The mean age being over 80 years and the higher proportion of women in the studied LTCFs in this study resemble other studies in Brazil [21, 22], as well as those conducted in other countries [2, 23, 24]. The prevalence of drug use in the geriatric population is high, averaging from two to five drugs, depending on the methodology used, with higher consumption among female patients [24]. The use of pharmaceuticals by geriatric female patients may be connected to other singular factors specific to the aging process such as biological, social, and cultural problems [17]. In this sense, it is suggested that pharmaceutical interventions should be aimed specifically at women’s health needs, including increased training of the healthcare staff regarding the pharmacotherapy of morbidities affecting the female population.
Assessment of the pharmacotherapeutic profile
In terms of prevalence of the number of medicines being used, the present study did not exhibit significant differences compared to similar studies [25, 26]. The clinician responsible for each long-term care facility prescribed all medications and, in all three institutions, these were administered by a nursing professional in a similar way to the study by Advinha et al. [24], which adopted as criteria the existence of individual drug records, nursing and medical support. This may help in the transcription of the pharmacotherapeutic profile and the assessment of the MRCI by the pharmacist.
Regarding the occurrence of therapeutic duplicity, the psycholeptic drugs (N05) were the most commonly identified agent in events of redundancy. According to Aguiar et al. [27], the use of psycholeptic drugs in geriatric patients is a common practice. Although the prescription of such drugs is common in Brazil, lack of clinical evidence-based indicators makes this a questionable practice [28]. The literature confirmed that the American Diabetes Association expects the duplication of the use of medicines for diabetes (A10) [29]. Furthermore, studies show that the use of multiple drugs is required to control diabetes and other conditions associated with it [30, 31]. In this sense, the assessment of therapeutic duplicity should not be directly linked to the quality of pharmacotherapy, in which evaluations about the risk-benefit balance cannot be carried out concurrently.
Overall, this study identified significant potential drug interactions in most institutionalized geriatric patients. We suggest requiring the monitoring of the outcomes of treatments prescribed to analyze whether the pharmaceutical interventions prescribed by the physician were of positive clinical significance. The literature confirms a positive association between the number of medicines and the presence of drug interactions pointing to polypharmacy as a precipitating factor of interactions and high mortality rates [32, 33].
Tarantino et al. [39] states that during the aging process there is a decrease in the overall hepatic metabolism of many drugs through the CYP enzyme system, and physiological changes from aging may increase the risk of drug-induced liver injury (DILI). Thus, polypharmacy and the presence of multiple diseases are considered factors that may increase the risk of drug interactions, as well as may cause exponential increase of drug-induced liver injury [34]. Studies have shown that clinically significant interactions are present in the pharmacotherapy of most geriatric patients presenting polypharmacy [16, 35,36,37].
In this study, most geriatric patients used at least one potentially inappropriate medicine. This often presents greater risk than corresponding benefits among this age group because of the increased probability of the incidence of intolerable adverse drug reactions and/or drug interactions. This type of situation is not limited to emerging countries; it is also common in developed countries [38, 39]. This may demonstrate a lack of knowledge regarding potentially inappropriate medications for geriatric patients by clinicians, which may introduce unnecessary risks to institutionalized geriatric patents and, therefore, higher costs for the institution.
It must be emphasized that the majority of potentially inappropriate medications prescribed in the LTCFs were present in the national list of essential and available medicines in the Brazilian health system. As the original foundation of the essential medicines list is to serve all ages and demands 80% of the diseases, we highlight the need for the development of a medications list directed specifically towards the treatment of geriatric patients, ensuring a more appropriate, effective, and safe pharmacotherapy [27]. Moreover, the participation of the clinical pharmacist as a member of the multidisciplinary team can help guide the physician in making decisions about appropriate pharmacotherapy, and evaluate the risk-benefit that the use of potentially inappropriate drugs may provide to the pharmacotherapy of these patients [4, 39].
