Methadone

Methadone is a synthetic opioid, used medically as an analgesic and anti-addictive. It was developed in Germany in 1937.

Although chemically unlike morphine or heroin, methadone also acts on the opioid receptors and thus produces many of the same effects.

Methadone maintenance therapy is the most studied, most successful, and the most politically controversial therapy for the treatment of drug addiction.

Methadone is also used in managing chronic pain due to its long duration of action and very low cost. In late 2004, the cost of a one-month supply of methadone was $20, as compared to an equivalent analgesic amount of Demerol at $120.

Today a number of pharmaceutical companies produce and distribute methadone. However, the major producer remains Mallinckrodt. Mallinckrodt sells bulk methadone to most of the producers of generic preparations and also distributes its own brand name product in the form of tablets, dispersible tablets and oral concentrate under the name Methadose in the United States.

Methadone (as Dolophine) was first manufactured in the USA by Mallinckrodt Pharmaceuticals, a St. Louis-based subsidiary of the Tyco International corporation. Mallinckrodt held the patent up until the early 1990s, and is still the major producer.

Generally, one will only hear "dolophine" used by older addicts who used the product in the 1960s and 1970s. Medical professionals who believe that dolophine is the generic name for methadone, when actually it is the reverse, may also use the old brand name.

Methadone acts by binding to the NMDA receptor. It is metabolized by the enzymes CYP3A4 and CYP2D6, with great variability between individuals. Its main route of administration is oral. Adverse effects include hypoventilation, constipation and miosis, in addition to tolerance, dependence and withdrawal symptoms. The latter are less severe compared to those of e.g. morphine and heroin, but are on the other hand more prolonged.

As with other opioid medications, tolerance and dependence usually develop with repeated doses. Tolerance to the different physiological effects of methadone varies. Tolerance to analgesia usually occurs during the first few weeks of use; whereas with respiratory depression, sedation, and nausea it is seen within approximately 5-7 days. There is no tolerance formed to constipation produced by methadone or other opioids; however, effects may be less severe after time and can often be alleviated through dietary fiber supplements.

Uses for Pain Relief

In recent years, methadone has gained popularity among physicians for the treatment of other medical problems, such as an analgesic in chronic pain. The increased usage comes as doctors search for an opioid drug that can be dosed less frequently than short-acting drugs like morphine or hydrocodone. Another factor in the increased usage is the low cost of methadone. A month's supply will typically have a retail cost of $30-50 in the United States, compared to hundreds of dollars for alternative opioids. Methadone, with its long half-life (and thus long duration of effect) and good oral bioavailability, is a common second-choice drug for pain that does not respond to weaker agonists.

A major drawback is that unlike OxyContin (oxycodone continuous release), methadone is not technologically engineered for sustained release of the drug so blood concentrations will fluctuate greatly between dosing. This problem is overcome to a great extent by the practice of dosing methadone two or three three times a day in pain patients. Some physicians also choose methadone for treating chronic pain in patients who are thought to have a propensity for addiction, because it causes less of an intoxicated or euphoric "high". The effect is of morphine-equivalent origin.

On November 29, 2006, the U.S. Food and Drug Administration issued a Public Health Advisory about methadone titled "Methadone Use for Pain Control May Result in Death and Life-Threatening Changes in Breathing and Heart Beat." The advisory went on to say that "the FDA has received reports of death and life-threatening side effects in patients taking methadone. These deaths and life-threatening side effects have occurred in patients newly starting methadone for pain control and in patients who have switched to methadone after being treated for pain with other strong narcotic pain relievers. Methadone can cause slow or shallow breathing and dangerous changes in heart beat that may not be felt by the patient." The advisory urged that physicians use caution when prescribing methadone to patients who are not used to the drug, and that patients take the drug exactly as directed