Abstract
Objectives
Anxiety and sleep disorders are common in the population and anxiolytics and sedatives are widely used. Our aim was to describe the drug utilization of new users of anxiolytics and sedatives in adults including type of drug, doses, prescribers' characteristics, and psychiatric comorbidity.
Methods
A register‐based cohort study of new users (18–64 years) of anxiolytics and sedatives in 2015–2019, free of any such drug 5 years prior to inclusion. The individuals were linked to national registers on dispensed drugs and recorded diagnoses.
Results
In total, 764,432 new users of anxiolytics and sedatives were identified, which corresponds to an incidence of 26/1000 inhabitants and year. The proportion of new users of benzodiazepines (including both anxiolytics and sedatives) decreased, whereas the proportion of sedative antihistamines and melatonin increased. The most common drug dispensed was hydroxizin (33%) followed by benzodiazepine related drugs (zopiclone and zolpidem; 20%), propiomazine (14%) and benzodiazepines (13%). The majority (68%) of the prescriptions were from primary care. Most new users were prescribed 1–30DDDs and 52% among women and 49% among men were dispensed their drug only once during the first year. Half of the new users had a previous comorbid psychiatric disorder.
Conclusions
The findings are well reflecting the recommendations in national guidelines.
Keywords: anxiety, benzodiazepines, incidence, new users, sedatives
1. INTRODUCTION
Anxiety‐ and sleep disorders are common in the population. Globally, 46 million patients were estimated to be newly diagnosed with anxiety disorders in 2019 (Yang et al., 2021). In the European Union, the prevalence of sleep disorder was estimated to 7% of the population (Wittchen et al., 2011). Comorbidity with psychiatric and somatic diseases is common, for example, among individuals with a current anxiety disorder, more than 80% were also diagnosed with depression at some point in life (Lamers et al., 2011). Despite that non‐pharmacological treatment such as sleep hygiene interventions and cognitive behavioural therapy are first line treatments for sleep disorders, drugs such as anxiolytics and sedatives are widely prescribed (Huerta et al., 2016; Islam et al., 2014; Kjosavik et al., 2012; Kurko et al., 2018). Anxiolytics and sedatives include different types of pharmacological and chemical drug classes including benzodiazepines, sedative antihistamines, propiomazine and melatonin. In clinical praxis, also other drug classes are used to treat anxiety disorders such as selective serotonin reuptake inhibitors (SSRIs). The group of anxiolytics and sedatives includes drugs with a known risk of developing addiction, in particular benzodiazepines and benzodiazepine related drugs. In most countries, these drugs are regulated under drug control laws and are available on prescriptions only (European Monitoring Centre for Drugs and Drug Addiction, 2021). National guidelines in Sweden now aim to reduce their use in the population (The National Board of Health and Welfare, 2021a).
Globally, the utilization of anxiolytics has decreased in approximately 70% of the countries included in the organisation for economic co‐operation and development (OECD) statistics during the years 2015–2019 (OECD Stat, 2022). During the same period, the use of hypnotics and sedatives varied across countries with an increased use observed in for example, Canada, Finland, Lithuania and Spain and a decrease in for example, Austria, Iceland, Luxembourg and Slovenia among others (OECD Stat, 2022). The utilization of anxiolytics and sedatives increase steadily with age and the usage is more common among women than men (Huerta et al., 2016; Kjosavik et al., 2012; van der et al., 2009). The most prevalent anxiolytics were oxazepam and diazepam and the most prevalent hypnotics were zopiclone and zolpidem (Islam et al., 2014; Kjosavik et al., 2012; Kurko et al., 2018). Even though anxiolytics and sedatives are widely used, there are few studies describing the number of dispensations and the amount prescribed. The Swedish Medical Products Agency was given a mission by the Swedish Government to monitor the utilization of these drugs, with a special focus on drugs with a known risk of developing addiction. The mission was to describe the use of anxiolytics and sedatives regardless of the indication for treatment and regardless of if other drug classes are first line treatment for these conditions. Therefore, the aim of this study was to describe the drug utilization of new users of anxiolytics and sedatives in adults including type of drug, doses, prescribers' characteristics, and psychiatric comorbidity.
