Prescription psychotropic medication use among the U.S. adult population: results from the third National Health and Nutrition Examination Survey, 1988–1994

Journal of Clinical Epidemiology 57 (2004) 309–317

Prescription psychotropic medication use among the U.S. adult population: results from the third National Health and Nutrition Examination Survey, 1988–1994 Ryne Paulose-Rama,*, Bruce S. Jonasb, Denise Orwigc, Marc A. Safrand a

Division of National Health and Nutrition Examination Survey, National Center for Health Statistics, Centers for Disease Control and Prevention, 3311 Toledo Road, Hyattsville, MD 20782, USA b Office of Analysis, Epidemiology, and Health Promotion, National Center for Health Statistics, Centers for Disease Control and Prevention, 3311 Toledo Road, Hyattsville, MD 20782, USA c Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, 660 West Redwood Street, Baltimore, MD 21201, USA d Mental Health Work Group, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA Accepted 14 May 2003

Abstract Objective: We estimated prescription psychotropic medication use among US adults. Methods: We examined household interview data from the third National Health and Nutrition Examination Survey (1988–1994) for persons 17 years and older (n ⫽ 20,050). Study Design and Setting: An estimated 10 million adults (5.5%) reported psychotropic medication use during a 1-month period. The use of anxiolytics, sedatives, and hypnotics (ASH) was most common (3.2%), followed by antidepressants (2.3%), antipsychotics (0.7%), and antimanics (0.1%). Psychotropic medication use was more prevalent among women than men (P ⬍ .001), non-Hispanic whites than non-Hispanic blacks (P ⬍ .001) and Mexican Americans (P ⬍ .001), and older rather than younger age groups (P ⬍ .001). Psychotropic medication use was also most common among those below the federal poverty level, those with no high school education, and among insured persons. Only 1% of adults used two or more psychotropic medications monthly. Conclusion: Many adults use psychotropic medications on a monthly basis. ASH users comprised the largest proportion of psychotropic medication users. Patterns of use varied by several socio-demographic factors. 쑖 2004 Elsevier Inc. All rights reserved. Keywords: Psychotropics; Antidepressants; Anxiolytics; Antipsychotics; NHANES III; Medication use

1. Introduction Psychotropic medications are among the most widely prescribed medications in the United States. During 1993– 1994, 6.5% of physician office visits in the United States resulted in a psychotropic medication prescription [1]. Psychotropic medications are intended to affect mental processes (i.e., they may sedate, stimulate, or change mood, thinking, or behavior) [2]. These drugs can be placed into four major categories: anxiolytics, sedatives, and hypnotics (ASH); antidepressants; antipsychotics; or antimanics. Used appropriately, psychotropic medications are generally safe and effective for a wide variety of mental disorders; however, there is potential for serious side effects, toxicity, and drug interactions. Adverse consequences associated with

* Corresponding author. Tel.: 301-458-4655; fax: 301-458-4028. E-mail address: [email protected] (R. Paulose-Ram). 0895-4356/04/$ – see front matter 쑖 2004 Elsevier Inc. All rights reserved. doi: 10.1016/j.jclinepi.2003.05.001

psychotropic medication use are well documented, especially among older adults, and include falls, hospitalizations, and cognitive impairment [3–6]. Psychotropic medications also have a great potential for misuse and dependency. A recent report by the National Institute on Drug Abuse identified certain psychotropic medications among the most commonly abused prescription drugs in the United States [7]. Prevalence and patterns of psychotropic medication use in the United States were estimated in the late 1960s and 1970s using pharmacy prescription audits and national, local, and regional surveys [8,9]. During the 1980s and 1990s, psychotropic medication research primarily focused on specific populations (e.g., the elderly population) [10–12], certain drug classes (e.g., ASHs) [13], or the analysis of potential risks (e.g., drug dependency or misuse). As a result, the recent prevalence of prescription psychotropic medication use in the United States, overall and for specific subgroups, has not been well defined.

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Given the high psychotropic medication prescribing rates, lack of recent information on patterns of prescription psychotropic medication use, possible side effects, and potentially inappropriate long-term use and abuse, a detailed examination of prescription psychotropic medication use in the United States is needed to provide accurate prevalence estimates for public health planning and for tracking changes in psychopharmacologic treatment patterns over time. Using a nationally representative dataset (NHANES III), we report population-based prevalence estimates of prescription psychotropic medication use among U.S. adults by psychotropic drug classes and certain socio-demographic variables.

2. Methods 2.1. Sample The NHANES III was a cross-sectional survey conducted between October 1988 and October 1994. A multistage, stratified probability cluster design was used to select a sample representative of the civilian, noninstitutionalized population, aged 2 months and older, residing in the United States. Children younger than 5 years of age, adults aged 60 years and older, black, and Mexican American persons were oversampled to improve the precision of estimates for these subgroups. NHANES III participants were interviewed within their homes, and health history, health behaviors, risk factors, and prescription medication use were determined. Participants subsequently underwent a health examination conducted at a mobile examination center. The NHANES III plan of operation and sample design has been described in detail elsewhere [14]. Of those eligible to participate in NHANES III, 33,994 infants, children, adolescents, and adults received the household interview (86% interview response rate). This study focused on the sample of persons who were aged 17 years and older (defined by NHANES III as adults) at the time of the interview (n ⫽ 20,050). Thirty-six persons were excluded due to item nonresponse for the prescription medication use question (refused, don’t know, or missing response).

