Patterns of non-medical use of benzodiazepines and Z-Drugs among adolescents and young adults: gender differences and related factors

ABSTRACT

Background: We aimed to report the prevalence and factors associated with non-medical use of BZD and Z-Drugs in adolescents and young adults residing in Spain from a gender perspective. Nationwide, cross-sectional study on the misuse of BZD and Z-Drugs by young adult population of both sexes.

Method: We used individualized secondary data retrieved from the 2015–2016 Household Survey on Alcohol and Drugs in Spain. A total of 10,824 survey respondents aged 15 to 34 years.

Results: Prevalence of non-medical use of BZD and Z-Drugs was.42%, 1% in men vs. 1.84% in women, p = .00. Zolpidem presents the highest misuse rate in young males (45.8%), females showing a greater misuse prevalence for Lormetazepam (35.8%). The variables associated with a greater probability of misuse were, smoking habit, consumption of an illicit drug other than marijuana during last year. Low-perceived risk for BZD and Z-Drug consumption, was the variable showing the greatest value in young population (aOR = 3.88, 95% CI 2.53–5.93).

Conclusions: Spanish young women are more likely to misuse BZD and Z-Drugs than men. Differentiated consumption is observed for these substances. A low perception of consumption risk and negative perception of health are strongly associated with non-medical use of BZD and Z-Drug among young Spanish population.

KEYWORDS:

• Adolescents
• benzodiazepines
• gender
• non-medical use
• young people

Introduction

The non-medical use of prescription medications (NUPM), defined as the use of a medication without a corresponding medical prescription and in a manner other than normally prescribed, or in order to experience sensations the drug provides (Substance Abuse and Mental Health Services Administration [SAMHSA], 2015) has significantly increased in the last decade, mainly among adolescents and young adults (Kelly et al., 2013; McCabe et al., 2011; Miech et al., 2013; Schepis et al., 2018). The last World Drug Report (United Nations Office on Drug and Crime [UNODC], 2018) indicates that it is during young adulthood (18–25 years) that people are at their highest risk for beginning to consume psychoactive substances. In countries such as the USA, young people present the highest NUPM rates (LeClair et al., 2015; Tapscott & Schepis, 2013), with consumption prevalence values ranging from 4.9% among adolescents aged 12 to 17 years to 14.4% among young adults aged 18 to 25 years, according to data from the National Survey on Drug Use and Health (Substance Abuse and Mental Health Services Administration [SAMHSA], 2018).

Benzodiazepines (BZD) and non-benzodiazepine hypnotic drugs (Z-Drugs) are among the most frequently prescribed drugs worldwide. Inappropriate use of these drugs is one of the most prevalent and consequential forms of prescription drug misuse, reaching values of 7.7% in such countries as the United Kingdom (Kapil et al., 2014)¹⁰, a figure comparable to data for North America (Maust et al., 2019).

Misuse of these drugs may be increasing among adolescents and young adults. A recent study of U.S. high-school seniors found that 7.5% of these students had made non-medical use of benzodiazepine/anxiolytics at least once in their lifetime (McCabe & West, 2014). Similarly, results from the latest European School Survey Project on Alcohol and other Drugs (ESPAD) show a6% rate of tranquilizer and sedative misuse among European adolescents (European Monitoring Centre for Drugs and Drug Addiction, 2015).

Gender differences in psychoactive substance use rates have been studied in the general population. Males present significantly higher rates of consumption, abuse, and dependence (Becker et al., 2016; Fernandez-Montalvo et al., 2014), although females present other specific patterns of substance abuse (Ait-Daoud et al., 2017; Tuchman, 2010). But if one type of legal psychoactive substance should be highlighted because of how it affects all age groups differently with regard to gender, that type would be psychoactive drugs for both medically prescribed drugs and drugs ingested for non-medical use (Boyd et al., 2015; Meng et al., 2013; Mojtabai & Olfson, 2010).

Female consumption of legally purchased and socially accepted psychoactive drugs has become invisible in the drug addiction context (Jiménez Rodrigo & Ordaz, 2012). This situation is particularly relevant for young females who are a particularly vulnerable group for non-medical consumption of psychoactive drugs.

