Substitution treatment methadone

The particular properties which have made methadone attractive for substitution treatment since the days of the early trials (Dole Nyswander 1965) are indicated in Table 1.1. 

The above drugs have been discussed as possible substitute treatments which are more euphoriant than methadone. The evidence relating to their use is limited in comparison to that for methadone, and they seem likely for the time being to remain relatively peripheral possibilities compared to methadone and buprenorphine. The euphoriant properties have been identified as a rationale for treatment, and this has various implications both for the individuals concerned, and in terms of overall treatment within a clinic. 

Table 2.1. Possible advantages of buprenorphine over methadone as substitution treatment in opiate misuse Safer overall...

For those of us in countries where buprenorphine and methadone are absolutely direct alternatives, with very broadly about half of presenting patients choosing one medication and half the other, there are two characteristics of the literature on buprenorphine from other countries which strike unusual notes. For anyone reviewing this area they will soon notice that an exceptional proportion of the literature comes from France (e.g. Auriacombe et al. 1999, Carrier et al. 2006), and this is because even though buprenorphine use in substitution treatment there is recent, as it is everywhere else, methadone had not been... 

Ongoing substitution treatment, usually with methadone or buprenorphine... 

Analgesic efficacy and clinical use Levomethadone like racemic methadone is a potent and long-acting opioid analgesic and can be used for the treatment of moderate to severe pain (Jamison, 2000 Davis and Walsh, 2001). It has an action profile similar to morphine and has significant antitussive properties, for which it is used in terminal lung cancer. The long duration of action makes the compound suitable for substitution treatment of opioid addiction (Joseph et al., 2000 Pallenbach, 2002). For practical and economic reasons the racemate instead of the levo-enantiomer is used in addicts. 

The potential role of methadone in drug deaths has been highlighted in some countries. Research shows that substitution treatment reduces the risks of drug-related death. However, since methadone substitution has increased substantially in Europe (see Chapter 4), toxicological examinations of overdoses, AIDS deaths or accidents increasingly indicate the presence of methadone, regard-... 

In all countries, drug services are dealing increasingly with multiple-drug use. In Denmark, 75 % or more of those admitted to treatment use several drugs. Germany reports problem use of substitution substances such as methadone and codeine (substitution treatment is discussed in detail... 

As mentioned, the simultaneous analysis for drugs, their metabolites, diuretics, stimulants, (3-blockers, and pharmaceuticals offers a more complete overview about the clinical global situation of the patient. An interesting example is represented by the panel of substances found in the urine of a patient (11). The presence of morphine, codeine, noscapine, and 6-MAM indicated a probable consumption of heroin, but the same urine sample also contained an important quantity of methadone, widely used in heroin substitution treatment programs, and its metabolite EDDP. The sample also included fentanyl, which can serve as a direct pharmacological substitute for heroin in opiate-dependent individuals, and a certain amount of tramadol, generally used as an analgesic. 

Replacement of one of the phenyl groups by an alkyl group of similar bulk, on the other hand, alters the biologic activity in this series. Alkylation of phenylacetonitrile with isopropyl bromide affords the substituted nitrile, 136. Treatment of the anion prepared from 136 with strong base with 2-dimethylamino-l-chloropropane gives isoaminile (137). It is of note that alkylation of this halide, isomeric with that used in the early methadone synthesis, is apparently unaccompanied by isomer formation. Isoaminile is an agent with antitussive activity. 

Substitution therapy with methadone or buprenorphine has been veiy successfiil in terms of harm reduction. Some opiate addicts might also benefit from naltrexone treatment. One idea is that patients should undergo rapid opiate detoxification with naltrexone under anaesthesia, which then allows fiuther naltrexone treatment to reduce the likelihood of relapse. However, the mode of action of rapid opiate detoxification is obscure. Moreover, it can be a dangerous procedure and some studies now indicate that this procedure can induce even more severe and long-lasting withdrawal symptoms as well as no improvement in relapse rates than a regular detoxification and psychosocial relapse prevention program. 

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