How To Find A Doctor That Will Prescribe Benzodiazepines
J Gen Intern Med. 2016 Sep; 31(nine): 1027–1034.
Benzodiazepines are Prescribed More than Frequently to Patients Already at Risk for Benzodiazepine-Related Adverse Events in Primary Intendance
David S. Kroll, MD, 
i, ii Harry Reyes Nieva, BA,1, 3 Arthur J. Barsky, MD,one, 2 and Jeffrey A. Linder, MD1, 3
David S. Kroll
iHarvard Medical Schoolhouse, Boston, MA U.s.a.
2Section of Psychiatry, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02120 USA
Harry Reyes Nieva
1Harvard Medical School, Boston, MA United states
iiiDivision of Full general Medicine and Master Care, Brigham and Women's Hospital, Boston, MA United states
Arthur J. Barsky
aneHarvard Medical School, Boston, MA USA
twoDepartment of Psychiatry, Brigham and Women'southward Hospital, 75 Francis Street, Boston, MA 02120 U.s.a.
Jeffrey A. Linder
1Harvard Medical School, Boston, MA USA
3Division of Full general Medicine and Primary Intendance, Brigham and Women'due south Infirmary, Boston, MA The states
Received 2015 Oct 20; Revised 2016 Mar 31; Accepted 2016 May ii.
Abstract
Background
Benzodiazepine employ is associated with agin drug events and higher mortality. Known take chances factors for benzodiazepine-related adverse events include lung disease, substance utilise, and vulnerability to fracture.
Objective
To make up one's mind whether benzodiazepine prescribing is associated with risk factors for agin outcomes.
Design
Longitudinal cohort study between July one, 2011, and June 30, 2012.
Participants
Patients who visited hospital- and community-based practices in a primary care practice-based inquiry network.
Main Measures
Odds ratio of having a target medical diagnosis for patients who received standard and loftier-dose benzodiazepine prescriptions; rates per 100 patients for outpatient and emergency department visits and hospitalizations.
Key Results
Among 65,912 patients, clinicians prescribed at to the lowest degree one benzodiazepine to 15 % (9821). Of benzodiazepine recipients, five % received high doses. Compared to non-recipients, benzodiazepine recipients were more probable to have diagnoses of low (OR, ii.7; 95 % CI, 2.half-dozen–2.9), substance corruption (OR, 2.two; 95 % CI, 1.nine–2.5), tobacco utilize (OR, 1.vii; 95 % CI, ane.5–1.8), osteoporosis (OR, 1.6; 95 % CI, 1.5–one.7), chronic obstructive pulmonary disease (OR, 1.6; 95 % CI, i.5–1.7), alcohol abuse (OR, 1.5; 95 % CI, one.iii–1.vii), slumber apnea (OR, one.5; 95 % CI, 1.3–one.6), and asthma (OR, 1.v; 95 % CI, 1.four–1.5). Compared to low-dose benzodiazepine recipients, high-dose benzodiazepine recipients were fifty-fifty more likely to have certain medical diagnoses: substance corruption (OR, 7.v; 95 % CI, 5.5–10.ane), alcohol abuse (OR, 3.2; 95 % CI, two.ii–four.5), tobacco employ (OR, two.7; 95 % CI, 2.ane–iii.five), and chronic obstructive pulmonary disease (OR, 1.5; 95 % CI, 1.two–1.9). Benzodiazepine recipients had more than primary care visits per 100 patients (408 vs. 323), specialist outpatient visits (815 vs. 578), emergency department visits (47 vs. 29), and hospitalizations (26 vs. 15; p < .001 for all comparisons).
Conclusions
Clinicians prescribed benzodiazepines and high-dose benzodiazepines more often to patients at higher risk for benzodiazepine-related adverse events. Benzodiazepine prescribing was associated with increased healthcare utilization.
Electronic supplementary textile
The online version of this article (doi:ten.1007/s11606-016-3740-0) contains supplementary fabric, which is bachelor to authorized users.
KEY WORDS: psychopharmacology, benzodiazepines, feet, sleep disorders
INTRODUCTION
Benzodiazepines are usually used to treat anxiety and sleep disorders, likewise every bit a number of master medical conditions. However, they are frequently prescribed to patients who either do not have a clear indication1 or accept poor indications such as depression.2
The use of benzodiazepines is associated with higher mortality.3 , 4 National registries in Europe and the United States take linked benzodiazepines utilise to elevated rates of respiratory suppression in patients with chronic obstructive pulmonary disease (COPD)v and with overdose expiry in substance use disorders.6 , vii Benzodiazepines may besides exist linked to cancer risk and to exacerbation of obstructive slumber apnea (OSA) severity.8 , 9 In the elderly, benzodiazepines are associated with delirium in the hospital10 , 11 and with hip fractures,12 disability,thirteen and dementia14 , fifteen in the customs.