The objective of our study is to describe the prevalence and identify the factors associated with non-medical use of Benzodiazepine and Z-Drug in young population residing in Spain from a gender perspective.

Methods

Data source and study population

We used individualized secondary data retrieved from the 2015/2016 Encuesta Domiciliaria sobre Alcohol y Drogas en España (EDADES, Household Survey on Alcohol and Drugs in Spain) to conduct a nationwide, cross-sectional epidemiological study on the non-medical use of Benzodiazepines and Z-Drugs by the young Spanish population of both sexes aged 15 to 35 years.

The Spanish National Drug Plan carries out the EDADES survey, which is a representative survey of the non-institutionalized population residing in Spain aged 15 to 64 years that has been carried out bi-annually since 1995 with the objective of monitoring the population’s use, perceptions, and opinions regarding alcohol and drug consumption.

Information collection takes place through personal interviews at home. The interviewer remains present during the whole process and collects the questionnaire when finished. The questionnaire contains two parts: interviewer’s questionnaire and self-administered questionnaire. The questionnaire is completed in writing (pencil and paper).

The survey uses a three-stage cluster sample design without replacement and includes urban and rural populations from all the Spanish autonomous regions and cities. In the first stage, random census sections are selected with a probability proportional to the section size. In the second stage, homes are selected following a systematic random procedure. And in the third stage, an individual is selected within each home using tables of random numbers.

Questionnaires and methodologies used for this survey are very similar to those used in other countries in the European Union and the United States thus allowing for international comparison.

Our study population included 10,824 young people aged 15 to 34 years of both sexes residing in Spain at the moment when the survey was carried out. Information was collected from December 1 to 18, 2015, and again from February 7 to April 29, 2016. Details of EDADES Survey methodology are reported elsewhere (Ministerio de Sanidad, Consumo y Bienestar Social, 2016).

Measures

Information for creating the dependent variables was obtained from the “yes” or “no” answers to the prompt: “In the last 12 months, indicate which of the following medications you have consumed without a prescription.” This was followed by a list of trade names and generic drugs, including Bromazepam, Alprazolam, Lorazepam, Diazepam, Potassium clorazepate, Zolpidem, and Lormetazepam.

The independent variables were the primary sociodemographic characteristics of the population – namely age, sex, nationality, occupational status, and educational level.

In order to determine the use of other legal psychoactive substances, there were questions about alcohol consumption and smoking during the previous 12 months (dichotomous variable, yes/no). Regarding the concurrent use of illegal psychoactive substances, there were questions about marijuana consumption in the previous year, and the abuse of other drugs besides marijuana (LSD, hallucinogens other than LSD, amphetamines, cocaine, heroin) in the previous 12 months.

The survey also included variables related to risk perception for non-medical consumption of BZD and Z-Drugs (Few or no problems/Several or a lot of problems), and availability (Impossible or very difficult/Easy or very easy), as well as the perception of health condition as declared by the young adults in the study.

Statistical analysis

We calculated the prevalence of non-medical use of BZD and Z-Drug according to the study variables. All data analyses were performed separately for women and men. Pearson’s χ² test was used for the bivariate comparison of proportions, and statistical significance was set at a p value <.05 (2-tailed).

We analyzed the association between the independent variables studied and the non-medical use of BZD and Z-Drug using the crude odds ratio (OR) and its 95% confidence interval. To estimate the independent effect of each of the study variables on the nonmedical use of tranquilizers, sedatives, and sleeping pills (TSSp), we also obtained the corresponding adjusted odds ratio (aOR) using multivariate logistic regression analysis. The multivariate models included those variables that showed a significant association in the bivariate analysis and the adjustment variables that were considered relevant in the scientific literature. Estimates were made using the svy function (survey command) of the STATA program (STATA Corp, College Station, Texas, USA), which enabled us to incorporate the sampling design and weights into all statistical calculations (descriptive, χ², and logistic regression). Statistical significance was established as a 2-tailed α < 0.05.

