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Vol. 75.
(January 2020)
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Vol. 75.
(January 2020)
ORIGINAL ARTICLE
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Benzodiazepine use in Sao Paulo, Brazil
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934
Angela Maria CampanhaI,II,
Corresponding author
amcampanha@uem.br

Corresponding author.
, Beatriz RavagnaniI, Igor André MilhorançaI,III, Márcio Antonini BernikIV, Maria Carmen VianaV, Yuan-Pang WangI, Laura Helena AndradeI
I Nucleo de Epidemiologia Psiquiatrica (LIM-23), Departamento e Instituto de Psiquiatria, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, BR
II Departamento de Farmacia, Universidade Estadual de Maringa, Maringa, PR, BR
III Instituto de Matematica e Estatistica, Universidade de Sao Paulo, Sao Paulo, SP, BR
IV Programa de Ansiedade, Departamento e Instituto de Psiquiatria, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, BR
V Departamento de Medicina Social, Programa de Pos-Graduacao em Saude Coletiva, Centro de Estudos e Pesquisa em Epidemiologia Psiquiatrica (CEPEP), Universidade Federal do Espirito Santo, Vitoria, ES, BR
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OBJECTIVES:

To report the prevalence and factors associated with the use of benzodiazepines in the general population and those with a mental health condition in the metropolitan area of São Paulo, Brazil.

METHODS:

5,037 individuals from the Sao Paulo Megacity Mental Health Survey data were interviewed using the Composite International Diagnostic Interview, designed to generate DSM-IV diagnoses. Additionally, participants were asked if they had taken any medication in the previous 12 months for the treatment of any mental health condition.

RESULTS:

The prevalence of benzodiazepine use ranged from 3.6% in the general population to 7.8% among subjects with a mental health condition. Benzodiazepine use was more prevalent in subjects that had been diagnosed with a mood disorder as opposed to an anxiety disorder (14.7% vs. 8.1%, respectively). Subjects that had been diagnosed with a panic disorder (33.7%) or bipolar I/II (23.3%) reported the highest use. Individuals aged ≥50 years (11.1%), those with two or more disorders (11.2%), those with moderate or severe disorders (10%), and those that used psychiatric services (29.8%) also reported higher use.

CONCLUSION:

These findings give an overview of the use of benzodiazepines in the general population, which will be useful in the public health domain. Benzodiazepine use was higher in those with a mental health condition, with people that had a mood disorder being the most vulnerable. Furthermore, females and the elderly had high benzodiazepine use, so careful management in these groups is required.

KEYWORDS:
Psychiatry
Pharmacy
Psychotropic Drugs
Hypnotics and Sedatives
Benzodiazepines
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INTRODUCTION

Since its introduction in the early 60s (1), benzodiazepines (BZDs) have been the most prescribed psychotropic medication worldwide (2), despite their various therapeutic and side effects (2,3). Therapeutic indications for the use of BZDs are diverse and include the treatment of seizures (4), alcohol and barbiturate withdrawal symptoms (5), psychomotor agitation (6), insomnia and other sleep disorders (7), panic disorders (8), social phobia, generalized anxiety disorder (9), and as an adjunctive treatment for both depression and mania (10). Common side effects of BZD are drowsiness associated with incoordination or ataxia, which may lead to car accidents, problems with operating machinery, and, especially among the elderly, falls (11). Memory impairments that are potentially non-reversible have also been observed (3,12). Long-term use of BZDs is related to physical dependence. Discontinuation from chronic BZD use can result in withdrawal syndrome, particularly among the elderly (10). Withdrawal symptoms that have been reported include anxiety, sleep disturbance, irritability, a hand tremor, and rarely, more severe conditions such as seizures and psychosis (13).

Current guidelines such as the National Institute of Health and Care Excellence (NICE) (14) recommend that BZD should be used at the lowest possible dose for the shortest period possible. There are considerable evidence-based concerns regarding the serious adverse consequences of BZD use, such as falls (14), risk of suicide, abuse, dependence (10), and risk of Alzheimer's disease (15). In a series of pharmacoepidemiological studies conducted by the World Mental Health Survey Initiative (WMHS) (16,17), the use of psychotropic agents was evaluated in the general population. In addition, if a respondent had been diagnosed with a psychiatric disorder in the 12 months preceding the survey, this was recorded (18,19). The observed prevalence of BZD use in the general population ranged between 3.2% and 18.6% (Table 1). These rates were even higher among individuals that had been diagnosed with a psychiatric disorder, with a range between 9.2% and 41.9%. Generally, the prevalence of BZD use was higher among subjects with a mood disorder as opposed to an anxiety disorder. High consumption of BZD was also observed among females and older people (16,17,18,19,20). However, methodological diversity hampered a direct comparison of the rate of BZD use among participant countries of the WMHS Initiative.

Table 1.

Pharmacoepidemiological studies conducted within the World Mental Health survey initiative and other studies in South America.