Although benzodiazepines are frequently prescribed by primary intendance physicians (PCPs),16 few studies have described in item which primary intendance patients receive benzodiazepine prescriptions. Most studies that have explored this question were performed outside of Due north America.17 – 26 These works identified some demographic predictors of benzodiazepine prescription (due east.g., increased age and female person gender) and an association with higher medical comorbidity in general, but did not focus on specific medical diagnoses. While benzodiazepines have known risks of adverse events in the elderly, including fractures, and in patients with lung illness and substance use disorders, no prior studies take examined benzodiazepine prescriptions within the distribution of atmospheric condition that increase the adventure of benzodiazepine-related agin events in primary intendance in North America.
We hypothesized that clinicians prescribe benzodiazepines disproportionately to primary care patients with factors or diagnoses that increment the risk of benzodiazepine-related adverse events, and that patients who receive benzodiazepines accept higher healthcare utilization rates. If confirmed, such risk factors and utilization rates could explain some of the association between benzodiazepine use and higher mortality. We performed a longitudinal cohort written report to identify associations between benzodiazepine prescribing, take a chance factors for benzodiazepine-related agin events, and healthcare utilization.
METHODS
Setting
The Brigham and Women's Primary Care Practice-Based Research Network (BWPC PBRN) includes sixteen hospital- and community-based practices and community wellness centers in eastern Massachusetts. The BWPC PBRN practices used a fully functional, Certification Commission for Healthcare Information Technology (CCHIT)-certified electronic health tape (EHR), which included problem lists, medication lists, and prescriptions. By policy, all medicines were prescribed through the EHR. Medications non prescribed past affiliated clinicians were listed in the EHR without dosing information.
Sociodemographic information was collected during registration and was updated periodically. Billing codes were recorded in a dissever, defended billing system. Partners HealthCare—an integrated health delivery arrangement in eastern Massachusetts, of which Brigham and Women'south Hospital is a role—had an information system that captured outpatient visits, emergency room visits, and hospitalizations for all Partners HealthCare facilities.
Blessing for the acquit of this study was obtained from the Partners HealthCare Institutional Review Board.
Information Extraction
We used the Partners HealthCare Enquiry Patient Data Repository, which aggregates data from throughout Partners HealthCare facilities, to identify all patients who made at to the lowest degree one visit to whatsoever of the ten BWPC PBRN practices that were participating in an unrelated clinical trial between July 1, 2011, and June 30, 2012.27 – 29 Nosotros extracted and combined sociodemographic and clinical data from the EHR with billing codes.
We included all coded benzodiazepine prescriptions and listings. From the EHR we extracted prescription details that included the name of the medication, dose, frequency, total number of units prescribed, number of refills, and prescribing clinician. Our data source included prescriptions; we could not measure out prescription fills or actual benzodiazepine use by patients.
We extracted medical diagnoses from the EHR problem list and ICD-9 billing codes associated with individual encounters (see online appendix). We extracted medical diagnoses divers past the Healthcare Effectiveness Data and Information Set (HEDIS; asthma, COPD, cardiovascular disease, depression, diabetes, hypertension, obesity, osteoporosis, and tobacco use),thirty psychiatric diagnoses for which benzodiazepines are commonly prescribed (anxiety and insomnia), and diagnoses for which benzodiazepines are contraindicated or controversial (alcohol abuse, slumber apnea, and substance corruption).6 , seven , ix , 31
We too extracted information nigh antidepressant medication prescribing from the EHR, considering these are commonly considered offset-line agents for depression and anxiety. We included the antidepressants fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, mirtazapine, bupropion, venlafaxine, desvenlafaxine, duloxetine, nefazodone, amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, nortriptyline, protriptyline, trimipramine, phenelzine, tranylcypromine, isocarboxazid, trazodone, and vilazodone.
Nosotros extracted medical encounters from encounter-level billing information, including primary care visits (both any visit to the primary care clinic and any visit with the PCP of record), specialist outpatient visits, emergency department (ED) visits, and hospitalizations, and length of stay for patients with one or more hospitalizations. We defined a patient'southward PCP as the PCP of record from the EHR. Listed PCPs are virtually always chief intendance clinicians.
