Research Articles

[Melis11577]

BMJ 1996;313:481-482 (24 August)

Education and debate
Lesson of the Week: Fatal methadone overdose
T J Hendra, consultant physician,a S P Gerrish, consultant anaesthetist,a A R W Forrest, consultant chemical pathologist a
a Directorate of Medicine, Intensive Care Unit and Department of Clinical Chemistry, Royal Hallamshire Hospital, Sheffield S10 2JF

Correspondence to: Dr T J Hendra, Department of Geriatric Medicine, Royal Hallamshire Hospital, Sheffield S10 2JF.

Methadone is a synthetic opioid with potent analgesic effects often used for the detoxification or maintenance of an opiate addict. It differs from morphine in that it has an exceptionally prolonged duration of action with a half life averaging 25 hours, although durations of up to 52 hours have been reported during long term maintenance treatment.1 The variation in metabolism may be responsible for the irregular and unpredictable clinical course of patients who have taken overdoses of this agent.




Methadone
overdose can
follow an
unpredictable
course in non-
tolerant patients,
who are at risk of
sudden death



Case report

A 22 year old man presented to the accident and emergency department at 1400 hours having taken an overdose of 420 mg of methadone three hours earlier; he had obtained the drug illicitly. He was a known drug misuser who had epilepsy, treated with sodium valproate. He had been treated before for depression with amitriptyline and fluoxetine. A heavy cigarette smoker with a high alcohol intake, he had taken four overdoses within the past two months.

On arrival he was drowsy and refused to submit to regular nursing observations. On leaving the hospital, he collapsed on the pavement while smoking a cigarette. After being brought back into the department, unconscious and unresponsive to pain, he was given three 0.4 mg boluses of intravenous naloxone and 0.4 mg flumazenil, with a prompt improvement in his level of consciousness. He was transferred to the admissions ward, where he cooperated poorly with monitoring by the nursing staff and hindered the use of a pulse oximeter by frequently getting out of bed and wandering out of the ward. At 1830 hours he had an episode of altered consciousness and responded to 0.4 mg naloxone within two minutes. At 2130 hours a naloxone infusion of 0.3 mg/hour was started following another episode of unconsciousness associated with an oximeter oxygen saturation of 22%.

He was transferred to the intensive care unit, where he remained haemodynamically stable but had a fluctuating level of consciousness, varying from wide awake to rousable on request. The naloxone infusion of 0.3 mg/hour was continued, and a bolus injection of 0.2 mg given at 2345 hours greatly improved his level of consciousness. Blood was taken for toxicological analysis and oxygen administered via a face mask.

The following morning the naloxone infusion was temporarily stopped to assess whether it was still required and he got up to smoke a cigarette under nursing supervision. After he became sleepy, but was still rousable and able to communicate, the naloxone infusion was restarted at a rate of 0.2 mg/hour with good effect. He was seen by the on call psychiatric team and a decision was made to discharge him back to the general medical ward if stable. Before leaving the intensive care unit at 1800 hours the serum toxicology results were reported as methadone 353 µg/l, temazepam <50 µg/l, desipramine <50 µg/l, diazepam 813 µg/l, and nordiazepam 990 µg/l. The therapeutic ranges given were up to 250 µg/l for diazepam and up to 1000 µg/l for methadone. The laboratory also commented that while serum methadone concentrations of up to 1000 µg/l were found in patients receiving methadone maintenance treatment, death following overdose might be associated with a concentration as low as 200 µg/l in blood. He was transferred awake and alert to a general medical ward with instructions for the naloxone infusion to finish later that evening.

On the medical ward he was mobile and talking to the nursing staff until 0200 hours, when he had a cup of hot chocolate before retiring to bed. He was not being monitored by an oximeter at this time. The naloxone infusion was slow to complete, eventually finishing at 0330. He was observed to be sleeping and breathing satisfactorily at 0400 but was found dead in bed at 0655.

At necropsy there were no clinically relevant physical findings: his methadone concentration was 822 µg/l in femoral blood and 7 µg/l in stomach contents. Diazepam and nordiazepam blood concentrations were 103 µg/l and 165 µg/l, respectively. The pathologist's opinion of the cause of death was methadone overdose.

Comment

This young man took an opiate overdose and initially responded to the specific antagonist naloxone but then died unexpectedly 44 hours later within a few hours of the naloxone infusion being completed. Although methadone overdose can require high doses of naloxone, in this patient the quantities needed were not large either as bolus or infusion. Current recommendations for naloxone infusion are to administer two thirds of the initial reversal bolus hourly, with half of the reversal dose being administered as a bolus 15 minutes after the infusion is started. Infusions can usually be tapered after several hours but may be needed for much longer for long acting drugs.1

The toxicological data are consistent with death from methadone toxicity becoming manifest after discontinuation of the naloxone infusion. The benzodiazepine concentrations had fallen significantly after death and are unlikely to have contributed to his death. The methadone concentrations in plasma before death, and blood after death, were in the range potentially associated with severe toxicity in a person who does not take methadone regularly. An antemortem plasma methadone concentration of 353 µg/l would convert to a whole blood concentration of about 460 µg/l, which is significantly less than that found in the blood after death. Although there may be a slight increase in blood methadone concentration after death, due to tissue redistribution, this is unlikely to account for the significant increase in this case. The possibilities are either that absorption of methadone from the gut was not complete at the time that the antemortem sample was obtained or that the patient took further methadone while in hospital after transfer from the intensive care unit. The low concentration of methadone in the stomach contents after death makes the latter hypothesis unlikely, although this possibility cannot be totally excluded.

The delay between stopping the naloxone infusion and death may be related to the rate of methadone absorption from the gut. There is anecdotal evidence that deaths from methadone overdose have occurred shortly after eating food, so it is possible that the chocolate he drank at 0200 hours stimulated his gut, leading to increased absorption of methadone while he slept.

The clinical usefulness of methadone lies in its ability to suppress the symptoms of heroin withdrawal, a starting dose being in the region of 36-40 mg/day, with an experienced addict taking up to 80-100 mg daily. Methadone is well absorbed orally, producing peak plasma concentrations within two to four hours and peak clinical effects within one to two hours. The drug concentrations correlate well with respiratory depression and miosis, with the clinical effects lasting more than 72 hours in some subjects after a single oral dose.2 As little as 40-50 mg may produce coma and respiratory depression in a non-tolerant adult.3 As the half life of methadone varies between 25 and 52 hours, overdose can lead to a protracted clinical course.

Methadone toxicity is more likely in those trying the drug for the first time before tolerance has had time to develop.4 Deaths related to methadone are increasing,5 with patients starting on maintenance programmes being at particular risk.6 Because the sedative and depressant effects of methadone do not develop immediately, it is easy to take a large amount without being aware that harm is being done. One addict's daily maintenance dose of 50-100 mg can cause life threatening poisoning in a non-tolerant adult.7 Although plasma methadone concentrations have been recommended as a routine way of monitoring treatment,8 interpretation must take into account whether the individual has recently started treatment or is stabilised on a maintenance dose.

We recommend that patients with methadone overdose are admitted to hospital empirically for 72 hours, during which time their oxygen saturation should be continuously monitored with an oximeter and prompt referral made to intensive care if they suffer altered consciousness or hypoxia. Regardless of the duration of hospital stay, we also suggest that patients should be monitored with an oximeter for a further 24 hours after discontinuation of naloxone infusion.