            Prevalence of use
Reference  Location  Period  Names of studies  Sample  Age  General population  12-month diagnosis 
Alonso et al. (25)  Europe  2001-2003  ESEMeDa  21,425  ≥18  9.8%  25.5% 
Bruffaertes et al. (16)  Belgium  2001-2002  ESEMeDa  2,419  ≥18  12.3%  25.5% 
Codony et al. (18)  Spain  2001-2002  ESEMeDa  5,473  ≥18  11.4%  32.7% 
Campanha et al. (20)  Brazil  2005-2007  SPMHSb  2,935  ≥18  3.6%  7.8% 
Gasquet et al. (17)  France  2001-2003  ESEMeDa  2,894  ≥18  18.6%  41.9% 
Grinshpoon et al. (19)  Israel  2003-2004  INHSc  4,859  ≥21  3.2%  9.2% 
Other studies in South America
Rojas et al. (21)  Chile  1996-1998    3,870  16-64  04% 
Quintana et al. (22)  Rio de Janeiro  2007-2008    1,208  ≥15  1.6%  3.4% 
Quintana et al. (23)  São Paulo  2007    2,536  15-75  2.7%  7.1% 

Several studies on BZD use have been conducted in the non-developed regions. In Chile, the estimated prevalence of BZD use in the general population was 4% (21) (Table 1). Few studies have been conducted on the prevalence of BZD use in Brazil (20). The relationship between BZD use and mental health disorders in the general population has rarely been investigated (22). The reported prevalence of BZD use over one month in the general population was 2% and 3% in Rio de Janeiro and São Paulo, respectively (23). Among individuals who had been diagnosed with a mental health disorder, the one-month prevalence of BZD use was lower in Rio de Janeiro than in São Paulo (3.4% vs. 7.1%, respectively). However, the methodological differences regarding the period investigated, sample characteristics, and data collection preclude any direct comparisons being made (20). There is a lack of knowledge regarding the use of BZDs over a period longer than 12-months, its monotherapy or polypharmacy patterns, the prevalence of BZD use in specific mental health disorders, and the impact of BZD use on symptom severity, comorbidities, health insurance coverage, and health service use.

Given the scarcity of epidemiological data, we aimed to report the prevalence of BZD use in a representative sample of the general population and those with a mental health condition (diagnosed in the last 12 months) in São Paulo, Brazil. Information about monotherapy and the combined use of BZDs along with its relationship to symptom severity, comorbidities, health insurance coverage, and health service use are also discussed.

METHODSSão Paulo Megacity Mental Health Survey

Data for this report were sourced from the São Paulo Megacity Mental Health Survey (SPMHS). The SPMHS is the Brazilian segment of the World Mental Health Survey Initiative, coordinated by the World Health Organization and Harvard University. It was conducted in more than 28 research centers around the world. The SPMHS is a cross-sectional, population-based study. It was designed to estimate the prevalence of mental health disorders, mental health services, and psychotropic drug utilization in a representative sample of the general population. By design, individuals over 18 years old, living in the São Paulo metropolitan area were interviewed by trained lay interviewers (24).

Sample

A sample of 5,037 individuals (response rate: 81.3%) were assessed using the Composite International Diagnostic Interview (CIDI), which generates DSM-IV diagnoses. We report on a subsample of 2,935 subjects who were submitted to a more extended version of the interview, which included questions on psychotropic drug use (24).

Data collection

Participants were asked about prescription medicines that they had used in the previous 12 months for emotional issues, nerves, mental health, substance use, energy, concentration, sleep, or stress. According to the Anatomical Therapeutic Chemical (ATC) index 2018 (https://www.whocc.no/atc_ddd_index/), the medicines focused on in this report were anxiolytics (alprazolam, bromazepam, clobazam, chlordiazepoxide, cloxazolam, diazepam, and lorazepam), hypnotics and sedatives (chloral hydrate, flunitrazepam midazolam, zolpidem), and antiepileptics (clonazepam). The term “benzodiazepines” (BZDs) will be used henceforth to refer to all the above medicines.

Data analysis

The data analysis examined both the prevalence of BZD use in the general population and among individuals who had been diagnosed with a mental health disorder. Diagnostic categories included in the analysis were anxiety, mood, substance use, and impulse-control disorders. Other clinical information included in the analysis was related to comorbidities and symptom severity.

Socio-demographic information collected included age, sex, education, family income, marital status, and employment status. Information about service use and health insurance was also analyzed.

The factors associated with BZD use were explored through a logistic regression analysis. The data analysis was performed using Statistical Analysis System (SAS).

RESULTS

The prevalence of BZD use in the general population in the previous year was 3.6%. Diazepam (1.3%) and clonazepam (0.8%) were the most frequently used BZDs. Females used BZDs more often than males (5.5% vs. 1.6%). The use of BZD was also higher among subjects aged over 65, compared to those aged 50-64 and 18-24 years (7.8% vs. 6.1% vs. 1.8%, respectively) (Table 2).

Table 2.

Prevalence of benzodiazepine use in the previous 12 months in the general population according to sex and age. São Paulo Megacity Mental Health Survey (N=2935).

