Conclusions

The overall increase in prevalence rates of BZD dispensations during the study period and the unexpectedly high proportion of individuals who were prescribed a BZD on a long-term basis at a young age indicate a lack of congruence with international and national guidelines. These findings highlight the need for close monitoring of prescribing practices, particularly in non-psychiatric settings, in order to build an evidence base for safe and efficient BZD treatment in young persons.

Background

Pharmacoepidemiological studies have long raised concerns on widespread use of benzodiazepines and benzodiazepine-related drugs (BZDs), in particular long-term use, among adults and the elderly. In contrast, evidence pertaining to the rates of BZD use at younger ages is still scarce, and the factors that influence BZD utilisation and shape the different prescribing patterns in youths remain largely unexplored. We examined the prevalence rates, relative changes in rates over time, and prescribing patterns for BZD dispensation in young people aged 0–24 years in Sweden during the period January 1, 2006–December 31, 2013, and explored demographic, clinical, pharmacological, and prescriber-related attributes of BZD prescribing in this group.

Methods and findings

Through the linkage of 3 nationwide Swedish health and administrative registers, we collected data on 17,500 children (0–11 years), 15,039 adolescents (12–17 years), and 85,200 young adults (18–24 years) with at least 1 dispensed prescription for a BZD during 2006–2013, out of 3,726,818 Swedish inhabitants aged 0–24 years. Age-specific annual prevalence rates of BZD dispensations were adjusted for population growth, and relative changes in rates were calculated between 2006 and 2013. We analysed how BZD dispensation varied by sex, psychiatric morbidity and epilepsy, concurrent dispensation of psychotropic medication, type of dispensed BZD, and type of healthcare provider prescribing the BZD. Prescribing patterns were established in relation to duration (3 months, >3 to ≤6 months, or >6 months), dosage (<0.5 defined daily dosage [DDD]/day, ≥0.5 to <1.5 DDD/day, or ≥1.5 DDD/day), and “user category” (“regular users” [≥0.5 to <1.5 DDD/day for ≥1 year], “heavy users” [≥1.5 DDD/day for ≥1 year], or otherwise “occasional users”). Multinomial regression models were fitted to test associations between BZD prescribing patterns and individual characteristics of study participants. Between 2006 and 2013, the prevalence rate of BZD dispensation among individuals aged 0–24 years increased by 22% from 0.81 per 100 inhabitants to 0.99 per 100 inhabitants. This increase was mainly driven by a rise in the rate among young adults (+20%), with more modest increases in children (+3%) and adolescents (+7%). Within each age category, overall dispensation of BZD anxiolytics and clonazepam decreased over time, while dispensation of BZD hypnotics/sedatives, including Z-drugs, showed an increase between 2006 and 2013. Out of 117,739 study participants with dispensed BZD prescriptions, 65% initiated BZD prescriptions outside of psychiatric services (92% of children, 60% of adolescents, 60% of young adults), and 76% were dispensed other psychotropic drugs concurrently with a BZD (46% of children, 80% of adolescents, 81% of young adults). Nearly 30% of the participants were prescribed a BZD for longer than 6 months (18% of children, 31% of adolescents, 31% of young adults). A high dose prescription (≥1.5 DDD/day) and heavy use were detected in 2.6% and 1.7% of the participants, respectively. After controlling for potential confounding by demographic and clinical characteristics, the characteristics age above 11 years at the first BZD dispensation, lifetime psychiatric diagnosis or epilepsy, and concurrent dispensation of other psychotropic drugs were found to be associated with higher odds of being prescribed a BZD for longer than 6 months, high dose prescription, and heavy use. Male sex was associated with a higher likelihood of high dose prescription and heavy use, but not with being prescribed a BZD on a long-term basis (> 6 months). The study limitations included lack of information on actual consumption of the dispensed BZDs and unavailability of data on the indications for BZD prescriptions.

Why was this study done?

  • Benzodiazepines and benzodiazepine-related drugs (BZDs) are among the most widely used psychotropic medications in the world and have long raised public health concerns due to the risk for their users of developing dependence and severe adverse effects, in particular among long-term users.
  • The prevalence rates and attributes of BZD use have been well described in adults and the elderly.
  • In contrast, evidence regarding BZD prescribing for younger populations is scarce and fragmented, and factors influencing BZD utilisation in children, adolescents, and young adults remain largely unexplored.

What did the researchers do and find?

  • We linked nationwide Swedish health and administrative registers on 3,726,818 individuals aged 0–24 years living in Sweden between 2006–2013, among whom 17,500 children (0–11 years), 15,039 adolescents (12–17 years), and 85,200 young adults (18–24 years) were dispensed a BZD prescription at least once during that period.
  • The prevalence rate of BZD dispensation has increased by 22% between 2006 and 2013, and has increased particularly in young adults.
  • For nearly 65% of all study participants with 1 or more dispensed BZD prescriptions, the first prescription was issued outside specialised psychiatric services. Most first prescriptions originated from primary care (41%) and non-psychiatric specialist settings (24%) such as paediatrics and internal medicine.
  • Over 75% of study participants were dispensed other psychotropic medication concurrently with a BZD, raising concerns about the potential risk of drug interactions.
  • Almost 30% were prescribed a BZD for longer than 6 months, contradicting international and national guidelines that advise against BZD use beyond 2–4 weeks for adults and generally discourage prescribing BZDs for ages below 18 years.

What do these findings mean?

  • There is a need for clinicians, particularly those working in non-psychiatric services, to implement strategies to avoid potentially harmful patterns of prescribing BZDs to young people.
  • Young individuals who are prescribed BZDs should be closely monitored, in particular, with respect to duration of BZD treatment and concurrent prescription of other psychotropic drugs.
  • Citation: Sidorchuk A, Isomura K, Molero Y, Hellner C, Lichtenstein P, Chang Z, et al. (2018) Benzodiazepine prescribing for children, adolescents, and young adults from 2006 through 2013: A total population register-linkage study. PLoS Med 15(8): e1002635. https://doi.org/10.1371/journal.pmed.1002635