Pharmacologic Therapeutic Classification System for categorizing all prescription psychotropic medications. This system classifies drugs based on the drug’s activity and primary indication. Based on the AHFS, each psychotropic medication was assigned to one of the following therapeutic drug categories: antidepressants (AHFS Drug Code: 28:16:04); antipsychotics (28:16:08); anxiolytics, sedatives, and hypnotics (ASH; 28:24); and antimanics (28:28). We did not examine psychostimulants (e.g., dextroamphetamine, methylphenidate, pemoline) because of the law prevalence of use of these drugs among adults at the time of the NHANES III survey. Drugs that contained a psychotropic drug ingredient and some other ingredient were assigned to one of the above categories if the product’s primary indication was as a psychotropic medication. Only the following multiple ingredient drugs were identified in this study as psychotropic medications based on their primary indication and were categorized accordingly: chlordiazepoxide drug combinations were categorized as ASHs, amitriptyline drug combinations as antidepressants, and drug combinations containing both amitriptyline and chlordiazepoxide were categorized as antidepressants. Because of limited sample sizes, overall antimanic and antipsychotic prevalence estimates are provided, but antimanics are not analyzed in further detail and antipsychotics are only analyzed when sample sizes permitted. Antimanics and antipsychotics are, however, included in all total estimates for any psychotropic medication use. A person who reports using multiple psychotropic medications within the past month is only counted once for any psychotropic medication use and, depending upon which classes of psychotropic medications (i.e., ASH, antidepressant, antipsychotic, and antimanics) are reported, is counted only once within the drug class. Each psychotropic medication that is reported is used to compute the total number of psychotropic medications used within the past month. Persons reporting more than one psychotropic medication are identified as multiple psychotropic medication users. Multiple psychotropic medication use does not imply concurrent drug use because data on the frequency of use within the month is not available. 2.3. Demographic variables

2.2. Medication data collection During an in-person household interview, respondents were asked, “Have you taken or used any medicines for which a doctor’s or dentist’s prescription is needed, in the past month?” For each medication reported, the interviewer asked to see the medication container to record the product name. If the container was unavailable, the interviewer probed the subject for this information. Participants were also asked how long they had been taking the medication. No information was collected on dosage or daily frequency of use. Each reported drug in the survey was identified in the Physicians’ GenRx [15] and assigned a standard generic name and four-digit generic code. For this study, we applied the American Hospital Formulary Service (AHFS) [16]

Age was reported at interview as the respondent’s age in years at last birthday. Gender was recorded as observed by the interviewer. Race/ethnicity was categorized according to the NHANES III analytic guidelines [17] as non-Hispanic white (NHW), non-Hispanic black (NHB), Mexican American (MA), and other (included all other race/ethnicities not captured in first three categories, e.g., Asian, nonMexican American Hispanics, etc.). Because of limited sample size, estimates for persons from other race/ethnicity groups are not provided separately, but members of these groups are included in total estimates. Education was categorized as less than high school (HS) (0–8 years), some HS (9–11 years), HS completed (12 years), and more than HS education (13 or more years).

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Poverty status was defined by the poverty-income ratio (PIR), which is a ratio of the total yearly family income to the national poverty threshold for the interview year. PIR was categorized as very low (⬍1.00), low (1.00–1.99), and middle or high income (⭓2.00). Health insurance status was defined as “yes” if the participant reported health insurance coverage through Medicare, Medicaid, the military, a private plan, or an employer or union plan during the past month. No information was collected on prescription drug coverage. 2.4. Statistical analysis Statistical analyses were conducted using SAS [18] and SUDAAN [19]. Survey sample weights were used that accounted for the complex survey design by adjusting for differential selection, nonresponse, and noncoverage probabilities for each respondent. These weights were used to produce estimates representative of the noninstitutionalized civilian US population. Using total 6-year (1988–1994) interview weights, SUDAAN was used to calculate variance estimates. All estimates provided here are 1-month period prevalences. Age-adjusted prevalence estimates were calculated using the direct method and were adjusted to the age distribution of the 2000 U.S. Bureau of the Census population [20]. In this study, the average design effect was used to determine the minimum sample size needed to reliably estimate means and percentiles [17]. The design effect is the ratio of the complex sampling design variance to the simple random sample variance. Within gender and race/ethnic subdomains, an average design effect is calculated by taking the mean of the design effects across age groups within gender and race/ethnicity subgroups. If an estimate is based on a sample size of ⬍30 times the average design effect or has a coefficient of variation ⬎30%, it is statistically unreliable. Such estimates have been identified in tables. Chi-square tests of independence were first used to determine the association between categorical variables and binary outcomes of interest. SUDAAN’s DESCRIPT procedure with the CONTRAST option was then used to statistically test for differences between groups within categorical variables. There was total concordance between the initial chi-square tests and subsequent paired contrasts. Therefore, chi-square tests of independence are not shown in tables.

3. Results 3.1. Demographics Demographic characteristics of persons 17 years of age and older in the United States are presented in Table 1. Fiftythree percent were female, 11% were NHB, 5% were MA, and about one third were 50 years of age and older. Approximately 13% were living below the federal poverty level, and 13% had no health insurance coverage. Eleven percent

311

Table 1 Sociodemographic characteristics of persons aged 17 years and older by gender: United States, 1988–1994 Male Characteristics

Number Percent Number Percent interviewed (weighted) interviewed (weighted)

Total 9401 Age groups, yr 17–39 4006 40–59 2278 60⫹ 3117 Race/ethnicitya Non-Hispanic white 3879 Non-Hispanic black 2503 Mexican American 2682 Poverty income ratiob Middle/high (⭓2.0) 4296 Low (1.0–1.99) 2377 Very low (⬍1.0) 1764 Health insurance coverageb No 1649 Yes 7286 Education completedb, yr 0–8 2424 9–11 1773 12 2519 13 or more 2568 a b

