Pharmacological enhancement of naltrexone treatment for opioid dependence: a review

PURPOSE: Opioid dependence (OD) is a serious and growing clinical condition with increasing social costs that requires expanding treatment beyond opioid agonist substitution. The opioid antagonist naltrexone has displayed a remarkable association of theoretical effectiveness and poor clinical utility in treating OD due to noncompliant behavior and low acceptability among patients, only partly modified by psychosocial interventions. We reviewed pharmacological studies, including naltrexone depot formulations and combination treatments. METHOD: We searched PubMed for clinical studies on the use of naltrexone implants and slow-release injections in OD, and investigations using adjunct medications to improve naltrexone maintenance therapy of OD. We discussed the results in view of their application to the clinical practice. RESULTS: Significant reduction in opioid use and improved retention in treatment have been found in several studies using depot naltrexone formulations, some of which are controlled clinical trials. Pilot investigations have gathered initial positive results on the use of naltrexone in combination with serotonin reuptake inhibitors, α-2 adrenergic, opioid, and γ-aminobutyric acid agonist medications. CONCLUSION: Current evidence suggests that more research on effectiveness and safety is needed in support of depot naltrexone treatment for OD. Further research comparing slow-release with oral naltrexone and opioid agonist medications will help characterize the role of opioid antagonist-mediated treatment of OD. Preliminary investigations on naltrexone combination treatments suggest the opportunity to continue study of new mixed receptor activities for the treatment of OD and other drug addictions.