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The American Journal of Managed Care December 2010
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Comparison of Healthcare Utilization Among Patients Treated With Alcoholism Medications
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Comparison of Healthcare Utilization Among Patients Treated With Alcoholism Medications

Tami L. Mark, PhD; Leslie B. Montejano, MA; Henry R. Kranzler, MD; Mady Chalk, PhD; and David R. Gastfriend, MD

Treatment of alcohol dependence with medications offered advantages in reduced healthcare utilization and costs compared with usual treatment without medications.

Objectives: To determine in a large claims database the healthcare utilization and costs associated with treatment of alcohol dependence with medications vs no medication and across 4 US Food and Drug Administration (FDA)-approved medications.

Study Design: Claims database analysis.

Methods: Eligible adults with alcohol dependence claims (n = 27,135) were identified in a commercial database (MarketScan; Thomson Reuters Inc, Chicago, Illinois). Following propensity score-based matching and inverse probability weighting on demographic, clinical, and healthcare utilization variables, patients who had used an FDA-approved medication for alcohol dependence (n = 2977)were compared with patients who had not (n =2977). Patients treated with oral naltrexone hydrochloride(n = 2064), oral disulfiram (n = 2076), oral acamprosate calcium (n = 5068), or extendedrelease injectable naltrexone (naltrexone XR) (n = 295) were also compared for 6-month utilization rates of alcoholism medication, inpatient detoxification days, alcoholism-related inpatient days, and outpatient services, as well as inpatient charges.

Results: Patients who received alcoholism medications had fewer inpatient detoxification days (706 vs 1163 days per 1000 patients, P <.001), alcoholism-related inpatient days (650 vs 1086 days, P <.001), and alcoholism-related emergency department visits (127 vs 171, P = .005). Among 4 medications, the use of naltrexone XR was associated with fewer inpatient detoxification days (224 days per 1000 patients) than the use of oral naltrexone (552 days, P = .001), disulfiram (403 days, P = .049), or acamprosate (525 days, P <.001). The group receiving naltrexone XR also had fewer alcoholism-related inpatient days than the groups receiving disulfiram or acamprosate. More patients in the naltrexone XR group had an outpatient substance abuse visit compared with patients in the oral alcoholism medication groups.


Conclusion: Patients who received an alcoholism medication had lower healthcare utilization than patients who did not. Naltrexone XR showed an advantage over oral medications in healthcare utilization and costs.

(Am J Manag Care. 2010;16(12):879-888)

Retrospective comparisons among similar patients taking any alcoholism medication vs no alcoholism medication and among similar patients taking 1 of 4 alcoholism medications found the following:


  • Filling a prescription for alcoholism medication was associated with fewer inpatient detoxification days, alcoholism-related inpatient days, and alcoholism-related emergency department visits.


  • Using extended-release naltrexone hydrochloride was associated with fewer inpatient detoxification days and fewer alcoholism-related inpatient days compared with using oral naltrexone, disulfiram, or acamprosate calcium.
Alcohol use disorders (AUDs), including alcohol abuse and dependence, occur commonly in the general population, with an estimated 12-month prevalence of 8.46%.1 Alcohol abuse and dependence are associated with a range of adverse medical, psychiatric, family, legal, and work-related problems. Although alcoholism is a leading cause of preventable death in the United States,2 evidencebased treatment of AUDs is not commonly used.3 Since 2005, the National Institute on Alcohol Abuse and Alcoholism4 has recommended that medication should be considered for every patient with alcohol dependence. In practice, few patients with alcohol dependence are prescribed medications approved by the US Food and Drug Administration (FDA) to treat the disorder.5 Moreover, among patients who are prescribed such medication, adherence is low, which significantly reduces efficacy.6-10

