At the end of the study, 81.5 % of elderly patients achieved deprescription, with clinically irrelevant signs and symptoms. This rate of deprescription was similar to that observed in a study carried out in a long-term institution in Belgium (84 %), however, the frequency of total deprescription was higher than the present study: 65.8 % stopped consuming benzodiazepine compared to 22.2% of the present work [33]. The fact that the Belgian study presented a total deprescription greater than our study can be explained by the fact that in long-term institutions, the health professional has greater control over the daily dose used and can offer more constant care to the elderly, and in the case of the present study the elderly are in the community, which can make it difficult to control the daily dose and have immediate access to information.
In another study, carried out in health centers in Spain, the general rate of deprescription (67.1 %) was lower when compared to our data. However, the total withdrawal rate was higher (45.2 %) than our study [34]. Another research team, also in Spain, obtained as a result 64.3 % of total benzodiazepine deprescription with the help of melatonin [35]. Other possible reasons for this difference observed among the individuals who achieved total deprescription in the aforementioned studies are different follow-up times, sociodemographic and economic differences between research participants, different clinical conditions, and medications in use, in addition to covering the entire class of benzodiazepines and not just a single medication, as is the case with our protocol.
The main reasons for using clonazepam (anxiety, insomnia and depression) found in our study were the same reported in studies conducted in the United States and Spain, which pointed out that insomnia and anxiety are the reasons why 75 % of patients (older adults or not) use benzodiazepines [34, 36]. The chronic use of these medications is not indicated for the causes mentioned [5–11], and may lead to serious adverse reactions, such as falls and fractures. Our study found a prevalence of 40 % of falls. Falls associated with the use of benzodiazepines have been reported by several authors; Coutinho and Dutra concluded that the risk of a benzodiazepine user suffering falls is 109 % higher than those who do not use this class of medication [37–40]. A study conducted in the Netherlands found that approximately 60 % of patients using medication suffered one or more falls, and exposure to psychotropic drugs increases the chance of an individual falling by 96 % [41].
Regarding the signs and symptoms of withdrawal from clonazepam, these were uncommon and of no clinical relevance. Several authors report that withdrawal syndrome, when using long duration benzodiazepines (as is the case with clonazepam), is milder than in relation to short duration benzodiazepines, which show symptoms of lack of medication more quickly and intensely [42–45]. However, the increase in some symptoms such as insomnia, nightmares and hallucinations, in addition to the change in blood pressure in some patients in the two weeks after the last withdrawal of the dose (between the fourth and fifth meetings), highlights the need to review the last fraction of withdrawal of the medication, since in the tested protocol, 25 % of the initial dose was withdrawn, and other benzodiazepine protocols in general recommend that the last and penultimate withdrawal be 12.5 % [46–47].
Analyzing this last withdrawal of the dose of clonazepam, it was observed that sleep disorders, which obtained their lowest rates in intermediate meetings, practically returned to the numbers before the intervention. Several studies show that sleep quality improves with the use of melatonin [34, 48–49]. The systematic review conducted by Reeve et al. evidenced that the majority of the studies did not show significant difference in the quality of the sleep before and after deprescription, but that during the process of the gradual withdrawal, there can be a worsening of the quality of sleep, a fact that we observed only in the last withdrawal of the dose, between the fourth and fifth meetings [48].
Regarding the average daily dose of clonazepam, it is important to note that the increase in the average dose observed in the fourth meeting can be explained by the behavior of a patient, who at the beginning of the study used 7 mg of the drug, and went to 5.3 mg and 4 mg in the second and third meetings, respectively. On the fourth meeting they doubled the dose and ended the follow-up using 8 mg of clonazepam per day.
A positive impact on the quality of life of patients who achieved deprescription has been reported in several studies [50–52], corroborating our results. It should be noted that quality of life, sleep, and the signs and symptoms of withdrawal from clonazepam and other benzodiazepines were measured in different instruments in different studies, making the comparison between studies limited.
Regarding the difference between the number of potential patients identified and those who achieved deprescription (only 27.2 % continued in the study), it was observed that this also occurs in other studies. Research carried out in Belgium and Finland obtained results of 28 % and 24 %, respectively, showing how low the proportion of eligible patients is and who accept the process of deprescription [33, 35].
This loss is mainly due to the fear of not being able to sleep and/or increased anxiety. These too, were the main reasons reported in other studies [53, 54]. Analyzing the causes of exclusion of patients from the study, the history of suicidal thoughts and attempts at suicide stood out for their frequency and clinical relevance. In the literature there is a meta-analysis carried out in 2019, which explains the association between the use of benzodiazepines and ideation and suicide attempts. The authors identified that these suicide attempts also occur when psychiatric symptoms are already under control [35]. This spells out the need for caution before and during the benzodiazepine deprescription process.
Regarding the limitations of this study, the small number of participants stands out, in addition to the absence of a control group and a random sample. Patient availability and the involvement of the entire primary health care team are also major challenges to implement this type of protocol in the real world. However, among the potentialities, it is important to highlight that this is the first study that analyzes the applicability of a specific clonazepam deprescription protocol, and that considers the reality of elderly Brazilians attended in the primary care of the Brazilian Unified Health System (SUS). Finally, it is important that the effectiveness of this protocol is tested in a randomized clinical trial, with a significant sample, and with the necessary adjustments so that it is widely used in health systems.