Female

100.0

10,649

100.0

50.9 30.0 19.1

4596 2574 3479

47.7 28.9 23.4

76.3 10.4 5.7

4604 2983 2624

75.8 11.9 4.8

69.0 20.2 10.8

4274 2670 2464

62.6 22.7 14.7

14.4 85.6

1631 8615

11.5 88.5

11.5 16.2 30.7 41.6

2363 1956 3435 2789

11.4 14.7 36.5 37.4

Other race/ethnicity group not shown. Numbers do not add to total due to missing data.

had 0 to 8 years of education, and 40% had 13 or more years of education. 3.2. Psychotropic medication use and duration of use by drug class Approximately 5.5% of the U.S. adult population reported using a prescription psychotropic medication within a 1month period (Table 2). ASHs were most commonly used Table 2 Prevalence of prescription psychotropic medication use by persons aged 17 years and older: United States, 1988–1994 Number of psychotropic medication users Any psychotropic medication 1179 Anxiolytics, sedatives, 700 and hypnotics Benzodiazepines 536 Barbiturates 50 Miscellaneous 138 Antidepressants 453 Tricyclics 276 Selective serotonin 107 reuptake inhibitors Mono-amine oxidase inhibitors Antipsychotics 168 Antimanics 22

Percentage of sample (weighted)a 95% CI 5.5 3.2

5.0–6.0 2.8–3.6

2.5 0.1 0.6 2.3 1.3 0.7

2.1–2.9 0.0–0.2 0.4–0.8 1.9–2.7 1.0–1.6 0.5–0.9

—b 0.7 0.1

—b 0.5–0.9 0.0–0.2

a Percentages do not add to totals because a person may report use of multiple psychotropic medications across and within drug classes. b Sample size too small to provide a statistically reliable estimate.

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(3.2%), followed by antidepressants (2.3%), antipsychotics (0.7%), and antimanics (0.1%). Among ASH users, more than three quarters reported benzodiazepine use (78%, 95% confidence interval [CI] 72–84), approximately 19% reported miscellaneous ASH use (95% CI 13–25), and 4.5% barbiturate use (95% CI 3–6). The three most frequently used ASHs were the following benzodiazepines: alprazolam (26%) (Table 3), diazepam (13%), and lorazepam (12%). The median days of benzodiazepine use was slightly less than 2 years (data not shown; 95% CI 548–813 days) with 50% of users reporting 6 months to 5 years of use (interquartile range: 178–1814 days). More than half of all antidepressant users reported using a tricyclic agent (see Table 2) (58%, 95% CI 51–65) and 28% a selective-serotonin-reuptake inhibitor (SSRI) (95% CI 21–35). The number of persons reporting monoamine oxidase inhibitor use was too small to provide a statistically reliable national estimate. Amitriptyline hydrochloride (27%) and fluoxetine hydrochloride (20%) were the most commonly reported antidepressants (see Table 3). The median days of antidepressant use was approximately 1 year (data not shown; 95% CI 210–510 days), with about 50% of users reporting 3 months to 3 years of use (interquartile range 91–1102 days). For antipsychotics, trifluoperazine HCl, thioridazine HCl, and haloperidol were each reportedly used by approximately 20% of antipsychotic users (see Table 3). Due to limited sample sizes, duration of use of antipsychotics and antimanics could not be analyzed to provide statistically reliable estimates. 3.3. Psychotropic medication use by socio-demographic factors Psychotropic medication use varied by several sociodemographic factors (Table 4). Overall, the prevalence of any psychotropic medication, ASH, and antidepressant use was

significantly higher among women than men and among NHWs than NHBs and MAs. For antipsychotics (data not shown), there were no differences by gender (men: 0.7%, 95% CI 0.4–0.9; women: 0.8%, 95% CI 0.5–1.0) or race/ ethnicity (NHW: 0.7%, 95% CI 0.5–0.9; NHB: 1.0%, 95% CI 0.6–1.5; MA: 0.5%, 95% CI 0.3–0.7). With respect to age, persons 40 years and older had a significantly higher use of any psychotropic medication, ASH, and antidepressant use compared with persons 17 to 39 years of age. This age difference was also seen with antipsychotic use (17–39 years: 0.4% [95% CI 0.2–0.6] versus 40⫹ years: 1.0% [95% CI 0.7– 1.4], P ⬍ .01). Persons with low or very low incomes had a significantly higher prevalence of any psychotropic medication and ASH use compared with middle/high income persons. Although antidepressant use also increased with lower income level, these differences did not reach statistical significance. Examination of education showed that persons with some years of HS education or more had a generally lower prevalence of any psychotropic medication, ASH, and antidepressant use compared with persons with no HS education. Persons with no health insurance had significantly lower prevalence of any psychotropic medication, ASH, and antidepressant use compared with the insured persons. 3.4. Psychotropic medication use by sex and race/ethnicity Further examination of gender and race/ethnicity differences showed that psychotropic medication prevalence of use significantly varied between race/ethnicity groups by gender (Table 5). For men, there was no significant difference in the age-adjusted prevalence of any psychotropic medication use across race/ethnicity groups. However, when examining specific drug classes, NHB men had a significantly lower age-adjusted prevalence of ASH and antidepressant use than NHW men. MA men had a lower prevalence of AD use than NHW men but did not differ in terms of ASH use.

Table 3 Top four most frequently used prescription psychotropic medications in the past month: United States, 1988–1994.