In part, the reluctance of physicians to prescribe alcoholism medications and of patients to take the medications stems from  skepticism about their efficacy.11 Comparative effectiveness investigations, particularly comparing alcoholism medication treatment with standard care, are needed to address this information gap. Efficacy studies12-15 using randomized controlled trial (RCT) designs have found that pharmacotherapy is superior to psychosocial treatment alone. However, there are inconsistencies in results across studies, with large multisite RCTs failing to meet their specified end points for disulfiram,16 oral naltrexone hydrochloride,17 and acamprosate calcium.18 Furthermore, where efficacy trials have shown positive findings, results have demonstrated only modest effects.15

Information is also needed to compare the relative efficacy of existing alcoholism medications, particularly their ability to address the problem of poor adherence. There are 4 FDA-approved medications for the treatment of alcohol dependence. Disulfiram, an aversive agent, acts as a deterrent to drinking.16 Naltrexone is an opioid antagonist and is thought to reduce the rewarding effects of alcohol.19 Acamprosate is believed to reduce the risk of relapse by stabilizing glutamatergic pathways in individuals during the postwithdrawal phase.20 First approved as an oral treatment, naltrexone was subsequently approved also as an extended-release injectable suspension (naltrexone XR). In contrast to oral naltrexone, disulfiram, and acamprosate, which require daily dosing, naltrexone XR is administered as a monthly injection. Because naltrexone XR was designed to enhance patient adherence, comparison of the effect of that formulation vs oral medications on treatment outcomes is of considerable interest.21

Although RCTs are an important source of information on comparative effectiveness, they pose obstacles to external validity that limit their applicability to clinical practice. These include enrollment that favors highly motivated patients, compliance-inducing pill accounting procedures, unblinding because of adverse events, and assessment reactivity in research subjects.22,23 In contrast to data from RCTs, observational studies can reflect the experiences of a broad sample of patients with alcoholism who receive care in naturalistic settings. In particular, retrospective analysis of large data sets (such as those composed of insurance claims) does not impose artificially constrained treatment frequencies, fixed duration of treatment, visits with nonprovider research assistants, or incentives for participation. In addition, providers of services detailed in these data sets represent the full spectrum of disciplines and settings that exist in the real world. These features favor generalizability. The main drawback of observational data is the potential for selection bias, which may be addressed with statistical controls.

This study evaluated approved treatments for alcohol dependence in a naturalistic population using a 2-stage approach. First, we compared the use of any of the FDA-approved medications vs no medication treatment. Second, we compared 4 alcoholism medications with one another relative to treatment persistence and healthcare utilization and cost outcomes.


Data were obtained from the Thomson Reuters MarketScan Commercial Claims and Encounter database that comprises enrollment information and medical and prescription medication claims from approximately 150 large self-insured employers and regional health plans located throughout the United States (yielding approximately 25 million individuals per year). The contributors to the database provide insurance coverage under various fee-for-service and capitated health plans, including  preferred provider organizations, indemnity plans, and health maintenance organizations.

For comparison of patient groups receiving any vs no alcoholism medication, the index date was defined as the earliest date of utilization of 1 of 4 alcoholism medications or as the alcohol dependence diagnosis date for the group receiving no alcoholism medication. Patients in the latter group had no prescription fills for an alcoholism medication, while patients in the group receiving any alcoholism medication had at least 1 fill for any of 4 alcoholism medications. Patients were required to be 18 years or older and to have at least 6 months of continuous enrollment before the index date and 6 months after the index date. Patients were required to have at least 1 claim for alcohol dependence (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV] code 303.xx) during the pre–index date or post–index date periods and to have a diagnosis of alcohol dependence or abuse (DSM-IV code 303.xx or 305.xx) before the index date. The study required an alcohol dependence diagnosis to be consistent with the labeled indication for the medications. A preperiod alcohol dependence or abuse diagnosis was required for the analysis of any vs no alcoholism medication use, as otherwise it would be likely that the group receiving no alcoholism medication would be earlier in their treatment course than the group receiving any alcoholism medication. These inclusion and exclusion criteria led to final samples of 4047 patients in the group receiving any alcoholism medication and 4730 patients in the group receiving no alcoholism medication. eAppendix A (available at gives sample sizes after applying each inclusion or exclusion criterion.