Ethical statement

This article does not contain any studies with human participants or animals performed by any of the authors. This article does not require any certificate from the ethics committee, given the nature of the research. All analyzed surveys were anonymous and dissociated and contained no recognizable personal information. All content is in accordance with that stated in the second paragraph, section 5 (SAS/3470/2009 Order, December 16th), and does not fall within the assumptions established in Article 2.e (Law 14/2007, June 3rd) concerning biomedical research.

Results

The prevalence of total BZD and Z-Drug consumption among adolescents and young adults in Spain reaches values of 6.2%. When we analyze the non-medical use of these medications within the study population, we find prevalence values of 1.42% (1% in men vs. 1.84% in women, p = .002). Figure 1 shows total consumption and non-medical use for differing active ingredients. Differentiated consumption is observed for these substances, with young males making more non-medical use of Zolpidem (45.8%), and females showing a greater non-medical use prevalence for Lormetazepam (35.8%).

Figure 1. Prevalence of total consumption and non-medical use of Benzodiazepine and Z-hypnotics in young adults EDADES Survey 2015–2016

* Consumption of benzodiazepines and Z-drugs with or without prescription

Table 1 presents non-medical use prevalence data for both sexes according to sociodemographic variables, variables related to concurrent use of other legal and illegal psychoactive substances, risk perception, availability, and health perception.

Table 1. Prevalence of non-medical use of BZD and Z-drugs, according to sociodemographic variables, use of licit and illicit psychoactive drugs and variables related to perceived health risk, perceived availability. EDADES Survey 2015–2016

	Male	Female	Both Genders
	% (n)	% (n)	% (n)	p-value*
Age
15–18 years	0.28 (2)	0.80 (4)	0.53 (6)	.20
19–34 years	1.13 (37)	2.02 (65)	1.57 (103)	.00
Nationality
Immigrants	1.24 (6)	2.27 (12)	1.78 (29)	.22
Spanish	0.97 (33)	1.78 (57)	1.36 (90)	.00
Occupational status
Employed	1.09 (19)	1.96 (30)	1.49 (49)	.04
Unemployed	1.52 (12)	2.81 (18)	2.08 (30)	.08
Inactive	0.62 (7)	1.49 (22)	1.11 (29)	.04
Educational level
Primary school	1.10 (5)	0.87 (3)	1.00 (8)	.72
Secondary school	0.82 (23)	1.90 (49)	1.34 (72)	.00
Higher education	1.80 (11)	2.10 (17)	1.97 (28)	.68
Alcohol use in the past 12 months
No	1.06 (7)	1.11 (11)	1.09 (18)	.93
Yes	0.99 (32)	2.11(59)	1.51 (90)	.00
Any cigarette smoking in the past 12 months
No	0.80 (17)	1.03 (25)	0.92 (42)	.39
Yes	1.27 (21)	3.30 (45)	2.17 (66)	.00
Any marijuana use in the past 12 months
No	0.82 (25)	1.73 (58)	1.30 (83)	.00
Yes	1.64 (14)	2.81 (11)	2.00 (26)	.18
Any illicit psychoactive drug use other than marijuana in the last 12 months
No	0.82 (30)	1.71(63)	1.27 (93)	.00
Yes	3.67 (9)	7.40 (7)	4.67 (16)	.17
Perceived health risk for consumption of BZD and Z-hypnotics
No/few problems	1.63 (25)	3.69 (54)	2.64 (79)	.00
Quite a few/many problems	0.59 (14)	0.66 (15)	0.63 (29)	.74
Perceived availability of BZD and Z-hypnotics
Impossible/very difficult to obtain	0.81 (15)	1.01 (19)	0.91 (34)	.53
Easy/very easy to obtain	1.19 (24)	2.68 (50)	1.91 (74)	.00
Self-assessment of health status
Very good/Good	0.88 (33)	1.77 (64)	1.32 (96)	. 71
Fair/Poor/Very poor	3.90 (6)	3.27 (6)	3.57 (12)	. 00
TOTAL MISUSE	1.00(39)	1.84 (70)	1.42 (109)	.00

* Statistically significant differences on analyzing prevalence of non-medical use between young men and women (p < 0.05)

BZD and Z-Drug consumption increase with age in both sexes, with prevalence values greater for young females (p = .00). Regarding concurrent use with other psychoactive substances, non-medical use prevalence is greater among young population of both sexes who declare that they have consumed alcohol, tobacco, and marijuana in the previous year. Non-medical use prevalence among young women who have consumed other illegal psychoactive drugs other than marijuana reaches values of 7.40%.

