Methadone physical dependence

The patient who uses methadone long-term may develop a tolerance to the drug s analgesic effect and physical dependence. 

This book is mainly concerned with the treatment of opiate misuse, for the simple reason that that is the form of drug misuse for which there are the most effective clinical approaches. As we have discussed, the treatment scene for opiate misusers, in contrast to other groups, is fundamentally altered by the widespread availability of the substitution option, in the form of methadone or alternative opioids. Physical dependence is part of the rationale for that approach, and the occurrence of clear-cut withdrawal symptoms also indicates the use of drugs such as lofexidine or clonidine, followed where possible by naltrexone. For reasons of severity of dependence and treatment options, it is therefore understandable that services are inclined to have caseloads dominated by opiate users. 

Methadone is widely used in the treatment of opioid abuse. Tolerance and physical dependence develop more slowly with methadone than with morphine. The withdrawal signs and symptoms occurring after abrupt discontinuance of methadone are milder, although more prolonged, than those of morphine. These properties make methadone a useful drug for detoxification and for maintenance of the chronic relapsing heroin addict. 

The most widely used approach to treating opioid addiction is methadone maintenance. Methadone, shown in Figure 14.44, is a synthetic opioid derivative that has most of the effects of other opioids, including euphoria, but differs in that it retains much of its activity when taken orally. This means that doses are very easy to control and monitor. The withdrawal symptoms of methadone are also far less severe, and the addict may be slowly weaned off the opioid without excessive stress. An addict may be freed of physical dependence in a matter of months. The psychological dependence, however, usually persists throughout the individual s life, which is why the relapse rate is so high. 

Methadone is used for the treatment of narcotic withdrawal and dependence. It occupies the opioid receptor in the brain and is the stabilizing factor that permits addicts to change their behavior and to discontinue heroin use. Methadone suppresses narcotic withdrawal for between 24 and 36 hours, and because it is effective in eliminating withdrawal symptoms, it is used in detoxifying opiate addicts. Ultimately, the patient remains physically dependent on the opioid, but is freed from the uncontrolled, compulsive, and disruptive behavior seen in heroin addicts.42... 

Others have reported good results from the use of clonidine (69,70). Of 25 inpatients physically dependent on methadone, 20 were able to withdraw completely from methadone at the end of 2 weeks. In most patients, 10-11 days of clonidine, in a peak dose of 16 micrograms/kg/day, produced a perceived reduction in symptoms compared with previous attempts to become opioid-free. In these dosages, clonidine significantly reduced standing blood pressure without producing clinical problems. 

The outstanding properties of methadone are its analgesic activity, its efficacy by the oral route, its extended duration of action in suppressing withdrawal symptoms in physically dependent individuals, and its tendency to show persistent effects with repeated administration. Miotic and respiratory-depressant effects can be detected for more than 24 hours after a single dose, and on repeated administration, marked sedation is seen in some patients. Effects on cough, bowel motility, biliary tone, and the secretion of pituitary hormones are qualitatively similar to those of morphine. 

Development of physical dependence during the longterm administration of methadone can be demonstrated by drug withdrawal or by administration of an opioid antagonist. Subcutaneous administration of 10 to 20 mg methadone to former opioid addicts produces definite euphoria equal in duration to that caused by morphine, and its overall abuse potential is comparable with that of morphine. 

Although abstinence phenomena from methadone are comparatively mild, the euphoric effects are so marked and emotional dependence so strong, that the total addiction liability (physical dependence plus psychic... 

In the second study there were 174 patients in two similar experimental groups in whom injectable rather than inhaled heroin was used (5). A response to treatment was defined as at least a 40% improvement in physical, mental, or social domains of quality of life, if not accompanied by a substantial (over 20%) increase in the use of another illicit drug, such as cocaine or amphetamines. After 12 months those who took methadone and heroin (smoked or injected) had significantly better outcomes. The incidences of adverse effects (constipation and drowsiness) were similar in all the groups. However, owing to the limitations of the study and the complex nature of drug dependence, the therapeutic outcomes could not be justifiably and solely attributed to the specific drug(s). 

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