Data Analysis
We calculated benzodiazepine dosing and days prescribed based on a combination of pill dose/strength, dosing frequency, and number of pills prescribed during the study catamenia. We converted prescriptions of lorazepam, clonazepam, and alprazolam—which, together with diazepam, accounted for 97 % of benzodiazepine prescriptions—to "average daily diazepam-equivalent dosages." Only days for which benzodiazepines were prescribed were included in the calculation of average daily dose.
High-dose benzodiazepine prescribing has been defined in the literature equally a daily dose equivalent of ≥30 mg per day of diazepam.32 Although potency equivalence betwixt benzodiazepine agents is not conspicuously established, we defined 30 mg diazepam equivalents as three mg/d alprazolam, three mg/d clonazepam, and 5 mg/d lorazepam.32 , 33 For patients with multiple benzodiazepine agents (iii % of patients receiving benzodiazepines) for which diazepam-equivalent dosing could exist calculated, nosotros added them together every bit though they were concurrent or consecutive prescriptions of a unmarried diazepam-equivalent agent. Other benzodiazepine prescriptions and benzodiazepine prescriptions without complete prescribing data were not included in the comparison betwixt high-dose and standard-dose prescriptions.
To decide which patients were most likely to receive benzodiazepine prescriptions, nosotros compared patients who received at to the lowest degree one benzodiazepine prescription with those who did not. We assessed differences in demographic variables, medical diagnoses, and inpatient and outpatient encounters. Among benzodiazepine recipients, we fabricated parallel comparisons between patients who did and did not receive high-dose prescriptions.
Statistical Analysis
Nosotros used means, medians, percentages, odds ratios, and rate ratios with 95 % confidence intervals to compare patients who did and did non receive benzodiazepines and those who received high doses versus standard doses. Nosotros compared categorical variables using the chi-foursquare test and continuous variables using Student'south t examination. We performed the Isle of mann–Whitney–Wilcoxon exam to compare days dosed among categorical variables with two groups and the Kruskal-Wallis test for the same comparison among chiselled variables with three or more than groups. We calculated odds ratios using logistic regression, and we used Poisson regression to calculate charge per unit ratios. We used SAS software (version nine.iii; Cary, NC) for all analyses and considered p values < 0.05 statistically meaning.
RESULTS
Cohort Characteristics
Among 65,912 patients who visited one of the ten included primary care practices during the study year, at least ane benzodiazepine prescription was issued to 15 % (9821); of these patients, 44 % received at least one benzodiazepine prescription from their PCPs of record as opposed to other providers within or outside their primary care practices. Among the 9821 patients who received a benzodiazepine prescription, the mean age was 55 years, 77 % were white, 7 % were black, and 59 % had private insurance. Patients received a median of 30 (IQR = ten–60) days of benzodiazepines at a mean daily diazepam dose equivalent of 11 mg. In that location were 9532 (97 %) patients who received only one type of benzodiazepine amanuensis during the study period, 280 (3 %) who received two, eight (<i %) who received three, and one (<i %) who received more than iii. The most commonly prescribed benzodiazepines were lorazepam (n = 5057; 51 %;), clonazepam (n = 2007; 20 %), diazepam (n = 1372; 14 %), and alprazolam (north = 1371; 14 %). The mean daily dose prescribed, by benzodiazepine, was 1.7 mg for lorazepam (ten.0 mg diazepam-equivalent), 1.five mg for clonazepam (14.v mg diazepam-equivalent), 10.8 mg for diazepam, and 1.0 mg for alprazolam (ten.1 mg diazepam-equivalent).
Benzodiazepine Prescribing
Clinicians prescribed benzodiazepines more commonly to patients who were older, were women, had Medicare or Medicaid insurance, and were divorced, widowed, or separated (Tabular array ane). Clinicians prescribed to white patients at a college charge per unit than to non-white patients. Medical diagnoses associated with a higher likelihood of existence prescribed a benzodiazepine included substance abuse, depression, tobacco apply, alcohol abuse, osteoporosis, chronic obstructive pulmonary illness (COPD), sleep apnea, and asthma. Clinicians prescribed a higher median days dosed to Medicare recipients and a lower median days dosed to blackness patients. Simply 43 % of patients who were prescribed a benzodiazepine had a diagnosis of anxiety or insomnia noted on a problem list or coded in billing data, and 44 % were concurrently prescribed antidepressants.