Sex    N (%)  SE  p-value 
Total    162 (3.6)  0.5  0.0004 
  Female (N=1697)  122 (5.5)  0.9   
  Male (N=1238)  40 (1.6)  0.3   
Age        0.0687 
  18-24 (N=406)  09 (1.8)  0.9   
  25-34 (N=684)  18 (2.6)  0.7   
  35-49 (N=1,026)  68 (3.4)  0.6   
  50-64 (N=590)  48 (6.1)  1.4   
  ≥65 (N=229)  19 (7.8)  3.5   

Weighted proportions.

The use of BZD monotherapy was reported in 1.8% of the sample. Antidepressants (1.4%) were the most commonly used psychiatric medication in combination with BZD (Table 3).

Table 3.

Prevalence of monotherapy and combined use of benzodiazepines in the previous 12 months in the general population by sex. São Paulo Megacity Mental Health Survey (N=2935).

  N (%)  SE  OR (95% CI) female/male  X2  p-value 
Benzodiazepinesa  162 (3.6)  0.5  3.7 (2.0-6.7)  18.2  <0.0001 
Monotherapyb  65 (1.8)  0.4  3.6 (2.0-6.5)  18.5  <0.0001 
Combined usec           
Benzodiazepines +antidepressant  79 (1.4)  0.2  6.2 (2.3-16.7)  13.3  0.0003 
Benzodiazepines + antipsychotics  11 (0.2)  0.1  11.3 (2.7-48.0)  10.9  0.001 
Benzodiazepines + mood stabilizer  20 (0.4)  0.1  1.5 (0.5-5.2)  0.5  0.4904 

Weighted proportions. OR, odds ratio; CI, confidence interval. aAt least one psychotropic drug. bOnly benzodiazepines. cAny benzodiazepine drug plus another psychiatric medication. Sex comparison: males were used as the reference group.

Table 4 presents the correlates of BZD use according to the socio-demographic variables, psychiatric diagnoses, comorbidities, symptom severity, use of health services, and the possession of private health insurance coverage.

Table 4.

Correlates of benzodiazepine use in the previous 12 months with sociodemographic variables, mental health disorders, disorder severity, comorbidities, use of health services, and the existence of private health insurance coverage. São Paulo Megacity Mental Health Survey (N=1,271).

      Model 1Model 2
Variable  Total sample  N (%)  OR (95% CI)  p-value  OR (95% CI)p-value 
Sex           
Female  836  85 (8.7)  1.5 (0.7-3.2)  0.3563   
Male  435  32 (6.2)     
Age (years)        0.0418   
18-34  481  20 (4.7)     
35-49  472  56 (10.2)  2.3 (1.1-4.7)  0.0197   
≥50  318  41 (11.1)  2.6 (1.2-5.3)  0.0127   
Education (years)        0.4799   
Low (0-4)  346  36 (9.5)  1.3 (0.7-2.4)  0.421   
Low-average (5-8)  330  28 (6.8)  0.9 (0.5-1.8)  0.7639   
High-average/high (≥9)  595  53 (7.5)     
Family income        0.3014   
Low (≤0,5)  344  18 (5.5)  0.5 (0.2-1.0)  0.0641   
Low-average (0.5-1.0)  344  34 (7.5)  0.7 (0.37-1.2)  0.1714   
High-average (1.0-2.0)  292  30 (7.6)  0.7 (0.4-1.3)  0.2091   
High (>2.0)  291  35 (10.9)     
Marital status           
Married/cohabiting  777  80 (8.7)     
Previously married/Never married  494  37 (6.7)  0.8 (0.5-1.2)  0.2566   
Employment status        0.0058   
Employed/student  729  58 (5.9)     
Homemaker/retired  331  42 (11.8)  2.2 (1.4-3.5)  0.0014   
Unemployed  211  17 (10.1)  1,8 (0.8-4.4)  0.1839   
Anxiety disorder           
No  435  28 (7.3)    1 
Yes  836  89 (8.1)  1.1 (0.7-1.7)  0.585  3.5 (1.6-7.8)0.0019 
Mood disorder           
No  704  35 (3.2)    1 
Yes  567  82 (14.7)  5.2 (2.6-10.3)  <0.0001  5.7 (2.5-13.0)<0.0001 
SUDa           
No  1108  104 (7.8)   
Yes  163  13 (7.9)  1.0 (0.5-2.1)  0.984  2.9 (1.5-5.7)  0.0019
ICDb           
No  1080  101 (8.2)     
Yes  191  16 (5.8)  0.7 (0.4-1.3)  0.2634   
Comorbidity           
No  731  48 (5.6)   
Yes  540  69 (11.2)  2.1 (1.3-3.5)  0.0035  0.4 (0.2-1.0)  0.0255
Severity           
Mild  397  19 (3.7)     
Serious/Moderate  874  98 (10.0)  2.8 (1.7-4.8)  0.0001   
Service use           
No  935  15 (1.3)   
Yes  336  102 (29.8)  31.2 (19,3-50.4)  <0.0001  25.0 (13.7-45.6)  <0.0001
Health insurance           
No  798  56 (6.1)     
Yes  473  61 (10.7)  1.9 (1.0-3.4)  0.0505   

Weighted proportions. OR, odds ratio; CI, confidence interval. aSubstance use disorders. bImpulse control disorders. Model 1: crude. Model 2: All variables were analyzed together.