Anxiolytics, sedatives, and hypnotics Alprazolam Diazepam Lorazepam Hydroxyzine hydrochloride Antidepressants Amitriptyline hydrochloride Fluoxetine hydrochloride Trazadone hydrochloride Doxepin hydrochloride Antipsychotics Trifluoperazine hydrochloride Thioridazine hydrochloride Haloperidol Chlorpromazine hydrochloride a

Number of users (weighted)

Percentage of sample (weighted)

95% CI

700 164 86 84 51 453 117 73 50 57 168 26 42 35 20

3.2 0.82 0.41 0.38 0.30 2.3 0.62 0.46 0.28 0.24 0.73 0.15 0.14 0.14 0.06a

2.8–3.6 0.64–1.0 0.27–0.55 0.26–0.50 0.14–0.46 1.9–2.7 0.42–0.82 0.32–0.60 0.18–0.38 0.14–0.34 0.53–0.93 0.07–0.23 0.08–0.20 0.06–0.22 0.02–0.10

Figure does not meet standard of reliability or precision due to CV ⬎ 30% or small sample size.

Percentage of drug class users

95% CI

25.6 12.9 11.9 9.3

21.1–30.1 9.2–16.6 8.6–15.2 4.8–13.8

27.1 20.1 12.0 10.4

21.0–33.2 13.6–26.6 7.5–16.5 6.3–14.5

20.5 19.9 19.4 8.6a

11.8–29.1 10.7–29.1 9.6–29.2 3.1–14.1

R. Paulose-Ram et al. / Journal of Clinical Epidemiology 57 (2004) 309–317

313

Table 4 Psychotropic medication use among persons aged 17 years and older by demographic variables: United States, 1988–1994 Any psychotropic druga

Anxiolytics, sedatives, and hypnotics

Antidepressants

95% CI

Number of users

% (weighted)

95% CI

Number of users

% (weighted)

95% CI

5.5

5.0–6.0

700

3.2

2.8–3.6

453

2.3

1.9–2.7

393 786

3.9 7.0***

3.3–4.5 6.2–7.8

237 463

2.2 4.1***

1.7–2.7 3.5–4.7

124 329

1.4 3.1***

1.1–1.7 2.5–3.7

193 343 643

2.3 7.7*** 9.9***

1.8–2.8 6.5–8.9 8.7–11.1

82 189 429

1.0 4.3*** 6.7***

0.7–1.3 3.4–5.2 5.8–7.6

100 158 205

1.2 3.6*** 3.1***

0.8–1.6 2.7–4.5 2.4–3.8

690 262 190

6.2 4.3*** 3.0***

5.5–6.8 3.5–5.1 2.5–3.5

439 129 111

3.7 2.1*** 1.7***

3.2–4.2 1.6–2.6 1.3–2.1

263 99 74

2.6 1.7** 1.2***

2.1–3.1 1.3–2.1 0.9–1.5

456 317 294

4.8 6.6** 7.7**

4.1–5.5 5.6–7.6 6.2–9.2

269 202 153

2.8 4.0** 3.8*

2.3–3.3 3.2–4.8 2.8–4.8

194 106 116

2.1 2.6 3.1

1.7–2.6 1.9–3.3 2.1–4.1

398 216 301 255

10.4 5.3*** 5.3*** 4.5***

8.8–12.0 4.4–6.2 4.3–6.3 3.6–5.4

259 129 166 140

7.0 3.5*** 2.7*** 2.5***

5.7–8.3 2.7–4.3 2.0–3.4 1.9–3.1

116 78 139 118

3.1 1.9* 2.7 1.9*

2.2–4.0 1.4–2.4 2.0–3.4 1.4–2.4

1091 70

6.0 2.8***

5.4–6.6 1.8–3.8

648 41

3.5 1.7***

3.0–4.0 1.0–2.4

416 29

2.5 1.3**

2.0–3.0 0.6–2.0

Number of users Totalb Gender Male (ref)c Female Age groups, yr 17–39 (ref)c 40–59 60⫹ Race/ethnicity Non-Hispanic white (ref)c Non-Hispanic black Mexican American Poverty income ratio Middle/high (⭓2.0; ref)c Low (1.0–1.99) Very low (⭐1.0) Education completed, yr 0–8 (ref)c 9–12 12 13⫹ Health insurance Yes (ref)c No

1179

% (weighted)

* P ⬍ .05, ** P ⬍ .01, *** P ⬍ .001 for comparison with reference group. a Includes antipsychotic and antimanic agents not shown separately. b Total includes other race/ethnicity group not shown separately. c Ref ⫽ reference group used in statistical analyses.

The pattern is different for women. MA and NHB women had a significantly lower age-adjusted prevalence of any psychotropic medication and ASH use compared with NHW women. With antidepressant use, MA but not NHB women had a lower age-adjusted prevalence of use than NHW women. 3.5. Multiple psychotropic medication use One percent of U.S. adults reported using two or more prescription psychotropic medications during a 1-month

period, whereas 4.5% used only one (Table 6). Multiple psychotropic medication use was more common among women than men and among persons 40 years and older than younger. MAs had a significantly lower use of multiple psychotropic medications than NHWs, although there was no difference between NHBs and NHWs. Persons with very low or low income had significantly higher multiple psychotropic medication use than persons with middle or high income. Persons with some HS education or more had a lower prevalence of use compared with persons with no

Table 5 Age-adjusted prevalence of prescription psychotropic medication use by gender and race/ethnicity for persons aged 17 years and older: United States, 1988–1994 Any psychotropic druga

Men Non-Hispanic white (ref)b Non-Hispanic black Mexican American Women Non-Hispanic white (ref)b Non-Hispanic black Mexican American

Anxiolytics, sedatives, and hypnotics

Antidepressants Number of users

Number of users

% (weighted)

95% CI

Number of users

% (weighted)

95% CI

226 91 66

4.6 3.6 3.5

3.7–5.4 2.5–4.7 2.6–4.4

152 39 41

2.7 1.7* 2.4

2.0–3.4 1.1–2.3 1.6–3.2

72 27 20

464 171 124

7.9 6.1** 5.2***

6.9–9.0 5.1–7.1 4.2–6.2

287 90 70

4.7 3.2** 2.8**

4.0–5.4 2.3–4.1 1.9–3.7

191 72 54

* P ⬍ .05, ** P ⬍ .01, *** P ⬍ .001 for comparison with reference group. a Includes antipsychotic and antimanic agents not shown separately. b Ref ⫽ reference group for statistical analyses.