2. METHODS
2.1. Study design
This cohort study used individual data of new users of anxiolytics and sedatives linked from several national health data registers to assess first time prescription of anxiolytics and sedatives by drug type, doses, and psychiatric comorbidity. The study cohort comprises all adults aged 18–64, residing in Sweden and with a first dispensed prescription of an anxiolytic or sedative in 2015–2019. The date of the first prescription was defined as their index date. To select only new users of anxiolytics and sedatives, those with any prescription of an anxiolytic or sedative drug within 5 years prior to index date were excluded. The total Swedish population in 2015 was 9,851,017 of whom 5,878,713 were aged 18–64 years (Ludvigsson et al., 2016; Statistics Sweden, 2022).
2.2. National health data registers
The nationwide Prescribed Drugs Register, which started in July 2005, was used to identify prescriptions for anxiolytics and sedatives and concomitant psychiatric medication (Wallerstedt et al., 2016; Wettermark et al., 2007). The National Patient Register, was used to identify diagnoses in both in‐patient and specialised out‐patient care related to records of psychiatric specialized care and care for addiction disorders (Ludvigsson et al., 2011). Sweden has a universal and tax‐financed health care systems, and reporting to national registers is mandatory.
2.3. Anxiolytics and sedatives
Anxiolytics and sedatives were defined using Anatomical Theraputic Chemical (ATC)‐codes as: Benzodiazepines (anxiolytics; N05BA) including diazepam, oxazepam, lorazepam and alprazolam; Benzodiazepines (sedatives and anxiolytics; N05CD) including nitrazepam, flunitrazepam; Benzodiazepine and related drugs (sedatives; N05CF) including zopiclone and zolpidem; Propiomazine N05CM06; Sedative antihistamines including hydroxyzine (N05BB01), alimemazine and promethazine (R06AD); and Melatonin (N05CH01) (WHO Collaborating Center for Drug Statistics Methodology, 2021).
The first prescribed drug was defined as the first prescription (index) after a drug free period of 5 years for each patient. For patients dispensed more than one of the anxiolytic and sedative drugs included in the study at index, the following hierarchic order was used to decide which drug was included in the analyses: (i) N05BA, (ii) N05CD, (iii) N05CF, (iv) N05CM06, (v) Other (all other drugs included and not listed elsewhere), (vi) N05CH01.
2.4. Volume and frequency dispensed
The dispensed volume of anxiolytics and sedatives were measured using the defined daily dose (DDD). DDD is a measure assigned by the World Health Organization (WHO) defined as the assumed average dose per day for a drug used for its main indication in adults (WHO Collaborating Center for Drug Statistics Methodology, 2022). The number of DDDs were calculated for the first dispensed prescription and categorized into the following groups: 1–10, 11–30, 31–50, 51–100 and 101 or more DDDs. The number of dispensations within 365 days of the index date were summed and categorized into the following groups: 1, 2, 3, 4 and 5 or more dispensations.
The prescriptions to patients with dispensable doses were excluded when calculating the number of DDDs and the number of dispensations during the first year, because dispensable doses drugs normally correspond to 14 days of use (The Pharmaceutical Benefits Act).
2.5. Prescriber characteristics
The workplace of the prescriber of the first anxiolytic or sedative prescription of each patient was defined based on the type of workplace. The workplace was categorized as: (i) Psychiatric care, (ii) Primary care and (iii) Other (all workplaces not listed in i‐ii).
For each patient, the number of unique workplaces prescribing benzodiazepines (ATC‐codes N05BA, N05CD and N05CF) during the indexyear was calculated.
2.6. Comorbid psychiatric and addiction disorders
Comorbid psychiatric disorder was defined as having any visit in psychiatric specialized out‐patient care or hospitalization with a main diagnosis of mental or behavioural diagnosis according to the Swedish clinical modification of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD‐10‐SE: F20‐F99) within 5 years before the index date (Swedish translation of the International).