The use of BZD was higher in those aged between 35-49 years (10.2% vs. 4.7%; OR=2.3; 95%CI=1.1-4.7), and over 50 years (11.1% vs. 4.7%; OR=2.6; 95%CI=1.2-5.3), than those between 18-34 years (4.7%). The use of BZDs was also higher among homemakers, retired subjects, and the unemployed compared to employed individuals (11.8% vs. 10.1% vs. 5.9%, respectively (Table 4).

Concerning psychiatric disorders, individuals diagnosed with a mood disorder (14.7%; OR=5.7; 95%CI=2.5-13), anxiety disorder (8.1%; OR=3.5; 95% CI=1.6-7.8), or substance use disorder (7.9%; OR=2.9; 95%CI=1.5-5.7) were more likely to use BZD than those without these disorders (Table 4).

Psychiatric comorbidities and symptom severity also play a role in the use of BZDs. Although individuals who had been diagnosed with two or more disorders used more BZDs than those with a single diagnosis (11.2% vs. 5.6%; OR=2.1, 95%CI=1.3-3.5), the likelihood of using BZD was lower in the adjusted model 2 (OR=0.4; 95%CI=0.2-0.9). The likelihood of BZD use was higher among patients with disorders that were considered to be serious or moderate than among those with a mild disorder (10.0% vs. 3.7%; OR = 2.8; 95%CI=1.7-4.8) (Table 4).

There was a trend (p = 0.0505) of higher BZD use among individuals who had health insurance coverage than those who did not (10.7% vs. 6.1%; OR=1.9; 95%CI=1.0-3.4). Remarkably, BZD use among individuals who reported using psychiatric services was almost 30 times higher than those who did not (29.8% vs. 1.3%; OR=25.0; 95%CI=13.7-45.6) (Table 4).

BZD use among subjects who had been diagnosed with a mental health disorder was 7.8%. Among the diagnostic classes, mood disorders displayed the highest prevalence of BZD use (14.7%). Participants who had been diagnosed with a panic disorder or bipolar disorder (33.7% and 23.3%, respectively) reported using BZD the most (Table 5).

Table 5.

Twelve-month prevalence of benzodiazepine use according to the DSM-IV/WMH-CIDI diagnosis by sex. Results from the São Paulo Megacity, São Paulo, Brazil (N=1,271).