% (weighted)

95% CI

1.8 1.0* 0.8***

1.3–2.2 0.5–1.5 0.6–1.0

3.5 2.7 2.4*

2.8–4.3 2.0–3.4 1.7–3.1

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Table 6 Prevalence of prescription psychotropic medication use during the past month by number of psychotropic drugs used: United States, 1988–1994 Number of psychotropic drugs used 1

2⫹

Number % 95% of users (weighted) CI

Number % 95% of users (weighted) CI

Totala 947 Gender 308 Male (ref)b Female 639 Age groups, yr 153 17–39 (ref)b 40–59 267 60⫹ 527 Race/ethnicity Non-Hispanic 563 white (ref)b Non-Hispanic 209 black Mexican 154 American Poverty income ratio Middle/high 387 (ref; ⭓2.0)b Low 250 (1.0–1.99) Very low 226 (⭐1.0) Education completed, yr 325 0–8 (ref)b 9–12 168 12 240 13⫹ 209 Health insurance 876 Yes (ref)b No 215

use studies among persons in the United States, Pincus et al examined physician-prescribing patterns among U.S. officebased physician visits and found that 5.1% of visits in 1985 and 6.5% in 1993–1994 resulted in a psychotropic medication prescription [1]. Thus, the psychotropic medication prevalence of use identified in the present study closely matches the psychotropic medication physician-prescribing rate identified in the Pincus et al study. In terms of specific psychotropic drug classes, the current study found that 3.2% of U.S. adults used an ASH and 2.3% used an antidepressant. A cross-sectional household survey conducted in two southeastern New England communities reported a 3.1% prevalence of antidepressant use in 1992–1993 [21]. The reporting of ASH use in the current study was also similar to the 1993–1994 physician-prescribing rate of 2.6% for anxiolytics/hypnotics as reported by Pincus et al [1]. The reporting of antidepressant use, however, was slightly lower than the antidepressant prescribing rate of 3.6% [1]. This may indicate that individuals do not always disclose the use of certain medications during a face-to-face interview.

4.5

4.0–4.9 232

1.0

0.8–1.2

3.1 5.7***

2.6–3.6 85 5.0–6.4 147

0.7 1.3***

0.4–1.0 1.0–1.6

1.8 6.3*** 8.1***

1.4–2.2 40 5.2–7.4 76 7.0–9.2 116

0.4 1.4*** 1.9***

0.2–0.6 1.0–1.8 1.4–2.4

5.1

4.4–5.7 127

1.1

0.8–1.4

3.4***

2.8–4.0

53

0.9

0.5–1.2

2.4***

2.0–2.8

36

0.6**

0.4–0.8

4.1

3.5–4.7

69

0.7

0.5–0.9

4.2. ASH prevalence of use

5.1

4.2–6.1

67

1.5*

0.9–2.1

5.8*

4.6–7.0

68

1.9**

1.3–2.5

8.2 4.1*** 4.2*** 3.8***

6.9–9.5 3.3–4.9 3.3–5.1 3.0–4.6

73 48 61 46

2.2 1.2* 1.1* 0.6***

1.5–2.9 0.8–1.6 0.6–1.6 0.4–0.8

5.0 1.1***

4.4–5.6 0.9–1.3

58 12

2.1 0.6c

1.2–3.1 0.1–1.1

Benzodiazepines were the most frequently used psychotropic drug class, with 2.5% of U.S. adults reporting their use. This represents over three quarters of all ASH users. By the end of the 1980s, alprazolam was the most widely prescribed benzodiazepine in the United States [22]. This study, conducted between 1988 and 1994, found that alprazolam was the most frequently used benzodiazepine, with about a quarter of all benzodiazepine users reporting its use. Overall, this represents approximately 1% of the U.S. adult population. The recently conducted Slone study (1998–1999), which used a telephone survey to examine medication use in the previous week on a random sample of Americans aged 18 and older, identified alprazolam among the top 40 most commonly used prescription or over-thecounter drugs with a 1.1% weekly prevalence of use [23]. Among U.S. adults, the median duration of benzodiazepine use was close to 2 years, with 25% reporting use for more than 5 years. These results may be of particular interest because treatment regimens of this duration may be associated with tolerance and psychological and physical dependence [24,25]. However, in this study the assessment of risk associated with long-term use is limited due to the lack of information on dose, monthly frequency of use, and individual clinical indications for use. Our results on benzodiazepine length of use were similar to the results from a clinical records review of persons 15 years and older attending a primary health care center in Spain, which showed that the average duration of benzodiazepine treatment was 25 months, with about 18% of patients being prescribed a benzodiazepine for more than 3 years [26].

* P ⬍ .05, ** P ⬍ .01, *** P ⬍ .001 for comparison with reference group. a Total includes other race/ethnicity group not shown separately. b Ref ⫽ reference group for statistical analyses. c Figure does not meet standard of reliability or precision due to CV ⬎ 30% or small sample size.

