Methadone even at therapeutic levels can kill

Methadone is a possible cause of sudden cardiac death even when it isn’t overdosed but is taken at therapeutic levels primarily for relief of chronic pain or drug addiction withdrawal, a new study by Oregon Health & Science University researchers suggests.

The study’s findings, described in the January 2008 issue of The American Journal of Medicine, are based on an evaluation of all sudden cardiac deaths in the greater Portland, Ore., metropolitan area between 2002 and 2006 where detailed autopsies were performed.

The analysis was based on a comparison of two case groups. One group consisted of 22 sudden cardiac deaths in which toxicology screens turned up 1 milligram or less of methadone — defined as a therapeutic level. These cases were compared with a second group of 106 cases where no evidence of methadone was found. Seventeen of the first case group of 22 – or 77 percent – had no significant cardiac abnormalities, while five had evidence of significant coronary artery disease. By contrast, 60 percent of the case group where no methadone was present had identifiable evidence of cardiac disease or structural abnormalities, all of which are established potential causes of sudden cardiac death.

“The unexpectedly high proportion of otherwise unexplained sudden deaths in the therapeutic methadone group points to a significant contribution of this drug toward the occurrence of sudden cardiac death among these patients,” said Sumeet Chugh, M.D., lead investigator, director of OHSU’s Cardiac Arrhythmia Center, and associate professor of cardiovascular medicine in the OHSU School of Medicine.

The findings lend support to a growing body of individual case reports linking methadone to a rare ventricular arrhythmia, known as torsade de pointes, which can degenerate into ventricular fibrillation leading to sudden death in the absence of medical intervention.

The study’s authors conceded that they could not rule out the possibility that some of the deaths in the first case group actually were due to suppression of breathing, especially during sleep. Previous studies have found that stable patients in a methadone prevention program had more sleep architecture abnormalities and a higher prevalence of sleep apnea.

More than half – or 14 – of the 22 in the first case group were using the drug for pain control, three for drug addiction, three for recreational use and four for an undetermined reason. The mean age of the group was 37 and 68 percent were males. The mean age of the non methadone group was 42 and 69 percent were males.

The therapeutic use of methadone, a synthetic opiate, is increasing steadily not only for drug addiction but also among cancer patients for managing chronic pain largely because it is less costly than the alternatives and also because it is fast-acting and its effect is long-lasting. The OHSU study’s authors proposed that a large prospective evaluation of methadone therapy be undertaken since a sizeable and growing number of people benefit from therapeutic use of the drug. They also suggested that additional safeguards prior to therapy might be necessary, such as an electrocardiogram and an assessment of the potential risk for respiratory suppression both awake and asleep.

The OHSU research was based on the work of the landmark Oregon Sudden Unexpected Death Study (Ore-SUDS), which Chugh initiated five years ago. It is the latest among a series of studies done by Chugh and his team. The Ore-SUDS study is a community-based effort that includes a partnership with the emergency medical response system, the state medical examiner network and 16 area hospitals, enabling a systematic study of all sudden cardiac arrests that occur in the Portland metropolitan area. A separate collaborative effort also is under way with the Donald W. Reynolds Cardiovascular Clinical Research Center at Johns Hopkins University Reynolds Cardiovascular Center (Eduardo Marban, M.D., Ph.D., director) is focusing on the link between cardiac arrest and the human genome.

Source: Oregon Health & Science University

Related stories:

Variations in key genes increase Caucasians’ risk of heroin addiction
(PhysOrg.com) -- Sometimes, small changes do add up. In the case of addictive diseases, tiny variations in a few genes can increase or decrease the likelihood of some people developing a dependency on heroin. Now, by examining a select group of genetic variants in more than 400 former severe heroin addicts, Rockefeller University researchers have identified several genetic variations in American and Israeli Caucasians that influence the risk for becoming addicted to one of the world’s most powerful substances.
Study highlights risky behavior, lack of care among HIV-infected crack users
Doctors who treat HIV-infected crack users refer to them as "the forgotten population." A study being presented at this week's International AIDS Conference in Mexico City reveals that these patients frequently lack outpatient health care, do not receive life-saving antiretroviral therapy and continue to engage in risky sexual behavior that likely contributes to HIV transmission.
Opioids and cannabinoids influence mobility of spermatozoids
A PhD thesis from the University of the Basque Country has concluded that there are opioid and cannabinoid receptors in human sperm and that these influence the mobility of spermatozoid. The research by Mr Ekaitz Agirregoitia opens the door to more effective treatment of fertility problems.
Research sheds new light on heroin addiction
Researchers from the Howard Florey Institute in Melbourne have identified a factor that may contribute towards the development of heroin addiction by manipulating the adenosine A2A receptor, which plays a major role in the brain’s ‘reward pathway’.
Drug poisoning growing cause of death
A government report said poisoning is the second-leading cause of injury death in the United States after motor vehicle accidents.
Should heroin be prescribed to addicts?
In this week’s BMJ experts debate whether heroin should be prescribed to addicts who are difficult to treat.
Methadone deaths prompt N.C. investigation
Officials are investigating several North Carolina clinics following an increasing number of deaths involving methadone, a report says.
1 in 3 drivers under 'the limit' for alcohol still test positive for drugs
One in three drivers suspected of driving while ‘over the limit,’ but subsequently found to be below maximum permissible levels of alcohol, nevertheless tested positive for a range of drugs, reveals research in Injury Prevention.

News discussion:

Medicine & Health news