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Benzodiazepine and Unhealthy Alcohol Use Among Adult Outpatients
Matthew E. Hirschtritt, MD, MPH; Vanessa A. Palzes, MPH; Andrea H. Kline-Simon, MS; Kurt Kroenke, MD; Cynthia I. Campbell, PhD, MPH; and Stacy A. Sterling, DrPH, MSW
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Benzodiazepine and Unhealthy Alcohol Use Among Adult Outpatients

Matthew E. Hirschtritt, MD, MPH; Vanessa A. Palzes, MPH; Andrea H. Kline-Simon, MS; Kurt Kroenke, MD; Cynthia I. Campbell, PhD, MPH; and Stacy A. Sterling, DrPH, MSW
Among outpatients who were screened for alcohol use, those with unhealthy alcohol use, women, and those who were older, white, and of lower socioeconomic status were more likely to use benzodiazepines.
Our study adds to the literature by examining not only benzodiazepine use but also mean doses and prescription durations among subpopulations of primary care patients. Interestingly, we found that although patients with unhealthy alcohol consumption were more likely to use benzodiazepines, the benzodiazepines were prescribed to them at lower doses and for shorter durations. This pattern persisted even when accounting for the presence of an alcohol use disorder, for which benzodiazepines may be prescribed to manage alcohol withdrawal. These findings fail to confirm the first part of our hypothesis (ie, patients with unhealthy alcohol use are less likely to use benzodiazepines) but do confirm the second part of our hypothesis (ie, that these patients would use benzodiazepines for shorter periods and at lower doses). One possible explanation for this pattern of findings is that those drinking at unhealthy levels may be more likely to use multiple abusable substances,34 but that clinicians, aware of the contraindications of concomitant use, limit the dose and duration of benzodiazepines for these patients. It is also possible that patients with unhealthy alcohol use may voluntarily limit their use of benzodiazepines to avoid functional impairment associated with concurrent alcohol and high-dose benzodiazepine consumption.

We also found, similar to results of surveys3,17 and of studies based on Medicare18 and commercial insurance claims,28,35 that women were more likely, and nonwhite patients less likely, to use benzodiazepines. Furthermore, we found that women and nonwhite patients who used benzodiazepines used them at lower doses and for shorter durations compared with men and white patients who used benzodiazepines.36,37 Women may be more likely to seek treatment for an anxiety disorder.38 Therefore, women may be more likely than men to report anxiety relief and to require lower doses of benzodiazepines in part because they are simultaneously receiving nonbenzodiazepine treatments (eg, antidepressants, psychotherapy).39 Simultaneously, women may use benzodiazepines at lower doses and for shorter amounts of time compared with men in part because clinicians may believe sex moderates benzodiazepine metabolism, despite limited evidence to support this contention.40 Previous research demonstrates that nonwhite patients receive fewer benzodiazepine prescriptions than white patients; however, white patients were more likely to have a benzodiazepine dependence diagnosis.41,42 Nonwhite patients may be less trusting of the healthcare system, particularly as it relates to seeking help for mental health problems.43,44 White patients may be more assertive in requesting symptom relief45 compared with nonwhite patients, who may be less likely to seek medical help for psychiatric symptoms such as anxiety.46 Furthermore, some Asian patients may be more likely to seek nonallopathic remedies for mental health concerns in primary care.47 Symptoms of anxiety in nonwhite patients may also be underrecognized or undertreated by clinicians, resulting in fewer benzodiazepine prescriptions for nonwhite patients. These sex- and ethnicity-associated disparities in benzodiazepine prescribing may also be the result of implicit clinician biases.48

Limitations

These results should be interpreted in the context of several limitations. As with all observational studies, causality cannot be determined. Pharmacy data reflect dispensations and we are unable to measure patient medication consumption; nonetheless, dispensations are commonly used in pharmacoepidemiologic studies49,50 and, in the current sample, approximately 84% of prescribed benzodiazepines were filled in KPNC pharmacies. Additionally, our results may not be generalizable to uninsured populations. However, some of our findings are consistent with other, nationally representative samples (eg, lower benzodiazepine use among nonwhite patients41,42), suggesting that other findings in our study may also be applicable to the general US primary care adult population.

We are also unable to determine whether benzodiazepine use was inappropriate or unhealthy; subsequent studies may identify potentially inappropriate benzodiazepine use using algorithms, such as those used in geriatric samples.51 Likewise, by restricting our analyses to benzodiazepine use, we did not examine concurrent opioid use, especially among patients with chronic pain. Compared with patients who only use opioids, patients who use both opioids and benzodiazepines are at higher risk of overdose52; therefore, national guidelines recommend against prescribing benzodiazepines with opioids.53 Future studies may examine the association among benzodiazepine and opioid use with unhealthy alcohol consumption.
We included conditions frequently associated with benzodiazepine prescriptions; however, benzodiazepines may be prescribed for other disorders, such as anxious depression.54 Finally, statistically significant associations may be a product of the large sample size of our study; therefore, we have focused our conclusions on associations with larger AORs and ARRs, which are most likely to be clinically meaningful and successfully replicated in other primary care samples. If these associations are replicated in subsequent studies, they may be applied to develop and validate clinical decision support systems, such as a quantitative risk-stratification tool to identify patients at high risk of concomitant benzodiazepine and unhealthy alcohol use.

CONCLUSIONS

In this large primary care cohort, unhealthy drinking was associated with higher rates of benzodiazepine use. However, benzodiazepine mean dose was lower and duration of use was shorter among patients with unhealthy drinking. Nonetheless, these results suggest that concomitant benzodiazepine and excessive alcohol use among primary care patients should receive increased vigilance, and health system–wide efforts to reduce this potentially lethal combination should be considered.

Author Affiliations: Department of Psychiatry and the UCSF Weill Institute for Neurosciences, University of California, San Francisco (MEH), San Francisco, CA; The Permanente Medical Group, Department of Psychiatry (MEH), Oakland, CA; Division of Research, Kaiser Permanente of Northern California (MEH, VAP, AHK-S, CIC, SAS), Oakland, CA; Indiana University School of Medicine (KK), Indianapolis, IN; Regenstrief Institute, Inc (KK), Indianapolis, IN; VA Health Services Research and Development, Center for Health Information and Communication (KK), Indianapolis, IN.

Source of Funding: This research was supported by a grant from the National Institute on Alcohol Abuse and Alcoholism (grant number R01-AA025902-01).

Author Disclosures: The authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (MEH, VAP, KK, SAS); acquisition of data (VAP); analysis and interpretation of data (MEH, VAP, KK, CIC, AHK-S, SAS); drafting of the manuscript (MEH, VAP, CIC); critical revision of the manuscript for important intellectual content (MEH, VAP, AHK-S, KK, CIC, SAS); statistical analysis (VAP, AHK-S); provision of patients or study materials (SAS); obtaining funding (SAS); administrative, technical, or logistic support (SAS); and supervision (SAS).

Address Correspondence to: Matthew E. Hirschtritt, MD, MPH, Department of Psychiatry and the UCSF Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Ave, Box 0984, San Francisco, CA 94143. Email: matthew.hirschtritt@ucsf.edu.
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