FormalPara Key Points

The utilisation of atypical antipsychotic medicines relative to typical antipsychotics increased between 2005 and 2019 despite the risk of adverse metabolic effects posed by atypical antipsychotic medicines.

Despite a reduction in the utilisation of zopiclone in 2019 (25.67 defined daily dose/1000 older people per day) compared with 2005 (29.90 defined daily dose/1000 older people per day), its utilisation relative to other hypnotics and sedatives is greater in 2019.

An interrupted time series to understand the impact of coronavirus disease 2019 on psychotropic drug consumption will be of future interest.

1 Introduction

The utilisation of psychotropic medicines in older adults (aged 65 years or older) continues to be of interest because of overuse [1] and concerns surrounding their safety and efficacy [2]. Psychotropic medicines are associated with adverse clinical outcomes in older adults, including impairments in physical and cognitive functioning [3], greater hospitalisations [4] and a higher mortality risk [5]. Broadly, as a class, they can cause several adverse effects, including weight gain [6], oversedation [7], anticholinergic side effects [8, 9], extrapyramidal symptoms [10, 11] and dependence [12, 13].

Several factors drive psychotropic utilisation, including reimbursement policies [14, 15], subsidy arrangements [16], co-payments, clinical guidelines [7] and pharmaceutical policies [17]. For example, in New Zealand (NZ), the Pharmaceutical Management Agency (PHARMAC) subsidises prescription and therapeutics, and the Royal Australian and NZ College of Psychiatrist’s Faculty of Psychiatry of Old Age have recommended guidelines to rationalise psychotropic medicines [18, 19]. Collectively, examining psychotropic utilisation can inform research and clinical practice, help understand prescribing patterns, the rates of off-label use [20] and funding restrictions [21] and to study the impact of regulatory warnings on prescribing [22].

This study sequels our national study on psychotropic medicine utilisation in older people in NZ from 2005 to 2013 [23]. Several small-scale studies have been conducted on psychotropic utilisation in NZ. For example, in the residential care setting, Tucker and Hosford found that 54.7% of older people in the Hawke’s Bay region in NZ were prescribed one or more psychotropic medicines [24]. In addition, Roberts and Norris reported an increase in antidepressant utilisation between 1993 and 1997 in all regions of NZ [25]. Similarly, Ndukwe et al. found a variation in psychotropic prescribing from 7% to 74% across district health boards in NZ from 2000 to 2013 [26]. However, there are limited data on understanding the trends in psychotropic utilisation over a long period. Since the most recent study published in NZ in 2015 [23], antipsychotics (paliperidone) and hypnotics and sedatives (melatonin) have been introduced and psychotropics discontinued (mianserin, fluphenazine decanoate, trifluoperazine, alprazolam and lormetazepam). The aim of this study, therefore, was to provide an updated analysis to describe and characterise the national trend in the utilisation of psychotropic medicines in older people by age, sex, and type based on the World Health Organization (WHO) Anatomical Therapeutic Chemical (ATC) drug classification system of psychotropic medicines used in New Zealand from 2005 to 2019.

2 Methods

This study was approved by the Human Ethics Committee of the University of Bath, UK (form number 7423).

2.1 Study Design

A retrospective national study of medicine utilisation was undertaken for those aged 65 years and above.

2.2 Data Source

We obtained de-identified dispensing claims data for individuals aged 65 years or older for 2005–19 from the NZ Ministry of Health. The dispensing claims data were extracted from the Pharmaceutical collection by the information analyst at Data Services, Ministry of Health [27, 28]. The Pharmaceutical collection contains medicines funded by PHARMAC. PHARMAC is the New Zealand government agency that decides which pharmaceuticals to fund in NZ publicly and provides funded access to pharmaceuticals for all New Zealanders [18].

2.3 Defined Daily Dose per 1000 Older People Per Day

A defined daily dose (DDD) is the average maintenance dose for the medicine for its main indication in adults. The WHO Collaborating Centre for Drug Statistics Methodology updates DDDs every 3 years. It is a recommended metric for drug utilisation studies as it allows comparisons across countries and regions and evaluates trends over time [29]. The DDD per 1000 older people per day (TOPD) measures the proportion of people treated with a defined daily dose of medicine per 1000 older people per day [7].

