Methadone overdose

In overdose, methadone causes CNS and respiratory depression, miosis, bradycardia, hypotension, circulatory collapse, hypothermia, coma, seizures, and pulmonary edema (although less frequently than morphine). Treatment for methadone overdose includes supportive measures to maintain adequate respiration and blood pressure, and the administration of the opioid antagonist naloxone to reverse the effects of methadone. If repeated administration of naloxone is required, patients should be monitored for 48 to 72 hours following overdose. Dialysis is not an effective treatment modality, because methadone has a large volume of distribution (Vj = 4 to 5 L/kg) and is highly protein bound (87%). ... 

Two opioids are used in the treatment and management of opiate dependence levomethadyl and methadone. Levomethadyl is given in an opiate dependency clinic to maintain control over the delivery of the drug. Because of its potential for serious and life-threatening proarrhythmic effects, levomethadyl is reserved for use in the treatment of addicted patients who have no response to other treatments. Levomethadyl is not taken daily the drug is administered three times a week (Monday/Wednesday/Thursday or Tuesday/Thursday/ Saturday). Daily use of the usual dose will cause serious overdose. 

Even though methadone treatment reduces the high mortality of intravenous addicts to about 30% of controls, a number of patients and non-patients still overdose on methadone itself (Vormefelde and Poser, 2000), although the availability of methadone itself does not appear to be linked to increases in drug-related deaths (Oliver, 2002). 

Methadone is not without side effects. Although it is less addictive than other opiates, methadone can be abused and requires monitored use. Common side effects include sedation and constipation. Methadone is also safer than other opiates in overdose but does require careful monitoring of respiratory status when an overdose occurs. 

Respiratory depression Accidental overdose with long-acting opioids (eg, methadone, levomethadyl) may result in prolonged respiratory depression. While nalmefene has a longer duration of action than naloxone in fully reversing doses, be aware that a recurrence of respiratory depression is possible. Observe patients until there is no reasonable risk of recurrent respiratory depression. 

Fernandez et al. [27] applied HPLC with diode array detection (DAD) to the determination of heroin, methadone, cocaine and metabolites in plasma after mixed-mode SPE. Analytes were separated using a RP8 column (250 mm x 4.6 mm i.d., 5 jam particle size) and acetonitrile-phosphate buffer pH 6.53 as mobile phase with elution in the gradient mode. The method, which provides a LLOQ of 0.1 j,g/mL for all compounds, was successfully applied to 21 plasma samples from fatal overdoses. 

Evaluating the impact of methadone maintenance programmes on mortality due to overdose and AIDS in a cohort of heroin users in Spain. Addiction, 100, 981-9... 

Wodak A, Seivewright NA, Wells B, Reuter P, Des Jarlais DC, Rezza G et al. (1994). Comments on Ball van de Wijngaart s A Dutch addict s view on methadone maintenance - an American and a Dutch appraisal . Addiction, 89, 803-14 Wolff K (2002). Characterization of methadone overdose clinical considerations and the scientific evidence. Theraputic Drug Monitoring, 24, 457-70... 

The concurrent administration of methadone to heroin addicts known to be recidivists has been questioned because of the increased risk of overdose death secondary to respiratory arrest. Buprenorphine, a partial M-receptor agonist with long-acting properties, has been found to be effective in opioid detoxification and maintenance programs and is presumably associated with a lower risk of such overdose fatalities. 

Opioids (opium, morphine, heroin, meperidine, methadone, etc) are common drugs of abuse (see Chapters 31 and 32), and overdose is a common result of using the poorly standardized preparations sold on the street. See Chapter 31 for a detailed discussion of opioid overdose and its treatment. 

Diamorphine Diamorphine is relatively unstable in aqueous solutions, and minimum decomposition was observed at pH 4. Preparations should be used within 4 weeks when kept at room temperature, but degradation products also have analgesic activity.45,46 Diamorphine is used in the management of opioid dependence this is also a drug of abuse and the overdose is fatal47,48 Interactions are similar to those of opioid analgesics. Withdrawal symptoms of opioid dependence can be treated with diamorphine and methadone.49... 

Although methadone is used for the management of opioid dependence, symptoms of overdose are similar to those of morphine poisoning. 

Eli Lilly s methadone, used in drug addiction clinics as a substitute for other narcotics, has also drawn a great deal of persistent worldwide criticism. It has been diverted for illegal use as a highly addictive narcotic. It has caused many deaths, including a public health crisis that involved an unusual spike in methadone overdose deaths in the Portland area, according to the Drug Enforcement Administration (2007). 

It might be safer than methadone in overdose, but more evidence is needed. 

The role of methadone and opiates in accidental overdose deaths in New York City has been investigated using data from the Office of Chief Medical Examiner of all accidental drug overdose deaths between 1990 and 1998 (51). There were 7451 overdose deaths in all during this period, of which 1024 were methadone-induced, 4627 were heroin-induced, and 408 were attributable to both. Thus, 70% of the deaths from accidental overdose were due to opiates. Co-variates significantly associated with methadone-induced deaths were female sex, older age, and absence of cocaine, heroin, cannabis, and alcohol in toxic screens. Co-variates associated with heroin overdose were male sex, Caucasian or Hispanic ethnicity, younger age, and the absence of cocaine and methadone and the presence of cannabis and alcohol in toxic screens. 

Bryant WK, Galea S, Tracy M, Markham Piper T, Tardiff KJ, Vlahov D. Overdose deaths attributed to methadone and heroin in New York City, 1990-1998. Addiction 2004 99(7) 846-54. 

In studies of its use in treating alcohol, opioid, and nicotine dependence, naltrexone has not been reported to cause depression or dysphoria. Patients who complain of naltrexone-associated dysphoria often have co-morbid depressive disorders or depression resulting from opioid or alcohol withdrawal states (549). Co-morbid depression is not a contraindication to naltrexone. Small pilot studies have supported the use of naltrexone in combination with antidepressants for the treatment of patients with co-mor-bid depression. The risk of non-fatal overdose is significantly increased after naltrexone treatment, as a result of reduced tolerance, compared with patients taking substitution methadone (550). 

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