141,142 Furthermore, doses over 100 mg/day may be indicated in patients with persistent heroin abuse or with comorbid conditions such as HIV

infection, since some concomitant medications for AIDS increase metabolism of methadone.143,144 Tapering doses of methadone can be used in ambulatory detoxification, but the protracted withdrawal syndrome associated with methadone cessation contributes to a high rate of recidivism to opiate abuse.145,146 Methadone is therefore most often used in maintenance therapy and not for acute withdrawal or detoxification. Partial agonists act like agonists, but do not stimulate the receptor to the same degree. In combining both a blocking and substitution Inhibitors,research,lifescience,medical approach, buprenorphine, Inhibitors,research,lifescience,medical a partial agonist at the µ-opioid receptor, suppresses withdrawal symptoms and produces some subjective reinforcing properties at low doses. Initial clinical trials of see more buprenorphine demonstrated efficacy in the outpatient setting. At 8 mg, the sublingual buprenorphine (in liquid formulation) treatment group demonstrated better study retention and decreased opiate use than active placebo or lmg buprenorphine.147,148 At higher doses buprenorphine acts as an

antagonist, and blocks the reinforcing properties of the agonist, resulting in lowered risk of abuse liability and potential for abuse of the Inhibitors,research,lifescience,medical drug.149 Buprenorphine is available alone or in a 4:1 combination sublingual tablet with naloxone (Suboxone).150 A multicenter, randomized, placebo-controlled clinical trial comparing buprenorphine tablet, Suboxone tablet, and placebo in opiate-dependent patients found that both buprenorphine

Inhibitors,research,lifescience,medical alone and Suboxone reduced opiate use in the first month of the study compared with placebo.151 Suboxone also appears to decrease Inhibitors,research,lifescience,medical the potential for abuse or diversion compared with methadone.152 Injection of Suboxone could also precipitate opioid withdrawal. Opioid antagonists Naltrexone is an opioid antagonist that binds to receptors, but Instead of activating the receptors, it blocks them, effectively removing the opiate user’s ability to get high.153,154 Human laboratory studies of naltrexone have demonstrated the efficacy of naltrexone In blocking the effects of acute opioid use secondly In human volunteers who have been withdrawn from opioids.154,155 In clinical trials, high attrition rates and unbllndlng by study patients who guess their treatment regimen have limited the utility of naltrexone maintenance treatment trials,156,157 though a subgroup analysis In a large controlled trial Indicated potential efficacy In highly motivated patients and In those already in drug-free counseling.157 Naltrexone has relatively few side effects, but liver function should be monitored as per labeling guidelines.