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For example medications routes order lopid 300 mg on-line, a study where triple the daily buprenorphine maintenance dose was administered to symptoms nausea safe lopid 300 mg patients every 72 hours found some mild increase in opioid agonist effects in the first 24 hours and some mild withdrawal at 72 hours medicine ketoconazole cream discount generic lopid uk, but neither effect was robust or clinically significant (1368). A double-blind study examining a quadruple daily maintenance dose of buprenorphine given at up to 96-hour intervals (1369) did not find excessive opioid agonist effects 24 hours after the quadrupled dose and only mild withdrawal effects at 96 hours. A follow-up open report on double, triple, and quadruple buprenorphine doses for 48-, 72-, and 96-hour intervals, respectively, found similar tolerability of the 96-hour interval as well as a preference by patients for all intermittent, rather than daily, dosing schedules of buprenorphine (1368). These results suggest dosing with buprenorphine on every fourth day is clinically possible, with no significant adverse effects from the higher doses of buprenorphine and comparable efficacy with daily dosing. However, findings from studies that have tested even longer intervals between active buprenorphine doses suggest that 96 hours may be the upper limit of the interdose interval (1736, 1737). Studies have not tested if higher doses of buprenorphine, such as seven times a daily dose, might be effective and safe for shorter periods such as 5 days. One of the largest controlled clinical trials of intermittent buprenorphine dosing was a double-blind, randomized study comparing thrice-weekly to daily buprenorphine dosing (1738). This study assigned 92 opioid-dependent outpatients to receive sublingual buprenorphine solution daily or sublingual buprenorphine solution on Tuesdays, Fridays, and Sundays and placebo on the other four days. The 72-hour dosing interval was from Tuesday to Friday to avoid potential study confounders associated with the weekend. There were no differences in rates of opioid-positive urine tests, self-reports of illicit opioid use, treatment retention, and medication adherence between the two groups and no significant adverse events noted for either group. The results from this large controlled study suggest that intermittent buprenorphine can be as equally effective as daily buprenorphine. Although the studies reviewed here have all used the solution form of buprenorphine, there have also been studies of intermittent dosing with buprenorphine tablets. One double-blind outpatient clinical trial compared daily dosing of 8-mg buprenorphine tablets to thrice-weekly dosing with 16-mg tablets on Mondays and Wednesdays, 24-mg tablets on Fridays, and placebo tablets on the four nonactive dosing days. The study found equivalent retention for the two groups but a higher rate of opioid-positive urine samples in the intermittent dosing group (1739). These two studies provide evidence of the practicality of using buprenorphine tablets on an intermittent basis. Use of buprenorphine as a withdrawal (detoxification) agent Controlled clinical trials and reports of buprenorphine for the treatment of opioid withdrawal have varied in several ways. Some withdrawal studies have compared buprenorphine with methadone (1741), whereas others have compared it with clonidine (1393, 1742, 1743). Different formulations of buprenorphine (1384, 1744) and rapid or prolonged withdrawals (1392, 1745, 1746) have also been used in these studies. There has been some interest in and research on using buprenorphine as a bridging agent to treatment with naltrexone (1745, 1747). An early double-blind, double-dummy, random-assignment, outpatient clinical trial compared fixed doses of sublingual buprenorphine solution with oral methadone in the treatment of opioid withdrawal (1741). A total of 45 heroin-dependent male subjects were stabilized on 30 mg of methadone or 2 mg of buprenorphine for 3 weeks, underwent a dose taper for 4 weeks and then received placebo for 6 weeks. Results from the withdrawal assessments showed the two medications were quite similar on measures of treatment retention, drug use, and rating of withdrawal. However, results from the hydromorphone challenge sessions showed that methadone produced significantly greater blockade than buprenorphine. The results from this early buprenorphine withdrawal study demonstrate that similar outcomes can be achieved with these two medications, although the study used relatively low doses of both medications and the overall results showed poor outcomes for both groups. Treatment of Patients With Substance Use Disorders 171 Copyright 2010, American Psychiatric Association. An inpatient, randomized, double-blind clinical trial compared sublingual buprenorphine solution to oral clonidine in a relatively short opioid withdrawal procedure (1742). In this study of 25 opioid-dependent male and female patients, participants received 3 days of a fixeddose schedule of buprenorphine or a 5-day fixed-dose schedule of clonidine. Because this was an inpatient study, reports of withdrawal symptoms were not confounded by illicit substance use.
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