Determining effective methadone doses for individual opioid-dependent patients

Abstract

Background: Randomized clinical trials of methadone maintenance have found that on average high daily doses are more effective for reducing heroin use, and clinical practice guidelines recommend 60 mg/d as a minimum dosage. Nevertheless, many clinicians report that some patients can be stably maintained on lower methadone dosages to optimal effect, and clinic dosing practices vary substantially. Studies of individual responses to methadone treatment may be more easily translated into clinical practice.

Methods and findings: A volunteer sample of 222 opioid-dependent US veterans initiating methadone treatment was prospectively observed over the year after treatment entry. In the 168 who achieved at least 1 mo of heroin abstinence, methadone dosages on which patients maintained heroin-free urine samples ranged from 1.5 mg to 191.2 mg (median = 69 mg). Among patients who achieved heroin abstinence, higher methadone dosages were predicted by having a diagnosis of posttraumatic stress disorder or depression, having a greater number of previous opioid detoxifications, living in a region with lower average heroin purity, attending a clinic where counselors discourage dosage reductions, and staying in treatment longer. These factors predicted 42% of the variance in dosage associated with heroin abstinence.

Conclusions: Effective and ineffective methadone dosages overlap substantially. Dosing guidelines should focus more heavily on appropriate processes of dosage determination rather than solely specifying recommended dosages. To optimize therapy, methadone dosages must be titrated until heroin abstinence is achieved.

Figure 1. Cumulative Dose Histogram Depicting the Proportion of Patients at or below a Given Methadone Dose (in mg)

Black line: methadone doses received while patients maintained heroin abstinence ( n = 168). Gray line: average methadone doses received by patients who never achieved heroin abstinence ( n = 54). Black dashed line: average methadone doses received by patients at low guideline-adherence clinics ( n = 88). Gray dashed line: average methadone doses received by patients at high guideline-adherent clinics ( n = 134).