Schauben JL, Rose SR. Opiate overdose. In: Rippe JM, Irwin RS, Alpert JS, Fink MP, eds. Intensive care medicine. 2nd ed. Boston: Little Brown, 1991.
Olsen GD, Wendel HA, Livermore JD, Leger RM, Lynn RK, Gerber N. Clinical effects and pharmacokinetics of racemic methadone and its isomers. Clin Pharmacol Ther 1977;21:147-57. [Medline]
Garriot JC, Sturner WQ, Mason MT. Toxicological findings in six fatalities involving methadone. Clin Toxicol 1973;6:163-73. [Medline]
Clark JC, Milroy CM, Forrest ARW. Deaths from methadone overdose. Journal of Clinical Forensic Medicine 1995;2:143-4.
Marks J. Deaths from methadone and heroin. Lancet 1994;343:976.
Drummer OH, Opeskin K, Syrjanen, Cordner SM. Methadone toxicity causing death in ten subjects starting on a methadone maintenance program. American Journal of Forensic Medicine and Pathology 1992;13:346-50. [Medline]
Harding-Pink D. Methadone: one person's maintenance dose is another's poison. Lancet 1993;341:665-6. [Medline]
Loimer N, Schmid R. The use of plasma levels to optimize methadone maintenance treatment. Drug Alcohol Depend 1992;30:241-6. [Medline]


Related Articles


Fatal methadone overdose
Emyr W Benbow, Ian S D Roberts, and Alison Cairns
BMJ 1996 313: 1479. [Extract] [Full Text]

Naloxone infusion should have been started earlier
N Nichol, L Pieterse, and T Beattie
BMJ 1996 313: 1479-1480. [Extract] [Full Text]

Patient may have injected methadone while in hospital
Aidan J Byrne
BMJ 1996 313: 1480. [Extract] [Full Text]

Close observation in intensive care unit is required when naloxone infusion ends
Simon Finfer
BMJ 1996 313: 1480. [Extract] [Full Text]

http://www.bmj.com/cgi/content/full/313/7055/481

[Melis11577]

Naloxone in opioid poisoning: walking the tightrope
S F J Clarke1, P I Dargan2 and A L Jones3
1 Acting Consultant in Emergency Medicine, South Manchester University Hospital Trust, Manchester, UK
2 Consultant Physician and Clinical Toxicologist
3 Consultant Physician and Clinical Toxicologist, Honorary Senior Lecturer in Clinical Pharmacology, National Poisons Information Service (London), Guy’s and St Thomas’ NHS Trust, London, UK


Correspondence to:
Simon F J Clarke
Acting Consultant in Emergency Medicine, South Manchester University Hospital Trust, Manchester, UK; sfjclarke@doctors.org.uk

Accepted for publication
1 April 2004


ABSTRACT
Acute opioid intoxication and overdose are common causes of presentation to emergency departments. Although naloxone, a pure opioid antagonist, has been available for many years, there is still confusion over the appropriate dose and route of administration. This article looks at the reasons for this uncertainty and undertakes a literature review from which a treatment algorithm is presented.



--------------------------------------------------------------------------------

Abbreviations: AWS, acute withdrawal symptoms


Keywords: naloxone; opioid; overdose; poisoning

Although naloxone has been used as a specific antidote for opioid poisoning since the 1960s,8 there are variations in the recommended doses with the British National Formulary advising 0.8–2 mg boluses, repeated as necessary up to 10 mg for adults (10 µg/kg followed by 100 µg/kg boluses for children), and Poisindex suggesting 0.4–2 mg boluses. There is also wide variation in the route of administration.

There are a number of reasons for this. First, opioids exert their effect by binding to a series of receptors. Naloxone has antagonist activity at all of the receptor types9 and the amount needed to provide such an effect depends upon the number of receptors occupied. Recent evidence suggests that a dose of 13 µg/kg naloxone (approximately 1 mg in an 80 kg person) produces 50% receptor occupancy;10 however, this is also influenced by the dose of opioid ingested or injected. Unfortunately this is seldom known in clinical practice,11 and instances have been reported where over 20 times the recommended doses of naloxone have been needed to counteract massive opioid overdoses,12,13 and even more in body packers. Numerous case histories have revealed a 13-fold variation in rate of naloxone infusions given for prolonged overdoses.14–22

Second, opioid antagonists can precipitate acute withdrawal symptoms (AWS) in chronic opioid users11,23–28 provoking an often violent reaction. In one early study on the use of naloxone to reverse morphine anaesthesia in non-opioid dependent, general surgical patients, acute withdrawal-like symptoms were observed to occur after the administration of 15 µg/kg naloxone.29 In another study, behavioural changes, sweating, and yawning were observed in 14 healthy volunteers given 2–4 mg/kg naloxone, and these effects often lasted for a number of hours after its administration.30

Third, the pharmacodynamic actions of naloxone last for a briefer period than all but the most short acting opioids;8,24,29,31 although the elimination half life of naloxone is similar to that of morphine (60–90 minutes)9 it is redistributed away from the brain more rapidly.32 Consequently, the patients may become renarcotised and suffer harm if they self discharge from medical care early. Clinicians are clearly walking a tightrope between precipitating AWS and avoiding renarcotisation.

Numerous case reports describing possible adverse effects of naloxone have been published. Pulmonary oedema has been reported but most instances have occurred in the postoperative period33–39 or in the presence of pre-existing cardiorespiratory disease,40 and in many of these reports it can be difficult to differentiate between the effect of naloxone and the effect of the underlying disease process or other drugs that have been ingested or administered. Many episodes of pulmonary oedema secondary to opioid toxicity have been published since it was first noted by William Osler in the 1880s5,41–50 and it has been suggested that naloxone simply reveals the opioid induced pulmonary oedema that had been masked by the respiratory depression.51

Seizures52 and arrhythmias53–57 have also been noted, but could have been caused by hypoxia,54 the opioids themselves,44,55,58 their coingestants (most notably cocaine),57 or pre-existing disease.53,56 Interestingly, a number of episodes of severe hypertensive reactions have been reported following administration of naloxone to patients with pre-existing simple hypertension.59–63 In addition, one report showed a significant rise in serum catecholamine concentrations in a patient with a phaeochromocytoma following administration of naloxone without prior exposure to exogenous opioids.64 Currently, a great deal of research is being undertaken on the interaction of endogenous opioids and the autonomic nervous system and it would seem reasonable to postulate that the antagonistic action of naloxone may have an effect. Canine experiments have indicated that reducing hypoxia and hypercapnia lowers serum catecholamine concentrations. It has been proposed that hyperventilating patients prior to administration of naloxone would reduce the risk of sympathetic mediated adverse effects,58,65 although this has not been verified in human.

In contrast with the above concerns, extremely high doses (up to 5.4 mg/kg boluses and 4 mg/kg/h infusions) of naloxone have been given to non-opioid dependent subjects without any reported adverse effects.66–68

The aim of this review is to find evidence of the optimum dose and route for administration of naloxone and for how long patients need to be observed before it is safe to discharge them.


METHODS
The Medline and Embase databases were searched using the following terms:

"naloxone or naloxone" and "narcotics or opioid or opiate" or "morphine or buprenorphine or codeine or dextromoramide or diphenoxylate or dipipanone or dextropropoxyphene or diamorphine or dihydrocodeine or alfentenil or fentanyl or remifentanil or meptazinol or methadone or nalbuphine or oxycodone or pentazocine or pethidine or phenazocine or tramadol" and "overdose" or "overdos$" or "poisons" or "poison$" or "acute intoxic$" or "acute toxic$" and limited to human studies.

Studies were deemed to be relevant if they compared doses and routes of administration of naloxone or if they produced evidence about rates and timing of complications. Case histories were reviewed but were included only if they could be reasonably grouped together for comparison.

All papers, including review articles and case histories, had their references scrutinised for further articles that were in turn retrieved and reviewed; this process was repeated until no further articles were found (a total of five rounds).


SEARCH RESULTS
The initial search produced 185 papers; the subsequent series of reference reviews produced 10 relevant articles.65,69–77 These papers are summarised in tables 1 and 2, which can be found on the electronic version of this article.


DISCUSSION
Effect of dose on AWS
AWS include agitation, nausea, vomiting, piloerection, diarrhoea, lacrimation, yawning, and rhinorrhoea; these are generally not life threatening.78 Reported rates of AWS related complications vary widely from 7–46% with 2–4 mg boluses70,72,73,76 to 47% with a median of 0.9 mg;71 however, the actual outcome measures were not directly comparable. Only one study records AWS (12%),72 with one US paper quoting the number of patients (7%) who required restraint (presumably the most severely affected patients)76 and the other studies describing the proportion of patients who discharged against medical advice (18–47%).70,71,73 Patients self discharge for many reasons—for example, fear of police involvement—so that the numbers who do abscond do not necessarily equate to those who experience AWS, although clearly they are no longer narcotised in order to be able to leave the emergency department.

Another potential problem in interpreting the data is the lack of information comparing absolute doses given and rates of administration with AWS, and state of drug dependency/tolerance prior to AWS. Wanger’s study77 stated that the paramedics had the impression that patients who were given naloxone subcutaneously had a smoother emergence than those given it intravenously in spite of a larger dose. It is likely that this is because of a slower increase in concentrations at the receptors, but further research would be needed to confirm this; it may also reflect paramedics’ preference for an easier route of administration.

Effect of dose on recurrence of toxicity
Four papers quote the percentage of patients who require a second dose of naloxone,72,74,76,77 again with marked variation across the world and between centres in the same country. Watson’s72 and Sporer’s76 patients were given 2 mg boluses, and 14% and 35%, respectively, were given a second dose. In Christenson’s74 and Wanger’s77 studies, patients were given either 0.4 mg intravenously or 0.8 mg subcutaneously, with 55% overall having further naloxone in the former study compared with 15% (subcutaneously) and 35% (intravenously) in the latter paper. This marked variation may be explained by the studies having different thresholds for giving further doses of naloxone as opposed to treating the patients conservatively, as well as very different half lives of opioids taken—heroin versus methadone.