HS education. Although prevalence estimates were higher for persons with health insurance, these differences did not reach statistical significance.

4. Discussion 4.1. U.S. national data on psychotropic medication use To our knowledge, this is the first published data on the prevalence of prescription psychotropic medication use, overall and for specific subgroups, in a nationally representative sample of the U.S. population in the past two decades. These data from 1988 through 1994 indicate that 5.5% of the U.S. adult population, corresponding to approximately 10 million adults (95% CI 9 million to 11 million) used a prescription psychotropic medication during a 1-month period. Although we found no other recent prevalence of

4.3. Antidepressant prevalence of use Tricyclics such as amitriptyline and imipramine were the first successful antidepressants. They have been widely used

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for the treatment of major depression since the early 1960s [27]. This study found that 58% of antidepressant users were taking a tricyclic agent, and 28% were using an SSRI. The most frequently used antidepressant was amitriptyline, with about one out of four antidepressant users reporting use of this tricyclic agent. The second most frequently used antidepressant was the SSRI fluoxetine, with one out of five antidepressant users reporting its use. The Slone survey found that fluoxetine and two other SSRIs, sertraline and paroxetine, were among the 40 most commonly used medications, with each drug being used by approximately 1% of U.S. adults [23]. The lower estimates for these drugs found in the present study may be explained by the fact that sertraline and paroxetine entered the U.S. drug market toward the middle to the end of the survey. Additionally, it was by the mid-1990s, after NHANES III, that SSRIs, due to their relative safety and fewer side effects, became the most frequently prescribed antidepressant drug class in the United States [27,28]. 4.4. Antipsychotic prevalence of use We found that most antipsychotic users took traditional antipsychotic medications such as trifluoperazine, thioridazine, or haloperidol. The only newer “atypical” antipsychotic that was reportedly used during the NHANES III survey was clozapine. More atypical antipsychotic medications have become available since 1994 (the final year of the NHANES III survey) that have different therapeutic properties and side effect profiles than the traditional antipsychotics. These newer antipsychotics were reported to have specific clinical advantages and were being prescribed to increasing numbers of patients by the late 1990s [29]. Thus, future antipsychotic prevalence estimates will be different from those found for the period of this survey. 4.5. Demographic subgroups and psychotropic drug use Overall, psychotropic medication use was most common among women, older adults, NHW, persons with low/very low income, persons with no HS education, and insured persons. The higher prevalence of any psychotropic medication use and ASH and antidepressant use among women compared with men has been reported in several other studies [30–34] and may be explained by significant gender differences in the prevalence of psychological symptoms/ disorders [35–37], treatment-seeking behavior [38], and physician prescribing behavior [39,40]. The higher prevalence of psychotropic medication use among older adults, which is also well documented [31–33,41], also may be explained by the higher prevalence of anxiety, depression, and insomnia among this age group [36]. Because the proportion of the U.S. population 65 years and older is expected to increase in future years, we may also see increases in the number of older adults using psychotropic medications. Race/ethnicity differences in psychotropic medication use have also been identified in other studies [40,42]. Using 1989 NAMCS

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data, Simoni-Wastila [40] found that office visits by white women resulted in an 86% greater likelihood of receiving an antidepressant than office visits by black women. Using 1992 to 1995 NAMCS data, Sclar et al [42] identified higher antidepressant prescribing rates for whites compared with blacks and Hispanics. Our study showed that, in addition to antidepressant use, any psychotropic medication and ASH use were also higher for NHWs compared with NHBs and MAs. The race/ethnicity differences for ASH and antidepressant use were generally confirmed for men and women in separate age-adjusted analyses. Other differences between race/ethnicity groups, such as income and educational and insurance levels, need to be further examined. The association between psychotropic medication use and certain socio-economic variables is not as clear. Some studies have suggested that persons with less education or with a low-income consume more psychotropic medications [41,43–45]. However, other studies have shown that socioeconomic status is not significantly associated with psychotropic medication use [4,46,47]. We found that low or very-low income persons had a higher prevalence of any psychotropic medication use and specifically ASH use, whereas differences by income for antidepressant use did not reach statistical significance. We also found differences in psychotropic medication use by educational status. Persons with less than a HS education had more than double the prevalence of any psychotropic medication, ASH, and antidepressant use compared with those with 13⫹ years of education. Similarly, persons with health insurance had approximately double the prevalence of any psychotropic medication, ASH, and antidepressant use compared with those with no health insurance. Future studies need to more closely examine the association of multiple covariates and psychotropic medication use to discern the true effect of each covariate on psychotropic medication use and ASH and antidepressant use. 4.6. Multiple psychotropic medication users Among psychotropic medication users, approximately one out of five reported using two or more psychotropic medications during a 1-month period. Multiple psychotropic medication use was most common among women, persons 50 years and older, and persons with very low income and was lowest among Mexican Americans and persons with more than a HS education. Multiple psychotropic medication use also tended to be higher among persons with health insurance compared with uninsured persons, although differences did not reach statistical significance. A Finnish study that examined use of tranquilizers and sleeping pills also found that women were more likely to report multiple psychotropic medication use than men [34]. In the present study, using two drugs does not imply concurrent drug use because it is possible that an individual initiated on one drug switched to another drug within a