2.4 Psychotropic Drug Utilisation

Psychotropic medicines were categorised based on the ATC classification system of the WHO Collaborating Centre for Drug Statistics Methodology [28]. For this analysis, we considered antidepressants (NO6A), antipsychotics (NO5A), anxiolytics (N05B) and hypnotics and sedatives (N05C). We completed the analyses at the therapeutic and chemical levels. The total quantity dispensed for each chemical was extracted from Pharms data and converted to DDD equivalents. The DDD/TOPD was derived by summing the total DDD for 1 year, dividing by the census population and multiplying by 1000. For example, the value of 14 DDD for citalopram in 2005 suggests that 14 out of the 1000 older people in NZ were dispensed a standard dose of 20 mg of citalopram per day. Customised census population data were extracted from NZ statistics [30].

3 Results

3.1 Overall Psychotropic Medicine Utilisation

Psychotropic medicine utilisation was relatively unchanged from 2005 to 2019 (142.42–143.02 DDD/TOPD), corresponding to a 0.42% increase in psychotropic utilisation (Table 1). In addition, utilisation increased for antipsychotics (6.06–19.04 DDD/TOPD) and antidepressants (72.42–75.21 DDD/TOPD). In contrast, utilisation decreased for anxiolytics (10.20–9.87 DDD/TOPD) and hypnotics and sedatives (53.74–38.90 DDD/TOPD) (Table 1, Fig. 1).

Table 1 Psychotropic medicine utilisation in defined daily dose (DDD) per 1000 older people per day (TOPD) from 2005 to 2019
Full size table
Fig. 1
figure 1

Psychotropic utilisation in NZ in older adults aged 65 years and above, by psychotropic classes, 2005–19. The red dotted line represents the mean defined daily dose per 1000 older people per day and is calculated by dividing the sum of the defined daily doses per 1000 older people per day for all years by the study period (15 years)

Full size image

3.2 The Utilisation of Psychotropic Medicines by Age and Sex

The utilisation of psychotropic medicines by age (5-year bands) and sex (DDD/TOPD) and type from 2005 to 2019 increased and peaked in the 95 years and over age group (Fig. 2). The utilisation of antidepressants was highest among all age groups and across both sexes except for the 90–94 years and 95+ years age groups, where hypnotics and sedatives were higher than the utilisation of antidepressants. The utilisation of typical antipsychotics decreased across age groups in both sexes. In contrast, the utilisation of atypical antipsychotics increased remarkably across all age groups and in both sexes.

Fig. 2
figure 2

Psychotropic utilisation in NZ, by age groups and sex, 2005–19

Full size image

3.3 Antidepressants

The utilisation of antidepressants increased by 3.08% from 2005 to 2019 (72.42–75.21 DDD/TOPD). Specifically, the utilisation of selective serotonin reuptake inhibitors (SSRIs) declined slightly (47.67–45.36 DDD/TOPD). In contrast, tetracyclic antidepressants and serotonin noradrenaline reuptake inhibitors increased considerably. Interestingly, the utilisation of tricyclic antidepressants declined substantially (20.37–5.44 DDD/TOPD) (Table 1, Fig. 3).

Fig. 3
figure 3

Typical antipsychotic utilisation in older adults aged 65 years and above by Anatomical Therapeutic Chemical Classification (NO5A), 2005–19. The blue dotted line represents the mean defined daily dose per 1000 older people per day and is calculated by dividing the sum of the defined daily doses per 1000 older people per day for all years by the study period (15 years)

Full size image

3.4 Antipsychotics

Atypical antipsychotic medicine utilisation increased (4.06–18.72 DDD/TOPD) markedly, mainly driven by olanzapine (1.31–8.13 DDD/TOPD) and quetiapine (0.78 to 3.99 DDD/TOPD) (Table 1, Fig. 4). It is noteworthy that in 2014, PHARMAC funded paliperidone, and its utilisation in 2019 was 0.18 DDD/TOPD. In contrast, the utilisation of typical antipsychotic agents is relatively low and remains almost unchanged (2.00–2.06 DDD/TOPD) over the study period (Table 1, Fig. 5).