Watson72 found that recurrence of toxicity was significantly more likely when long acting opioids were ingested, although route of opioid administration and use of coingestants surprisingly did not have any noticeable effect.

Route of administration of naloxone
Only two papers compared routes of administration.76,77 Both studies used different criteria to define opioid intoxication (in terms of history and clinical findings) and naloxone was given in the prehospital setting; therefore, it is difficult to generalise the findings to other patient populations. In spite of these concerns, Sporer76 showed that 2 mg naloxone intramuscularly works as well as 2 mg intravenously (94% and 90% response rates, respectively); this is perhaps not surprising considering the relatively large dose given and it was not possible to distinguish differences in complication rate between the study groups.

Wanger’s study77 revealed that 0.8 mg naloxone subcutaneously worked as rapidly as 0.4 mg intravenously from time of arrival at the patient’s side to time of clinical effect, because the slower time of effect from administration was offset by not having to gain intravenous access first.

Neither of these studies settles concerns about unpredictable and erratic absorption from the intramuscular/subcutaneous injection sites in those patients who are hypotensive, but they may be useful alternative routes when intravenous access is difficult to obtain. No studies have evaluated the absorption kinetics of intramuscular administration of naloxone. It is likely that variables—including depth of injection, dose given, muscle blood flow, site, and so forth—would all alter the kinetics of absorption by the intramuscular route, particularly in the opioid poisoned patient with hypotension.

Recent case series and reports have suggested that both intranasal79,80 and nebulised81 naloxone may be effective, although they are subject to similar unanswered pharmacokinetic concerns. Also, there is no evidence about the rates of renarcotisation and AWS.

Goldfrank’s study75 provides a good practical dosing guide for patients who require prolonged opioid antagonism. It was a small study where the end point measured plasma naloxone levels and not clinical effect; however, it claimed only to be an initial guide to treatment, and stressed the importance of close observation of the patient and titration of dose as necessary. This makes sense because of individual tolerance and susceptibility to opioids—for example, clinical observation has shown that corpulent patients will absorb opioids into fatty tissues from which it is expected to redistribute out more slowly and such patients tend to need more prolonged naloxone infusions. Further research is required to validate formally and prospectively the Goldfrank protocol.

Timing of complications
Christenson et al74 suggested that if patients fulfilled certain criteria 1 hour after administration of naloxone then they could be discharged safely. However, one of their patients who had taken heroin needed further naloxone after 2 hours and Watson et al72 similarly noted that patients who had taken long acting opioids developed renarcosis up to 2 hours after their initial treatment. Since the half life of naloxone is 60–90 minutes, it would seem logical to observe patients for signs of recurrent toxicity for at least 2 hours, although further studies are needed to validate this.






View larger version (20K):
[in this window]
[in a new window]
Figure 1 Flowchart of treatment of opioid overdose.




With one exception, all other serious complications became apparent within 20 minutes of arrival and treatment in the emergency department.65,70,71 The one exception was a case of fatal pulmonary oedema, where the patient was found dead 7 hours after discharge (9 hours after ingestion of opioid). In this case, further opioid ingestion cannot be ruled out, and in any case it would seem that genuinely delayed adverse events are rare. Because it would be difficult to persuade opioid addicts to stay for 8 hours after they have had naloxone, it would be reasonable to discharge them if they fulfil Christenson’s criteria 2 hours after naloxone.
Research difficulties
The reasons for the dearth of randomised controlled clinical trials have been summarised recently by Whyte et al.82

Legal, political, and ethical difficulties, particularly in the context of obtaining consent, often hinder the recruitment of adequate numbers of patients. In addition, trials would have to be prohibitively large to achieve sufficient power when measuring outcomes that are rare.

It is difficult to eliminate confounding factors, such as the wide range of different opioids, co-ingestants, and adulterants that can be taken, the variety of routes by which they can be taken (orally, intravenously, subcutaneously, nasally, or by smoking), and the complex treatment regimes that are given. It is often difficult to determine what individual patients have taken because usually they do not know.

The external validity of the studies can be questioned because many are undertaken in regional poisons centres whereas most patients are treated in general hospitals where there is limited access to specialised toxochemical laboratory facilities. Similarly, it can be argued that patients who agree to participate in research are not representative of the whole population of opioid overdose patients.

Blinding of treatments is extremely difficult because patients are often in the emergency department for such a short period before they are discharged that the clinician who administers the treatment is usually the one who has to review the response to that treatment.

The research undertaken so far has relied heavily on observational studies, which have a number of well recognised limitations, such as difficulty in minimising confounding factors and retrospective data collection. Studies have often used different inclusion criteria in terms of degrees of sedation and respiratory rate as well as different thresholds for giving further doses of naloxone, which makes direct comparison of studies difficult.

Follow up of patients is difficult; Smith et al70 managed to contact only 32% of the patients who had been discharged. Other studies compared the lists of patients discharged with ambulance service records and death certificates issued by the local coroners. They may have been lost to follow up if they had given misleading demographical details and after discharge were taken to another healthcare facility by private transport, or if they had died later and been given an alternative cause of death.

In spite of these difficulties, a number of conclusions can be drawn but further trials are needed to validate them clinically in the emergency department and thus help clinicians walk the tightrope between over and under treating these patients. Clinical judgement and meticulous observation are required to successfully manage opioid intoxicated patients.


CONCLUSIONS
Although the evidence base is sparse at present, the following algorithm has been devised to summarise the research in a way that is clinically useful. References have been included where relevant otherwise the recommendations are based on consensus derived from the clinical experience of Medical Toxicology Units in Europe, the USA, and Australia. Although recent studies have suggested that intranasal and nebulised naloxone may be useful alternatives to parenteral administration, the authors think that the evidence is not strong enough yet to add them to the algorithm; however, they could be easily included in the flowchart as further evidence becomes available.

Opioid overdose is a challenging condition that requires a difficult balancing act between over and under treatment with naloxone.


FOOTNOTES
Competing interests: none declared


REFERENCES


Chamberlain JM, Klein BL. A comprehensive review of naloxone for the emergency physician. Am J Emerg Med 1994;12:650–60.[CrossRef][Medline]

Sporer KA. Acute heroin overdose. Ann Intern Med 1999;130:584–9.[Abstract/Free Full Text]

Christenson J, Etherington J, Grafstein E, et al. Early discharge of patients with presumed opioid overdose: development of a clinical prediction rule. Acad Emerg Med 2000;7:1110–18.[Abstract/Free Full Text]

Cherubin CE. The medical sequelae of narcotic addiction. Ann Intern Med 1967;67:23–33.[Medline]

Larpin R, Vincent A, Perret C. Hospital morbidity and mortality of acute opiate intoxication. Presse Med 1990;19:1403–6.[Medline]

Bateman DN, Bain M, Gorman D, et al. Changes in paracetamol, antidepressants and opioid poisoning in Scotland during the 1990s. QJM 2003;96:125–32.[Abstract/Free Full Text]

Flanagan RJ, Rooney C. Recording acute poisoning deaths. Forensic Sci International 2002;128:3–19.[CrossRef]

Sadove MS, Balagot RC, Hatano S, et al. Study of a narcotic antagonist – n-allyl-noroxymorphone. JAMA 1963;183:666–8.[Medline]

Howland MA. Opioid antagonists. In: Goldfrank LR, Flomenbaum NE, Lewin NA, Hoffman RS, eds. Goldfrank’s Toxicological Emergencies. 5th ed. Appleton and Lange 1998.

Melichar JK, Nutt DJ, Malizia AL. Naloxone displacement at opioid receptor sites measured in vivo in the human brain. Eur J Pharmacol 2003;459:217–19.[CrossRef][Medline]

Allen SC. Problems with naloxone (letter). BMJ 1975;3:434.