    At least one BZDExclusive use
Mental health disorder  Total  N (%)  SE  OR (95% CI)  X2  p-value  N (%)  SE  OR (95% CI) 
Anxiety Disorders                   
Panic disorder  61  17 (33.7)  8.9  1.7 (0.3-10.4)  0.4  0.542  04 (9.8)  4.2  0.4 (0.0-3.8) 
Generalized anxiety disorder  128  08 (8.4)  3.6  0.5 (0.1-3.3)  0.6  0.4391  03 (4.3)  3.1  0.1 (0.0-1.9) 
Specific phobia  471  54 (7.7)  1.3  0.8 (0.3-2.3)  0.2  0.6757  19 (2.8)  0.7  0.8 (0.2-3.4) 
Social phobia  174  23 (10.4)  3.1  2.3 (0.6-9.8)  1.3  0.25  05 (2.1)  1.1  0.8 (0.1-5.2) 
Agoraphobia without panic  88  16 (13.5)  3.3  9.9 (0.9-104.6)  3.6  0.0573  04 (3.9)  2.2  2.3 (0.2-26.5) 
Post-traumatic stress disorder  80  10 (6.6)  2.5  0.7 (0.1-4.7)  0.18  0.6714  03 (2.5)  1.6  0.1 (0-0.8) 
Obsessive-compulsive disorder  155  19 (8.8)  2.5  7.0 (1.6-30.0)  6.8  0.0094  04 (1.4)  0.8  0.4 (0.0-3.2) 
Adult separation anxiety  95  12 (12.6)  4.3  04 (4.2)  2.4 
Any anxiety disorder  836  89 (8.1)  1.0  1.1 (0.5-2,52)  0.0  0.8466  31 (2.9)  0.6  0.6 (0.2-1.5) 
Mood Disorders                   
Major depressive disorder  488  62 (13.4)  2.2  1.4 (0.4-4.28)  0.3  0.5879  17 (4.0)  1.0  0.9 (0.2-4.0) 
Dysthymia  62  09 (11.8)  5.6  7.5 (0.5-104.2)  2.2  0.1349  02 (2.7)  1.9 
Bipolar I and II disorders  73  19 (23.3)  5.5  1.4 (0.5-4.1)  0.4  0.5106  04 (4.5)  2.8  2.3 (0.5-10.7) 
Any mood disorder  567  82 (14.7)  2.3  1.3 (0.5-3.6)  0.3  0.6112  21 (4.0)  1.0  1.1 (0.3-4.1) 
Substance Use Disorders                   
Alcohol abuse  134  10 (7.8)  3.1  2.0 (0.5-8.05)  0.9  0.3492  04 (2.8)  1.7  0.9 (0.1-11.9) 
Alcohol dependence  64  07 (13.2)  6.3  2.1 (0.4-9.5)  0.8  0.3614  02 (3.9)  3.1 
Drug abuse  31  03 (6.6)  3.6  8.2 (1.9-36.4)  7.8  0.0054  01 (2.4)  2.2 
Drug dependence  21  03 (11.7)  7.4  9.3 (1.5-58.8)  5.6  0.0176  01 (2.6)  2.6 
Any substance use disorder  163  13 (7.9)  2.5  3.6 (0.9-15.1)  3.1  0.0763  04 (2.2)  1.3  0.8 (0.1-10.3) 
Impulse-control Disorders                   
Attention deficit disorder  45  07 (13.3)  6.0  17.5 (2.1-146.8)  6.98  0.0083  03 (10.1)  5.8  11.3 (1.4-90.6) 
Oppositional-defiant disorder  20  01 (3.8)  3.8       
Conduct disorder  17  03 (15.9)  9.3  01 (8.4)  8.0 
Intermittent explosive disorder  137  10 (4.6)  1.5  4.1 (0.7-23.3)  2.6  0.1096  03 (1.2)  0.7  2.3 (0.2-30.9) 
Any impulse-control disorder  191  16 (5.8)  1,7  5.6 (1.1-27.7)  4.4  0.0352  06 (2.9)  1.1  4.2 (0.5-37.6) 
Any 12-month Disorder                   
Any  1271  117 (7.8)  0.8  1.5 (0.7-3.2)  0.9  0.3563  40 (2.7)  0.4  0.8 (0.4-1.8) 
0 Disorders  1664  45 (1.9)  0.6  13.0 (4.1-41.3)  19.0  <0.0001  25 (1.4)  0.6  20.9 (5.4-81.9) 
1 Disorder  731  48 (5.6)  0.9  1.2 (0.5-3.0)  0.1  0.7294  20 (2.2)  0.5  0.6 (0.2-1.8) 
2 Disorders  262  19 (6.1)  1.0  1.2 (0.2-6. 3)  0.1  0.8004  08 (2.6)  1.0  1.4 (0.2-9.8) 
3+ Disorders  278  50 (16.3)  3.0  2.3 (0.9-6.1)  3.0  0.0836  12 (4.6)  1.4  1.1 (0.2-5.2) 
Severity                   
Serious  465  77 (15.3)  2.1  1.3 (0.6-2.9)  0.4  0.5226 
Moderate  409  21 (4.2)  1.1  2.2 (0.4-10.9)  0.9  0.3438 
Mild  397  19 (3.7)  0.8  3.4 (0.8-14.4)  2.7  0.0999 
None  1664  45 (1.9)  0.6  13.0 (4.1-41.3)  19.0  <0.0001 

Weighted proportions. OR, odds ratio; CI, confidence interval. Sex comparison: males were used as the reference group.

The likelihood of BZD use was also higher among those with obsessive-compulsive disorder (OR=7.0; 95%CI=1.6-30.0), drug abuse (OR=8.2; 95%CI=1.9-36.4), drug dependence (OR=9.3, 95%CI=1.5-58.8), impulse control disorders (OR=5.6, 95%CI=1.1-27.7), and attention deficit disorder (OR=17.5, 95%CI=2.1-146.8) (Table 5).

Subjects that had not been diagnosed with a mental health disorder reported infrequent BZD use (1.9%). This prevalence was much higher among females than males (OR=13.0; 95%CI=4.1-41.3) (Table 5).

Considering the number of psychotropics used, 3% of subjects that had been diagnosed with a mental health disorder reported using BZD as a monotherapy. This was most frequent in those who had been diagnosed with attention deficit disorder (10.1%). The mean frequency of monotherapy was 2.9% for anxiety disorders, and 9.8% for panic disorders. Lower rates of BZD use were observed among individuals with mood (4%), bipolar I/II (4.5%) or major depressive disorders (4%) (Table 5).

DISCUSSION

The 12-month prevalence of BZD use in the São Paulo metropolitan area was 3.6%. This rate is similar to that reported in a survey conducted in Rio de Janeiro (22). Similarly, in Chile, about 4% of individuals reported using hypnotics and anxiolytics (21). Conversely, the reported prevalence of BZD use in European countries (9.8% (25), 12.3% (16), 5.5% (19)), and the United States of America (5.2% (26)) is higher.

Even though the methodologies used were different, several studies have reported higher BZD use in Brazil previously. In 1979, the reported use of BZDs in São Paulo was 8.8% (27). Additionally, in 1993, 8.0% used tranquilizers and 1.2% used hypnotics (28). Recent studies have shown that the prevalence of use has indeed decreased to 1.6% and 2.7%, respectively, in Rio de Janeiro (22) and São Paulo (23).