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1-month period due to side effects or other reasons. Additionally, using more than one medication is sometimes the indicated and reasonable care. Therefore, multiple psychotropic medication use does not imply inappropriate use. The lack of information on monthly or daily frequency of psychotropic medication use also prevented an assessment of the potential risks associated with multiple psychotropic medication use. 4.7. Study strengths and limitations The major strength of this study was that we used the NHANES III data, which provided a large, nationally representative sample of the noninstitutionalized U.S. population. Furthermore, oversampling of key demographic subsamples, such as older persons, NHBs, and MAs, increased precision of estimates for these groups, which are often under-represented. Additionally, data were collected by trained interviewers, using an in-person, household interview protocol, with verification of reported medications with drug containers, which eliminates known biases with selfreport of medication use. However, the overall prevalence of psychotropic medication use reported in this study may be conservative. This household-based survey does not cover some groups who are at increased risk of psychotropic medication use, including nursing home residents, the homeless who do not reside in shelters, inmates in correctional facilities, and other institutionalized persons. Although survey sample weights account for some under-coverage, for example among demographic groups, if there is a differential response rate between psychotropic medication users and nonusers, it may not be accounted for. Additionally, although participants are asked to show all prescription medication containers to the interviewer, it is possible that certain participants may not choose to disclose the use of certain psychotropic medications to interviewers in a face-to-face household survey. Other limitations of the study are its inability to examine antipsychotic and antimanic use in further detail due to statistical limitations. The lack of data on daily drug dose and daily/monthly frequency of prescription medications limited any detailed risk assessment associated with psychotropic medication use and specifically with length of use. An understanding of symptomatology or treatment patterns was not possible due to lack of information on the drug’s indication for use. Direct comparison between the results of this survey and those of other studies is also difficult due to variations in the criteria used to define psychotropic drug classes and different time frames (past 2 weeks, past month, or past year). This study analyzed data collected between 1988 and 1994, and prevalence estimates are based on drugs available to the U.S. public during this period. Newer psychotropic medications that became available after the completion of the NHANES III survey, changes in general acceptance and attitudes of psychotropic medications, and other factors such as reimbursement patterns will affect more recent prevalence estimates of specific psychotropic drugs

and drug classes. These limitations not withstanding, the NHANES III data provide national baseline information on patterns of psychotropic medication use in the U.S. adult population by psychotropic drug classes and sociodemographic factors. 4.8. Summary The results presented here provide valuable baseline information on patterns of prescription psychotropic medication use, overall and for specific subgroups, in the U.S. adult population that can be used for tracking changes in psychopharmacologic treatment patterns across the population over time. As identified in previous studies, ASHs and antidepressants are the most commonly used psychotropic medications in the United States. Future studies may need to examine the effect of newly approved psychotropic medications and the expanded use of certain psychotropic medications on the overall prevalence of psychotropic medication use and on specific drug classes. This study shows that the association of certain socio-demographic covariates with prescription psychotropic medication use has essentially remained unchanged since the 1960s; that is, women, whites, and older adults have the greatest use of any psychotropic medications, ASHs, and antidepressants. Additionally, certain socio-economic variables, such as education, income, and health insurance status, are associated with psychotropic medication use. Future research may need to examine these and other variables more closely to better understand the patterns of psychotropic medication use presented in this study.

References [1] Pincus HA, Tanielian TL, Marcus SC, Olfson M, Zarin DA, Thompson J, Zito JM. Prescribing trends in psychotropic medications: primary care, psychiatry, and other medical specialties. JAMA 1998; 279:526–31. [2] Baldessarini RJ. Drugs and the treatment of psychiatric disorders: psychosis and anxiety. In: Hardman JG, Limbird LE, editors. Goodman and Gilman’s the pharmacological basis of therapeutics. 9th edition. New York: McGraw-Hill; 1996. p. 399–430. [3] Hanlon J, Schmader K, Koronski M, Weinberger M, Landsman P, Samsa G, Lewis I. Adverse drug events in high risk older outpatients. J Am Geriatr Soc 1997;45:945–8. [4] Dealberto MJ, Seeman T, Mcavay GJ, Berkman L. Factors related to current and subsequent psychotropic drug use in an elderly cohort. J Clin Epidemiol 1997;50:857–63. [5] Weiner DK, Hanlon JT, Studenski SA. Effects of central nervous system polypharmacy on falls liability in community-dwelling elderly. Gerontology 1998;44:217–21. [6] Foy A, O’Connell D, Henry D, Kelly J, Cocking S, Halliday J. Benzodiazepine use as a cause of cognitive impairment in elderly hospital inpatients. J Gerontol Med Sci 1995;50A:M99–106. [7] National Institute of Drug Abuse. Prescription drugs: abuse and addiction. NIH publication no. 01-4881. Bethesda: NIDA, NIH, DHHS; 2001. [8] Cooperstock R, Parnell P. Research on psychotropic drug use: a review of findings and methods. Soc Sci Med 1982;16:1179–96. [9] Parry HJ. Use of psychotropic drugs by U.S. adults. Public Health Rep 1968;83:799–810.