Moore RA, Rumack BH, Conner CS, et al. Naloxone after narcotic poisoning. Am J Dis Child 1980;134:156–8.[Abstract]

Schneir AB, Vadeboncoeur TF, Offerman SR, et al. Massive OxyContin ingestion refractory to naloxone therapy. Ann Emerg Med 2002;40:425–8.[CrossRef][Medline]

Waldron VD, Klimt CR, Seibel JE. Methadone overdose treated with naloxone infusion. JAMA 1973;225:53.[CrossRef][Medline]

Bradberry JC, Raebel MA. Continuous infusion of naloxone in the treatment of narcotic overdose. Drug Intell Clin Pharm 1981;15:945–50.[Abstract]

Redfern N. Dihydrocodeine overdose treated with naloxone infusion. BMJ 1983;287:751–2.[Medline]

Gourlay GK, Coulthard K. The role of naloxone infusions in the treatment of overdoses of long half-life narcotic agonists: application to nor-methadone. Brit J Clin Pharm 1983;15:269–72.[Medline]

Lewis JM, Klein-Schwartz W, Benson BE, et al. Continuous naloxone infusion in pediatric narcotic overdose. AJDC 1984;138:944–6.[Medline]

Tenenbein M. Continuous naloxone infusion for opiate poisoning in infancy. J Pediatr 1984;105:645–8.[CrossRef][Medline]

Romac DR. Safety of prolonged, high-dose infusion of naloxone hydrochloride for severe methadone overdose. Clin Pharm 1986;5:251–4.[Medline]

Hendra TJ, Gerrish SP, Forrest ARW. Fatal methadone overdose. BMJ 1996;313:481–2.[Free Full Text]

Sachdeva DK, Jolly BT. Tramadol overdose requiring prolonged opioid antagonism. Am J Emerg Med 1997;15:217–18.[CrossRef][Medline]

Wikler A, Fraser HF, Isbell H. N-allylnormorphone: effects of single doses and precipitation of acute "abstinence syndromes" during addiction to morphine, methadone or heroin in man (post-addicts). J Pharmacol Exp Ther 1953;109:8–20.[Free Full Text]

Evans LEJ, Roscoe P, Swainson CP, et al. Treatment of drug overdosage with naloxone, a specific narcotic antagonist. Lancet 1973;I:452–5.

Buchwald A. Naloxone use: side effects may occur (letter). Ann Emerg Med 1988;17:765.

Popper C, Kelen GD, Cunningham G. Naloxone hazard in drug abuser. Lancet 1989;8669:446.

Gibbs J, Newson T, Williams J, et al. Naloxone hazard in infant of opioid abuser (letter). Lancet 1989;8655:159.

Gaddis G, Watson WA. Naloxone-associated patient violence: an overlooked toxicity? Ann Pharmacotherapy 1992;26:196–7.[Abstract]

Longnecker DE, Grazis PA, Eggers GWN. Naloxone for antagonism of morphine-induced respiratory depression. Anesth Analg 1973;52:447–52.[Medline]

Cohen MR, Cohen RM, Pickar D, et al. Behavioural effects after high dose naloxone administered to normal volunteers (letter). Lancet 1981;8255:1110.

Evans JM, Hogg MIJ, Lunn JN, et al. Degree and duration of reversal by naloxone of effects of morphine in conscious subjects. BMJ 1974;2:589–91.[Medline]

Berkowitz BA. The relationship of pharmacokinetics to pharmacological activity: morphine, methadone and naloxone. Clin Pharmacokinetics 1976;1:219–30.[Medline]

Flacke JW, Flacke WE, Williams GD. Acute pulmonary edema following naloxone reversal of high-dose morphine anesthesia. Anesthesiology 1977;47:376–8.[CrossRef][Medline]

Taff RH. Pulmonary edema following naloxone administration in a patient without heart disease. Anesthesiology 1983;59:576–7.[Medline]

Prough DS, Roy R, Bumgarner J, et al. Acute pulmonary edema in healthy teenagers following conservative doses of intravenous naloxone. Anesthesiology 1984;60:485–6.[Medline]

Partridge BL, Ward CF. Pulmonary edema following low-dose naloxone administration. Anesthesiology 1986;65:709–10.[Medline]

Harrington LW. Acute pulmonary edema following use of naloxone: a case study. Crit Care Nurs 1988;8:69–73.

Wride SRN, Smith RER, Courtney PG. A fatal case of pulmonary oedema in a healthy young male following naloxone administration. Anaesth Intens Care 1989;17:374–7.[Medline]

Brimacombe J, Archdeacon J, Newell S, et al. Two cases of naloxone-induced pulmonary oedema – possible use of phentolamine in management. Anaesth Intens Care 1991;19:578–80.[Medline]

Schwartz JA, Koenigsberg MD. Naloxone-induced pulmonary edema. Ann Emerg Med 1987;16:1294–6.[CrossRef][Medline]

Louria DB, Hensle T, Rose J. The major medical complications of heroin addiction. Ann Intern Med 1967;67:1–22.[Medline]

Steinberg AD, Karliner JS. The clinical spectrum of heroin pulmonary edema. Arch Intern Med 1968;122:122–7.[CrossRef][Medline]

Gopinathan K, Saroja D, Spears JR, et al. Hemodynamic studies in heroin induced acute pulmonary edema. Circulation 1970;42 (supplement) :44.

Duberstein JL, Kaufman DM. A clinical study of an epidemic of heroin intoxication and heroin-induced pulmonary edema. Am J Med 1971;51:704–14.[CrossRef][Medline]

Fraser DW. Methadone overdose. JAMA 1971;217:1387–9.[CrossRef][Medline]

Bogartz LJ, Miller WC. Pulmonary edema associated with propoxyphene intoxication. JAMA 1971;215:259–62.[CrossRef][Medline]

Frand UI, Shim CS, Williams MH. Methadone-induced pulmonary edema. Ann Intern Med 1972;76:975–9.[CrossRef][Medline]

Robin ED, Cross CE, Zelis R. Pulmonary edema. N Eng J Med 1973;288:292–302.[Medline]

Lusk JA, Maloley PA. Morphine-induced pulmonary edema (letter). Am J Med 1988;84:367–8.[CrossRef][Medline]

Dettmeyer R, Schmidt P, Musshoff F, et al. Pulmonary edema in fatal heroin overdose: immunohistological investigations with IgE, collagen IV and laminin – no increase of defects of alveolar-capillary membranes. Forensic Sci International 2000;110:87–96.[CrossRef]

Allen T. No adverse reaction (letter). Ann Emerg Med 1989;18:116.

Mariani PJ. Seizure associated with low-dose naloxone (letter). Am J Emerg Med 1989;7:127–8.[CrossRef][Medline]

Michaelis Michaelis LL, Clark TA, Dixon WM. Ventricular irritability associated with the use of naloxone hydrochloride. Ann Thorac Surg 1974;18:608–14.[Medline]

Lawrence JR, Lee FR. Ventricular fibrillation after narcotic withdrawal (letter). Lancet 1975;2:717.

Andree RA. Sudden death following naloxone administration. Anesth Analg 1980;59:782–4.[Medline]

Cuss FM, Colaco CB, Baron JH. Cardiac arrest after reversal of effects of opioids with naloxone. BMJ 1984;288:363–4.[Medline]

Merigian KS. Cocaine-induced ventricular arrhythmias and rapid atrial fibrillation temporally related to naloxone administration. Am J Emerg Med 1993;11:96–7.[CrossRef][Medline]

Labi M. Paroxysmal atrial fibrillation in heroin intoxication. Ann Intern Med 1969;71:951–9.[Medline]

Tanaka GY. Hypertensive reaction to naloxone (letter). JAMA 1974;228:25–6.[CrossRef]

Azar I, Turndorf H. Severe hypertension and multiple atrial premature contractions following naloxone administration. Anesth Analg 1979;58:524–5.[Medline]

Estilo AE, Cottrell JE. Naloxone, hypertension, and ruptured cerebral aneurysm (letter). Anesthesiology 1981;54:352.[Medline]

Ward S, Corall IM. Hypertension after naloxone (letter). Anaesthesia 1983;83:1000–1.

Levin ER, Sharp B, Drayer JIM, et al. Case report: severe hypertension induced by naloxone. Am J Med Sci 1985;290:70–2.[Medline]

Mannelli M, Maggi M, De Feo ML, et al. Naloxone administration releases catecholamines (letter). N Engl J Med 1983;308:645–6.