Addiction disorder was defined as having any visit in psychiatric specialized out‐patient care or hospitalization with a main diagnosis of mental or behavioural diagnosis due to psychoactive substance use (ICD‐10‐SE: F10‐F19) within 5 years before the index date or a filled prescription of drugs used in addictive disorders (N07BB or N07BC) within 5 years before the index date.
Patients were classified as (i) Psychiatric disorder but not addiction disorder, (ii) Psychiatric‐ and addiction disorder, (iii) Addiction disorder but not psychiatric disorder, (iv) No psychiatric‐ or addiction disorder. Within the group of individuals with no recorded psychiatric‐ or addiction disorder in specialized psychiatric outpatient care or in patient care (group iv), a sub‐group with psychiatric co‐medication was defined. Psychiatric co‐medication was denoted when a patient was dispensed an antidepressant ATC‐code N06A or a psychostimulant N06B up to 365 days before the index date.
2.7. Statistical calculations
Standard descriptive statistics were used to describe the study cohort and the utilisation patterns. The number of individuals per 1000 inhabitants was calculated using the Swedish population as of November 1st 2015. The data on the number of dispensations within 365 days was age standardized using the same population data. The proportion of individuals with repeated prescriptions of benzodiazepines (ATC‐codes N05BA, N05SD, N05CF) up to three years after initiation was calculated. An individual was classified as a repeated user each year when at least three dispensations of benzodiazepines was done. The difference in proportions among women and men were tested using Fisher's exact test. Data processing and statistical analysis was performed in the SAS software, version 9.4 and R version 3.5.1 (R Core Team, 2020).
2.8. Ethical approval
The study was approved by the Swedish Ethical Review Authority (no 2020‐00338).
3. RESULTS
Among the 764,432 new users of anxiolytics and sedatives aged 18–64 years, 59% were women. The average annual incidence was 31 per 1000 inhabitants for women and 21 per 1000 inhabitants for men (Table 1). The incidence was highest among the youngest age group (35 per 1000 for women aged 18–24 years and 22 per 1000 for men) and decreased with increasing age. The overall number of new users decreased over the study period 2015–2019 for both women (Figure 1a) and men (Figure 1b). Benzodiazepines and related drugs (sedatives) decreased from 21,962 women in 2015 to 11,129 in 2019. The corresponding numbers for men were 17,467 in 2015 and 9827 in 2019. Sedative antihistamines increased by 14% among women and 16% among men over the study period. Melatonin increased by over 300% among both women and men.
TABLE 1.
New users of anxiolytics and sedatives in Sweden 2015–2019 (N = 764,432).
| Age group | Number (number per 1000 inhabitants) | ||
|---|---|---|---|
| Women | Men | All | |
| 18–64 years | 451,256 (31) | 313,176 (21) | 764,432 (26) |
| 18–24 | 70,169 (35) | 46,814 (22) | 116,983 (28) |
| 25–34 | 114,459 (34) | 76,305 (21) | 190,755 (28) |
| 35–44 | 97,612 (31) | 65,670 (20) | 163,282 (26) |
| 45–54 | 95,837 (29) | 66,154 (20) | 161,991 (24) |
| 55–64 | 73,188 (25) | 58,233 (20) | 131,421 (23) |
FIGURE 1.
(a) The number of new women per drug class and year. (b) The number of new men per drug class and year.
The prescribing physician's most common workplace was in primary care which accounted for 68% of the new users' prescriptions. Physicians in psychiatric care accounted for 14% of the prescriptions and the remaining 18% were a variety of prescribing specialities including occupational health services, internal medicine, and obstetrics.
The amount prescribed per individual at the first prescription was 1–30 DDDs for most of the prescriptions, 79% among women and 76% among men (Table 2). Among new users prescribed melatonin 20% of women and 25% of men were prescribed at least 101 DDDs. Among new users prescribed anxiolytics or sedatives 1% or lower were prescribed at least 101 DDDs.
TABLE 2.