The higher prevalence of BZD use among females may be due to females having a higher rate of mental health disorders, such as anxiety, major depression, and dysthymia (24). This sex difference persists even among individuals with a psychiatric diagnosis and among those without any psychiatric diagnosis. This suggests that other factors might be involved. Accordingly, the higher use of psychotropic drugs by females could also be explained by treatment-seeking behavior and lower alcohol and psychotropic drug use (25).

People working at home and those with low social functioning, such as retirees and the unemployed, also reported higher BZD use. This is in line with previous reports in Europe (29). In the current study, the use of psychiatric services increased the chance of using BZDs by 30%. Seeking help for emotional problems appears to be associated with the use of BZDs (29).

A surprising finding is the higher use of BZD among those subjects who had been diagnosed with a mood disorder compared to those with an anxiety disorder (14.7% vs. 8.1%, respectively), even regarding monotherapy (4.0% vs. 2.9%). However, this finding has been reported in a number of studies that have used a similar methodology (16). Sometimes, the use of BZDs among subjects with mood disorders has been comparable (16) or higher than the use of antidepressants (18,29). The non-specific effects of BZD appear to be less harmful than first-line antidepressants, which has prompted some clinicians to prefer BZD (10). In France, the use of hypnotics and anxiolytics was similar for those with depression or an anxiety disorder (43.4% vs. 42.5%). This finding reflects the challenges in diagnosing and managing mood disorders in primary care (17).

There was also increased use of BZDs in patients with more severe psychiatric disorders. One explanation for this could be the prescribing habits of clinicians. Usually, clinicians might include an adjunctive medication, such as BZD, for non-responders to treat residual symptoms such as insomnia and anxiety.

BZD is not considered to be the first-line treatment for most anxiety disorders, such as generalized anxiety disorder, phobias, and post-traumatic stress disorder, with antidepressants and antiepileptic drugs, usually prescribed (14). Nevertheless, the use of BZDs was also higher (18,25,29) or similar to the use of antidepressants among individuals with an anxiety disorder (16). It appears that in Brazil, patients are not receiving the most appropriate treatment option (22) because the use of BZD as a monotherapy was higher than that of other classes of psychotropic medications among subjects who had been diagnosed with an anxiety disorder. General practitioners issued 46.9% of the BZD prescriptions (28). Other specialists, such as cardiologists (15.3%) and neurologists (4.5%), issued more tranquilizer prescriptions than psychiatrists (11.7%).

The reported higher use of BZD in the elderly is in line with the patterns observed in most studies conducted in the United States of America (26), Canada (30), and Europe (25). In a systematic review (31) on inappropriate prescriptions for long-term BZD use and analogous non-BZD z-drugs, psychological dependence, absence of social support, ignorance about treatment options, withdrawal symptoms, and unfamiliarity with the potential side effects were the main drivers that perpetuate their use. Additionally, previous use was one of the main factors associated with the likelihood of BZD use among older patients (32). People from older cohorts that have been extensively exposed to BZD in their youth may become addicted (32), and become chronic users (32). Other factors included chronic illness, stress, pain, and insomnia (26). The higher BZD use in older cohorts is concerning due to older individuals being more at risk of falls (33,34,35), associated with healthcare utilization and decline in functional status (36). The causative effect of BZD on the risk of dementia is also a major concern (37). The literature suggests that long-term exposure to BZD is associated with an increased risk of Alzheimer's disease (38,15), without stringent confirmation (39).

Taken together, our data and the existing literature must be urgently reviewed by governments, policymakers, and medical societies. There is some consensus that BZD should be discontinued in subjects aged 65 years or older. The most recommended deprescribing strategy for long-term BZD and Z-drug use is pharmacologic interventions. Multidisciplinary reduction of BZD and Z-drug exposure with the addition of alternative pharmacological therapies, psychological therapies (anxiety management, stress management, and psychotherapy), mixed programs (psychological therapy, gradual dose reduction, and usual care), and psychological education are some of the recommended approaches. These interventions present numerous, heterogeneous, and poorly described results, suggesting that studies are needed on how to best deprescribe BZD and Z-drugs in the future (40).

CONCLUSION

According to the findings in the current study, the use of hypnotics and sedatives, which are mostly composed of BZD, has been declining over the last few decades in Brazil. Those that were older, female, or had lower social functioning tended to have higher BZD use. Subjects diagnosed with a mood disorder were more likely to use BZDs than those with an anxiety disorder. Individuals with disorders that were considered to be moderate or severe, those that used psychiatric services, and those with health insurance coverage tended to have higher BZD use. It is a public health challenge to find a surrogate for BZD and manage the existing chronic users.

AUTHOR CONTRIBUTIONS

Campanha AM was responsible for the conception, draft, statistics, critical intellectual contribution. Ravagnani B was responsible for the draft and critical intellectual contribution. Milhorança IA was responsible for the statistics and critical intellectual contribution. Bernik MA was responsible for the conception, draft and critical intellectual contribution. Viana MC was responsible for the data acquisition and critical intellectual contribution. Wang YP was responsible for the draft and critical intellectual contribution. Andrade LA was responsible for the conception, data acquisition, statistics and critical intellectual contribution.