Table one
Patient Characteristics past Benzodiazepine Prescription and Days Dosed
| Feature | Benzodiazepine prescription (n = 9821) | No benzodiazepine prescription (n = 56,091) | Odds ratio (95 % CI) | P value | Days dosed | P value |
|---|---|---|---|---|---|---|
| Mean (± SD) | ||||||
| Patient age, years | 55 (15) | 52 (17) | i.12 (i.10–1.13)* | <0.001 | north/a | |
| Number of medications | 1.83 (1.48) | 1.06 (1.33) | 1.39 (ane.37–1.41) | <0.001 | n/a | |
| N (column %) | Median (IQR) | |||||
| Patient gender | <0.001 | <0.001 | ||||
| Men | 2699 (27) | 20,732 (37) | Referent | xxx (14–ninety) | ||
| Women | 7122 (73) | 35,359 (63) | 1.55 (1.48–1.62) | 30 (ten–lx) | ||
| Patient race/ethnicity | <0.001 | <0.001 | ||||
| White† | 7607 (77) | 36,110 (64) | Referent | 30 (12–75) | ||
| Black | 687 (seven) | 7182 (13) | 0.45 (0.42–0.49) | 20 (seven.5–40) | ||
| Hispanic | 715 (7) | 5588 (ten) | 0.61 (0.56–0.66) | 30 (10–lx) | ||
| Asian | 122 (i) | 2165 (4) | 0.27 (0.22–0.32) | 30 (xv–90) | ||
| Other | 71 (one) | 583 (ane) | 0.58 (0.45–0.74) | 30 (x–60) | ||
| Unknown | 619 (6) | 4463 (eight) | 0.66 (0.60–0.72) | 30 (x–60) | ||
| Language | <0.001 | 0.009 | ||||
| English | 9203 (94) | 51,093 (91) | Referent | 30 (x–60) | ||
| Spanish | 153 (2) | 2756 (5) | 0.76 (0.68–0.84) | xxx (xv–90) | ||
| Other | 375 (iv) | 1603 (3) | 0.53 (0.45–0.63) | 30 (xv–ninety) | ||
| Unknown | 90 (1) | 639 (1) | 0.78 (0.63–0.98) | 30 (15–60) | ||
| Insurance | <0.001 | <0.001 | ||||
| Individual | 5842 (59) | 38,172 (68) | Referent | thirty (10–60) | ||
| Medicare | 3041 (31) | 12,639 (23) | 1.57 (ane.50–1.65) | 45 (xx–90) | ||
| Medicaid | 816 (viii) | 4447 (8) | 1.20 (ane.11–1.30) | 30 (10–60) | ||
| None or other | 122 (ane) | 833 (1) | 0.96 (0.79–1.16) | xx (10–35) | ||
| Marital status | <0.001 | <0.001 | ||||
| Married | 5131 (52) | thirty,533 (54) | Referent | 30 (10–65) | ||
| Single | 2954 (30) | 17,792 (32) | 0.99 (0.94–1.04) | thirty (x–lx) | ||
| Divorced/separated | 948 (10) | 3752 (seven) | ane.l (1.39–1.62) | 30 (xv–60) | ||
| Widowed | 569 (6) | 2579 (5) | 1.31 (ane.nineteen–one.44) | 45 (25–ninety) | ||
| Unknown | 219 (ii) | 1435 (ii) | 0.91 (0.79–1.05) | 30 (15–90) | ||
| Education | <0.001 | <0.001 | ||||
| Completed post-secondary | 5378 (55) | 29,937 (53) | Referent | 30 (ten–60) | ||
| Some post-secondary | 1769 (18) | 9256 (17) | ane.06 (1.00–1.xiii) | 30 (10–lx) | ||
| Completed high school/GED | 1681 (17) | 9697 (17) | 0.97 (0.91–ane.02) | 30 (xv–75) | ||
| Some high schoolhouse | 291 (iii) | 1559 (3) | 1.04 (0.91–1.eighteen) | 30 (15–xc) | ||
| 8th grade or less | 216 (2) | 1404 (3) | 0.86 (0.74–0.99) | 30 (15–90) | ||
| Unknown | 486 (five) | 4238 (eight) | 0.64 (0.58–0.seventy) | thirty (10–60) | ||
| Diagnoses and other prescriptions‡ | ||||||
| Alcohol abuse | 292 (3) | 1128 (ii) | ane.50 (1.31–1.70) | <0.001 | thirty (fifteen–xc) | 0.fifty |
| Antidepressant | 4345 (44) | 9795 (17) | 3.75 (3.58–3.92) | <0.001 | thirty (15–xc) | <0.001 |
| Anxiety | 3803 (39) | 5603 (10) | v.69 (five.42–five.98) | <0.001 | 30 (15–75) | <0.001 |
| Asthma | 1788 (18) | 7484 (13) | i.45 (1.37–1.53) | <0.001 | 30 (15–90) | 0.004 |
| COPD | 1727 (18) | 6720 (12) | ane.57 (ane.48–1.66) | <0.001 | xxx (fifteen–xc) | <0.001 |