Number of DDDs at first prescription by sex and drug class.
| Number of DDDs at first prescription | |||||
|---|---|---|---|---|---|
| 1–10 | 11–30 | 31–50 | 51–100 | 101+ | |
| N (%) | N (%) | N (%) | N (%) | N (%) | |
| Women | 181,051 (40) | 173,379 (39) | 49,271 (11) | 38,949 (9) | 5183 (1) |
| Benzodiazepines (anxiolytics, N05BA) | 43,573 (78) | 11,126 (20) | 903 (2) | 164 (0) | 33 (0) |
| Benzodiazepines (anxiolytics and sedatives, N05CD) | 46 (8) | 315 (56) | 126 (23) | 69 (12) | <5 |
| Benzodiazepine and related drugs (sedatives, N05CF) | 25,805 (30) | 55,031 (64) | 784 (1) | 3870 (5) | 28 (0) |
| Propiomazin (N05CM06) | a | 29,122 (52) | 22,063 (39) | 4836 (9) | 66 (0) |
| Sedative antihistamines (N05BB01, R06AD) | 111,627 (48) | 66,867 (29) | 24,836 (11) | 25,657 (11) | 1212 (1) |
| Melatonin (N05CH01) | a | 10,918 (55) | 559 (3) | 4353 (22) | 3841 (20) |
| Men | 116,562 (38) | 116,230 (38) | 41,318 (13) | 29,916 (10) | 5311 (2) |
| Benzodiazepines (anxiolytics, N05BA) | 29,506 (72) | 10,240 (25) | 948 (2) | 334 (1) | 148 (0) |
| Benzodiazepines (anxiolytics and sedatives, N05CD) | 37 (6) | 299 (50) | 143 (24) | 103 (17) | 11 (2) |
| Benzodiazepine and related drugs (sedatives, N05CF) | 20,340 (29) | 44,107 (64) | 611 (1) | 4206 (6) | 45 (0) |
| Propiomazin (N05CM06) | a | 22,995 (48) | 20,090 (42) | 5156 (11) | 119 (0) |
| Sedative antihistamines (N05BB01, R06AD) | 66,679 (50) | 30,303 (23) | 19,144 (14) | 16,206 (12) | 882 (1) |
| Melatonin (N05CH01) | a | 8286 (50) | 382 (2) | 3911 (23) | 4114 (25) |
No approved package sizes.
Most new users (52% among women and 49% among men) were only dispensed anxiolytics and sedatives once during the first year (Figure 2). The proportion of women aged 18–24 years with at least five dispensations the first year was 14%. And the corresponding proportion for men were 15%.
FIGURE 2.
Number of dispensations per patient during the first year by sex and age group, age standardized.
In total, 48% of the new users of anxiolytics and sedatives had a previous comorbid psychiatric or addictive disorder, where of, 14% had a recorded diagnosis in specialized outpatient care or inpatient care and 34% had no recorded diagnosis but had a dispensation of either an antidepressant or psychostimulant within the last year. Among new users of benzodiazepines (anxiolytics), 11% had a previous psychiatric disorder recorded (Table 3). The corresponding proportion for new users of benzodiazepines (sedatives and anxiolytics) was 19%. For new users of Melatonin, 30% had a previous psychiatric or addictive disorder recorded.
TABLE 3.
The number of new users with previous specialized psychiatric‐ and addiction care and psychiatric co‐medication (dispensed up to 365 days before the index date) by drug class.
