Psychometric properties of the Benzodiazepine Dependence Self-Report Questionnaire – Portuguese Version (BENDEP-SRQ-PV)

Abstract Objective To assess psychometric properties of the Benzodiazepine Dependence Self-Report Questionnaire – Portuguese Version (BENDEP-SRQ-PV) in a sample of Brazilian chronic hypnotic users. Methods One hundred and seventy-nine chronic hypnotic users (benzodiazepines and Z-drugs) were recruited, attended a psychiatric evaluation, and answered the BENDEP-SRQ-PV. Factor structure, reliability, and influence of covariates (dependence diagnosis and type of drug consumed) were assessed in a structural equation modelling environment. Discrimination was assessed with receiver operating characteristic (ROC) plots and stability with the test-retest method. Results Participants, mostly women (91.6%), aged 51 to 64 years old, had been using hypnotics for an average of 34.8 months, with a mean defined daily dose of 0.72. Psychometric analysis demonstrated construct and criterion validity, reliability, and response stability. The factor structure was maintained as originally proposed: problematic use (ω = 0.73), preoccupation (ω = 0.74), lack of compliance (ω = 0.74), and withdrawal (ω = 0.93). Conclusion The BENDEP-SRQ-PV is an adequate measure of hypnotic dependence in the Brazilian population of chronic users. Our results support using the scale for follow-up in clinical and research applications and in correlational studies.


Introduction
Benzodiazepines (BZD) and Z-drugs are psychotropic medications, recommended for short-term management of anxiety and insomnia, 1,2 since it is recommended that treatment duration should not exceed four weeks. 3 However, an estimated 1 in 5 patients given a first prescription become chronic users, as described by

Schonnman et al. in a large-scale longitudinal study in
Israel. 4 A study investigating the period from 1993 to 2007 examined trends in prescription of hypnotics and found that while growth in use of BZDs had remained low, there had been a 30-fold increase in Z-drug use. 5 More recent epidemiologic data (2006-2014) shows a downward trend in prescription of several hypnotics, except for clonazepam and zolpidem, which increased. 6 There is growing evidence regarding the side effects associated with hypnotic medications. Long-term use of both high and therapeutic doses of BZDs can cause cognitive and psychomotor deficits, increasing risks of falls, fractures, traffic accidents, mortality, abuse and dependence. 3 The same has been observed for Z-drugs, both for the impairments listed above 7 and also for dependence, 8 even though they were originally marketed as safer substitutes for BZDs. 1 Only a few existing instruments were developed to measure hypnotic use and dependence. Initially, such instruments mostly measured aspects of drug withdrawal. [9][10][11][12][13] More recently, with the acceptance of the biopsychosocial model of dependence, it has been shown that physical signs are not sufficient measures of dependence and that the psychological and social dimensions are also prevalent in the population of benzodiazepine users. 14 Therefore, self-report instruments that also consider the psychosocial aspects of dependence, [15][16][17] or craving 18 were developed. Most of these questionnaires left aside withdrawal aspects and have not been validated in Brazil, except for the Severity of Dependence Scale, which is not specific to hypnotics. 19 A study aiming to evaluate the homogeneity of the criteria for dependence from the International Classification of Diseases, 10th revision (ICD-10), and the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, Revised (DSM-III-R), demonstrated that the abstinence criteria could possibly constitute a separate dimension. 20  written consent was obtained from all the participants.

Participants
The sample comprised 179 chronic hypnotic users, recruited using several different means of communication. Sample size was calculated based on recommendations of a minimum of 5 participants per question on the instrument being validated. 25 The following inclusion criteria were applied: participants over the age of 18 and literate in Brazilian Portuguese, since they needed to be able to understand the content of the BENDEP-SRQ-PV items; the criterion for chronic use was established as use of BZD or Z-drugs for at least 3 months, with a minimum frequency of once a week.

Procedures
The author of the BENDEP-SRQ 17 was contacted and gave permission for the validation process. The first part of the study consisted of translation and cultural adaptation of the scale, following steps proposed by Beaton et al. 26 Potential participants were requested to contact the research staff to undergo brief phone screening covering the inclusion criteria. A psychiatric evaluation was then scheduled that was based on ICD-10 criteria for mental and behavioral disorders due to use of sedatives and hypnotics -dependence syndrome (F13.2). 27 Presence of psychiatric symptoms, medical supervision, and usage history were also assessed.
Self-report instruments were administered after the consultation. They were administered using the RedCap platform hosted at UNIFESP 28,29 or in pen-and-paper format. Completion of all questionnaires was supervised by the main investigator. As a benefit, participants were invited to participate in meditation groups (using the mindfulness-based relapse prevention [MBRP] protocol) free of charge. 30

Measures
The following self-report instruments were

Data analyses
All analyses were conducted with R software, version 3.6.1, using the packages lavaan 31 and semTools 32  that are typically employed in research studies may not achieve strict fit criteria when tested in independent samples and may not be discredited. 34