ACKNOWLEDGMENTS

The São Paulo Megacity Mental Health Survey was funded by the Fundação de Amparo è Pesquisa do Estado de São Paulo (São Paulo Research Foundation; FAPESP 03/00204-3), and the Brazilian Conselho Nacional de Desenvolvimento Científico e Tecnológico (National Council for Scientific and Technological Development; CNPq 307623/2013-0) supported Dr. L. H. Andrade and Dr. Maria Carmen Viana (CNPq 314218/2018-1). The São Paulo Megacity Mental Health Survey was conducted in conjunction with the World Health Organization World Mental Health Survey Initiative. The main coordination center activities at Harvard University were supported by the United States National Institutes of Mental Health (R01-MH070884), John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, and the US Public Health Service (R13-MH066849, R01-MH069864, and R01-DA016558) as well as by the Fogarty International Center (FIRCA R03-TW006481), the Pan American Health Organization, Eli Lilly and Company Foundation, Ortho-McNeil Pharmaceutical, GlaxoSmithKline, Bristol-Myers Squibb, and the Shire. A complete list of the World Mental Health publications can be found at http://www.hcp.med.harvard.edu/wmh/. The current study received financial support from the Araucária Foundation for the Support of Scientific and Technological Development in the State of Paraná (01/2009-457/2010-17975, Angela Maria Campanha was the recipient of the scholarship for doctoral thesis), the Programa de Excelência Acadêmica (PROEX, Academic Excellence Program) of the Brazilian Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Office for the Advancement of Higher Education), and Dr Maria Carmen Viana received support for instrument development from the Fundo de Apoio è Ciência e Tecnologia de Vitória (FACITEC, Vitória [Municipal] Fund for the Support of Science and Technology; 002/2003. None of the sponsors had any role in the design, analysis, interpretation of results, or preparation of this paper.