| CVD | 2130 (22) | 9154 (xvi) | ane.42 (1.35–one.50) | <0.001 | xxx (15–90) | <0.001 |
| Depression | 3077 (31) | 8043 (14) | 2.73 (2.60–2.86) | <0.001 | 30 (15–90) | <0.001 |
| Diabetes | 1250 (13) | 7437 (13) | 0.95 (0.89–1.02) | 0.15 | thirty (xv–90) | <0.001 |
| Hypertension | 4133 (42) | 21,113 (38) | ane.20 (1.15–1.26) | <0.001 | 30 (fifteen–ninety) | <0.001 |
| Insomnia | 815 (8) | 1588 (iii) | 3.11 (2.84–iii.39) | <0.001 | 30 (20–90) | <0.001 |
| Obesity | 1664 (17) | 8707 (sixteen) | 1.11 (1.05–1.eighteen) | <0.001 | 30 (ten–threescore) | 0.30 |
| Osteoporosis | 1119 (11) | 4220 (eight) | i.58 (one.47–ane.69) | <0.001 | xxx (20–90) | <0.001 |
| Sleep apnea | 730 (7) | 2922 (5) | 1.46 (1.34–one.59) | <0.001 | 30 (15–ninety) | 0.002 |
| Substance abuse | 252 (3) | 668 (1) | 2.19 (one.89–2.53) | <0.001 | 30 (14–75) | 0.92 |
| Tobacco use | 738 (8) | 2611 (5) | 1.66 (one.53–1.81) | <0.001 | 30 (15–90) | 0.03 |
Patients to whom benzodiazepines were prescribed were higher users of medical care. On average, they made more principal intendance, specialist outpatient, and emergency section visits, were hospitalized more ofttimes, and when hospitalized, had a slightly longer length of stay (Table two).
Tabular array 2
Utilization by Benzodiazepine Prescription and Dose
| Benzodiazepine prescription (n = 9831) | No benzodiazepine prescription (n = 56,091) | Charge per unit ratio (95 % confidence interval) | P value | Loftier dose (n = 481) | Standard dose (n = 9340) | Rate ratio (95 % confidence interval) | P value | |
|---|---|---|---|---|---|---|---|---|
| Primary intendance visits* | ||||||||
| Master care medico visit rate (per 100 patients) | 299 | 242 | ane.23 (one.22–ane.25) | <0.001 | 324 | 297 | 1.12 (ane.07–1.eighteen) | <0.001 |
| Primary care clinic visit charge per unit (per 100 patients) | 408 | 323 | ane.26 (one.25–ane.28) | <0.001 | 440 | 406 | 1.12 (i.07–i.17) | <0.001 |
| Specialist outpatient visits | ||||||||
| Patients with specialist visits (%) | 9062 (92) | 49,404 (88) | <0.001 | 431 (90) | 8631 (92) | 0.025 | ||
| Visit rate (per 100 patients) | 815 | 578 | 1.41 (one.40–1.42) | <0.001 | 887 | 810 | 1.13 (1.09–i.16) | <0.001 |
| Emergency visits | ||||||||
| Patients with emergency visits (%) | 2275 (23) | 9433 (17) | <0.001 | 144 (xxx) | 2131 (23) | <0.001 | ||
| Visit rate (per 100 patients) | 47 | 29 | 1.62 (ane.56–1.67) | <0.001 | 73 | 45 | 1.66 (1.49–1.85) | <0.001 |
| Hospitalizations | ||||||||
| Patients with hospitalizations (%) | 1202 (12) | 4631 (8) | <0.001 | 88 (18) | 1114 (12) | <0.001 | ||
| Hospitalization rate (per 100 patients) | 26 | xv | ane.74 (1.67–ane.82) | <0.001 | 44 | 25 | i.81 (i.57–2.08) | <0.001 |
| Mean length of stay | 3.5 | 3.4 | <0.001 | 3.1 | three.three | 0.0052 | ||
*All patients included in the analysis made at least ane main intendance visit
High-Dose Benzodiazepine Prescribing
Among patients with benzodiazepine prescriptions, the PCPs of record prescribed high doses to 5 %, including to 3 % of lorazepam recipients, 9 % of clonazepam recipients, 2 % of diazepam recipients, and 6 % of alprazolam recipients. Other clinicians prescribed loftier doses to 5 % of lorazepam recipients, ten % of clonazepam recipients, 3 % of diazepam recipients, and 6 % of alprazolam recipients.
