Rob J. van Marum

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of medication indicated; (ii) does the patient adhere to his/her medication schedule; (iii) which drug(s) can be withdrawn or which drugs(s) is/are inappropriate for the patient; (iv) which adverse effects are present; (v) which clinically relevant interactions are to be expected;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.

Reasons to Prescribe Antipsychotics for the Behavioral Symptoms of Dementia: A Survey in Dutch Nursing Homes Among Physicians, Nurses, and Family Caregivers

OBJECTIVES 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. DESIGN Questionnaire used in a one-on-one interview with elderly care physicians, nurses, and family caregivers. SETTING We conducted a survey in 23 nursing homes in the Netherlands. METHOD 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. RESULTS 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. CONCLUSION 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.

Antipsychotic-induced hyponatraemia: a systematic review of the published evidence

Hyponatraemia is known to occur as a rare but clinically important adverse reaction to treatment with different psychotropic drugs, including selective serotonin reuptake inhibitors and antiepileptic drugs. In past decades, reports have been published that describe the development of hyponatraemia in association with antipsychotic drug treatment. Our objective was to systematically review the available evidence on antipsychotic-induced hyponatraemia, focussing on patient characteristics, drug dosage, polydipsia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH).A search was carried out in the MEDLINE and EMBASE databases from January 1966 to 11 April 2009. Inclusion criteria were (i) hyponatraemia (serum sodium level <136 mmol/L) occurring after the start of treatment with an antipsychotic drug; and (ii) that the hyponatraemia potentially occurred as an adverse reaction to antipsychotic drug treatment in accordance with the WHO definition. Articles in languages other than English, Dutch, German, French and Spanish were excluded. Information on patient characteristics, medical and diagnostic data, pharmacological treatment, drug dechallenge and drug rechallenge were extracted from the publications whenever available. A causality assessment was performed on all case reports using Naranjo’s adverse drug reaction probability scale. Correlational analysis was performed to assess correlations between antipsychotic drug dosage and both serum sodium level and time to onset of hyponatraemia.We included four studies and 91 publications containing case reports and case series; no randomized controlled studies were identified. Data from the identified case reports were further analysed. The mean age of the patients was 46 years; 57% were male. The diagnosis was schizophrenia in 70% of the cases. A history of polydipsia was diagnosed as positive in 67% of the cases and negative in 23% of the cases. Polydipsia occurred in the remaining 10% of cases, although it was reported to be drug-induced (i.e. a severe increase in water intake was observed in relation to treatment with the suspected drug). Analysis of the case reports using the adverse drug reaction probability scale indicated possible causality in most cases (80%), probable causality in a significant amount of cases (19%) and unlikely causality in one case (1%). Overall correlational analysis yielded no significant correlations between defined daily dose-equivalent dosages and serum sodium or time to onset of hyponatraemia.The incidence of hyponatraemia induced by antipsychotics may be much higher than is currently thought. Both the newer atypical antipsychotics and the older drugs have been associated with the development of hyponatraemia. Physicians, psychiatrists and other healthcare workers should be aware of the possibility of hyponatraemia associated with the use of antipsychotics. Further studies are required to establish the risks of and risk factors associated with antipsychotic-induced hyponatraemia.

Hypothermia following antipsychotic drug use

ObjectiveHypothermia is an adverse drug reaction (ADR) of antipsychotic drug (APD) use. Risk factors for hypothermia in ADP users are unknown. We studied which risk factors for hypothermia can be identified based on case reports.MethodCase reports of hypothermia in APD-users found in PUBMED or EMBASE were searched for risk factors. The WHO international database for Adverse Drug Reactions was searched for reports of hypothermia and APD use.ResultsThe literature search resulted in 32 articles containing 43 case reports. In the WHO database, 480 reports were registered of patients developing hypothermia during the use of APDs which almost equals the number of reports for hyperthermia associated with APD use (n = 524). Hypothermia risk seems to be increased in the first days following start or dose increase of APs. APs with strong 5-HT2 antagonism seem to be more involved in hypothermia; 55% of hypothermia reports are for atypical antipsychotics. Schizophrenia was the most prevalent diagnosis in the case reports.ConclusionEspecially in admitted patients who are not able to control their own environment or physical status, frequent measurements of body temperature (with a thermometer that can measure low body temperatures) must be performed in order to detect developing hypothermia.

Psychotropic medications, including short acting benzodiazepines, strongly increase the frequency of falls in elderly

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.

