A common problem in treating methadone overdoses is that, given the short action of naloxone (versus the extremely longer-acting methadone), a dosage of naloxone given to a methadone-overdosed person will initially work to bring the person out of overdose, but once the naloxone wears off, if no further naloxone is administered, the person can go right back into overdose (based upon time and dosage of the methadone ingested). Tolerance and dependence
As with other opioid medications, tolerance and dependence usually develop with repeated doses. There is some clinical evidence that tolerance to analgesia is less with methadone compared to other opioids; this may be due to its activity at the NMDA receptor. Tolerance to the different physiological effects of methadone varies; tolerance to analgesic properties may or may not develop quickly, but tolerance to euphoria usually develops rapidly, whereas tolerance to constipation, sedation, and respiratory depression develops slowly (if ever). Methadone fills the same opioid receptors in the brain as heroin and other prescription painkillers making it a suitable substitute. Driving
Methadone treatment may impair driving ability. Drug abusers had significantly more involvement in serious crashes than non-abusers in a study by the University of Queensland. In the study of a group of 220 drug abusers, most of them poly-drug abusers, 17 were involved in crashes killing people, compared with a control group of other people randomly selected having no involvement in fatal crashes. However, there have been multiple studies verifying the ability of methadone maintenance patients to drive.
In the UK, persons who are prescribed oral methadone can continue to drive after they have satisfactorily completed an independent medical examination which will include a urine screen for drugs. The license will be issued for 12 months at a time and even then, only following a favourable assessment from their own doctor. Individuals who are prescribed methadone for either IV or IM administration cannot drive in the UK, mainly due to the increased sedation effects that this route of use can cause. Mortality
In the United States, deaths linked to methadone more than quadrupled in the five-year period between 1999 and 2004. According to the U.S. National Center for Health Statistics, as well as a 2006 series in the Charleston Gazette (West Virginia), medical examiners listed methadone as contributing to 3,849 deaths in 2004. That number was up from 790 in 1999. Approximately 82 percent of those deaths were listed as accidental, and most deaths involved combinations of methadone with other drugs (especially benzodiazepines). Although deaths from methadone are on the rise, methadone-associated deaths are not being caused primarily by methadone intended for methadone treatment programs, according to a panel of experts convened by the Substance Abuse and Mental Health Services Administration, which released a report titled "Methadone-Associated Mortality, Report of a National Assessment". The consensus report concludes that "although the data remains incomplete, National Assessment meeting participants concurred that methadone tablets or Diskets® distributed through channels other than opioid treatment programs most likely are the central factors in methadone-associated mortality.