Opioid Use Disorder __________________________________________________________________________
alcohol, other opioids, and illicit drugs. Neonatal withdrawal has also been reported after use of buprenorphine during pregnancy. Buprenorphine is not recommended for patients with severe hepatic impairment [55; 107]. Higher doses of buprenorphine (12 mg or greater) are more effective than lower doses in reducing illicit opioid use, with some studies reporting similar efficacy to methadone on major treatment-outcome measures. One systematic review was con- ducted to evaluate buprenorphine maintenance compared to placebo and methadone maintenance in the management of opioid dependence [157]. Outcomes considered were treat- ment retention, suppression of illicit drug use, and reduction in criminal activity and mortality. A total of 31 trials involving 5,430 participants with moderate- to high-quality evidence were included in the review. According to the data reviewed, buprenorphine retained participants better than placebo at low doses (2–6 mg), at medium doses (7–15 mg), and at high doses (≥16 mg). Only high-dose (≥16 mg) buprenorphine was more effective than placebo at suppressing illicit opioid use (as mea- sured by urinanalysis). Buprenorphine in flexible doses (i.e., adjusted to participant need) was less effective than methadone in retaining participants, and for those retained in treatment, no difference was observed in suppression of illicit opioid use. In low fixed-dose studies, methadone (≤40 mg) was more likely to retain participants than low-dose (2–6 mg) buprenorphine. However, there was no difference between medium-dose (7–15 mg) buprenorphine and medium-dose (40–85 mg) methadone in retention or in suppression of illicit opioid use. Similarly, there was no difference between high-dose (≥16 mg) buprenor- phine and high-dose (≥85 mg) methadone in retention or sup- pression of self-reported heroin use [157]. In a study of 34,000 Massachusetts Medicaid beneficiaries, the incidence of relapse was greater with buprenorphine than with methadone [156]. The primary advantage of buprenorphine over methadone is
lation of patients, further studies using standardized protocols are needed. Significantly, studies so far clearly indicate that heroin maintenance, with or without methadone, can be implemented safely. The relatively high cost of heroin mainte- nance compared with standard methadone or buprenorphine treatment is a drawback of this approach. However, at least one study suggests that heroin combined with methadone may be more cost-effective than methadone alone [30]. The results of medically prescribed heroin administration to chronic, treatment-refractory, heroin-dependent patients have been detailed in two reports. One report from Switzerland concluded that supervised medical prescription of heroin was associated with favorable treatment retention, reduced illicit drug use, reduced criminality, and improved health outcomes and social functioning. These findings were also reported in a controlled trial from Spain and Germany [77]. Research projects were also performed in the Netherlands, Canada, and England, and others are planned in Belgium and Denmark. Based on the positive outcomes thus far, heroin maintenance has become routine treatment for otherwise untreatable heroin addicts in Switzerland, the Netherlands, Germany, and England and is being recommended in Canada [161; 162]. Agonist Replacement and Psychosocial Therapy The addition of any psychosocial support modality to agonist replacement therapy significantly reduces illicit use during treatment, and treatment retention and results at follow-up are also improved [140; 141]. There are two general types of psychosocial therapy used for treating addictive disorders. The first includes therapies developed for treating depres- sion and anxiety that were later adapted for treating persons with addictive disorders, examples of which include cognitive behavioral therapy, supportive expressive therapy, and interper- sonal therapy. The second type includes therapies developed specifically for persons with addictive disorders, such as the closely-related motivational interviewing and motivational enhancement therapy [163]. Drug counseling, another approach specific to addictive disor- ders, emphasizes abstinence, involvement in 12-step programs, and assistance with social, family, and legal problems. Drug counseling is not considered psychotherapy because it focuses on behaviors and external events rather than the intrapsychic processes [163]. Most studies of psychotherapy with opioid-dependent patients have been conducted in methadone programs and are actu- ally pharmacotherapy/psychotherapy studies. In addition to pharmacologic intervention, methadone programs typically use behavioral contingencies that are based on cessation of illicit drug use and other improvements [163]. A review of the literature on psychosocial therapy outcomes with opioid-dependent patients receiving methadone has found evidence of an interaction between measures of psy- chiatric symptoms, therapy assignment, and outcomes [163]. Patients with minimal psychiatric symptoms did equally well
its superior safety profile [30]. Slow-Release Oral Morphine
Slow-release formulations of morphine that are effective with once-daily dosing are a viable alternative in the treatment of opioid dependence. These formulations considerably delay time to peak concentration after oral administration, resulting in delayed onset of action and making the reinforcing effects very weak when it is administered orally. Several trials have suggested that slow-release morphine has approximately equal efficacy with methadone; however, there is no definitive evi- dence of this effect [30; 158; 159]. Slow-release oral morphine may be a viable alternative for patients who are intolerant to methadone [160]. Diacetylmorphine (Heroin) The pharmacokinetic properties of heroin make it less than ideal for use as a maintenance drug, and the main rationale for heroin maintenance has been the treatment of patients who simply do not respond to any other treatment modality. Although preliminary results seem to be positive, before sug- gesting that heroin treatment may have a place with a subpopu-
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MDRI2026
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