| Benzodiazepines (anxiolytics, N05BA) | Benzodiazepines (sedatives and anxiolytics, N05CD) | Benzodiazepine and related drugs (sedatives, N05CF) | Propiomazine (N05CM06) | Sedative antihistamines (N05BB01, R06AD) | Melatonin (N05CH01) | |
|---|---|---|---|---|---|---|
| N (%) | N (%) | N (%) | N (%) | N (%) | N (%) | |
| All | 99,221 (100) | 1197 (100) | 156,628 (100) | 105,535 (100) | 364,929 (100) | 36,922 (100) |
| Specialized psychiatric care, not addiction care | 10,458 (11) | 227 (19) | 13,668 (9) | 12,020 (11) | 45,434 (12) | 9643 (26) |
| Specialized psychiatric care AND addiction care | 765 (1) | 27 (2) | 1130 (1) | 1429 (1) | 4420 (1) | 837 (2) |
| Addiction care, not specialized psychiatric care | 2122 (2) | 43 (4) | 2426 (2) | 3230 (3) | 8518 (2) | 856 (2) |
| Neither specialized psychiatric care nor addiction care | 85,876 (87) | 900 (75) | 139,404 (89) | 88,856 (84) | 306,557 (84) | 25,586 (69) |
| Subgroup with co‐medication of N06A | 39,583 | 263 | 47,673 | 33,252 | 126,999 | 8905 |
| N06B | 639 | 16 | 927 | 585 | 2034 | 1334 |
Among the 122,451 new users of benzodiazepines in 2015–2016, 20,423 (17%) were dispensed benzodiazepines at least three times the index year. The proportion of these patients with at least three dispensations also the year after was 40% among women and 39% among men (Figure 3). There was no difference in the proportion among women or men with at least three dispensations up to 3 years after index (p = 0.45). Of the 20,423 new users with at least three dispensations during the index year, the majority was only prescribed benzodiazepines from one workplace (67% of women and 65% of men). The proportion of patients with three or more different workplaces was 7%.
FIGURE 3.
New users with at least three dispensations of benzodiazepines (ATC‐codes N05BA, N05CD, N05CF) and the number refilling their prescriptions up to three years after initiation (indexyear).
4. DISCUSSION
In this cohort study of new users of anxiolytics and sedatives, the proportion initiating treatment were similar over the study period 2015–2019. Among new users, there were more women than men. The proportion of new users of benzodiazepines (including both anxiolytics and sedatives) decreased, whereas the proportion of sedative antihistamines and melatonin increased during the study period. The amount prescribed at initiation corresponded to a small package for use up to 30 days. In addition, most new users were dispensed their drug only once during the first year. Half of the new users had comorbid psychiatric disorder that is, previous recorded psychiatric disorder, addiction disorder or previous dispensed antidepressants or psychostimulants.
The incidence of new users was lower in our study compared to a Norwegian study (Kjosavik et al., 2012). One explanation for the discrepancy can be that all individuals 20 years and above were included in that study whereas we only included individuals 18–64 years of age. Also, we used a 5‐year drug free period to classify an individual as a new user whereas the Norwegian study used a 1‐year period. Hence, in the Norwegian study, some of the new users were recent recurrent users (e.g., users with a dispensation within 1–5 years, that would not be regarded as new users in our study). A higher incidence and prevalence among women has been established (Huerta et al., 2016; Kjosavik et al., 2012; van der et al., 2009). In our study, the highest incidence was found in the youngest age group both for women and men. This is the inverse trend of the findings in the Norwegian study and can probably be explained by our strict definition of new users. When using aggregated Swedish data by age and sex of anxiolytics and sedatives use, the proportion of prevalent users increases by age (The National Board of Health and Welfare, 2021b).
Our findings of a declining trend in the dispensing patterns of benzodiazepines (both anxiolytics and sedatives) were confirmed in other studies (Islam et al., 2014; Kurko et al., 2018). In general, the same type of benzodiazepines was dispensed in our study as has been shown by others (Islam et al., 2014; Kjosavik et al., 2012). The most common benzodiazepines were diazepam and oxazepam and the most common sedatives were zopiclone and zolpidem. As in other studies, most new users in our study were initiated treatment with anxiolytics or sedatives in primary care (Kjosavik et al., 2012; Panes et al., 2020). The proportion of individuals with repeated benzodiazepine dispensations after 3 years was lower in our study (Kurko et al., 2018). This may in part be explained by the different age distributions of the studies where we only included new users aged 18–64 years and the other study included all new users without age restrictions.