R. Paulose-Ram et al. / Journal of Clinical Epidemiology 57 (2004) 309–317 [10] Stewart RB, May FE, Moore MT, Hale WE. Changing patterns of psychotropic drug use in the elderly: a five-year update. Ann Pharmacother 1989;23:610–3. [11] Gleason PP, Schulz R, Smith NL, Newsom JT, Kroboth P, Kroboth FJ, Psaty BM. Correlates and prevalence of benzodiazepine use in community-dwelling elderly. J Gen Intern Med 1998;13:243–50. [12] Dealberto MJ, Seeman T, McAvay GJ, Berkman L. Factors related to current and subsequent psychotropic drug use in an elderly cohort. J Clin Epidemiol 1997b;50:357–64. [13] Balter MB, Manheimer DI, Mellinger GD, Uhlenhuth EH. A crossnational comparison of anti-anxiety/sedative drug use. Curr Med Res Opin 1984;8:5–20. [14] National Center for Health Statistics. Plan and operation of the Third National Health and Nutrition Examination Survey, 1988–94. Vital Health Stat 1 1994;32:1–407. [15] Denniston PL Jr, Epner JA, editors. Physicians GenRx, 1994: the official drug reference. Smithtown, NY: Data Pharmaceutica; 1993. [16] McEvoy GK, editor. American hospital formulary service drug information 96. Bethesda: American Society of Health-System Pharmacists; 1996. [17] National Center for Health Statistics. Analytic and reporting guidelines: the Third National Health and Nutrition Examination Survey, NHANES III (1988–94). Available at: http://www.cdc.gov/nchs/data/ nhanes/nhanes3/nh3gui.pdf. Accessed 17 July 2002. [18] SAS procedures guide, version 6. 3rd edition. Cary (NC): SAS Institute; 1990. [19] Shah BV, Barnwell BG, Bieler GS. SUDAAN user’s manual, release 7.0. Research Triangle Park, NC: Research Triangle Institute; 1996. [20] Klein RJ, Schoenborn CA. Age adjustment using the 2000 projected U.S. population. Healthy People Statistical Notes, no. 20. Hyattsville, Maryland: National Center for Health Statistics; 2001. [21] Hume AL, Barbour MM, Lapane KL, Carleton RA. Is antidepressant use changing? Prevalence and clinical correlates in two New England communities. Pharmacotherapy 1995;15:78–84. [22] Susmann N, Chou JCY. Current issues in benzodiazepine use for anxiety disorders. Psychiatr Ann 1988;18:139–45. [23] Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent patterns of medication use in the ambulatory adult population of the United States. JAMA 2002;287:337–44. [24] Physicians’ desk reference. 56th edition. Montvale (NJ): Medical Economics Company; 2002. p. 2865–8. [25] Drug facts and comparison. 55th edition. St. Louis (MO): Facts and comparison; 2001. p. 888-91. [26] De Las Cuevas C, Sanz E, De La Fuente JA, Cabrera C. Prescribed daily doses and ‘risk factors’ associated with the use of benzodiazepines in primary care. Pharmacoepidemiol Drug Saf 1999;8:207–16. [27] Baldessarini RJ. Drugs and the treatment of psychiatric disorders: depression and mania. In: Hardman JG, Limbird LE, editors. Goodman and Gilman’s the pharmacological basis of therapeutics. 9th edition. New York: McGraw-Hill; 1996. p. 431–60. [28] Zarit SH, Zarit JM. Mental disorders in older adults. New York: Guilford Press; 1998.

317

[29] U.S. Department of Health and Human Services . Mental health: a report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health; 1999. [30] Mellinger GD, Balter MB, Chase C, Manheimer DI. Patterns of psychotherapeutic drug use among adults in San Francisco. Arch Gen Psychiatry 1971;25:385–94. [31] Ohayon MM, Caulet M, Priest RG, Guilleminault C. Psychotropic medication consumption patterns in the UK general population. J Clin Epidemiol 1998;51:273–83. [32] Isacson D, Carsjo K, Haglund B, Smedby B. Psychotropic drug use in a Swedish community: patterns of individual use during 2 years. Soc Sci Med 1988;27:263–7. [33] Graham K, Vidal-Zeballos D. Analyses of use of tranquilizers and sleeping pills across five surveys of the same population (1985–1991): the relationship with gender, age and use of other substances. Soc Sci Med 1998;46:381–95. [34] Ettorre E, Klaukka T, Riska E. Psychotropic drugs: long-term use, dependency and the gender factor. Soc Sci Med 1994;39:1667–73. [35] Hidalgo RB, Davidson JR. Generalized anxiety disorder: an important clinical concern. Med Clin North Am 2001;85:691–710. [36] Paykel ES. Depression in women. Br Med J Psychiatry 1991;10:22–9. [37] Bourdon KH, Rae DS, Locke BZ, Narrow WE, Regier DA. Estimating the prevalence of mental disorders in U.S. adults from the Epidemiologic Catchment Area Survey. Public Health Rep 1992;107:663–8. [38] Julien RM. A primer of drug action. 6th ed. NY: WH Freeman and Co.; 1992. p. 41. [39] Lewis-Hall F. Gender differences in psychotropic medications. Mount Sinai J Med 1996;63:326–9. [40] Simoni-Wastila L. Gender and psychotropic drug use. Med Care 1998;36:88–94. [41] Preville M, Hebert R, Boyer R, Bravo G. Correlates of psychotropic drug use in the elderly compared to adults aged 18–64: results from the Quebec Health Survey. Aging Ment Health 2001;5:216–24. [42] Sclar DA, Robison LM, Skaer TL, Galin RS. Ethnicity and the prescribing of antidepressant pharmacotherapy. Harv Rev Psychiatry 1999;7:29–36. [43] Mazza D, Dennerstein L, Ryan V. Psychotropic drug use by women: current prevalence and associations. Med J Aust 1995;163:86–9. [44] Allard J, Allaire D, Leclero G, Langlois S. The influence of family and social relationships on the consumption of psychotropic drugs by the elderly. Arch Gerontol Geriatr 1995;20:193–204. [45] Laurier C, Dumas J, Gregoire JP. Factors related to benzodiazepine use in Quebec: a secondary analysis of survey data. J Pharmacoepidemiol 1992;2:73–86. [46] Gustafson TM, Isacson DGL, Thorslund M, Sorbom D. Factors associated with psychotropic drug use among the elderly living at home. J Appl Gerontol 1996;15:238–54. [47] Ried LD, Christensen DB, Stergachis A. Medical and psychosocial factors predictive of psychotropic drug use in elderly patients. Am J Public Health 1990;80:1349–53.