Psychometric properties of the BENDEP-SRQ-PV
Seven out of 179 participants had missing values for at least one of the 20 items and their data were therefore excluded from further analysis. 33 For participants who did not respond to the withdrawal questions because they had never tried to reduce their medication use, these answers were replaced with zeroes. This procedure was used so that analyses were not run using only data from those who had tried to reduce their medication use (82.1% of our sample). was not a significant improvement over Model 2 (Δχ² =   In a study assessing the prevalence of BZD use in the Brazilian population, women aged 40+, separated/ divorced, and with higher education and income had higher lifetime use prevalence rates. 38  Although originally marketed as safer alternatives to BZDs, evidence regarding the potential for dependence of Z-drugs is mounting. 8 In our study, mean scores obtained in the domains of problematic use, preoccupation, and lack of compliance were higher among BZD users than among users of Z-drugs. These results suggest milder cases of dependence among Z-drugs users, although previous studies did not find evidence pertaining to security, effectiveness, or costbenefit ratio that favor one class over the other. 39,40 These differences could be better understood by examining other factors, e.g., longer treatments are associated with a drop off in compliance with the therapeutic regimen. 41,42 Considering that BZDs were introduced onto the market in the 1960s and Z-drugs were introduced in the 1990s. 1,43 BZD users are more likely to present an increased duration of treatment, therefore, the increased lack of compliance could be due to treatment duration and not necessarily to the type of drug consumed. The problematic use subscale measures the degree of awareness respondents have of their hypnotic use, which is essential in a population of users who often do not recognize their drug dependence, 44 but can recognize individual behaviors presented in the form of items, illustrating the importance of adapting self-report instruments to assess hypnotic dependence. In a study assessing risk factors associated with benzodiazepine dependence, especially psychopathological risk factors, depression was found to partly predict problematic use, along with other sociodemographic variables such as younger age and lower educational level. 45 Manthey et al. found associations with insomnia severity and more frequent contact with the prescriber. 46 This domain was also associated with prolonged reaction times in an attentional task. 47 In a discontinuation trial using melatonin, even though 71% of patients who reported a low degree of awareness of problematic use were unable to quit the medication, no significant effects were found comparing them with those who were able to quit or those with high awareness. 48 The items and the theoretical rationale behind the preoccupation subscale reflect recently reviewed behavioral aspects of low-dose BZD dependence, such as anxiety or craving between doses and users carrying tablets with them or taking an extra dose of medication to avoid problems. 2 Increased preoccupation scores are associated with craving for BZDs. 49 In the abovecited discontinuation trial, individuals who successfully tapered off their medications, compared to those who did not, had significantly larger decreases in their scores for preoccupation and problematic use. 21 46 When assessing the ability of each BENDEP-SRQ subscale to predict successful tapering after a BZD discontinuation trial, lack of compliance and preoccupation had the highest independent predictive values. 21 Another discontinuation trial evaluating long-term abstinence found that lack of compliance significantly predicted success. 52 The items on the withdrawal subscale reflect symptoms reported as barriers that prevent users from reducing or cutting down their medication, which is also a means through which they report perceiving dependence. 44 The inability of this domain to discriminate those who are dependent from those who are not dependent is in accordance with the facts that hypnotic dependence is a biopsychosocial condition and abstinence is not its only good measure of discrimination, which might even constitute a separate dimension. 20  In a two-part intervention, those who did not succeed in discontinuing BZD use of their own accord, after receiving a letter from their general practitioner with advice to attempt gradual reduction, and who were then required to participate in a second intervention (a discontinuation trial), had higher scores in the domains of problematic use, preoccupation, and withdrawal. 53 Psychopathological risk factors that predicted this domain were anxiety and insufficient thinking and acting. 45 This study's strengths are founded on the relevance of measuring the construct of hypnotic dependence in both clinical practice and research settings. 15 The BENDEP-SRQ is a multidimensional instrument that encompasses the biopsychosocial aspects of dependence. The content of its four domains remains current, reflecting behavioral aspects of low-dose dependence on hypnotics. 2 This is the first study that has evaluated the psychometric properties of a scale to measure hypnotic dependence in Brazilian residents, which is relevant considering that the indiscriminate use of anxiolytics and hypnotics is considered a public health problem, 5 and its use could further improve the methodological quality of future studies assessing the construct in question. Since the scale was originally intended specifically for assessing dependence on BZD, the results of this study demonstrate that it is also applicabile to Z-drugs.
Limitations must be noted. The sample size was estimated based on recommendations that only consider the number of items in the instrument being validated and was smaller than is desirable for conducting analyses within a SEM framework (e.g., we were unable to assess model invariance across time, because only 51 individuals answered the BENDEP-SRQ-PV a second time). Dependence was not diagnosed using structured interviews. Selection bias may have occurred because of the recruitment method, which may selectively attract people who are more motivated to stop the use of hypnotics and more aware of their problematic medication use. The population is, therefore, very homogeneous, composed mainly of those classified as low-dose dependent, 3 which may hinder generalization of the results to other types of hypnotic users. Although women are prescribed hypnotics twice as often, 54 men more frequently misuse such medications. 55 Our sample was composed almost entirely of women (91.6%), which might also represent a limitation with regards to the capacity for generalizing our findings. Future studies could cross-validate the BENDEP-SRQ-PV for other groups of hypnotic users, e.g. those on alcohol withdrawal treatment or high-dose dependent users. The longitudinal applicability of the scale could also be tested, in clinical trials aiming to reduce or cut down medication use, both to assess the scale's sensitivity for detecting changes over the course of treatment and also as a tool for prediction of successful withdrawal.
Considering the neutral presentation of the questions, the scale's applicability to other pharmaceuticals used in psychiatric treatment could also be tested, since it has already been used for antidepressants. 56 The development and validation studies used item response theory and future studies could also use this approach, testing the fit of more complex models (such as multidimensional graded response or partial credit models), since this methodology requires larger samples.