A history of comorbid psychiatric or addiction disorder was common in our study. In a Belgian study using self‐reported questionnaire data, the proportion of anxiolytic users with comorbid mental health problems was higher compared to our study (van der et al., 2009). This could be explained by that questionnaire data also captures self‐reported less severe conditions that a person would not seek medical care for, compared to our data where all conditions have been diagnosed by a physician. Other studies have analysed co‐medications with psychotropic drugs and shown that around one fourth to one third of patients dispensed anxiolytic benzodiazepines were also dispensed at least one psychotropic drug (Benard‐Laribiere et al., 2017; Panes et al., 2020). A high proportion of concomitant dispensations of psychiatric medications was also found in a paediatric study of melatonin users (Kimland et al., 2021).
The major strength of our study is the population‐based cohort design, including unique individual data on all new users of anxiolytics and sedatives, complete follow‐up, and large sample size. Other advantages include the availability of excellent data on dispensed drugs, comorbid conditions, and prescriber characteristics from complete and valid nationwide Swedish registers.
However, there are some limitations to consider. Anxiolytics and sedatives given to hospitalized patients are not included as these data are not possible to link to a specific patient. The analyses are based on dispensed prescriptions of the patients, not the actual intake of medicine. Information on indication for treatment is not available. Also, DDD is a unit of measurement and does not necessarily correspond to the Prescribed Daily Dose. Hence, comparisons of DDD between substances can be problematic, especially for melatonin where the prescribed daily dose can vary substantially. The patient register contains information on hospitalizations and doctor's visits to specialized outpatient care, but there is some under‐reporting foremost from private care providers (Ludvigsson et al., 2011).
5. CONCLUSIONS
The drug utilization of benzodiazepines and benzodiazepine related drugs have decreased during the study period 2015–2019. During the same period, sedative antihistamines and melatonin have increased. In general, a small package was prescribed at initiation and most new users were dispensed their drug only once during the first year. The findings are well reflecting the recommendations in national guidelines.
AUTHOR CONTRIBUTIONS
All authors developed the hypothesis and study design. Carola Bardage obtained ethical approval. Elin Dahlén managed data and did the statistical analysis, with contributions from Rickard Ljung and a senior statistician. Elin Dahlén, Carola Bardage, Paulina Tuvendal and Rickard Ljung did the literature search. Elin Dahlén and Rickard Ljung wrote the first and successive draughts of the manuscript. All authors contributed to study concept and design, analysis, and interpretation of data, and drafting or critical revision of the manuscript for important intellectual content. Carola Bardage and Rickard Ljung had full access to the data in the study and had final responsibility for the decision to submit for publication.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.
Supporting information
Table S1
Dahlén, E. , Bardage, C. , Tuvendal, P. , & Ljung, R. (2024). New users of anxiolytics and sedatives in Sweden—Drug type, doses, prescribers' characteristics, and psychiatric comorbidity in more than 750,000 patients. International Journal of Methods in Psychiatric Research, e1998. 10.1002/mpr.1998
DATA AVAILABILITY STATEMENT
According to Swedish Law the data cannot be placed in a publicly available repository. Researchers can after ethical approval from the Swedish Ethical Review Authority (https://etikprovningsmyndigheten.se) apply for data from the National Board of Health and Welfare, Stockholm, Sweden (www.socialstyrelsen.se). The Swedish Medical Products Agency will consider proposals for research collaboration. Enquiries can be submitted to the agency (registrator@lakemedelsverket.se with a copy to the corresponding author elin.dahlen@lakemedelsverket.se).
REFERENCES
- Benard‐Laribiere, A. , Noize, P. , Pambrun, E. , Bazin, F. , Verdoux, H. , Tournier, M. , Bégaud, B. , & Pariente, A. (2017). Trends in incident use of benzodiazepines and Z‐drugs in France from 2006 to 2012: A population‐based study. Pharmacoepidemiology and Drug Safety, 26(2), 162–169. 10.1002/pds.4123 [DOI] [PubMed] [Google Scholar]
- European Monitoring Centre for Drugs and Drug Addiction . (2021). New benzodiazepines in Europe—a review. Accessed November 2022.