Demographic characteristics associated with a higher likelihood of existence prescribed a high-dose benzodiazepine included younger age, male gender, Medicaid insurance, not-married status, and lower education level (Tabular array iii). Medical diagnoses associated with a college likelihood of receiving a loftier-dose benzodiazepine prescription included booze corruption, anxiety, asthma, COPD, low, diabetes, obesity, substance abuse, and tobacco use. Amongst patients with high-dose prescriptions, 52 % were concurrently prescribed antidepressants.
Tabular array iii
Patient Characteristics by Benzodiazepine Dose
| Characteristic | Loftier dose* (n = 481) | Standard dose (due north = 9340) | Odds ratio (95 % CI) | P value |
|---|---|---|---|---|
| Mean (± SD) | ||||
| Patient historic period, years | 51 (13) | 55 (fifteen) | 0.81 (0.77–0.86)† | <0.001 |
| Number of medications | 2.04 (1.64) | 1.82 (1.47) | one.09 (1.04–1.15) | <0.001 |
| Northward (%) | ||||
| Patient gender | <0.001 | |||
| Men | 179 (37) | 2520 (27) | Referent | |
| Women | 302 (63) | 6820 (73) | 0.62 (0.52–0.75) | |
| Patient race/ethnicity‡ | 0.28 | |||
| White | 367 (76) | 7240 (78) | Referent | |
| Blackness | 29 (6) | 658 (seven) | 0.87 (0.59–1.28) | |
| Hispanic | 45 (ix) | 670 (7) | one.33 (0.96–one.82) | |
| Asian | 5 (1) | 117 (1) | 0.84 (0.34–ii.08) | |
| Other | 1 (0) | 70 (1) | 0.28 (0.04–two.04) | |
| Unknown | 34 (7) | 585 (6) | 1.15 (0.80–1.65) | |
| Linguistic communication | 0.39 | |||
| English | 452 (94) | 8751 (94) | Referent | |
| Spanish | 22 (5) | 353 (iv) | one.21 (0.78–1.88) | |
| Other | 5 (1) | 148 (2) | 0.65 (0.27–1.60) | |
| Unknown | 2 (0) | 88 (one) | 0.44 (0.11–1.79) | |
| Insurance | <0.001 | |||
| Private | 220 (46) | 5622 (xxx) | Referent | |
| Medicare | 154 (32) | 2887 (31) | 1.36 (1.ten–1.68) | |
| Medicaid | 100 (21) | 716 (8) | 3.57 (two.78–4.58) | |
| None/other | 7 (i) | 115 (1) | i.56 (0.72–3.38) | |
| Marital Status | <0.001 | |||
| Married | 260 (43) | 4925 (53) | Referent | |
| Single | 191 (40) | 2763 (30) | one.65 (ane.35–ii.02) | |
| Divorced/separated | 55 (11) | 893 (10) | 1.47 (ane.08–ii.00) | |
| Widowed | 17 (4) | 552 (6) | 0.74 (0.45–1.22) | |
| Unknown | 12 (2) | 207 (2) | 1.39 (0.76–two.52) | |
| Education | <0.001 | |||
| Completed postal service-secondary | 192 (40) | 5186 (56) | Referent | |
| Some post-secondary | 121 (25) | 1648 (18) | 1.98 (1.57–2.51) | |
| Completed high school/GED | 96 (20) | 1585 (17) | one.64 (1.27–two.10) | |
| Some high school | 36 (7) | 255 (3) | 3.81 (2.61–5.56) | |
| eighth course or less | seven (1) | 209 (2) | 0.91 (0.42–1.95) | |
| Unknown | 29 (vi) | 457 (5) | one.71 (i.15–2.56) | |
| Diagnoses and other prescriptions§ | ||||
| Alcohol abuse | 39 (8) | 253 (three) | three.17 (2.23–four.50) | <0.001 |
| Antidepressant | 251 (52) | 4094 (44) | 1.forty (1.16–1.68) | <0.001 |
| Anxiety | 228 (47) | 3575 (38) | ane.45 (1.21–1.75) | <0.001 |
| Asthma | 110 (23) | 1678 (18) | i.35 (i.09–ane.69) | 0.007 |
| COPD | 117 (24) | 1610 (17) | 1.54 (i.24–1.91) | <0.001 |
| CVD | 99 (21) | 2031 (22) | 0.93 (0.74–1.17) | 0.55 |
| Depression | 201 (42) | 2876 (31) | ane.61 (i.34–ane.94) | <0.001 |
| Diabetes | 70 (fifteen) | 1180 (13) | 1.18 (0.91–ane.53) | 0.22 |
| Hypertension | 201 (42) | 3932 (42) | 0.99 (0.82–1.nineteen) | 0.89 |
| Insomnia | 38 (8) | 777 (eight) | 0.95 (0.67–ane.33) | 0.75 |
| Obesity | 110 (23) | 1554 (17) | i.49 (1.19–1.85) | <0.001 |
| Osteoporosis | 38 (viii) | 1081 (12) | 0.66 (0.47–0.92) | 0.013 |
| Sleep apnea | 45 (ix) | 685 (7) | 1.thirty (0.95–1.79) | 0.099 |