The results of the multivariate analysis performed using logistic regression models (Table 2) indicate that young females are more likely to non-medical use of BZD and Z-Drugs than young males (aOR = 2.21, 95% CI 1.45–3.35).

Table 2. Multivariable logistic regression of non-medical use of Benzodiazepine and Z-Drugs among young adults population in Spain. EDADES Survey 2015–2016

	OR	CI 95%	aOR	CI95%
Sex
Male	1	-	1	-
Female	1,85	(1,24–2,76)	2,21	(1,45–3,35)
Age
15–18 years	1	-	1	-
19–34 years	3.00	(1.17–7.70)	1.05	(1.01–1.08)
Any cigarette smoking in the last 12 months
No	1	-	1	-
Yes	2.38	(1.60–3.55)	1.84	(1.21–2.81)
Any illicit psychoactive drug use other than marijuana in the last 12 months
No	1	-	1	-
Yes	3.81	(2.18–6.66)	3.02	(1.70–5.36)
Perceived health risk for consumption of BZD and Z-hypnotics
Quite a few/many problems	1	-	1	-
No/few problems	4.29	(2.82–6.53)	3.88	(2.53–5.93)
Perceived availability of BZD and Z-hypnotics
Impossible/very difficult to obtain	1	-	1	-
Easy/very easy to obtain	2.12	(1.39–3.23)		n.s.
Self-assessment of health status
Very good/Good	1	-	1	-
Fair/Poor/Very poor	2.77	(1.64–4.68)	2.21	(1.30–3.76)

OR = odds ratio; aOR = adjusted OR; CI = confidence interval. n.s.: non-significant association

The variables associated with the consumption of legal and illegal psychoactive substances in the previous 12 months that proved to be independently and significantly associated with a greater probability of misusing these drugs are tobacco consumption and the use of any type of illicit drug other than marijuana (aOR = 3.02, 95% CI 1.70–5.36).

A negative health perception and low-perceived risk for BZD and Z-Drug consumption act as predictors for the non-medical use of these psychoactive substances. Risk perception is the variable with the strongest association (aOR = 3.88, 95% CI 2.53–5.93).

Discussion

In the scientific literature, BZD and Z-Drugs misuse characteristics among the general population have been extensively documented (Blanco et al., 2018; Hayhoe & Lee-Davey, 2018; Kapil et al., 2014; Lyphout et al., 2019), but there have been significantly fewer studies describing misuse patterns for these drugs among young adults.

In our investigation, we found that the prevalence of non-medical use of BZD and Z-Drug in young people residing in Spain is at 1.42%. These values are inferior to the 7.7% found by Kapil et al. in their study carried out in the UK to estimate misuse prevalence for these drugs. That study used an online questionnaire directed to the general population aged 15 to 59, and so the results do not report specifically on young population (Kapil et al., 2014). Another study that examined BZD dependence and abuse among young participants in the electronic dance music culture in Miami-Dade County, Florida (USA) also showed higher results, with 21.1% of participants reporting BZD abuse (Kurtz et al., 2017).

