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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.

SUBMITTER: Trafton JA

PROVIDER: S-EPMC1360079 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundNaloxone is the usual drug used in opioid-induced respiratory depression but it has a short half-life, precipitates withdrawal in dependent patients, and thus for persistent reversal of long-acting opioids has to be given by titrated doses and infusions. The partial agonist buprenorphine has a much longer duration of action and causes less severe withdrawal, but still should largely reverse respiratory depression induced by full agonist opioids. We aimed to compare the efficacy/safety of buprenorphine and naloxone in reversing respiratory depression in methadone-poisoned opioid-dependent patients.MethodsPatients with methadone-induced respiratory depression were randomized to receive naloxone (titrated doses), or lower or higher doses of buprenorphine (10 μg/kg or 15 μg/kg). The primary outcome was immediate reversal of respiratory depression. We also recorded acute opioid withdrawal, need for intubation/recurrent apnea, repeated doses of opioid antagonists, length of hospital stay, other morbidity, and mortality. The study was registered with the Iranian Registry of Clinical Trials (Trial ID: 18265; Approval code: IRCT2015011020624N1).ResultsEighty-five patients were randomized; 55/56 patients who received buprenorphine had rapid reversal of respiratory depression, which persisted for at least 12 h. Naloxone was effective in 28/29 patients, but often required very high titrated doses (thus delaying time to respond) and prolonged infusions. Intubation (8/29 vs 5/56) and opioid withdrawal (15/29 vs 7/56) were less common with buprenorphine. There were no serious complications or deaths in those receiving buprenorphine. The 15-μg/kg buprenorphine dose appeared to provide a longer duration of action, but precipitated withdrawal more frequently than the 10-μg/kg dose.ConclusionBuprenorphine appears to be a safe and effective substitute for naloxone in overdosed opioid-dependent patients. Further studies are warranted to explore the optimal dosing strategy for buprenorphine to consistently maintain reversal of respiratory depression but not precipitate withdrawal.Trial registration numberIRCT2015011020624N1. Registered 30 September 2015.

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