Precipitated withdrawal during maintenance opioid blockade with extended release naltrexone

Dept of Psychiatry, Johns Hopkins University School of Medicine, Mountain Manor Treatment Center, Baltimore, MD 21229, USA.
Addiction (Impact Factor: 4.74). 09/2008; 103(8):1399-401. DOI: 10.1111/j.1360-0443.2008.02252.x
Source: PubMed


Background There has been increasing interest in the use of extended release injectable naltrexone for the treatment of opioid dependence. Case description We report a case of precipitated withdrawal in a 17-year-old adolescent female receiving extended release naltrexone (Vivitrol) for opioid dependence, following her third serial monthly dose of the medication, several days after using oxycodone with mild intoxication. Conclusions This case suggests that, in some circumstances, the opioid blockade may be overcome when naltrexone levels drop towards the end of the dosing interval, producing vulnerability to subsequent naltrexone-induced withdrawal. This may provide cautionary guidance for clinical management and dosing strategies.

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Available from: Marc Fishman, Nov 16, 2015
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    • "An abuser may attempt to override naltrexone’s receptor blockade with higher doses of opioid agonists, or by taking opioids at the end of naltrexone’s dosing interval, a time when plasma levels are decreasing and the blockade is diminishing.49,62 None of the studies presented in this review indicated any overdose cases, but there have been reports of opioid overdose in patients after discontinuation of oral naltrexone maintenance.63,64 "
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    ABSTRACT: The United States Food and Drug Administration (FDA) approved naltrexone, a synthetic competitive antagonist at opioid receptors, in oral form in 1984 for use in the management of opioid abuse and addiction. Because naltrexone and its major metabolite, 6-β-naltrexone, are both competitive antagonists at opioid receptors - and thereby inhibit opioid agonist-induced effects including those desired by abusers - it was hypothesized that once maintained on naltrex-one, opioid-induced desirable effects would be diminished to the point that relapse to illicit use would decline because it was no longer rewarding. However, good medication compliance is a requisite for such a strategy to be effective and a systematic review of oral naltrexone concluded that this method of treatment was not superior for any outcomes measured (ie, retention, abstinence, or side effects) to placebo, psychotherapy, benzodiazepines, or buprenorphine treatment. In addition, the retention rate on oral naltrexone was very low (less than 30%). Recently, the FDA approved an extended-release formulation (intramuscular depot injection) of naltrexone for prevention of relapse to opioid dependence following opioid detoxification and to be used along with counseling and social support. Since it needs to be administered only monthly, as opposed to the daily administration required for the oral formulation, naltrexone injection has the potential for increasing adherence and retention rates. Concerns include liver damage at high doses (oral formulation) and possible opioid overdose if an attempt is made to surmount receptor antagonism by taking higher doses of an opioid agonist or if opioid receptors become "sensitized" under long-term antagonism. The focus of the present review is the current information regarding the safety and efficacy of naltrexone extended-release therapy.
    12/2011; 2:219-226. DOI:10.2147/SAR.S17920
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    ABSTRACT: Oral naltrexone hydrochloride effectively antagonizes heroin, but its utility is limited by patient noncompliance. Sustained-release preparations may overcome this limitation. To compare the safety and efficacy of a single-treatment sustained-release naltrexone implant with daily oral naltrexone treatment. Seventy heroin-dependent volunteers entered a randomized, double-blind, double-placebo controlled trial with a 6-month follow-up period. Eligibility criteria were DSM-IV opioid (heroin) dependence; age 18 years or older; willingness to be randomized; residing in the Perth, Western Australia, metropolitan area; and completion of preclinical screening and written consent. A total of 129 eligible participants were identified, and 70 (54%) provided informed consent and were randomized as per the study design. Participants received oral naltrexone, 50 mg/d, for 6 months (plus placebo implants) or a single dose of 2.3 g of naltrexone implant (plus placebo tablets). (1) Maintaining therapeutic naltrexone levels above 2 ng/mL; (2) return to regular heroin use (>or=4 d/wk); (3) other heroin use and abstinence; (4) use of illicit nonopioid drugs; (5) number of opiate overdoses requiring hospitalization; (6) treatment-related unexpected and expected adverse events; and (7) blood naltrexone levels (ie, pharmacokinetic profile) for recipients of active naltrexone implants. More participants in the oral vs the implant group had blood naltrexone levels below 2 ng/mL in months 1 (P < .001) and 2 (P = .01); in addition, more oral group participants had returned to regular heroin use by 6 months (P = .003) and at an earlier stage (median [SE], 115 [12.0] days vs 158 [9.4] days). There were 10 trial-related, unexpected adverse events. One serious adverse event, a wound hematoma, was associated with surgical implantation. Naltrexone blood levels in implant recipients were maintained above 1 and 2 ng/mL for 101 (95% confidence interval, 83-119) and 56 (39-73) days, respectively, among men and 124 (88-175) and 43 (16-79) days among women. The naltrexone implant effectively reduced relapse to regular heroin use compared with oral naltrexone and was not associated with major adverse events. Clinical Trial Registration Identifier: ACTRN12606000308594.
    Archives of general psychiatry 10/2009; 66(10):1108-15. DOI:10.1001/archgenpsychiatry.2009.130 · 14.48 Impact Factor
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    ABSTRACT: The major problem with the oral formulation of naltrexone for heroin dependence is poor compliance (adherence). Long-acting sustained release formulations of naltrexone (implantable and injectable) might help to improve compliance and, thus, increase the efficacy of abstinence-oriented treatment of heroin dependence with naltrexone. There have been several implantable and injectable formulations of naltrexone developed within the last decade. It was demonstrated that some of them are effective and relatively well tolerated medications for relapse prevention in heroin addicts. However, advantages and disadvantages of these new medications have never been systematically analyzed. Long-acting sustained release formulations of naltrexone are well tolerated and more effective for relapse prevention in heroin addicts than the oral ones.
    Current opinion in psychiatry 03/2010; 23(3):210-4. DOI:10.1097/YCO.0b013e3283386578 · 3.94 Impact Factor
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