Evidence-based information leads to reduction in inappropriate drug prescribing: Results from Indian older inpatients

Abstract

BACKGROUND:

Although several guidelines for appropriate prescribing are available, inappropriate drug prescription remains noteworthy problem among older adults. Indian older patients are also not spare from this issue and existing literature indicates a fair level of inappropriate drug use (IDU).

OBJECTIVES:

Identified potentially IDU and documented their reduction based on provided evidence-based information and also identified possible predictors of IDU in older inpatients.

SETTING:

Three years prospective study included 1510 inpatients aged 60 years or over, of both sexes. IDU identified using the Modified Updated AGS Beers Criteria 2012.

RESULTS:

The patients had an average age of 67.10±0.23 years and on an average were prescribed 9.29±0.11 medications. Using AGS Beers Criteria 2012, total IDU was found to be 21% (n = 325). Of total 287 patients received only one inappropriate drug whereas 38 patients received two or more inappropriate drug(s). According to first list of criteria long acting benzodiazepines, anticholinergics, nitrofurantoin and digoxin were most common IDU. Prescription of theophylline in insomnia followed by aspirin in gastric ulcer and calcium channel blocker in constipation were listed from second list of criteria. 31% reductions in IDU were observed based on evidence-based information regarding each identified inappropriate drugs.

CONCLUSIONS:

The findings of this study provide evidence that provision of unbiased evidenced based information is the best possible means for improvement of pharmacotherapy in older patients.

Keywords

Older adults inpatient IDU AGS Beers criteria 2012 India

1 Introduction

Prescribing of potentially inappropriate drugs to the older patients worldwide is a common issue in healthcare system. It is likely to increase the risk of drug-related problems often leading to substantial morbidity and mortality as well as increased healthcare expenditure [1, 2]. The results of studies in different parts of the world have showed a very high prevalence and recently up to 47% of inappropriate medication use among older patients [3, 4]. Few published reports from India had indicated a higher level of inappropriate drug use in Indian older inpatients [5, 6].

The safer use of medicines in the older patients is an important issue because of multiplicity of drugs prescribed and/or used by them. It is well known fact that prescribing in older is challenging as medication must be considered in the context of altered pharmacokinetics, altered pharmacodynamics and age-related changes in body composition and physiology [7].

By 2040, the world is projected to have 1.3 billion older accounting for 14% of the total population. Developing countries, like India and China, are likely to be home to more than 1 billion people aged 65 years and more (76% of the projected world total) [8]. Simultaneously, with increase in older population, the problems with medicines have also increased [9]. The increase in the number of older adults who need healthcare; due to presence of age related diseases, increase in the chances of hospital admissions, longer hospital stays and more extensive drug therapies. Prescribing in older adults has increased concern among healthcare researchers, providers and policy makers. However, the knowledge among healthcare professionals on the specific health care needs of the older is often controversial and deficient, because the older adults are often exempted from real time clinical safety and efficacy studies and, therefore, the adverse effects of certain medicines on older adults may not be well identified. Only possible way to reduce medicines related problem is reduction of inappropriate medication prescription in older patients.

The assessment of appropriateness of pharmacotherapy should aim to improve the healthcare of the older patients. In India, efforts to assess the geriatric pharmacotherapy have been initiated and initial findings are now available [5, 10]. Therefore, this study aimed to identify potentially inappropriate drug prescribing and document their reduction based on provided evidence-based information and also identify possible predictors of inappropriate drug use (IDU) in older inpatients from medical wards of public tertiary care teaching hospital.

2 Methods

The data on patient files of 1545 older inpatients was collected prospectively from four medical wards of a public teaching hospital. Patients with incomplete information were excluded from the study.

2.1 Study design and population

A prospective study was carried out in an inpatient setting of a public teaching hospital in North India. The inclusion criteria were age of 60 years and above, patients suffering from one or more disease conditions and receiving medications for their ailments.

2.2 Data collection and assessment

Randomly chosen patients’ files of inpatients were studied. The data was assessed using the methodology adopted by Mandavi et al. [5]. Briefly, the patients’ files were checked for an inappropriate drug and a relative severity for each of the medications using Modified American Geriatrics Society Beers Criteria 2012 (AGS Beers criteria 2012) [11]. Concurrent feedback was given to the physician for each identified inappropriate drug and confirmed by physicians, in order to validate the findings.

