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NIDA-supported researchers have been testing a long-lasting "depot" formulation of naltrexone that is aimed at reducing the three-times-a-week frequency with which patients must now take the medication to prevent them from getting high if they use heroin. The formulation is packaged in microcapsules injected under the skin that slowly release medication for several weeks. The sustained release of naltrexone is meant to maintain enough medication in the patient to suppress heroin's euphoric effects for an extended time.
Clinical trials now under way are assessing the safety and efficacy of depot
naltrexone. In a recent trial, Dr. Sandra D. Comer and a team of researchers
from the New York State Psychiatric Institute and Columbia University tested
depot naltrexone in an 8-week inpatient study with 12 heroin-dependent subjects
to see how long the medication remains active in the human body and blocks heroin's effects. After detoxification, six patients received a low dose (192
mg) and six received a high dose (384 mg) of the medication. Patients in both
groups subsequently were given a placebo or intravenous heroin once a day
from Monday through Friday for 6 weeks. Each week, daily doses of heroin
started at 6.5 mg and increased to 12.5, 18.75, and 25 mg; the placebo was
administered randomly on one of the days.
Researchers assessed subjective, performance, and physiological effects
after each dose of heroin or placebo and measured plasma levels of naltrexone
over the course of the study. They found that both doses of depot naltrexone
substantially suppressed the patients' ratings of heroin's pleasurable effects and how much they "liked" the drug and wanted to take it again. With the high dose of naltrexone, patients' positive ratings of heroin's pleasurable effects remained low for 5 weeks. In the 6th week, ratings increased significantly relative to week one after patients received the 18.75- and 25-mg injections of heroin. The low dose suppressed positive ratings of heroin for 3 weeks. Plasma levels of naltrexone remained above 1 ng/mL for 4 weeks with the high dose and 3 weeks with the low dose. Though these levels are low compared to those resulting from standard naltrexone treatment doses, other studies have reported that even with negligible plasma levels, naltrexone continues to counter heroin's effects. Other than initial discomfort at the site of naltrexone injection, there were no untoward side effects.
The results suggest that once-a-month administration of the depot formulation
can provide safe, long-lasting blockade of the effects of intravenous "streetlevel" heroin doses in patients who have undergone detoxification. Future studies will address questions that remain about optimal dose levels for naltrexone treatment of heroin dependence, such as what effects different doses have on withdrawal, craving, and the ability to reduce heroin use.
Source: Comer, S.D., et al. Depot naltrexone: Long-lasting antagonism of the effects of heroin in humans. Psychopharmacology 159:351-360, 2002.
Volume 17, Number 6 (March 2003)
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