in clinical trials can hinder the comparison of clinical trial findings in systematic reviews. Moreover, the outcomes that matter most to older patients might be under-reported or disregarded altogether. A core outcome set can address this issue as it defines a minimum set of outcomes that should be reported in all clinical trials in any particular field of research. As part of the European Commission-funded project, called OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly, this paper describes the methods used to develop a core outcome set for clinical trials of medication review in older patients with multimorbidity. Methods/design The study was designed in several steps. First, a systematic review established which outcomes were measured in published and ongoing clinical trials of medication review in older patients. Second, we undertook semistructured interviews with older patients and carers aimed at identifying additional relevant outcomes. Then, a multilanguage European Delphi survey adapted to older patients was designed. The international Delphi survey was conducted with older patients, health care professionals, researchers, and clinical experts in geriatric pharmacotherapy to validate outcomes to be included in the core outcome set. Consensus meetings were conducted to validate the results. Discussion We present the method for developing a core outcome set for medication review in older patients with multimorbidity. This study protocol could be used as a basis to develop core outcome sets in other fields of geriatric research.

Prophylactic Use of Haloperidol and Changes in Glucose Levels in Hospitalized Older Patients

Background Treatment with antipsychotic drugs has been associated with glucose dysregulation in older outpatients, especially in the early stage of therapy. The underlying mechanism is, however, unclear. The aim of this study was to investigate changes in glucose levels during haloperidol use compared with the use of placebo among older hospitalized patients. Methods This substudy was part of a larger multicenter, randomized, double blind, placebo-controlled clinical trial among hospitalized patients aged 70 years and older who had an increased risk of in-hospital delirium. Patients who were admitted to the Jeroen Bosch Hospital in s-Hertogenbosch between June 2014 and February 2015 were invited to participate in the study. Participating patients were randomized for treatment and given 1 mg of haloperidol or a placebo twice daily for a maximum of 7 consecutive days (14 doses). Exclusion criteria for this substudy were the use of corticosteroids and changes in diabetes medication. Random blood samples to determine glucose levels were collected before day 1 and on day 6 of the study. Student independent sample t test was used to determine differences in glucose changes between both groups. Results Twenty-nine patients were included (haloperidol, n = 14; placebo, n = 15). The mean glucose level for placebo users was 139.3 mg/dL (SD, 50.1) on day 1 and 140.8 mg/dL (SD, 45.7) on day 6, and the mean glucose level for haloperidol users was 139.9 mg/dL (SD, 71.0) on day 1 and 150.2 mg/dL (SD, 39.1) on day 6. The difference was not statistically significant (P = 0.685). Conclusions Short-term prophylactic use of haloperidol was not associated with changes in glucose levels in older hospitalized patients compared with those given a placebo in this small study.