The study was approved by Ethics Committee of Government Medical College and Hospital. Each patient had given written informed consent. Each patient was assigned a sequential identification number for study purposes.

2.3 Data analysis

All the data was represented as average±SEM or percentages, as appropriate. Odds ratio was used to assess the most common predictors for inappropriate prescribing by comparing inappropriate with appropriate drug use. Statistical significance was determined at 95% level of confidence. A p value ≤0.05 was taken for statistical significance. The potential predictors assessed were age, number of medications, number of diagnoses and length of stay in hospital. The data was analyzed using statistical package for the social sciences (SPSS), Version 16 [12].

3 Results

A total of 1545 patient data were collected during the period of the study. However, 35 were excluded because of incomplete information. Therefore, the findings of this study are based on the data from 1510 hospitalized patients.

Of the 1510 inpatients, 943 were male. The average age of the patients was 67.25±0.2 years. Of the 1510, more than half of the patients belonged to the age group of 60–69 years (62%) while 27.5% belonged to the age group of 70–79 years, and only 10.5% were over 80 years of age.

The average number of diagnosis and average length of stay in the hospital was found to be 2.63±0.03 and 7.40±0.11days days, respectively. The average number of medications prescribed to the patients was 9.15±0.03. The evaluation of the number of medications prescribed showed that 22.5% of the patients received 1–5 medications, 39% received 6–10 medications and 32% received 11–15 medications. Only 6.7% of the patients received more than 15 medications.

The analysis of data for inappropriateness of drug therapy according to Modified AGS Beers criteria showed that 325 patients received at least one inappropriate drug (21%). Over 78.5% of the patients did not have any instance of an IDU. A total of 287 patients received only one inappropriate drug whereas 38 patients received two or more inappropriate drug(s). 365 instances of potentially inappropriate drug use were identified in 325 patients. Therefore, total inappropriate drug use was found to be 24% . The most commonly identified inappropriate drugs were drugs acting on drugs acting on nervous system, anticholinergics, anti-infective for systemic use and cardiovascular system.

The most common inappropriate classes/drugs according to the first list of Modified AGS Beers criteria (Table 1) were long acting benzodiazepines (diazepam, chlodiazepoxide), anticholinergics (promethazine, chlorpheniramine), nitrofurantoin and digoxin.

According to criteria, Nitrofurantoin is inappropriate to prescribe among older not only because it has a potential for toxicity in patients with renal impairment but also the fact that safer alternatives are available. The rationale behind prescription of nitrofurantoin in this study was sensitivity testing that showed only nitrofurantoin as sensitive and flouroquinolones as resistant which is considered as a safer alternative in criteria. On provision of information, only 20 prescriptions with nitrofurantoin were considered inappropriate by physician and patients were switched to other antimicrobial. Other IDUs were anticholinergics and antihistamines (chlorpheniramine, promethazine), amitriptyline, high dose of short-acting benzodiazepines (lorazepam), Amiodarone and mineral oil like.

Inappropriate drugs identified according to the second list of Modified AGS Beers criteria 2012 (Table 2) were theophylline in insomnia, aspirin in gastric ulcer and calcium channel blocker in constipation.

Only inappropriate drug was not identified rather prescribers were also provided evidenced based information for each identified inappropriate drug prescriptions. Upon providing evidence based information about inappropriate drug prescription, changes in the therapy (dose modification or discontinuation of drug) was documented 30.69% reduction in inappropriateness (112 out of 365 inappropriate drugs Table 3).

In this study, the predictors of inappropriate prescribing were also evaluated using odds ratio. Two sets of predictors were determined, i.e. socio-demographic variables (age) and continuous clinical variables like number of medication, number of diagnoses and length of stay in hospital. It was noted that advanced age significantly increased the likelihood of receiving potentially inappropriate medications. Inappropriateprescription was associated with patients with polypharmacy (OR = 5.4), advanced age (>70 years) (OR-1.5) multiple diagnosis (OR-2.4) and increased length of hospital stay (OR-2.2). The effect of each predictor on inappropriate drug prescribing is given in Table 4.

4 Discussion

It was found that 21% of patients were prescribed at least one of the potentially inappropriate medicines listed in the Modified AGS Beers Criteria 2012. The prevalence of inappropriate drug prescription in the current study is higher than that reported earlier (18%) from same setting [5]. This finding is likely due to various reasons such as differences in patients characteristics, chief complaints, diagnoses, prescribing behavior of different physician, introduction of drugs with different brand name and ignorance of age related changes of older.

