Pregnancy Category B

Uses. This drug was invented by Germany's Nazi regime in 1941 as a substitute for inadequate morphine supplies. Today methadone is best known as a legal substitute for heroin. In addition to that use in addiction treatment programs, methadone is given to adults and children as a pain reliever for surgery, cancer, burns, and other conditions. The substance is used as a cough suppressant and also has calming qualities. In racehorses the drug can promote running ability and is banned from the sport. A human dose can last for 24 hours, rather long for a drug of this type and class. For pain relief a dose of methadone may be roughly 2.5 to 14.3 times stronger than morphine, depending on how and why the drug is administered.

Drawbacks. Some persons experience euphoria from methadone. Unwanted effects can include vitamin deficiency, constipation, sleepiness, breathing difficulty, and low blood pressure. People may feel faint if they suddenly stand up from a sitting or prone position. Nausea, vomiting, constipation, urinary difficulty, sweating, lowered sex drive, and impaired sexual performance are other well-known problems. Liver disease may allow dangerous buildup of methadone levels from normal doses.

Abilities to operate dangerous machinery such as automobiles may be reduced. Tests of persons undergoing methadone maintenance therapy indicate they may be able to drive satisfactorily if they use no other drugs, but most methadone maintenance patients also use other drugs that worsen driving performance and exhibit assorted types of personality problems that leak over into driving habits.

In the 1970s methadone was suspected of causing memory trouble, but a group of researchers who investigated the question found no such difficulties. In 2000 a study reported significant memory problems in a group of metha-done maintenance recipients, but the same group also had confounding conditions such as head injury and alcoholism that may have affected memory test performance. Another 2000 study comparing methadone users to nonusers concluded that life factors other than methadone were the best explanation for differences in scores on thinking tests.

Abuse factors. Although methadone is sometimes described as blocking heroin's effects, the two drugs simply have cross-tolerance, meaning one of them can substitute for the other in some ways. In addition, persons who find one of the drugs pleasant will probably find the other one just as appealing. For those reasons, heroin addicts can often be switched to methadone in order to maintain their drug habit legally, but the switch does not cure their drug addiction. Some heroin users even like methadone better; some methadone recipients continue using heroin on the side. On the basis of death statistics, some authorities feel methadone is more dangerous than heroin.

Addicts in methadone maintenance programs have chaotic lives. One study of program participants found 7% were likely to be pathological gamblers; another study of methadone program participants found 16% to be pathological gamblers and an additional 15% to have a gambling problem. Researchers have noted that violent traumas are more frequent among methadone program participants than among the average population. In one survey 34% of patients said they received treatment for mental disorder, 64% of the women said they used psychoactive drugs during pregnancy, 80% of parents said they were arrested while their children were growing up, and parents reported that 30% of their children were suspended from school and 41% failed at least one grade in school and had to take that year of education again. For meth-adone maintenance patients and their families, drug abuse is simply one element in multiproblem lifestyles.

A rhesus monkey experiment showed the animals having no preference between water and a methadone solution. Such lack of interest is consistent with human experience. Some persons find opiates or opioids attractive, but most do not. Personality and life circumstances have much to do with such choices.

Methadone's calming qualities dissipate if tolerance occurs, so some other antianxiety medicine must then be used. Methadone's abstinence syndrome is reminiscent of morphine's but is generally described as more gradual in development and disappearance, longer lasting but with symptoms of lesser severity. Some research, however, has found no difference in morphine and methadone withdrawal, and some addicts say withdrawal from methadone is more difficult than withdrawal from heroin. Evidence suggests that metha-done withdrawal symptoms are harsher in nonblack infants than in blacks.

Drug interactions. Using other depressants (including alcohol) or tricyclic antidepressants with methadone can increase the risk of a cumulative overdose—each individual dose may be safe, but all together may be dangerous.

Methadone should be used cautiously if a person is also taking monoamine oxidase inhibitors (MAOIs, found in some antidepressants and other medicine). Blood levels of methadone can be drastically altered by phenobarbital, by the epilepsy medicines phenytoin and carbamazepine, and by the tuberculosis medication rifampin. A case report notes that the HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) drug ritonavir reduces methadone blood levels, and methadone interacts with other HIV/AIDS drugs as well. Taking doses of methadone along with the psychiatric medicine fluvoxamine (Luvox) can be fatal. Depending on how a person uses alcohol, that drug can raise or lower blood levels of methadone. Data from one study showed that methadone did not decrease likelihood for alcohol abuse and that persons already abusing alcohol drank even more while on methadone. Other drug combinations common among illicit users can be hazardous with methadone, and methadone alone can be dangerous if a person who once had tolerance resumes usage at the old high-dose level. Experiments have found that consumption and enjoyment of tobacco cigarettes increase after volunteers use methadone, and another experiment found that methadone consumption increases after volunteers use nicotine (in gum or cigarettes).