When we observe the generic designation of these drugs to determine which is the most used, we find differentiated consumption according to gender, since zolpidem was the most frequently misused medication among men, and lormetazepam among women, with prevalence rates of 45.8% and 35.8%, respectively. According to data from the Agencia Española de Medicamentos y Productos Sanitarios (AEMPS, Spanish Agency on Drugs and Healthcare Products), the most consumed BZD and Z-Drugs in Spain in 2012 were lormetazepam and zolpidem, at 20.3 and 8.0 doses per inhabitant and day (DHD), respectively. These drugs experienced the greatest increase in use (126% and 98% during the study period, respectively) (Ministerio de Sanidad, Consumo y Bienestar Social, 2012). Higher prescribing rates for these medicines are associated with increased misuse. A Swedish study by Sidorchuk et al., the objectives of which included analyzing prescription patterns for BZD and Z-Drugs for the young population aged 0 to 24, found an increase in the dispensing of these medications for the study period and also showed that 33.20% of the young Swedish subjects aged 18 to 24 years had been prescribed zolpidem (Sidorchuk et al., 2018). BZD y Z-Drugs are abused because of their euphoric effects which may have dangerous consequences. According to the European Drug Emergencies Network (Euro-DEN), emergency department visits associated with the non-medical use of benzodiazepines and/or Z-drugs are common, reaching values of 19.3% (Lyphout et al., 2019). A retrospective revision of all cases related to zolpidem ingestion reported to the Illinois Poison Center by Zosel et al. , showed that 44% of cases required admission to an intensive care unit (Zosel et al., 2011).

Lormetazepam is the benzodiazepine with the highest non-medical use values among young Spanish females (20.5%). In countries such as Italy, benzodiazepine presents the highest rate of consumption and there is a recent trend toward lormetazepam abuse in clinical practice (Faccini et al., 2012).

From a gender perspective, BZD and Z-Drug use are more frequent among females than among males (Boyd et al., 2015; Estancial Fernandes et al., 2018; Mojtabai & Olfson, 2010). A gender perspective also specifies differences in male and female consumption and makes female usage more visible. Our results show that young females are two times more likely to misuse medicines than are males. This is in line with the study by Young et al. which, through a systematic review of the scientific literature regarding the non-medical use of prescription medications among American adolescents, found that in most studies, female gender was more highly associated with tranquilizer use (Young et al., 2012). Similar results to our own appear in the study by Opaleye et al. the objective of which was to estimate the prevalence of non-prescribed use of tranquilizers/sedatives by adolescents in Brazil, and which showed Brazilian adolescent females presenting twice the probability [aOR = 2.19; 95% CI: 1.75–2.75] of reporting non-medical use of these medicines than males (Opaleye et al., 2013).

Regarding concomitant consumption of BZD and Z-Drugs with other legal psychoactive substances, we found that tobacco consumption among young Spanish adults was significantly associated with the misuse of these drugs. This is consistent with previous studies showing that smokers are at a greater risk of making non-medical use of prescription medications than nonsmokers (Bali et al., 2013; Kokkevi et al., 2008). Recent studies show that the gender gap in tobacco consumption is decreasing (Gabrhelik et al., 2012; Sweeting et al., 2011). Normative standards are changing, and this contributes to closing gender gaps within Spanish society resulting in more female adolescents using legal psychoactive drugs including tobacco. Tobacco use is now greater among females than among males, as the results of the EDADES 2015–16 survey (Ministerio de Sanidad, Consumo y Bienestar Social, 2016) or the Romo (2018) investigation show in their analyses of available evidence of gender influence on several aspects and dimensions linked to substance use and abuse prevention.

It is well documented that the consumption of illegal psychoactive substances is a risk factor associated with the onset of prescription drug misuse. Novak et al., in their cross-national study of the non-medical use of prescription medications, carried out on the general populations of five European countries found that 21% of those who had made non-medical use of sedatives in the previous year had also consumed illegal drugs (Novak et al., 2006).

Our study shows that the use of illegal psychoactive substances, other than marijuana, is the most strongly associated variable with non-medical use of BZD and Z-Drug, since young Spanish who reported using illegal drugs, showed a three times greater probability of misusing these drugs than those who did not report such use. In the same vein, Mateu-Gelabert et al. (2017), analyzing the non-medical use of benzodiazepines in young adults in New York, and its association with the use of opioids found a prevalence of 93% for non-medical use of benzodiazepines in young subjects who reported misuse of opioids. Risk behaviors, including having ever used cocaine regularly (aOR = 1.587, 95% CI 1.001–2.521) and binging on drugs in the previous 30 days (aOR = 2.561, 95% CI 1.580–4.191) were strongly associated with benzodiazepine misuse.

