Divided Doses for Methadone Maintenance
Abstract
Opioid dependence, when untreated, typically progresses in a downhill course. Periods of remission are, more often than not, followed by a return to drug use accompanied by psychiatric and medical morbidity, incarceration, and frequently death. Opioid agonist therapy has proven to be a highly effective treatment for this otherwise highly morbid disorder (1). Both methadone and buprenorphine dramatically attenuate the painful drug craving experienced during opioid withdrawal and abstinence, thus mitigating the perceived need for the drug. Key components of agonist therapies are their oral formulation and long half-life, allowing once-a-day dosing in a clinic or outpatient setting. Nevertheless, a sizable number of patients who undergo agonist therapy persist in their illicit opioid use despite medication compliance. Continued, or a return to, opioid use during agonist therapy is often the result of breakthrough craving. When this occurs, increasing the agonist dose is typically the most appropriate intervention. For a small number of patients, breakthrough craving occurs because of 1) a genetic variant of the P450 3A4 or 2D6 enzymes, which increases methadone metabolism; 2) the concomitant use of other medications or alcohol that also induces P450; or 3) the hypermetabolism and increased volume of distribution during pregnancy. These