The National Health and Morbidity Survey (NHMS) 2015 reported that there is an increasing trend in the prevalence of mental health problems among adults. The prevalence of approximately escalates threefold from 10.7% in 1996 to 29.2% in 2015 . Naturally, in keeping with the increasing cases, we would expect a similar increase in the prescribing trends of psychotropic drugs, especially benzodiazepines. However, the Malaysian Statistics on Medicines (MSOM) 2015 reported a drop of 22% in the overall usage of benzodiazepines; from 1.313 DDD/1000 patients/day in 2011 to 1.024 DDD/1000 patients/day in 2014 . In summary, our study showed similar decreasing trends on the number of patients receiving benzodiazepines, the number of benzodiazepines prescriptions and also the DDD of benzodiazepines in comparison to the MSOM 2015. However, the prescribing trends of this study are comparatively low in contrast to other research outside Malaysia that was done during the same study period. Prior research in Australia also showed decreasing trends in benzodiazepines utilisation, though the overall benzodiazepines consumption remained relatively high. There were a total of 27.7, and 20.8 DDD/1000 patients/day of benzodiazepines dispensed in 1992 and 2011, while 14.2 DDD/1000 people/day were dispensed between 2013 to 2016, respectively [19, 20]. Furthermore, the yearly study in Finland also documented a declining trend from 15.7, 14.69 and 13.6 DDD/1000 people/day in 2014, 2015 and 2016, respectively .
The overall reduction trends in the number of prescriptions and the benzodiazepines defined daily dose is likely due to strict governmental enforcement and establishment of levels of authority in relation to prescriber’s category that prevented the widespread usage and over-prescribing of benzodiazepines in government healthcare facilities. The law and regulations covering the benzodiazepines have also prevented ‘doctor shopping’ and self-prescribes by patients via community pharmacies or illegal online stores since a prescription is compulsory for the purchasing of benzodiazepines. Moreover, there are also public educations of benzodiazepines potential adverse effects in this country. The reduction of trends can also be attributed to the changes in the price of benzodiazepines in the market throughout the year of study. However, since the study did not include the estimation of sales and procurement data, we cannot confidently associate to this factor.
Consequently, the prescribing trends of benzodiazepines can be seen as a result of multimodal influence including from patient, prescriber and local prescribing practice [22–25]. Verily, the use of benzodiazepines in each region varies greatly, depending on the nation, legislature and local practice. Benzodiazepine was not uncommon in Japan and was found in up to 11.9% of annual prescriptions in a tertiary care hospital . In Hong Kong and Beijing, benzodiazepine prescription was found in up to 29.9% of prescriptions to 505 outpatients [25, 27]. In North India, half of the psychotic and bipolar patients and two-third of depressive patients of the study group received benzodiazepines .
On the other hand, Kaufmann et al., (2016), Tu, Mamdani, Hux, & Tu, (2001) and Cunningham, Hanley, & Morgan (2010) reported that the elderly (aged 65 and above) to be the majority in using BZDs [29–31]. Benzodiazepines are more dominant in female, and its use is increased steadily with age, which indicates the elderly are usually the highest receiver [18, 30, 32–37].
Nevertheless, there is a significant similarity in view to the age group of benzodiazepines patient of this study compared with other established studies. Most of the patient that received benzodiazepines falls under the age of 45 years old and above. The lower rates of benzodiazepines prescribing to the elderly patients (65 years old and above) receiving benzodiazepines compared to other age groups in this study can be contributed to the practice guidelines which strongly recommended initiation of non-pharmacologic approaches and then the use of antidepressant over benzodiazepines as first-line treatment for insomnia and anxiety among the elderly . Conversely, this finding provides evidence of the prescriber’s adherence to the guidelines.
Alprazolam remained as the most frequent benzodiazepines prescribed to the study cohort throughout the study period. In Malaysia, alprazolam is available in three strength of tablet (0.25mg, 0.5mg and 1mg) while other benzodiazepines only have one strength of tablet. This could be one of the reasons that appointed them as the golden choice for prescribers. Variable options in tablet strength ensure convenience in dose tapering and high suitability for patient compliance. Alprazolam was observed in our study as the most prescribed benzodiazepines in which it is consistent with the findings in the previous works of literature [37, 39–40]. Though the choice of prescribing alprazolam seems to have its legitimacy, it is essential to note that, while alprazolam has a short duration of action, it has higher toxicity in overdose, and has been reported to be associated with fatality in relative to other benzodiazepines .
The choice of benzodiazepines frequently prescribed in the current study differs from other studies, which have been published previously. For instance, Sundaran et al., (2019), Grover et al. (2012) and Tor et al. (2011) found that the most commonly prescribed benzodiazepines were lorazepam and clonazepam [23, 28, 36]. A 20 years (1992–2011) study on benzodiazepines trends in Australia found that surprisingly, temazepam is the most dispensed benzodiazepines in the country, accounting to 35% of the whole prescriptions studied. Meanwhile, previous studies had reported diazepam as the most frequently prescribed [20, 41–43]. Although clonazepam and diazepam both are listed as prescriber category B (ie. a prescription item) by the Ministry of Health Malaysia, they are not as frequently prescribed compared to other benzodiazepines. This gives rise to a question of whether the prescriber who prescribed alprazolam correctly fulfill the authorisation level provided. Therefore, we found that the differences in the choice of benzodiazepines in each country are assumed to be due to availability factors and differences in clinical practice.
Short-acting benzodiazepines such as alprazolam and midazolam are an excellent choice for acute relief of anxiety, panic attack, and stabilising mood. This is because they are rapidly absorbed, thus takes effect more quickly, and their therapeutic effect did not last too long to affect daily life routine. A recent study mentioned that short-acting benzodiazepines are recommended over long-acting benzodiazepines to alleviate the risk of dependency . Furthermore, previous studies also recorded the long-acting formulations of benzodiazepines such as diazepam and lorazepam are the dominant choices among the prescribers [35–36, 42]. Both the usage of short and long-acting benzodiazepines is recommended in many guidelines for different medical conditions. Due to the insufficient data to support the reason behind the selection of short or long-acting formulation, the study could not justify such preference.
In the present study, findings showed that the male patient is more likely to be prescribed with anxiolytics, short-acting benzodiazepines and alprazolam. Additionally, looking into the duration of supply patterns, male patients are more likely to be dispensed with duration of 15 to 30 days, and the benzodiazepines were ordered with a fixed dosing schedule. The significantly higher odds of male prescribed with benzodiazepines can be seen in another study as well . There is a statistically significant association seen between the tested variables and majority of patients aged 45–54 years old are very likely to receive anxiolytics, short-acting benzodiazepines, the duration of supply and the dosing schedule. Referring to Jessell et al., (2020) and Bushnell et al., (2017), they had described that patient aged 40 years and above and diagnosed with psychiatric disorders are more likely to be dispensed with benzodiazepines, especially if the prescribers are from the psychiatric department, compared with if other departments manage the patient [44–45]. The high occurrence of benzodiazepines prescriptions in older patients may reflect an association between age, the prevalence of psychiatric illness and longer benzodiazepine prescriptions. The combination of the above may contribute to adverse clinical outcomes that frequently associated with benzodiazepines in the elderly, such as the risk of fall, dose-dependency and mortality.