According to the Modified AGS Beers criteria 2012, there are three types of inappropriate prescriptions. First, the prescription potentially inappropriate medications and classes to avoid in older adults, second is the lists of the potentially inappropriate medications and classes to avoid in older adults with certain diseases and syndromes that the drugs listed can exacerbate and third is the lists medications to be used with caution in older adults.

The most frequently prescribed inappropriate medications were long acting benzodiazepine, anticholinergics, nitrofurantoin and digoxin which belong to the first list while theophylline in insomnia, aspirin in gastric ulcer and calcium channel blockers (amlodipine and diltiazem) in constipation were from the second list of Modified AGS Beers criteria 2012.

Long acting benzodiazepines were the most commonly identified inappropriate drug in this study which is in agreement with other results [13]. These are relatively contraindicated for elderly patients because they increase the risk of impaired cognitive function, falls, and hip fractures [14]. Short-acting benzodiazepines, such as alprazolam, are usually recommended for older for short duration because these agents do not accumulate in the blood, are rapidly cleared from circulation, and offer greater dosage flexibility [15]. In this study, 21 prescriptions (out of 65) were changed from long-acting benzodiazepines to short-acting alternatives.

The second most commonly identified inappropriate drug was anticholinergics and its prevalence was in approximate concordance with the recently published reports from other country (18% vs 24%) [16]. Anticholinergic medications are associated with multiple adverse effects to which older individuals are particularly susceptible. Adverse effects associated with anticholinergic use in older adults include memory impairment, confusion, hallucinations, dry mouth, blurred vision, constipation, nausea, urinary retention, impaired sweating, and tachycardia. Studies have also shown relationship between cognitive impairment and anticholinergic use among older adults [17]. In this study, only 8 prescriptions (out of 26) were changed from chlorphenaramine to alternatives.

The second list of inappropriate prescribing according to the Modified Beers criteria was drugs which are to be avoided in specific disease condition(s).

The most common IDU from second list was prescription of theophylline in insomnia. Theophylline is known to alter sleep architecture because of its affinity to adenosine receptors. One of the consequences of disrupted sleep is impaired cognitive performance. Of the methylxanthines, theophylline has been in use for several decades now. In addition to bronchodilation, it has immunomodulatory, anti-inflammatory and bronchoprotective effects also. However, theophylline often results in a wide range of adverse effects involving cardiac, GIT and central nervous systems which account for the poor compliance and high dropout rates reported with its use. Moreover, it has a narrow therapeutic index which warrants strict monitoring of its levels in the blood. A new methylxanthine derivative (doxophylline) that possesses similar efficacy as theophylline, but has significantly less side effects, may immensely benefit the patients [18].

Of total IDU, 18 patients were prescribed aspirin having history of gastric ulcer which was second most common inappropriate drug from second list of AGS Beers criteria. Upon provision of information to prescriber, dose reductions of aspirin as well as addition of proton pump inhibitors were done to meet the needs of fifteen patients (out of 18 prescription) with previously mentioned condition. This change in therapy was remarkable achievement of information system based IDU reduction.

This study had also evaluated the predictors of inappropriate prescribing. It was found that patients’ characteristics have significant effect on inappropriate prescribing. The most important factors assessed for inappropriate prescription were advanced age (70 years or more), number of medication prescribed, number of diagnosis and longer stay in the hospital.

The number of diagnoses had significant impact on the inappropriate prescribing. This may be explained by simple example that as the number of diagnosis increases, number of medications to treat each particular disease condition also increases [19]. The higher number of medications could trigger inappropriate drug use. These results provide evidence that polypharmacy is common and is significantly associated with inappropriate prescribing. The length of hospital stay also contributed to inappropriate prescribing [20]. The patients staying for more than ten days were more likely to receive an inappropriate medication than patients staying for less than ten days. This finding is explained by the fact that hospitalized patients are frail and at a higher risk of experiencing drug related illnesses.

5 Conclusions

The findings of this study provide evidence that provision of unbiased information is the best possible means for improvement of pharmacotherapy in older inpatients. Informational interventions regarding ASG Beers criteria identified inappropriate drugs avoided occurrence of any adverse event in this older population. In conclusion, the present study suggests that implementation of different criteria useful in identification of inappropriate drug in hospitals is required to reduce inappropriate prescribing among older patients.

Conflict of interest

The authors have no financial conflicts of interest to disclose with respect to this work.

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