- Huerta, C. , Abbing‐Karahagopian, V. , Requena, G. , Oliva, B. , Alvarez, Y. , Gardarsdottir, H. , Miret, M. , Schneider, C. , Gil, M. , Souverein, P. C. , d e Bruin, M. L. , Slattery, J. , d e Groot, M. C. H. , Hesse, U. , Rottenkolber, M. , Schmiedl, S. , Montero, D. , Bate, A. , Ruigomez, A. , …, & de Abajo, F. J. (2016). Exposure to benzodiazepines (anxiolytics, hypnotics and related drugs) in seven European electronic healthcare databases: A cross‐national descriptive study from the PROTECT‐EU project. Pharmacoepidemiology and Drug Safety, 25(Suppl 1), 56–65. 10.1002/pds.3825 [DOI] [PubMed] [Google Scholar]
- Islam, M. M. , Conigrave, K. M. , Day, C. A. , Nguyen, Y. , & Haber, P. S. (2014). Twenty‐year trends in benzodiazepine dispensing in the Australian population. Internal Medicine Journal, 44(1), 57–64. 10.1111/imj.12315 [DOI] [PubMed] [Google Scholar]
- Kimland, E. E. , Bardage, C. , Collin, J. , Jarleborg, A. , Ljung, R. , & Iliadou, A. N. (2021). Pediatric use of prescribed melatonin in Sweden 2006–2017: A register based study. European Child & Adolescent Psychiatry, 30(9), 1339–1350. 10.1007/s00787-020-01598-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kjosavik, S. R. , Ruths, S. , & Hunskaar, S. (2012). Use of addictive anxiolytics and hypnotics in a national cohort of incident users in Norway. European Journal of Clinical Pharmacology, 68(3), 311–319. 10.1007/s00228-011-1124-2 [DOI] [PubMed] [Google Scholar]
- Kurko, T. , Saastamoinen, L. K. , Tuulio‐Henriksson, A. , Taiminen, T. , Tiihonen, J. , Airaksinen, M. , & Hietala, J. (2018). Trends in the long‐term use of benzodiazepine anxiolytics and hypnotics: A national register study for 2006 to 2014. Pharmacoepidemiology and Drug Safety, 27(6), 674–682. 10.1002/pds.4551 [DOI] [PubMed] [Google Scholar]
- Lamers, F. , van Oppen, P. , Comijs, H. C. , Smit, J. H. , Spinhoven, P. , van Balkom, A. J. , Nolen, W. A. , Zitman, F. G. , Beekman, A. T. F. , & Penninx, B. W. J. H. (2011). Comorbidity patterns of anxiety and depressive disorders in a large cohort study: The Netherlands study of depression and anxiety (NESDA). The Journal of Clinical Psychiatry, 72(3), 341–348. 10.4088/jcp.10m06176blu [DOI] [PubMed] [Google Scholar]
- Ludvigsson, J. F. , Almqvist, C. , Bonamy, A. K. , Ljung, R. , Michaelsson, K. , Neovius, M. , Stephansson, O. , & Ye, W. (2016). Registers of the Swedish total population and their use in medical research. European Journal of Epidemiology, 31(2), 125–136. 10.1007/s10654-016-0117-y [DOI] [PubMed] [Google Scholar]
- Ludvigsson, J. F. , Andersson, E. , Ekbom, A. , Feychting, M. , Kim, J. L. , Reuterwall, C. , Heurgren, M. , & Olausson, P. O. (2011). External review and validation of the Swedish national inpatient register. BMC Public Health, 11(1), 450. 10.1186/1471-2458-11-450 [DOI] [PMC free article] [PubMed] [Google Scholar]
- OECD stat‐pharmaceutical market. [Internet]. Available online: https://stats.oecd.org 2022.