Osterwalder JJ. Naloxone – for intoxications with intravenous heroin and heroin mixtures – harmless or hazardous? A prospective clinical study. J Toxicol Clin Toxicol 1996;34:409–16.[Medline]

Gurll NJ, Reynolds DG, Vargish T, et al. Naloxone without transfusion prolongs survival and enhances cardiovascular function in hypovolaemic shock. J Pharmacol Exp Ther 1982;220:621–4.[Abstract/Free Full Text]

Groeger JS, Inturrisi CE. High-dose naloxone: pharmacokinetics in patients in septic shock. Crit Care Med 1987;15:751–6.[Medline]

Bracken MB, Shepard MJ, Collins WF, et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. N Engl J Med 1990;322:1405–11.[Abstract]

Yealy DM, Paris PM, Kaplan RM, et al. The safety of prehospital naloxone administration by paramedics. Ann Emerg Med 1990;19:902–5.[CrossRef][Medline]

Smith DA, Leake L, Loflin JR, et al. Is admission after intravenous heroin overdose necessary? Ann Emerg Med 1992;21:1326–30.[CrossRef][Medline]

Osterwalder JJ. Patients intoxicated with heroin or heroin mixtures: how long should they be monitored? Eur J Emerg Med 1995;2:97–101.[CrossRef][Medline]

Watson WA, Steele MT, Muelleman RL, et al. Opioid toxicity recurrence after an initial response to naloxone. J Toxicol Clin Toxicol 1998;36:11–17.[Medline]

Vilke GM, Buchanan J, Dunford JV, et al. Are heroin overdose deaths related to patient release after prehospital treatment with naloxone? Prehosp Emerg Care 1999;3:183–6.[Medline]

Christenson J, Etherington J, Grafstein E, et al. Early discharge of patients with presumed opioid overdose: development of a clinical prediction rule. Acad Emerg Med 2000;7:1110–18.[Abstract/Free Full Text]

Goldfrank L, Weisman RS, Errick JK, et al. A dosing nomogram for continuous infusion intravenous naloxone. Ann Emerg Med 1986;15:566–70.[CrossRef][Medline]

Sporer KA, Firestone J, Isaacs M. Out-of-hospital treatment of opioid overdoses in an urban setting. Acad Emerg Med 1996;3:660–7.[Abstract]

Wanger K, Brough L, Macmillan I, et al. Intravenous vs subcutaneous naloxone for out-of-hospital management of presumed opioid overdose. Acad Emerg Med 1998;5:293–9.[Abstract]

Chiang WK, Goldfrank LR. Substance withdrawal. Emerg Clin North Am 1990;8:613–32.

Barton ED, Ramos J, Colwell C, et al. Intranasal administration of naloxone by paramedics. Prehospital Emergency Care 2002;6:54–8.[Medline]

Kelly A-M, Koutsogiannis Z. Intranasal naloxone for life threatening opioid toxicity (letter). Emerg Med J 2002;19:375.[Free Full Text]

Mycyk MB, Szyszko AL, Aks SE. Nebulized naloxone gently and effectively reverses methadone intoxication. J Emerg Med 2003;24:185–7.[CrossRef][Medline]

Whyte IM, Buckley NA, Dawson AH. Data collection in clinical toxicology: are there too many variables. J Toxicol Clin Toxicol 2002;40:223–30.[CrossRef][Medline]

http://emj.bmj.com/cgi/content/full/22/9/612

[zinger]

http://www.medsafe.govt.nz/profs/PUarticles/methadone.htm

All about the sudden heart attack risk - if you're old, female, dehydrated, on a range of other pills including most antidrepessants, on over 100mg or on it over 2 months.... and you get palpitations or feel faint - get to ER (and best not drive).

Round ?122 deaths reported tho its thought many dying of this would just be written off as ODs if no-one saw them go from fine one minute to cardiac arrest next. Prolly why this major issue not uncovered earlier.

[Melis11577]

Increases in Methadone-Related Deaths: 1999-2004
by Lois A. Fingerhut, Office of Analysis and Epidemiology

Introduction

Poisoning deaths include those resulting from accidental overdoses of a drug, being given the wrong drug, taking the wrong drug in error, or taking a drug inadvertently. Poisoning also includes deaths that are unintentional, intentional, or of undetermined intent from ingestion of other solid or liquid substances, or exposure to or inhalation of gases or vapors (1). Such deaths can be defined either by their International Classification of Diseases and Related Health Problems (ICD)-10th revision external cause of injury codes or by their ICD-10 diagnosis codes. The external cause codes have two dimensions that indicate: 1) the broad categories of substances involved such as drugs, alcohol, or other solid or liquid biological substances, gases or vapors, or other substances such as pesticides or unspecified chemicals; and 2) the intentionality of the death, reflecting whether the death was certified as unintentional, a suicide, homicide or legal intervention, or of undetermined intent. The ICD-10 external cause codes used to define poisoning as an underlying cause of death include X40-X49, X60-X69, X85-X90, Y10-Y19, Y35.2 or *U01(.6-.7). These are the codes that have been adopted internationally to define poisoning in the external cause of injury matrix for ICD-10.

Poisoning diagnosis codes are used in conjunction with external cause codes to identify the specific substance(s) or agent(s) responsible. A poisoning death can have one or multiple substances listed on the death certificate; the ICD-10 codes range from T36.0-T65.9. While these codes help to describe a poisoning-related underlying cause, they are not used for underlying cause of death coding (2). Rather, the corresponding external cause code will be designated as the underlying cause.

Methadone is classified separately from other opiates and related narcotics in ICD-10, which has been in use in the United States since 1999, but was not classified separately in ICD-9. Vital statistics data from the period 1999-2004, therefore, provide the first opportunity to examine a 6-year trend in methadone-related deaths in this country. The ICD-10 code for methadone is T40.3. This drug is listed within the overall category, ICD-10 T40, for “Poisoning by narcotics and psychodysleptics (hallucinogens).”

Since 1999, between 73 and 79 percent of poisoning deaths mentioning methadone have been classified as unintentional (3,202 such deaths in 2004), with an additional 11-13 percent being of undetermined intent, 5-7 percent as suicides, less than 1 percent as homicides, and about 1 percent were injuries other than poisoning. Over this same period, only 4-6 percent of deaths where methadone was mentioned were not coded as injury deaths (Table 1).

Trends

The number of all poisoning deaths increased 54 percent to 30,308 over the 1999-2004 period, while the number of poisoning deaths mentioning methadone increased 390 percent to 3,849 (Figure 1). Poisoning deaths mentioning methadone increased from 4 percent of all poisoning deaths to 13 percent of all poisoning deaths. Most recently, all poisoning deaths increased 6 percent from 2003-04, while those mentioning methadone increased 29 percent.

Of all narcotics (ICD-10 T40.0-T40.9) mentioned in poisoning deaths, methadone had the largest relative increases. The absolute number of poisoning deaths mentioning methadone was less, however, than the number of deaths mentioning cocaine (ICD-10 T40.5) or other opioids (T40.2). Other opioids include pain relief drugs such as oxycodone and hydrocodone among others (Table 2). The relative increase in methadone-related poisoning deaths from 1999 to 2004 was greater than for any individual substance in the T36-T65 range of codes (data available upon request).

Age

Age specific rates of methadone death are higher for persons age 35-44 and 45-54 years than for those younger or older. This pattern has been true for most of the 1999-2004 period (Figure 2). Admittedly, the rates are quite low relative to all poisoning, but the patterns are similar in that the rates are high for those in middle-age groups. Among those age 55-64 years, the rate in 2004 was seven times the rate in 1999; for those in each of the 10-year age groups covering the span 25-54 years, the rates in 2004 were 3-5 times the rates in 1999. The largest increase, however, is noted for young persons 15-24 years; the rate in 2004 was 11 times that in 1999.

Table 3 shows data for all deaths for which the underlying cause was unintentional poisoning with a mention of methadone. The number of these deaths increased 414 percent to 3,202 over the 1999-2004 period; that is, the number of deaths in 2004 was five times the number in 1999. State specific comparisons should be interpreted with caution as many of the State-specific data are based on very small numbers. Therefore rather than provide a state-by-state ranking, Table 2 subdivides the states into groups based on ratio ranges (ratio of deaths in 2004 to those in 1999) and then orders the states within the groups alphabetically.

Following are examples of 1999-2004 ratios in states with “large” numbers of methadone–related deaths (greater than 50 for at least 3 of the 6 years): West Virginia (25:1), Kentucky (15:1), Florida and Oregon (14:1), North Carolina and Texas (7:1), Virginia (6:1) and Washington (5:1). New York showed no overall change during the 6 years (1:1).

References

1. World Health Organization. International Statistical Classification of Diseases and Related Health Problems (Tenth revision), volume 1. Geneva, World Health Organization. 1992.

2. Miniño AM, Anderson RN, Fingerhut LA, Boudreault MA, Warner M. Deaths: Injuries, 2002. National vital statistics reports; vol 54 no 10. Hyattsville, Maryland: National Center for Health Statistics. 2006.