REFERENCES
[1]
M Lader .
History of benzodiazepine dependence.
J Subst Abuse Treat, 8 (1991),
[2]
S Michelini , GB Cassano , F Frare , G Perugi .
Long-term use of benzodiazepines: tolerance, dependence and clinical problems in anxiety and mood disorders.
[3]
C Gorenstein , MA Bernik , S Pompéia , T Marcourakis .
Impairment of performance associated with long-term use of benzodiazepines.
[4]
P Wolf .
Acute drug administration in epilepsy: a review.
[5]
L Amato , S Minozzi , S Vecchi , M Davoli .
Benzodiazepines for alcohol withdrawal.
Cochrane Database Syst Rev, (2010),
[6]
MP Wilson , D Pepper , GW Currier , GH Holloman Jr , D Feifel .
The psychopharmacology of agitation: consensus statement of the American association for emergency psychiatry project Beta psychopharmacology workgroup.
[7]
S Schutte-Rodin , L Broch , D Buysse , C Dorsey , M Sateia .
Clinical guideline for the evaluation and management of chronic insomnia in adults.
J Clin Sleep Med, 4 (2008), pp. 487-504
[8]
MB Stein , MK Goin , MH Pollack , P Roy-Byrne , J Sareen , NM Simon , et al.
Practice guidelines for the treatment of patients with panic disorder. 2nd ed.
American Psychiatric Association Work Group on Panic Disorder, (2009),
[9]
MA Katzman , P Bleau , P Blier , P Chokka , K Kjernisted , M Van Ameringen , et al.
Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress, and obsessive-compulsive disorders.
[10]
LN Yatham , SH Kennedy , SV Parikh , A Schaffer , DJ Bond , BN Frey , et al.
Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder.
[11]
JK Aronson .
Meyler's Side effects of drug: the international encyclopedia of adverse drug reactions and interactions. 15th ed.
Elsevier, (2006),
[12]
HV Curran , S Barrow , H Weingartner , M Lader , M Bernik .
Encoding, remembering and awareness in lorazepam-induced amnesia.
[13]
H Pétursson .
The benzodiazepine withdrawal syndrome.
[14]
National Institute for Health and Care Excellence .
Generalised anxiety disorder and panic disorder in adults: management.
National Institute of Health and Care Excellence, (2011),
[15]
V Tapiainen , H Taipale , A Tanskanen , J Tiihonen , S Hartikainen , AM Tolppanen .
The risk of Alzheimer’s disease associated with benzodiazepines and related drugs: a nested case-control study.
[16]
R Bruffaerts , A Bonnewyn , H Van Oyen , S Demarest , K Demyttenaere .
Consommation de médicaments psychotropes dans la population belge: Résultats de l'European Study of the Epidemiology of Mental Disorders (ESEMeD) [Psychotropic drug use in the Belgian non-institutionalized population].
Rev Med Liege, 60 (2005), pp. 181-188
[17]
I Gasquet , L Nàgre-Pagàs , A Fourrier , G Nachbaur , A El-Hasnaoui , V Kovess , et al.
Usage des psychotropes et troubles psychiatriques en France: résultats de l’étude épidémiologique ESEMeD/MHEDEA 2000/(ESEMeD) en population générale [Psychotropic drug use and mental psychiatric disorders in France; results of the general population ESEMeD/MHEDEA 2000 epidemiological study].
[18]
M Codony , J Alonso , J Almansa , G Vilagut , A Domingo , A Pinto-Meza , et al.
Uso de fármacos psicotrópicos en Espaãa. Resultados del estudio ESEMeD-Espaãa [Psychotropic medications use in Spain. Results of the ESEMeD-Spain study].
Actas Esp Psiquiatr, 35 (2007), pp. 29-36
[19]
A Grinshpoon , E Marom , A Weizman , AM Ponizovsky .
Psychotropic drug use in Israel: results from the national health survey.
Prim Care Companion J Clin Psychiatry, 9 (2007), pp. 356-363
[20]
AM Campanha , ER Siu , IA Milhorança , MC Viana , YP Wang , LH Andrade .
Use of psychotropic medications in São Paulo Metropolitan Area, Brazil: pattern of healthcare provision to general population.
Pharmacoepidemiol Drug Saf, 24 (2015), pp. 1207-1214
[21]
G Rojas , R Fritsch , J Gaete , I González , R Araya .
Use of psychotropic medication in Santiago, Chile.
J Mental Health, 14 (2005), pp. 407-414
[22]
MI Quintana , SB Andreoli , FG Moreira , WS Ribeiro , MM Feijo , RA Bressan , et al.
Epidemiology of psychotropic drug use in Rio de Janeiro, Brazil: gaps in mental illness treatments.
[23]
MI Quintana , SB Andreoli , MP Peluffo , WS Ribeiro , MM Feijo , RA Bressan , et al.
Psychotropic Drug Use in São Paulo, Brazil-An Epidemiological Survey.
[24]
LH Andrade , YP Wang , S Andreoni , CM Silveira , C Alexandrino-Silva , ER Siu , et al.
Mental disorders in megacities: findings from the São Paulo megacity mental health survey, brazil.
[25]
J Alonso , MC Angermeyer , S Bernert , R Bruffaerts , TS Brugha , H Bryson , et al.
Psychotropic drug utilization in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project.
Acta Psychiatr Scand Suppl, (2004), pp. 55-64
[26]
M Olfson , M King , M Schoenbaum .
Benzodiazepine use in the United States.
[27]
FB Tancredi .
Aspectos Epidemiológicos do Consumo de Medicamentos Psicotrópicos pela População de Adultos do Distrito de São Paulo [dissertation].
Faculdade de Saúde Pública, Universidade de São Paulo, (1979),
[28]
JJ Mari , N Almeida-Filho , E Coutinho , SB Andreoli , CT Miranda , D Streiner .
The epidemiology of psychotropic use in the city of São Paulo.
[29]
K Demyttenaere , A Bonnewyn , R Bruffaerts , G De Girolamo , I Gasquet , V Kovess , et al.
Clinical factors influencing the prescription of antidepressants and benzodiazepines: results from the European study of the epidemiology of mental disorders (ESEMeD).
[30]
CM Cunningham , GE Hanley , S Morgan .
Patterns in the use of benzodiazepines in British Columbia: examining the impact of increasing research and guideline cautions against long-term use.
[31]
C Sirdifield , SY Chipchase , S Owen , AN Siriwardena .
A Systematic Review and Meta-Synthesis of Patients’ Experiences and Perceptions of Seeking and Using Benzodiazepines and Z-Drugs: Towards Safer Prescribing.
[32]
CI Neutel .
The epidemiology of long-term benzodiazepine use.
[33]
By the American Geriatrics Society 2015 Beers Criteria Update Expert Panel .
American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.
[34]
MR de Jong , M Van der Elst , KA Hartholt .
Drug-related falls in older patients: implicated drugs, consequences, and possible prevention strategies.
[35]
CI Neutel , S Perry , C Maxwell .
Medication use and risk of falls.
Pharmacoepidemiol Drug Saf, 11 (2002), pp. 97-104
[36]
HJ Luijendijk , H Tiermeier , A Hofman , J Heeringa , BH Stricker .
Determinants of chronic benzodiazepine use in the elderly: a longitudinal study.
[37]
S Billioti de Gage , B Bégaud , F Bazin , H Verdoux , JF Dartigues , K Péràs , et al.
Benzodiazepine use and risk of dementia: prospective population based study. Version 2.
[38]
S Billioti de Gage , Y Moride , T Ducruet , T Kurth , H Verdoux , M Tournier , et al.
Benzodiazepine use and risk of Alzheimer’s disease: case-control study. Version 2.
[39]
SL Gray , S Dublin , O Yu , R Walker , M Anderson , RA Hubbard , et al.
Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study. Version 2.
[40]
AS Pollmann , AL Murphy , JC Bergman , DM Gardner .
Deprescribing benzodiazepines and Z-drugs in community-dwelling adults: a scoping review.

No potential conflict of interest was reported.

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