Concern about poor adherence with oral pharmacotherapy by patients with substance use disorders has often been raised in the literature. Nevertheless, there has been a limited effort to measure the problem, despite the recognition that it adversely affects treatment outcomes (13
). The results of the present analysis underscore the magnitude of this problem: less than 15% of patients treated with oral naltrexone for AUDs over a 6-month period were able to persist with refills for at least 80% of the time, while more than 85% were identified as non-persistent. This finding contrasts with the situation that exists in clinical trials, where a concerted effort is generally made to enhance adherence with the medication (15
). In this database, more than half of patients filled only 1 prescription for naltrexone during the assessment period. Because the database did not permit us to determine the number of patients who were prescribed naltrexone but did not fill the first prescription, the low rate of persistence is likely an underestimate of the poor adherence to naltrexone oral therapy.
Several factors were associated with persistence with oral naltrexone prescriptions, including having been a salaried rather than hourly employee at the time of treatment or being retired, living in an area with a higher median household income, and not having both alcohol- and drug-related claims prior to treatment. Further, differences in healthcare utilization were associated with persistence during the treatment period. Specifically, persistent patients were more likely to utilize counseling and outpatient general medical care, while non-persistent patients were more likely to undergo inpatient detoxification, emergency room visits, and inpatient admissions. The greater use of outpatient services in the group that was persistent with naltrexone prescriptions may reflect a greater motivation on their part to change drinking behavior, though it could also reflect a beneficial effect on adherence of more frequent contact with a healthcare professional. The correlational nature of the findings makes it impossible to ascertain the causal direction of this association. Greater medication compliance has been associated with better drinking outcomes irrespective of treatment group in a large, placebo-controlled trial of naltrexone for alcohol dependence (25
). The adverse effects of naltrexone could also have reduced the rate of persistence.
There are considerable public health and economic implications of non-persistence with oral naltrexone therapy. In clinical practice, however, given the preponderance of non-persistence, efforts to increase persistence will be needed for the vast majority of patients. Such efforts can include a variety of behavioral interventions that have been shown to enhance adherence with alcohol pharmacotherapy (22
) and the use of extended-release naltrexone (26
These findings must be interpreted in light of some relevant study limitations. The retrospective and naturalistic design of the study limits the degree to which bias can be controlled for in the two patient groups. This is balanced to a degree by the fact that the assessment process is transparent to patients and seemingly has little chance of influencing patient behavior. Some factors that may have an impact on medication persistence (e.g., out-of-pocket expenses by patients) were not measured. Another issue is the persistence measure itself. There is no universally accepted method to measure adherence in either research or clinical practice (13
). The measurement of persistence in medication usage by quantifying prescription refills means is only a proxy for day-to-day pill taking adherence. In reality, persistence is probably an overly optimistic measure, i.e., although approximately 14% of patients were in possession of naltrexone for 80% of the intended time, the proportion that actually took the medicine during this period was probably lower. Also, the approach we used to differentiate healthcare costs into alcohol-related and non-alcohol-related is limited by the fact that a patient may receive alcohol-related services during a visit with a different primary diagnosis, thereby understating the alcohol-related utilization rates. Finally, the healthcare utilization data were analyzed for only a six-month period. This is a relatively short duration for comparative analysis of healthcare utilization patterns following an alcohol treatment intervention; many studies use a 2-year trial design. The relatively short interval over which utilization was monitored may make the finding of a consistent pattern of over utilization of more intensive medical services by the non-persistent patients more compelling.
These findings can be compared to two prior analyses of oral pharmacotherapy adherence rates in patients with alcohol use disorders (27
). In a retrospective analysis of data on naltrexone prescriptions in a large mid-Atlantic health plan, approximately 50% of patients received only 30 days or less of medication, a rate that did not improve over a three-year period (27
). In an analysis of utilization of medications for alcoholism treatment in a Veterans Administration population, Hermos and colleagues found that only 21.8% of 921 patients filled oral naltrexone prescriptions and only 22.7% of 754 patients filled oral disulfiram prescriptions for 6 months (28
). The duration of treatment episodes was similar for both drugs, with more than 35% of episodes being 1 month or shorter, more than 50% being 2 months or shorter, and 75% being 5 months or shorter. Although the study by Hermos et al. (28
) and the present study involve different populations, medications, and treatment systems, the similarity of findings between the studies (which together examined the behavior of approximately two thousand patients) demonstrates the limitations of oral pharmacotherapy for the rehabilitation treatment of alcoholism: less than 25% of patients are able to complete a course of therapy lasting only 6 months.
There are serious implications of the very high rates of non-persistence to oral naltrexone and the pattern of significantly greater utilization of intensive medical services among non-persistent patients that were seen in this study. In view of the low rates at which medications are prescribed for the treatment of alcoholism (27
), the fact that only a small percentage of patients who are prescribed oral naltrexone persist in using the medication is of particular concern. These findings underscore the need to educate physicians in the use of medications with demonstrated efficacy for the treatment of alcohol dependence and in methods to enhance patients' adherence with the treatments.