NCHS Home | Health E-Stats Home
CDC/NCHS Privacy Policy Notice | Accessibility
Search NCHS | NCHS Definitions | Contact us



CDC Home | Search | Health Topics A-Z


This page last reviewed December 21, 2006


U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Centers for Disease Control and Prevention
National Center for Health Statistics
Hyattsville, MD
20782

(301) 458-4000 or 1-866-441-NCHS

http://tinyurl.com/yyfu5x

[Melis11577]

Methadone - Friend or Foe?
by Dr. Clifford Bernstein

The United States has added yet another menacing substance to the ever-growing problem of drug abuse. Methadone, a medication typically used as replacement or maintenance for opiate-dependent patients, has become the substitute drug of choice for heroin and the popular painkiller turned street drug, OxyContin.

The Drug Abuse Warning Network reported that across the nation, Methadone-related incidents requiring emergency room treatment has increased 37 percent between 2000 and 2001. Florida saw an 80 percent increase in Methadone related deaths in the same period, and North Carolina's fatalities increased eight times from 1997 to 2001. Virginia is witnessing similar trends, and data predicts that we will soon be seeing significantly more Methadone-related abuse than OxyContin.

Like Vicodin and Lortab, the frequency in which Methadone is being prescribed for pain is also increasing. Patients who were prescribed Methadone by their physicians to treat the pain of common ailments such as chronic back pain, sports-related injuries, or migraine headaches, are now seeking treatment for a dependency on a drug that was originally intended to help them.

For many years, Methadone was not considered an addictive threat because of the length of time (several hours) between taking it and experiencing the narcotic effect. Additionally, it has a sedative, rather than stimulant, effect. As an opiate-based painkiller, Methadone can serve as an adequate stand-in for heroin or OxyContin. This can be extremely dangerous due to the delayed and subtle effect of the "high". People can overdose because they don't anticipate or feel the actual damage being done until it is too late.

Methadone has become more widely available in recent years, due in part to the increased number of clinics using Methadone to treat heroin and OxyContin addictions. This makes it difficult to determine whether the drug is friend or foe. Ryan Curry, a 21 year-old Maine resident, began taking OxyContin to get high with his friends several years ago. Like many people who use OxyContin recreationally and for medical purposes, his body became dependent. Ryan decided he wanted to break his dependency so he sought treatment at a local Methadone clinic. Ryan was put on a low dose of Methadone to replace the OxyContin he had been abusing. As he became tolerant of the effects of the Methadone, doctors gradually increased his dose.
Ryan continued to take the Methadone supplied to him by the clinic for two years with his prescribed dose having more than quadrupled during that time.

"I couldn't understand why they kept increasing my dose when I was supposed to be getting the drugs out of my system," said Ryan. "My body would grow accustomed to the dose and I would need it increased just to make it through the day. It was not helping me."

Methadone treatment facilities traditionally service the patient on an outpatient basis, administering medication with a drive-thru mentality. A patient's vulnerability, compounded by a lack of sufficient medical supervision and psychological support, can sometimes result in the emergence of the new dependency. More so, a doctor may have difficulty judging the proper Methadone dose for a first-time user. Additionally, patients are escalated to Methadone doses much higher than the original opiate in order to allow for 24-hour dosing. The consequence of this is that Methadone patients are much more difficult to detox.

Ryan left the clinic and was treated at the Beverly Hills-based Waismann Institute, through the Waismann Method of Accelerated Neuro-Regulation. This procedure cleansed his brain's opiate receptors of the opiates in a few hours in the intensive care unit of a hospital. He now takes a monitored dose of Naltrexone, a non-addictive, non-mood altering drug which prevents him from feeling cravings for Methadone, and should he take Methadone, OxyContin, or other opiates, Naltrexone will thwart the narcotic effect.

Experts argue that people who are prescribed Methadone for dependency on heroin or another opiate can lead normal lives and should be praised for giving up their addictions. However, these people may need to take Methadone forever, unable to function without it. Like any other dependency, quitting Methadone can cause withdrawal symptoms because the user is still dependent on opiates. Fundamentally, Methadone treatment neither addresses nor reverses the core issue of dependency, and studies of former heroin dependents have shown that withdrawal from heroin was far less excruciating and lengthy than withdrawal from Methadone.

Is substituting one form of dependency for another really the way to approach this life-threatening problem?

For more information, please call (310) 205-0808 or (888) 987-HOPE or send us a confidential email.

[Melis11577]

http://hsgac.senate.gov/_files/080603burton.pdf

[Melis11577]

http://www.communityhealth.dhhs.state.nc.us/Injury/unintentional%20poisonings%20report-9-02-final.pdf

[Melis11577]

Substance Abuse in Brief Fact Sheet
Summer 2006, Volume 4, Issue 1

Center for Substance Abuse Treatment
Substance Abuse and Mental Health Services Administration (SAMHSA)
U.S. Department of Health and Human Services (HHS)

Pain Management Without Psychological Dependence: A Guide for Healthcare Providers
More than half of adults in the United States experienced chronic or recurrent pain in 2003 (Peter D. Hart Research Associates 2003). Effective management of pain not only reduces suffering, but also improves sleep, reduces affective stress, and increases levels of daily functioning (Roper Public Affairs & Media 2004; Schneider 2005). This publication will assist healthcare providers in understanding that opioid medications can effectively manage pain, distinguishing between physical and psychological dependence, and reducing their patients’ risk of psychological dependence on opioids during pain management.

Nonopioid Pain Management
Pain ManagementWith Opioid Medications
Physical Dependence, Psychological Dependence, and Pseudoaddiction
Reducing the Risk of Psychological Dependence on Opioids
What To Do if Opioid Abuse or Dependence Is Suspected
Possible Signs of Inappropriate Opioid Use by Patients
How To Talk to Patients With Pain About Substance Use Problems
Resources
Ordering Information
Substance Abuse in Brief Fact Sheet
References


--------------------------------------------------------------------------------

Nonopioid Pain Management

When patients present with chronic pain, providers should first offer patients one of several nonopioid pharmacological treatments. Acetaminophen and nonsteroidal anti-inflammatory medications can be used alone to treat mild to moderate pain or in combination with opioids to treat more severe pain (American Chronic Pain Association 2005; Hansen 2005; Jones et al. 2003; Strassels et al. 2005). Topical and injected anesthetics can also provide pain relief (Beers 2004–2005; Hainline 2005; Wisconsin Medical Society 2004). Adjuvant medication, such as antidepressants, anticonvulsants, steroids, anxiolytics, and muscle relaxants, can also be considered for pain relief (American Chronic Pain Association 2005; Beers 2004–2005; Hainline 2005; Hansen 2005; Wisconsin Medical Society 2004). Many medications with proven efficacy in pain management have also established potential for abuse and possible progression to psychological dependence. This potential for abuse requires some caution in their short- and long-term use that initially may increase a clinician’s reluctance to appropriately use medication that might be required to alleviate pain.

Complementary nonpharmacological approaches should also be employed, especially when longer term pain management is needed. Cognitive–behavioral techniques, such as relaxation training, biofeedback, stress management, and self-hypnosis (Beers 2004–2005; Hainline 2005; Jones et al. 2003) have been shown to increase pain thresholds, thus reducing the necessity for pharmacological treatments. Acupuncture, physical therapy, and neurostimulatory treatments can also effectively manage pain (Beers 2004–2005; Hainline 2005; Hansen 2005; Jones et al. 2003; Primm et al. 2004).


--------------------------------------------------------------------------------
Pain Management With Opioid Medications
Providers can also prescribe opioids, such as fentanyl, hydrocodone, morphine, and oxycodone, alone or in combination with nonopioid treatments for pain relief. Opioids have been shown to effectively reduce cancer and acute pain, and most clinicians believe they also share a role in the management of chronic pain (Bloodworth 2005; Christo et al. 2004; Coluzzi and Mattia 2005). Healthcare providers may be reluctant to prescribe opioids to treat pain (Morley-Forster et al. 2003), especially for patients with substance use disorders (Cook et al. 2004). Reluctance may stem from inadequate training in pain management and/or addiction medicine, a lack of clinical practice guidelines that address pain management in patients with a substance use disorder, or fear of sanctions from regulatory agencies (Gourlay et al. 2005; Primm et al. 2004). Concerns about side effects, such as functional impairment and physical inactivity (Morley-Forster et al. 2003), and concerns about physical or psychological dependence (Cook et al. 2004; Morley-Forster et al. 2003) may also discourage providers from prescribing opioids to treat pain.