The use of drugs among adolescents has increased due to the low-risk perception associated with their consumption. We need to identify the factors that have led to this perception and to the corresponding increase in addictive drug behavior rates among adolescents (Uribe Alvarado et al., 2011). Spanish adolescents who declare a low-risk perception of BZD and Z-Drug misuse are almost four times more likely to consume these drugs than adolescents with a high perception of risk for misusing these legal psychoactive substances. Brandt et al. (2014), in a study with young subjects aged 18 to 23 on the reasons for use, frequency, and perceived risks of non-medical use of prescription medicines found that when users were asked if the drugs were rewarding (induced pleasure), 38% declared that they found misusing tranquilizers to be rewarding.

Our study found a relevant percentage of adolescents self-reporting bad health. Those adolescents who expressed a negative perception of their own health were up to two times more likely to misuse these medications than adolescents with a positive perception of their health. Our results agree with those of several authors in that they reveal negative perception of health to be a predictor for benzodiazepine consumption, as in a recent systematic review of epidemiological studies on benzodiazepines misuse carried out in USA, which showed a clear association between a poor quality of life perception and the misuse of these drugs (Votaw et al., 2019).

One of the main strengths of our study is that we used a national representative sample that has allowed us to identify BZD and Z-Drug patterns among young adults. We also stress that this is the first time that the EDADES survey has ever incorporated the generic name for BZD and Z-Drugs, which allows for identifying the drug involved in the misuse for both young men and young women.

However, our study is subject to a series of limitations. The first limitation arises from the cross-sectional nature of study data, which does not allow for establishing the direction of the associations discovered.

The second limitation comes from using self-declared data so that prevalence results used to generate misuse profiles for BZD and Z-Drugs could be underestimated. That is because sociocultural attitudes may lead to socially conditioned answers, and some adolescents will have reservations about openly confessing their non-medical use of these medications.

Conclusions

In our country, BZD and Z-Drug consumption in adolescents and young adults reaches values of 6.2%. When we analyze the non-medical use of these drugs, we find prevalence values of 1.42%, with young females the most likely to make non-medical use of these drugs.

There is differentiated consumption between the sexes: for young males, zolpidem presents the highest misuse rate while for young females, lormetazepam presents the highest misuse rate.

Tobacco and illegal psychoactive substance consumption act as predictor variables for BZD and Z-Drug consumption. It should be noted that young people who declare that they consume other illegal drugs besides marijuana are twice as likely to take these drugs for non-medical use.

It must lastly be pointed out that a low perception of consumption risk and negative perception of health are strongly associated with BZD and Z-Drug misuse among young Spanish population.

Findings from the present study have implications for identifying the subgroup-population, young adults in this case, who would benefit from prevention efforts against medication misuse, efforts that would also reinforce health education activities for this social group.

These results may also contribute to decision-making as to whether greater control and/or monitoring is required for both prescriptions and supplies of BZD and Z-Drugs by healthcare professionals, their obtention by means of illicit sources, and the general use of these drugs. Furthermore, there is a need for research to discover why these drugs are misused. This will help create activities aiming to minimize harm through appropriate responses adequately directed by public administrations.

Our research shows the need for health promotion efforts targeting prescription drug misuse among young adults who are highly socially active. Interventions seeking to decrease the non-medical use of prescription need to address larger social contexts such interventions must help young adults develop alternative strategies for dealing with these contexts.

Acknowledgments

Thanks to the Spanish National Drug Plan (Ministry of Health, Consumer Affairs and Social Welfare) for providing the surveys data.

Disclosure statement

The authors declare that there is no conflict of interest.

Additional information

Funding

This study was funded by the FIS (Fondo de Investigaciones Sanitarias—Health Research Fund, grant No. PI16/00691, Instituto de Salud Carlos III) co-financed by the European Union through the Fondo Europeo de Desarrollo Regional (FEDER, “Una manera de hacer Europa”). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.