Cancer. Chromosome damage is one measure of a drug's potential for causing cancer. A study of persons receiving methadone for 40 weeks found no more chromosome damage than a nondrug population would have.

Pregnancy. Safety for use during pregnancy is unknown. Researchers who gave various opioids to pregnant hamsters described methadone as one of the most powerful inducers of birth defects. Mice research shows that offspring are smaller than normal but have ordinary brain development. Compared to morphine, much more of a maternal methadone dose reaches a fetus. One group of investigators developed findings implying that methadone may harm human fetal central nervous system development. Those discoveries are consistent with research demonstrating abnormal development of neurons in rats that had prenatal methadone exposure; researchers speculate that such abnormalities may explain various behaviors in human infants who had prenatal methadone exposure. Use of methadone for easing pain of childbirth is not recommended because newborns can suffer breathing difficulty after picking up the drug from the maternal blood supply. Infants from women who use methadone chronically can be born with dependence to the drug.

A study compared pregnant women on methadone maintenance to a pregnant group on morphine maintenance and discovered that the morphine group used fewer benzodiazepine class drugs and fewer opiates than the methadone program participants. Another study noted that pregnant addicts in a methadone program received better prenatal care than addicts who were not in such programs, but program participants typically continued illicit drug use, their infants weighed no more than infants from pregnant addicts not in a methadone program, and infants from both those drug groups (program and nonprogram) weighed less than those of women who were not drug abusers. Such results have led more than one group of researchers to ask whether methadone maintenance helps pregnancy outcomes, but those researchers do not offer an answer. Nonetheless, some authorities report that pregnancy outcomes are substantially better for addicts in methadone programs.

A group of clinical observations found that infants from mothers addicted to heroin had better sucking ability than infants from methadone addicts (including those in methadone maintenance programs). Research finds that breast-feeding by methadone-using mothers does no harm to infants, and one investigator concluded that methadone in the milk helps ease a dependent child's withdrawal symptoms. Investigators have found that infants with fetal exposure to methadone eat more than normal but do not gain more weight than normal, a finding that suggests defective ability to use nutrition from food. A study of two-year-old children found that fetal exposure to methadone had no influence on ability to focus attention. Examination of school-age children who had fetal exposure to methadone found them to have normal scores in thinking tests and somewhat lower IQs than normal and to be more nervous and aggressive than typical children. How much of this is related to the drug and how much is related to tumultuous family life is uncertain. Another follow-up study found that girls had normal gender behavior, but boys had more female characteristics in their conduct.

A study found pregnancy outcomes to be much the same among methadone and cocaine users.

Additional scientific information may be found in:

Darke, S., et al. "Cognitive Impairment among Methadone Maintenance Patients." Addiction 95 (2000): 687-95. De Cubas, M.M., and T. Field. "Children of Methadone-Dependent Women: Developmental Outcomes." American Journal of Orthopsychiatry 63 (1993): 266-76. Fainsinger, R., T. Schoeller, and E. Bruera. "Methadone in the Management of Cancer

Pain: A Review." Pain 52 (1993): 137-47. Jarvis, M.A., and S.H. Schnoll. "Methadone Treatment during Pregnancy." Journal of

Psychoactive Drugs 26 (1994): 155-61. Martin, W.R., et al. "Methadone—A Reevaluation." Archives of General Psychiatry 28 (1973): 286-95.

Rossler, H., et al. "Methadone-Substitution and Driving Ability." Forensic Science International 62 (1993): 63-66. Schneider, J.W., and S.L. Hans. "Effects of Prenatal Exposure to Opioids on Focused Attention in Toddlers during Free Play." Journal of Developmental and Behavioral Pediatrics 17 (1996): 240-47. Specka, M., et al. "Cognitive-Motor Performance of Methadone-Maintained Patients." European Addiction Research 6 (2000): 8-19.

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