--------------------------------------------------------------------------------

Physical Dependence, Psychological Dependence, and Pseudoaddiction

Although most people being treated for pain with opioids do not become psychologically dependent1 on opioids (Coluzzi and Pappagallo 2005; Lussier and Pappagallo 2004; Strassels et al. 2005), some may become physically dependent on the medication. Physical dependence is often a natural part of the long-term use of opioids prescribed for pain and can be managed effectively with appropriate identification and treatment (Coluzzi and Pappagallo 2005; Heit 2003; Strassels et al. 2005). Distinguishing between physical and psychological dependence on opioids is critical for the well-being of the patient. Physical dependence is a physiological adaptation to a substance, defined by a growing tolerance for its effects and/or withdrawal symptoms when use is reduced or ends (American Psychiatric Association 2000). Psychological dependence is a primary, chronic, neurobiological disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations (Heit 2003). It may occur with or without physical dependence and is conceptually characterized by impaired control over drug use, compulsive use, continued use despite harm, and craving for the psychic effects of the drug (American Academy of Pain Medicine et al. 2001; American Psychiatric Association 2000; Heit 2003; Strassels et al. 2005).

Determining a diagnosis of psychological dependence on opioids in the context of pain management requires careful evaluation; behaviors suggestive of psychological dependence may be due to pain that is undertreated. Commonly, this has been referred to as pseudoaddiction—problem drug behaviors that are due to undertreated pain—and is often difficult to distinguish from psychological dependence on opioids (Alford et al. 2006; Christo et al. 2004; Coluzzi and Pappagallo 2005; Heit 2003; Savage 2002; Strassels et al. 2005; Weaver and Schnoll 2002). A patient who seems preoccupied with maintaining an adequate, continuous supply of medication or who spends a great deal of time trying to obtain additional medications may be seeking only pain relief (Alford et al. 2006; Christo et al. 2004; Heit 2003; Weaver and Schnoll 2002). Suspected inadequate pain management requires a comprehensive reassessment of the patient and changes to the treatment plan. When pain is adequately treated, pseudoaddictive behaviors should cease (Heit 2003).


--------------------------------------------------------------------------------

Reducing the Risk of Psychological Dependence on Opioids

Psychological dependence not only can hinder the effective treatment of pain, but also can lead to increased pain and related health and social effects (Currie et al. 2003). The following are recommended to reduce the risk of opioid psychological dependence while providing effective pain management:

Obtain relevant patient background information (Cole 2002; Dews and Mekhail 2004; Savage 2002). Be aware of patients with a history of personal or familial problems with alcohol or drugs, legal problems, or misuse of prescription drugs; they have an increased chance of becoming psychologically dependent on opioids prescribed for pain (Michna et al. 2004; Savage 2002).
Use screening instruments to identify patients who are at risk or may be opioid dependent. Use the Opioid Risk Tool (Webster and Webster 2005), the Pain Medication Questionnaire (Adams et al. 2004), the Screener and Opioid Assessment for Patients with Pain (Butler et al. 2004), and the Screening Tool for Addiction Risk (Friedman et al. 2003) to identify patients in pain who are at risk for addiction.
Document appropriately. Have patients sign an agreement outlining the risks and benefits of the proposed treatment plan (Federation of State Medical Boards 2004; Gourlay et al. 2005), the objectives that will be used to determine treatment success (Federation of State Medical Boards 2004), the policy for medication refills and laboratory testing, and patient responsibility for opioid prescriptions (Bloodworth 2005; Cole 2002; Dews and Mekhail 2004; Hansen 2005; Passik and Kirsh 2005; Primm et al. 2004; Schnoll and Weaver 2003; Weaver and Schnoll 2002). Maintain comprehensive records of each visit, including medication dose, effectiveness of dose, and concerns about inappropriate use (Cole 2002; Dews and Mekhail 2004; Wisconsin Medical Society 2004).
Manage medications. Use the minimum dose necessary to provide adequate pain relief (Cole 2002; Hansen 2005; Primm et al. 2004; Schnoll and Weaver 2003; Weaver and Schnoll 2002). Instruct patients to use only one pharmacy to decrease the chance of medication abuse (Cole 2002; Primm et al. 2004; Schnoll and Weaver 2003).
Monitor patients closely for symptoms of physical and psychological dependence. Continually evaluate whether pain is being managed effectively and treatment goals are being met by observing and documenting the “four As”: analgesia, activities of daily living, adverse effects, and aberrant behaviors (Gourlay et al. 2005; Passik and Kirsh 2005; Primm et al 2004; Schneider 2005).

--------------------------------------------------------------------------------

Possible Signs of Inappropriate Opioid Use by Patients

Patients taking opioids appropriately for pain management and those whose pain is inadequately relieved may occasionally display the behaviors listed below. However, the possibility of psychological dependence should be considered when a pattern of one or more of these behaviors is observed in patients.

Multiple episodes of “lost” or stolen prescriptions
Repeatedly running out of medication early
Aggressive complaints about the need for additional prescriptions
Drug hoarding during periods of reduced symptoms
Urgent calls or unscheduled visits
Injecting opioids intended for oral use
Using the medication to achieve euphoric effects
Unapproved use of prescribed opioid to self-medicate another problem, such as insomnia
Frequently missing appointments unless opioid renewal is expected
Unwillingness to try nonopioid treatments
Evidence of withdrawal symptoms visible at appointments
Concurrent alcohol or illicit drug abuse
Sedation, declining activity, sleep disturbances, or irritability unexplained by the pain or other co-occurring conditions
Deterioration of functioning at work, with family, or socially because of medication effects
Forging prescriptions or obtaining prescriptions from nonmedical or multiple medical sources
Selling prescription medicines
Sources: Breivik 2005; Coluzzi and Pappagallo 2005; Lussier and Pappagllo 2004; Primm et al. 2004; Savage 2002; Schneider 2005; Weaver and Schnoll 2002.


--------------------------------------------------------------------------------

What To Do if Opioid Abuse or Dependence Is Suspected

People diagnosed with either substance abuse or dependence can be effectively treated for pain—even with opioids—provided their substance use disorder is addressed (Passik and Kirsh 2004). Healthcare providers who are treating patients for pain who are known to be or suspected of being psychologically dependent on opioids or other drugs should follow these guidelines to promote effective pain management treatment:

Immediately address the substance use problem (Passik and Kirsh 2004, 2005; Weaver and Schnoll 2002).
Increase monitoring. Initiate more frequent visits, and limit the amount of medication available at one time (Coluzzi and Pappagallo 2005; Jones et al. 2003; Lussier and Pappagallo 2004; Passik and Kirsh 2004; Savage 2002; Weaver and Schnoll 2002). Random urine drug tests detect the presence of illicit drugs or substances not prescribed for pain management and verify that the patient is taking the prescribed opioid instead of selling it (Coluzzi and Pappagallo 2005; Lussier and Pappagallo 2004; Passik and Kirsh 2004; Weaver and Schnoll 2002).
Include treatment for substance dependence in the pain management plan. Refer to a certified substance abuse treatment provider, initiate appropriate medication-assisted treatment, and/or encourage participation in 12-Step programs (Compton and Athanasos 2003; Passik and Kirsh 2004; Savage 2002; Weaver and Schnoll 2002). With the patient’s permission, consult and coordinate with the designated substance abuse treatment provider on an ongoing basis (Compton and Athanasos 2003; Jones et al. 2003; Lussier and Pappagallo 2004; Savage 2002; Weaver and Schnoll 2002).
Discontinue opioid treatment when warranted. Providing opioid analgesia to patients who are psychologically dependent does not necessarily worsen their dependence, nor will withholding opioids increase their likelihood of recovery (Alford et al. 2006; Compton and Athanasos 2003). However, unrelieved pain can trigger relapse (Alford et al. 2006; Compton and Athanasos 2003; Gourlay et al. 2005). Opioid therapy should be discontinued if more serious problems occur, such as prescription forgery, diversion of opioids, or continued inappropriate opioid use (Coluzzi and Pappagallo 2005; Lussier and Pappagallo 2004; Weaver and Schnoll 2002). If discontinuation is called for, the opioid dosage should be tapered to avoid withdrawal symptoms and other forms of nonopioid pain treatment should be offered (Weaver and Schnoll 2002).

--------------------------------------------------------------------------------

How To Talk to Patients With Pain About Substance Use Problems

Be nonjudgmental—patients are more likely to be forthcoming.
Start with sweeping questions (e.g., “How helpful have your medications been for you?”) rather than begin with questions about medication misuse.
Avoid yes/no questions that do not allow patients to express their feelings.
Ask questions about warning signs (e.g., “Have you ever taken your pain medication for other reasons?”).
Listen to what patients says about how and why they take their medications.
Inquire about their willingness to try alternative, nonopioid forms of pain therapy.
Use existing tools such as the screening instruments discussed above.
Source: Passik and Kirsh 2005.