- Panes, A. , Pariente, A. , Benard‐Laribiere, A. , Lassalle, R. , Dureau‐Pournin, C. , Lorrain, S. , Tournier, M. , & Fourrier‐Réglat, A. (2020). Use of benzodiazepines and z‐drugs not compliant with guidelines and associated factors: A population‐based study. European Archives of Psychiatry and Clinical Neuroscience, 270(1), 3–10. 10.1007/s00406-018-0966-3 [DOI] [PubMed] [Google Scholar]
- R Core Team . (2020). R: A language and environment for statistical computing. R Foundation for Statistical Computing. Retrieved from https://www.R‐project.org/ [Google Scholar]
- Statistics Sweden . (2022). Population statistics. [Internet]. Retrieved from https://www.statistikdatabasen.scb.se/pxweb/sv/ssd/START__BE__BE0101__BE0101A/BefolkningR1860N/
- Swedish translation of the international classification of diseases, 10th revision (ICD‐10‐SE), World health organization. [Internet]. Available from: https://www.socialstyrelsen.se/statistik‐och‐data/klassifikationer‐och‐koder/icd‐10/
- The National Board of Health and Welfare . (2021a). Nationella riktlinjer för vård vid depression och ångest.
- The National Board of Health and Welfare . (2021b). Statistical database, pharmaceuticals.
- The pharmaceutical Benefits Act (SFS 2002:160 5§).
- v an der Heyden, J. H. , Gisle, L. , Hesse, E. , Demarest, S. , Drieskens, S. , & Tafforeau, J. (2009). Gender differences in the use of anxiolytics and antidepressants: A population based study. Pharmacoepidemiology and Drug Safety, 18(11), 1101–1110. 10.1002/pds.1827 [DOI] [PubMed] [Google Scholar]
- Wallerstedt, S. M. , Wettermark, B. , & Hoffmann, M. (2016). The first decade with the Swedish prescribed drug register—a systematic review of the output in the scientific literature. Basic and Clinical Pharmacology and Toxicology, 119(5), 464–469. 10.1111/bcpt.12613 [DOI] [PubMed] [Google Scholar]
- Wettermark, B. , Hammar, N. , Fored, C. M. , Leimanis, A. , Otterblad Olausson, P. , Bergman, U. , Persson, I. , Sundström, A. , Westerholm, B. , & Rosén, M. (2007). The new Swedish Prescribed Drug Register‐‐opportunities for pharmacoepidemiological research and experience from the first six months. Pharmacoepidemiology and Drug Safety, 16(7), 726–735. 10.1002/pds.1294 [DOI] [PubMed] [Google Scholar]
- WHO Collaborating Center for Drug Statistics Methodology . (2021). Oslo. Guidelines for ATC classification and DDD assignment. [Accessed 2021 June].
- WHO Collaborating Center for Drug Statistics Methodology . (2022). Oslo Guidelines for ATC classification and DDD assignment.
- Wittchen, H. U. , Jacobi, F. , Rehm, J. , Gustavsson, A. , Svensson, M. , Jonsson, B. , Olesen, J. , Allgulander, C. , Alonso, J. , Faravelli, C. , Fratiglioni, L. , Jennum, P. , Lieb, R. , Maercker, A. , van Os, J. , Preisig, M. , Salvador‐Carulla, L. , Simon, R. , & Steinhausen, H. C. (2011). The size and burden of mental disorders and other disorders of the brain in Europe 2010. European Neuropsychopharmacology, 21(9), 655–679. 10.1016/j.euroneuro.2011.07.018 [DOI] [PubMed] [Google Scholar]
- Yang, X. , Fang, Y. , Chen, H. , Zhang, T. , Yin, X. , Man, J. , Yang, L. , & Lu, M. (2021). Global, regional and national burden of anxiety disorders from 1990 to 2019: Results from the global burden of disease study 2019. Epidemiology and Psychiatric Sciences, 30, e36. 10.1017/s2045796021000275 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1
Data Availability Statement
According to Swedish Law the data cannot be placed in a publicly available repository. Researchers can after ethical approval from the Swedish Ethical Review Authority (https://etikprovningsmyndigheten.se) apply for data from the National Board of Health and Welfare, Stockholm, Sweden (www.socialstyrelsen.se). The Swedish Medical Products Agency will consider proposals for research collaboration. Enquiries can be submitted to the agency (registrator@lakemedelsverket.se with a copy to the corresponding author elin.dahlen@lakemedelsverket.se).