In a study conducted by Delgado Silveira et al. [40], pharmacist intervention integrated into the multidisciplinary team managing geriatric, multi-pathological patients achieved a significant 59.7% reduction in drug-related problems. For this, further studies should be conducted on the effects of pharmaceutical interventions in order to support this analysis. Another alternative would be to provide a list of inappropriate medications to prescribers delivering positive potential in terms of patient safety [41, 42].
In this study, a significant proportion of the sample presented an increased prevalence of polypharmacy when compared to the literature [16,17,18]. It is worth emphasizing that the number of prescription drugs can be considered a risk factor for possible side effects in this age group [17, 33, 42]. Therefore, more investment is necessary in carrying out interventions focusing on the reduction of polypharmacy, considering the risk of occurrence of clinically-important adverse drug reactions increases by 50% with the concurrent use of five medicines, and 100% in cases that seven or more medicines are used [7, 18]. The same study also identified that in 20% of such cases the polypharmacy may cause severe side effects.
Assessment of the complexity of pharmacotherapy
Few studies in the literature have used the MRCI as a tool to perform the assessment of complexity related to the pharmacotherapy [7, 43]. In this study, the complexity of pharmacotherapy measured by the MRCI obtained a mean of 15.1 ± 9.8 points (range 2–59), which is consistent with similar complexity results shown by Melchiors et al. [10], and demonstrated a mean MRCI of 15.7 points (±8.3, range 4–45.5).
When assessing the MRCI, the higher levels of complexity were associated with dose frequency, apparently related to the prescriptions with multiple schedules and scattered doses. This result differs from the literature, whereby the correlation between the total proportion of the complexity index and its three sections (A, B and C) did not reflect in a direct proportion, as it was expected by the developers of the original instrument [8, 24]. According to George et al. [8], the higher complexity index is the direct result of the individual growth of each section. However, this proportionality is not mentioned by the authors who validated the MRCI for the Brazilian Portuguese [10]. Since few studies have used the MRCI to assess the complexity index, further investigations are needed to confirm that the complexity of pharmacotherapy is not related to the direct proportion of each section (A, B and C) in the MRCI, and may occur disproportionality among them.
The present study found a direct association between the number of medicines used and the MRCI, which is confirmed by other studies in the literature [24, 44]. Although the results pointed out this relationship, the decrease in polypharmacy cannot be considered as the only protection against a higher MRCI [4, 7, 44]. Factors such as drug interactions, potentially inappropriate medications, and therapeutic duplicity may also influence the complexity of pharmacotherapy. Such data were confirmed by the logistic regression analysis where an increase in the MRCI values were associated with a significant increase in the probability of risk of polypharmacy, drug interactions, potentially inappropriate medications for the elderly and therapeutic duplicity. Therefore, pharmaceutical interventions to reduce the complexity index should not focus only on reducing the number of medications used.
The association of drug use with pharmacokinetic and pharmacodynamic changes linked to the aging process creates conditions for the higher risk of side effects and drug interactions observed among geriatric patients [45]. According to the literature, characterizing and simplifying the complexity of pharmacotherapy is necessary as the aging process creates appropriate conditions for the high risk of side effects and potential drug interactions [24, 45]. As a result, the pharmacist should identify and take action to avoid or mitigate potential drug interactions and therapeutic duplicity in order to optimize the risk-benefit relationship that such drugs can provide for these patients [46].
Regarding the three sections of the MRCI, which demonstrated higher levels of complexity, further studies are needed to guide future pharmaceutical interventions. It is believed that this is one of the first studies on Latin America that evaluates the MRCI in institutionalized geriatric patients.
The present study brings together diverse variables that have been analyzed in an isolated way in other studies such as: drug interaction, potentially inappropriate medication for the elderly, therapeutic duplicity and polypharmacy. Such fact allows a broad analysis of the complexity of pharmacotherapy of elderly patients, which may help to identify necessary points that aim towards interventions to reduce the complexity of pharmacotherapy. One limitation of this study is related to the fact that we did not stratify the sample study, considering obesity and mental disorder, once it may have underestimated some of the results. Moreover, this study cannot be generalized for all elderly patients since it was realized in LTCFs.