Fig. 4
figure 4

Atypical antipsychotic utilisation in older adults aged 65 years and above by Anatomical Therapeutic Chemical Classification (NO5A), 2005–19. The blue dotted line represents the mean defined daily dose per 1000 older people per day and is calculated by dividing the sum of the defined daily doses per 1000 older people per day for all years by the study period (15 years)

Full size image
Fig. 5
figure 5

Antidepressant utilisation in older adults aged 65 years and above by Anatomical Therapeutic Chemical Classification (N05A), 2005–19. The blue dotted line represents the mean defined daily dose per 1000 older people per day and is calculated by dividing the sum of the defined daily doses per 1000 older people per day for all years by the study period (15 years)

Full size image

3.5 Anxiolytics

Benzodiazepine (BDZ) utilisation decreased by 3.7% (10.05–9.68 DDD/TOPD) with a rise in the use of lorazepam (5.10–7.00 DDD/TOPD). In addition, for buspirone, a non-BDZ anxiolytic medicine, the utilisation was relatively steady (0.15–0.19 DDD/TOPD) (Table 1, Fig. 6).

Fig. 6
figure 6

Anxiolytic utilisation in older adults aged 65 years and above by Anatomical Therapeutic Chemical Classification (NO5C), 2005–19

Full size image

3.6 Hypnotics and Sedatives

In 2019, the utilisation of zopiclone was also relatively high (25.67 DDD/TOPD) compared with other hypnotics (13.23 DDD/TOPD). Interestingly, among the BDZ-hypnotic class, the utilisation for nitrazepam, temazepam, and triazolam decreased considerably by 85.9%, 57.0%, and 79.4%, respectively (Table 1, Fig. 7).

Fig. 7
figure 7

Hypnotic and sedative utilisation in older adults aged 65 years and above by Anatomical Therapeutic Chemical Classification (NO5C), 2005–19

Full size image

4 Discussion

4.1 Psychotropic Utilisation

The utilisation of psychotropic medicines measured in DDD/TOPD was relatively stable in people aged 65 years and older in New Zealand from 2005 to 2019.

4.2 Antidepressants

The slight increase in the utilisation of SSRI antidepressants and a corresponding decrease in utilisation of anxiolytics and tricyclic antidepressants in our study may be driven by multiple factors, including expanding indications for SSRIs beyond the treatment of depression, including obsessive-compulsive disorders [31], panic disorders [32], chronic pain [33] and its preferential use over anxiolytics for anxiety disorders [34]. Citalopram continued to be the favoured SSRI with the highest utilisation both in 2005 and 2019. An expert consensus guideline on the pharmacotherapy of depressive disorders for older adults rated citalopram the highest for efficacy and tolerability among the SSRIs [35]. The utilisation of tricyclic antidepressants decreased substantially. The increased utilisation of serotonin noradrenaline reuptake inhibitors and tetracyclic antidepressants is largely driven by venlafaxine and mirtazapine, respectively. Venlafaxine and mirtazapine are recommended second-line treatments for depression after an initial trial of an SSRI, and a systematic review found that they are more effective than paroxetine and fluoxetine [36].

Interestingly, randomised clinical trials that compared venlafaxine to other SSRIs found its safety in older adults is comparable to SSRIs, and the risk for venlafaxine-induced electrocardiogram changes and corrected QT prolongation is low [37, 38]. In clinical practice, the selection of antidepressants in older adults must be guided by patient-specific factors such as comorbidity and susceptibility to anticholinergic effects. Citalopram and sertraline have few drug interactions, are less anticholinergic than tricyclic antidepressants and are recommended for treating depression in older adults.