| Substance abuse | 64 (thirteen) | 188 (two) | 7.47 (5.53–10.09) | <0.001 |
| Tobacco use | 82 (17) | 656 (7) | 2.72 (2.12–3.50) | <0.001 |
On average, patients who received high-dose benzodiazepine prescriptions had a greater number of emergency visits and hospitalizations compared to patients who received standard-dose prescriptions (Table 2).
DISCUSSION
Benzodiazepine prescriptions come from multiple sources within the healthcare arrangement, including PCPs, specialists, and ED and inpatient clinicians. In our sample, close to half of the patients who received benzodiazepine prescriptions received at least one from their PCPs, reflecting the relevance of benzodiazepine prescribing amongst clinicians who work in primary care. Benzodiazepines take a well-established role in the handling of several weather ordinarily seen in primary care, including anxiety and insomnia, and it is likely that benzodiazepine prescribing is safe for many patients, peculiarly when treatment is limited in dose and duration.34 Our finding that clinicians prescribed benzodiazepines disproportionately to patients with at least some known risk factors for benzodiazepine-related adverse events—including increased age, pulmonary diseases, osteoporosis, and substance utilize disorders—may help to explain the human relationship between benzodiazepine employ and poor wellness outcomes.
Benzodiazepines are associated with adverse furnishings, including higher mortality.3 , 4 Although causality has not been definitively adamant, strong associations betwixt benzodiazepine prescribing and mortality take been described in certain patient groups. Higher bloodshed rates have been found in patients with COPD, presumably due to respiratory suppression.5 Patients with opioid use disorders accept a college take chances of overdose death—both suicide and not-suicide—when taking benzodiazepines.six , seven , 35 Senior patients are particularly vulnerable, because benzodiazepines are associated with falls,36 – 39 hip fractures,12 delirium,10 , 11 disability,13 dementia,14 , xv and motor vehicle accidents.40 Osteoporosis has been linked to fractures alongside benzodiazepine prescriptions in patients at risk of falls, although no direct relationship between osteoporosis and benzodiazepine prescriptions has been described.41 , 42 Prescribing benzodiazepines disproportionately to patients with COPD, substance apply disorders, and osteoporosis, and who are older may contribute to their mortality run a risk through these mechanisms. Associations between benzodiazepines and tobacco use have been cited every bit a possible explanation for the association between benzodiazepines and cancer chance;8 our finding of a like association supports the hypothesis that tobacco utilize confounds the relationship betwixt benzodiazepines and the risk of cancer, although we did not mensurate cancer diagnoses straight, and this relationship remains poorly understood.
Our finding that high-dose prescribing was besides associated with diagnoses of COPD and substance use disorders raises special concern. The magnitude of the association betwixt benzodiazepines and mortality in general appears to be dose-dependent,3 , 4 and dose-dependent relationships between benzodiazepines and mortality have been described independently for COPDv and overdose deaths.43 Therefore, the disproportionate prescribing of loftier-dose benzodiazepines to patients with COPD and substance use disorders may dilate the effect of prescribing standard-dose benzodiazepines to patients already at risk of adverse outcomes.