Patients in the comparison of 4 alcoholism medications were required to have 6 months of continuous enrollment before the index date and after the index date and to be 18 years or older. Patients treated with oral naltrexone, disulfiram, or acamprosate were identified using outpatient drug claims based on national drug codes. The index date was defined as the earliest utilization date of 1 of 4 medications. Patients treated with naltrexone XR were identified on the basis of an outpatient drug claim with a national drug code for naltrexone XR or a medical claim with a Healthcare Common Procedure Coding System code for naltrexone XR. The earliest such claim was set as the index date. The following numbers of patients from the database met the study criteria: 295 for naltrexone XR, 2064 for oral naltrexone, 2076 for disulfiram, and 5068 for acamprosate.

Drug utilization patterns and other outcomes were measured during the first 6 months following the index date. Naltrexone XR utilization amounts were calculated by determining the number of unique service dates (ie, injections) for naltrexone XR and multiplying those unique days by 30.5 days (the mean number of days per month in a year) to derive the total days a patient was receiving naltrexone XR. The total number of days of receiving naltrexone XR was then divided by 180 days to determine the percentage of time over 6 months that the patient was receiving naltrexone XR. For the oral agents, the percentage of days with medication fills was determined by adding the days supplied indicated on each prescription drug claim and dividing by 180 days.

The following inpatient utilization outcomes were examined: detoxification admissions (admissions with an International Classification of Diseases, Ninth Revision, Clinical Modification procedure code for detoxification), alcoholismrelated admissions (admissions with a principal diagnosis of alcohol dependence), and nonalcoholism-related admissions. Utilization was measured as the percentage of patients with admissions and the total inpatient days. Emergency department (ED) utilization was captured as the percentage of patients visiting an ED and the number of alcoholism-related ED visits. Outpatient behavioral health services utilization was captured as the percentage of patients having visits with a primary diagnosis of substance abuse or a combined substance abuse and mental health diagnosis. We also measured the occurrence of diagnoses of schizophrenia, bipolar disorder, depression, and anxiety disorder. Finally, we measured costs for inpatient detoxification days and alcoholism-related admissions by multiplying charges per day by the number of inpatient detoxification days or alcoholism-related inpatient days.

Charges for inpatient treatment were determined using the Healthcare Cost and Utilization Project National Inpatient Sample (NIS) data set ( The NIS is the largest all-payer inpatient care database in the United States. The sampling frame for the 2008 NIS is a hospital sample that comprises approximately 90% of all hospital discharges in the United States. Charge information is provided on all patients, regardless of payer, including persons covered by Medicare, Medicaid, and private insurance, as well as the uninsured. For this study, charges were used for patients with private insurance having a principal diagnosis of alcohol dependence.

We used propensity score–based matching and inverse probability weighting to reduce the potential for cohort selection bias. We developed propensity scores using a logit model to compare the groups receiving any vs no alcoholism medication.  Explanatory variables were selected based on their hypothesized confounding relationship with the outcome variables and included the following: (1) sex, (2) percentage of college graduates in the patient’s zip code, (3) log of the median household income in the patient’s zip code, (4) geographic region, (5) relationship to employee (employee, spouse, or child or dependent), (6) preperiod comorbidity burden measured using the Charlson Comorbidity Index,24 and (7) the chronic disease score.25 The following preperiod measures were also included: (8) comorbid psychiatric diagnosis, (9) AUD diagnosis, (10) drug abuse or dependence diagnosis, (11) detoxification admission, (12) alcoholism-related admission, and (13) nonalcoholism-related admission. Propensity scores were calculated as the predicted probability of being in the group receiving any alcoholism  medication given the demographic, geographic region, and clinical factors listed. A nearest neighbor matching with a 1:1 matching ratio was used to match the 2 groups based on their scores. The balancing of variables was examined using  standardized difference (threshold of 10), paired t test (for continuous variables), or McNemar test (for dichotomous variables). The matched sample comprised 2977 patients each in the group receiving any alcoholism medication and the group receiving no alcoholism medication.

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