Renal function assessment in older adults

AIMS The Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD) and the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formulae are often used to estimate glomerular filtration rate (GFR). The objective was to determine the best method for estimating GFR in older adults. METHODS A cross-sectional study was conducted at the geriatric wards of two hospitals in The Netherlands. Patients aged 70 years or above with an estimated (e)GFR below 60 ml min⁻¹  1.73 m⁻² were included. The CG, CG calculated with ideal bodyweight (IBW), MDRD and CKD-EPI formulae were compared with a criterion standard, sinistrin clearance. Renal function was classified into five stages according to the National Kidney Foundation Disease Outcomes Quality Initiative chronic kidney disease classification, as follows (in ml min⁻¹  1.73 m)⁻²: stage 1, eGFR ≥ 90; stage 2, eGFR of 60-89; stage 3, eGFR of 30-59; stage 4, eGFR of 15-29; and stage 5, eGFR < 15. RESULTS Sixteen patients, 50% male, with a mean age of 82 years (range 71-87 years) and mean body mass index 26 kg m⁻² (range 18-36 kg m⁻²), were included. On average, all formulae slightly overestimated GFR, as follows (in ml min⁻¹  1.73 m⁻²: CG +0.05 [95% confidence interval (CI) -28 to +28]; CG with IBW +0.03 (95% CI -20 to +20); MDRD +9 (95% CI -16 to +34); and CKD-EPI +5 (95% CI -20 to +29). They classified kidney disease correctly in 68.8% (CG), 75% (CG with IBW), 43.8% (MDRD) and 68.8% (CKD-EPI) of the participants, respectively. CONCLUSIONS The CG, CG with IBW, MDRD and CKD-EPI formulae estimate the mean GFR of a population rather well. In individual cases, all formulae may misclassify kidney disease by one stage.

Prevalence of hyponatremia on geriatric wards compared to other settings over four decades: A systematic review

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 <135 mM) 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<125 mM) 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.

Age-related decline in autonomic control of blood pressure: implications for the pharmacological management of hypertension in the elderly.

Autonomic control of blood pressure appears to decline with age giving rise to an increased risk of orthostatic hypotension and major hypotensive reactions to antihypertensive drugs. In the past few years, many workers have assessed autonomic function in the elderly and sometimes found controversial results. Baroreflex sensitivity, as measured by the steepness of the heart rate/mean pressure curve, decreases with age. However, this phenomenon does not correlate well with orthostatic impairment. Sympathetic dysfunction might be more responsible for syncopal symptoms in the elderly, a finding supported by the fact that elderly with orthostatic symptoms never collapse within a few seconds, but do so after 1 or more minutes of standing. However, the results of sympathetic function testing in the elderly indicate that sympathetic function in most elderly is not impaired and that sympathetic activity, as measured by circulating levels of catecholamines, is usually increased rather than decreased.In various populations with increased sympathetic activity, but not in the elderly, β-adrenoceptor antagonists (β-blockers) have been demonstrated to cause pressor effects, presumably due to α-adrenoceptor-mediated vasoconstriction unopposed by β-receptor-mediated vasodilation. In the past year, large studies have been completed indicating that the same is true for the elderly, and that the depressor effect on pulse pressure upon standing in this category of patients can be offset and turned into a pressor effect by long-term β-blocker treatment. This phenomenon could not be demonstrated with non-β-blocker antihypertensive drugs, including ACE inhibitors, calcium channel antagonists, diuretics and angiotensin II receptor antagonists. In elderly patients β-blockers may, therefore, be the most appropriate antihypertensive agents as they protect the elderly from orthostatic impairment.

Multidisciplinaire richtlijn Polyfarmacie bij ouderen

SamenvattingVerduijn MM, Leendertse AJ, Moeselaar A, De Wit NJ, Van Marum RJ. Multidisciplinaire richtlijn Polyfarmacie bij ouderen. Huisarts Wet 2013;56(8):414-9. 65-Plussers met multimorbiditeit die bij verschillende specialisten onder behandeling staan hebben een verhoogd risico op schade door gebruik van geneesmiddelen. Van veel geneesmiddelen zijn de effectiviteit en veiligheid bij deze kwetsbare patiëntengroep niet vastgesteld. De huisarts kan het risico beperken door bij het voorschrijven de aanbevelingen uit de multidisciplinaire richtlijn Polyfarmacie bij ouderen te volgen en gebruik te maken van de zogenaamde START- en STOPP-criteria in de richtlijn. Daarnaast kan de huisarts geïntegreerde farmacotherapeutische zorg verlenen door samen met de apotheker met behulp van de STRIP (Systematic Tool to Reduce Inappropriate Prescribing) systematisch de medicatie te beoordelen volgens het stappenplan medicatiebeoordeling. Om de medicatiebeoordeling goed te kunnen implementeren ontbreekt nog een aantal randvoorwaarden.AbstractVerduijn MM, Leendertse AJ, Moeselaar A, De Wit NJ, Van Marum RJ. Multidisciplinary guideline for polypharmacy in the elderly. Huisarts Wet 2013;56(8):414-9. Older (> 65 years) patients who are being treated by different specialists for multiple medical problems are at increased risk of medication-related adverse effects. Unfortunately, little is known about the efficacy and safety of many medicines in these vulnerable patients. General practitioners can limit the risk of adverse effects by following the recommendations of the ‘Polypharmacy for the Elderly’ guideline and by using the START (Screening Tool to Alert doctors to Right Treatment) and STOPP (Screening Tool of Older Person’s Prescriptions) criteria of the guideline. In addition, GPs can work with pharmacists to provide integrated pharmaceutical care by system atically evaluating the medicines prescribed using the stepwise approach of the STRIP (Systematic Tool to Reduce Inappropriate Prescribing). However, a number of preconditions for a good evaluation of medications have still to be met.

Structured history taking of medication use reveals iatrogenic harm due to discrepancies in medication histories in hospital and pharmacy records.

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