The association between higher days dosed and receipt of Medicare may reflect an association between older age and longer benzodiazepine prescriptions, but we did not measure out this directly and therefore cannot conclude that this is true. That clinicians prescribed shorter and fewer benzodiazepine prescriptions to black patients is notable, although nosotros practice not draw conclusions nearly medical risks of prescribing from this. We combined very cursory prescriptions (due east.g., unmarried doses) with longer prescriptions in our analysis because mortality risk is associated with single benzodiazepine doses in a dose–response mode.4 , viii
The increased frequency of medical diagnoses and higher rates of healthcare utilization associated with benzodiazepine prescriptions indicate that, in general, patients who receive benzodiazepines have higher levels of medical comorbidity. Prior studies in Brazil, the Netherlands, and Australia have linked benzodiazepine prescriptions—without a dose relationship—to patient cocky-reporting of poorer wellness condition.21 – 23 Benzodiazepine prescriptions were similarly linked to college frequencies of medical diagnoses in ii population-based Canadian studies,40 , 41 and with a college score on the Charlson comorbidity index in an Israeli study.xviii Studies linking benzodiazepines to a higher number of medical visits21 and increased length of infirmary stay26 accept been conducted in Israel and Japan, respectively.
The fact that the utilize of benzodiazepines was associated with higher rates of inpatient and outpatient utilization in our study is consistent with ii hypotheses: that patients with higher medical comorbidity are more probable to receive a benzodiazepine prescription, and that benzodiazepines may increase a patient's hazard of agin wellness outcomes. Both may be correct; our findings advise a possible mechanism past which benzodiazepine prescriptions are associated with agin outcomes for at least some patients.
Limitations
Our findings of an association do not necessarily signify causation. Some high-hazard medical diagnoses such every bit respiratory illnesses44 and substance use disorders45 are associated with feet, which may be advisable indications for a benzodiazepine prescription. Benzodiazepines may exist employed directly to treat breathlessness, particularly as a palliative intervention at the stop of life, although the testify supporting a favorable risk/benefit ratio for this is limited, 46 and we would expect these numbers to be small. Benzodiazepines as well have a office in the handling of alcohol withdrawal, although their apply in alcohol disorders or withdrawal is non typically recommended in convalescent settings.31 We did not tape other medical indications for benzodiazepines such every bit musculus spasms. Our report relied on electronic documentation of information, which approximates but may non equal actual benzodiazepine use by patients. Our report could underestimate benzodiazepine use if patients receive care exterior of our wellness system. Conversely, it could overestimate benzodiazepine use because we rely on prescribing information rather than filled prescriptions or claims. Because 56 % of prescriptions came from providers outside primary intendance, and prescriptions from all providers were grouped together in our data, our findings may not reflect prescribing patterns for PCPs specifically, although nosotros practice non believe this detracts from the relevance of our findings. Our definition of high-dose benzodiazepine prescribing might be considered arbitrary, given the absence of conspicuously established authorisation comparisons between benzodiazepine agents; however, the cutoffs we used were close to other measurements of the 90th percentile of hateful daily doses.33
Determination
We constitute that clinicians prescribed benzodiazepines more than frequently to patients with known run a risk factors for benzodiazepine-related adverse events. Prescribers should take into account their patients' risk factors for adverse events when considering a benzodiazepine. For patients with COPD, substance use disorders, osteoporosis, and advanced age—those who appear to exist the most likely to receive benzodiazepine prescriptions and, for the 2 old categories, at the highest doses—the pick of prescribing a benzodiazepine should be made with great caution.
Electronic supplementary material
Beneath is the link to the electronic supplementary material.
ACKNOWLEDGMENTS
We acknowledge Joji Suzuki, Doctor, Brigham and Women's Hospital, for aid with our report design.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they do not take a conflict of involvement.
Footnotes
Previous Presentations
Preliminary data from this study were presented at the 61st Annual Meeting of the University of Psychosomatic Medicine, Fort Lauderdale, Florida, November 14, 2014; additional data will be presented in office at the 62nd Almanac Coming together of the Academy of Psychosomatic Medicine, New Orleans, Louisiana, November 13, 2015.
Electronic supplementary textile
The online version of this article (doi:10.1007/s11606-016-3740-0) contains supplementary fabric, which is available to authorized users.
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