4.3 Antipsychotics

Despite the increased risk for cardiovascular and metabolic adverse effects [39, 40], the utilisation of atypical antipsychotic medicines increased (4.06–18.72 DDD/TOPD) in older people. However, a corresponding decline in typical antipsychotic medicine (2.00–2.60 DDD/TOPD) utilisation occurred, potentially because of the increased risk of extrapyramidal symptoms and the perceived benefit of better efficacy for atypical antipsychotics [41]. Nevertheless, the preferential use of atypical antipsychotics over typical antipsychotics is a consistent finding in NZ [42] and internationally despite no evidence for their superiority in terms of efficacy or safety [43, 44]. In 2019, among the typical antipsychotic medicines, haloperidol utilisation was the highest, and among the atypical antipsychotic medicines, olanzapine was the highest. Additionally, in a study comparing 16 countries, quetiapine was the antipsychotic used in most countries, followed by risperidone and olanzapine [45].

Furthermore, the increased use of atypical antipsychotics may be attributed to them often being prescribed for other mental disorders, including mood and anxiety disorders, insomnia and agitation [46]. The utilisation of clozapine increased from 0.18 to 0.81 DDD/TOPD. An international study involving 17 countries found that clozapine is still underutilised across several countries despite increased use in recent years. The study found that Finland, followed by New Zealand, has the highest clozapine utilisation rates [47].

In older adults, the risk of anticholinergic effects, extrapyramidal symptoms, the adverse cardiovascular effects of typical antipsychotic medicines and the risk of adverse metabolic effects posed by atypical antipsychotic medicines must be considered. Therefore, the recommendation to treat psychosis in older adults is to use low-dose atypical antipsychotic medicines for the shortest possible duration and wherever feasible on a case-to-case basis to switch to non-pharmacological options [48].

4.4 Anxiolytics

Benzodiazepine utilisation decreased slightly. In 2019, lorazepam was the most widely used benzodiazepine. In our published study in 2015, we highlighted concerns regarding using alprazolam and concerns about abuse, dependence and tolerance [49]. Interestingly, in 2016, PHARMAC stopped funding for alprazolam for new patients [50].

4.5 Hypnotics and Sedatives

Overall, the utilisation of hypnotics and sedatives has declined in NZ older adults (53.74–38.90 DDD/TOPD), but the higher utilisation of zopiclone relative to other BDZs is alarming. Similar concerns of high prescribing of zopiclone in older adults relative to other BDZs were reported in Europe and England [51]. In 2015, we highlighted the risk posed by zopiclone, which accounted for more than 50% of utilisation of hypnotics, as it has been associated with cognitive impairment [52], confusion, and falls or fractures in older people [53], the reduction in the utilisation of zopiclone in 2019 (25.67 DDD/TOPD) compared to 2005 (29.90 DDD/TOPD) is a welcome change.

The high utilisation of zopiclone relative to other hypnotics in 2019 could be attributed to the increased prevalence of insomnia in older adults [54, 55]. However, its use should be restricted to short-term use to mitigate harm in older adults, and non-pharmacological interventions for the management of insomnia must be given precedence [56].

4.6 Strengths and Limitations

One limitation of the study was that the WHO uses doses for the main indications to compute DDDs, but several psychotropic medicines have expanded indications. Therefore, we could not examine the appropriateness of treatment because of a lack of information on the indication for using psychotropic medicine. We also assumed that all adhered to their prescribed psychotropic regime; hence actual utilisation may be overestimated. However, it is pertinent to highlight that the Pharmaceutical collections maintained by the Ministry of Health are comprehensive. In addition, the reimbursement system captures greater than 95% of the prescription coverage of the census population of older adults, strengthening the validity of our study findings.

5 Conclusions

Psychotropic medicine utilisation was relatively stable from 2005 to 2019 in older adults in NZ. Though antidepressant utilisation remained relatively stable, there was a five-fold increase in antipsychotic medicine use mainly driven by the increased utilisation of atypical antipsychotics. Our findings suggest that a high proportion of older adults have been prescribed olanzapine and zopiclone, and the reasons for their use and the risk-benefit ratio warrant further investigation. In addition, the rising trend in the utilisation of melatonin recently funded by PHARMAC should be monitored closely. Continued monitoring of psychotropic medicine utilisation will be of great interest to understand if the utilisation of psychotropic medicines, particularly antidepressants and antipsychotic medicines during the coronavirus disease 2019 pandemic year, will change relative to previous years and how the changes will impact the health of older adults in the long term.