Methadone Deaths: Risk Factors in Pain and Addicted Populations

Abstract

Methadone is highly effective in treating opioid dependence, and it is also used as an analgesic for secondline management of chronic pain. However, recent increases in methadone-related deaths have instigated controversy about the use of this medication. In this paper, we evaluate risk factors for methadone mortality in opioid dependent and pain populations and present guidelines for initiating methadone treatment in these two populations to minimize the risk of death. Early research with methadone-maintained patients revealed that methadone fatalities occur primarily due to respiratory arrest during methadone induction and in the context of polysubstance use. Recent reports of methadone deaths emphasize chronic pain populations, methadone-related QTc prolongation, and the possibility of inducing Torsade de pointes (TdP), a potentially fatal ventricular arrhythmia. Retrospective analyses of these deaths show that patients who develop TdP often present with multiple risk factors, including high methadone doses, use of other medications that cause QTc prolongation, and electrolyte abnormalities. To minimize fatalities, guidelines are presented for initiating methadone in opioid treatment and pain populations that consider the drug's pharmacology along with behavioral, medical and psychiatric risk factors.

Dependência de opioide em pacientes com dor crônica

“…É usada para evitar a síndrome de abstinência e bloquear os efeitos de euforia do consumo de opioides. Entretanto, pode causar arritmia ventricular e aumento de morte associada a esse opioide, com controvérsias quanto a seu uso 32 . Geralmente, ocorre óbito quando há vários fatores de risco, incluindo grandes doses de metadona, outros medicamentos que prolongam o intervalo da onda QT e alterações eletrolíticas.…”

Methadone Deaths in Pain and Addiction Populations

“…As noted by Modesto-Lowe et al 1 , the second of methadone's very unfavorable properties is that its respiratory depressant effect persists much longer than its analgesic effect. This inherent property of methadone cannot be altered by risk reduction strategies.…”

“…Repeated dosing to control pain often leads to drug accumulation causing respiratory depression resulting in hypoxic brain injury or death. Citing Trescot et al 3 and Shaiova et al 4 , Modesto-Lowe et al 1 stated that methadone treatment for chronic pain has increased because of its long half-life, efficacy and low cost. However, the long-half life of methadone is for its respiratory depressant effect, not for its desired analgesic activity.…”

Differences in the implementation methadone programme to European countries

“…Првенствено се метаболише у јетри до неактивних метабо-лита преко цитохрома П450 изоформе ЦИП 3А4. Метадон је слаб инхибитор ове изо-форме, али је и делом супстрат за изоформе 2Ц19 и 2Д6 6 . Метаболизам се одвија демети-лацијом атома азота у молекулу метадона, а метаболит се елиминише и путем урина и пу-тем жучи 7 .…”

“…Акумулација метадона може довести до седације, продужетка QT интервала, депре-сије дисања, па чак и смрти 6 . Изоформе 3А4 и 2Д6 цитохрома П450 значајно учествују у метаболизму метадона, а активност ЦИП 3А4 варира међу поједин-цима, што објашњава варијабилност у распо-ложивости метадона 10 .…”