--------------------------------------------------------------------------------

Resources

Definitions Related to the Use of Opioids for the Treatment of Pain provides uniform definitions of terms relating to substance use disorders in the context of opioid pain management that were agreed on by three national organizations, the American Academy of Pain Medicine, the American Pain Society, and the American Society of Addiction Medicine (www.painmed.org/productpub/statements/pdfs/definition.pdf).
The Federation of State Medical Boards’ Model Policy for the Use of Controlled Substances for the Treatment of Pain, produced in collaboration with pain experts across the country, provides guidance to State medical boards in developing pain policies and regulations (www.fsmb.org/pdf/2004_grpol_Controlled_Substances.pdf).
The Federation of State Medical Boards’ Model Policy Guidelines for Opioid Addiction Treatment in the Medical Office, developed under contract with the Substance Abuse and Mental Health Services Administration’s (SAMHSA’s) Center for Substance Abuse Treatment, provides a framework for developing rules and regulations overseeing the office-based treatment of opioid addiction (www.fsmb.org/pdf/2002_grpol_Opioid_Addiction_Treatment.pdf).
The American Medical Association’s Pain Management: The Online Series offers 12 continuing medical education modules including “Assessing and Treating Pain in Patients with Substance Abuse Concerns” (www.ama-cmeonline.com).
The Wisconsin Medical Society’s Guidelines for the Assessment and Management of Chronic Pain provides guidelines on how to treat chronic pain using both opioid and nonopioid treatments (www.wisconsinmedicalsociety.org/uploads/wmj/pain_manageguides.pdf).
Each State has offices that provide information about licensed treatment programs (visit findtreatment.samhsa.gov/ufds/abusedirectors and www.mentalhealth.samhsa.gov/publications/allpubs/SMA01-3509/page4.asp). SAMHSA’s Substance Abuse Treatment Facility Locator can also help identify treatment centers (www.findtreatment.samhsa.gov; 800-662-HELP).

--------------------------------------------------------------------------------

References

Adams, L.L., Gatchel, R.J., Robinson, R.C., Polatin, P., Gajraj, N., Deschner, M., and Noe, C. Development of a self-report screening instrument for assessing potential opioid medication misuse in chronic pain patients. Journal of Pain Symptom Management 27(5):440–459, 2004.

Alford, D.P., Compton, P., and Samet, J.H. Acute pain management for patients receiving maintenance methadone or buprenorphine therapy. Annals of Internal Medicine 144(2):127–134, 2006

American Academy of Pain Medicine (AAPM), American Pain Society (APS), and American Society of Addiction Medicine (ASAM). Definitions Related to the Use of Opioids for the Treatment of Pain. Glenview, IL, and Chevy Chase, MD: AAPM, APS, and ASAM, 2001.

American Chronic Pain Association (ACPA). ACPA Medications & Chronic Pain. Rocklin, CA: ACPA, Supplement 2005.

American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: APA, 2000.

Beers, M.H., ed. Merck Manual of Medical Information, Second Home Edition, Online Version. Whitehouse Station, NJ: Merck Research Laboratories, 2004–2005.

Bloodworth, D. Issues in opioid management. American Journal of Physical Medicine and Rehabilitation 84(3 Suppl):S42–S55, 2005.

Breivik, H. Opioids in chronic noncancer pain, indications and controversies. European Journal of Pain 9(2):127–130, 2005.

Butler, S.F., Budman, S.H., Fernandez, K., and Jamison, R.N. Validation of a screener and opioid assessment measure for patients with chronic pain. Pain 112(1–2):65–75, 2004.

Christo, P.J., Grabow, T.S., and Raja, S.N. Opioid effectiveness, addiction, and depression in chronic pain. Advances in Psychosomatic Medicine 25:123–137, 2004.

Cole, B.E. Prescribing opioids, relieving patient suffering and staying out of personal trouble with regulators: Reprising old ideas and offering new suggestions. Pain Practitioner 12(3):5–8, 2002.

Coluzzi, F., and Mattia, C. Oxycodone: Pharmacological profile and clinical data in chronic pain management. Minerva Anestesiologica 71(7–:451–460, 2005.

Coluzzi, F., and Pappagallo, M. Opioid therapy for chronic noncancer pain: Practice guidelines for initiation and maintenance of therapy. Minerva Anestesiologica 71(7–:425–433, 2005.

Compton, P., and Athanasos, P. Chronic pain, substance abuse and addiction. Nursing Clinics of North America 38(3):525–537, 2003.

Cook, L., Sefcik, E., and Stetina, P. Pain management in the addicted population: A case study comparison of prescriptive practice. Journal of Addictions Nursing 15(1):11–14, 2004.

Currie, S.R., Hodgins, D.C., Crabtree, A., Jacobi, J., and Armstrong, S. Outcome from integrated pain management treatment for recovering substance abusers. Journal of Pain 4(2):91–100, 2003.

Dews, T.E., and Mekhail, N. Safe use of opioids in chronic noncancer pain. Cleveland Clinic Journal of Medicine 71(11):897–904, 2004.

Federation of State Medical Boards (FSMB). Model Policy for the Use of Controlled Substances for the Treatment of Pain. Dallas, TX: FSMB, 2004.

Friedman, R., Li, V., and Mehrotra, D. Treating pain patients at risk: Evaluation of a screening tool in opioid-treated pain patients with and without addiction. Pain Medicine 4(2):182–185, 2003.

Gourlay, D.L., Heit, H.A., and Almahrezi, A. Universal precautions in pain medicine: A rational approach to the treatment of chronic pain. Pain Medicine 6(2):107–112, 2005.

Hainline, B. Chronic pain: Physiological, diagnostic, and management considerations. Psychiatric Clinics of North America 28(3):713–735, 2005.

Hansen, G.R. Management of chronic pain in the acute care setting. Emergency Medicine Clinics of North America 23(2):307–338, 2005.

Heit, H.A. Addiction, physical dependence, and tolerance: Precise definitions to help clinicians evaluate and treat chronic pain patients. Journal of Pain & Palliative Care Pharmacotherapy 17(1):15–29, 2003.

Jones, E.M., Knutson, D., and Haines, D. Common problems in patients recovering from chemical dependency. American Family Physician 68(10):1971–1978, 2003.

Lussier, D., and Pappagallo, M. 10 most commonly asked questions about the use of opioids for chronic pain. Neurologist 10(4):221–224, 2004.

Michna, E., Ross, E.L., Hynes, W.L., Nedeljkovic, S.S., Soumekh, S., Janfaza, D., Palombi, D., and Jamison, R.N. Predicting aberrant drug behavior in patients treated for chronic pain: Importance of abuse history. Journal of Pain Symptom Management 28(3):250–258, 2004.

Morley-Forster, P.K., Clark, A.J., Speechley, M., and Moulin, D.E. Attitudes toward opioid use for chronic pain: A Canadian physician survey. Pain Research & Management 8(4):189–194, 2003.

Passik, S.D., and Kirsh, K.L. Assessing aberrant drug-taking behaviors in the patient with chronic pain. Current Pain and Headache Reports 8(4):289–294, 2004.

Passik, S.D., and Kirsh, K.L. Managing pain in patients with aberrant drug-taking behaviors. Journal of Supportive Oncology 3(1):83–86, 2005.

Peter D. Hart Research Associates. Americans Talk About Pain. Survey conducted for Research!America. Washington, DC: Peter D. Hart Research Associates, 2003.

Primm, B.J., Perez, L., Dennis, G.C., Benjamin, L., Clark, W., Keough, K., Leak, W.D., Payne, R., Smith, D., and Sullivan, L.W. Managing pain: The challenge in underserved populations, appropriate use versus abuse and diversion. Journal of the National Medical Association 96(9):1152–1161, 2004.

Roper Public Affairs & Media. Americans Living with Pain Survey. Conducted for the American Chronic Pain Association. New York: GFK NOP, 2004.

Savage, S.R. Assessment for addiction in pain-treatment settings. Clinical Journal of Pain 18(4 Suppl):S28–S38, 2002.

Schneider, J.P. Chronic pain management in older adults: With coxibs under fire, what now? Geriatrics 60(5):26–28, 30–31, 2005.

Schnoll, S.H., and Weaver, M.F. Addiction and pain. American Journal of Addictions 12(Suppl 2):S27–S35, 2003.

Strassels, S.A., McNicol, E., and Suleman, R. Postoperative pain management: A practical review, part 1. American Journal of Health-System Pharmacy 62(1:1904–1916, 2005.

Weaver, M.F., and Schnoll, S.H. Opioid treatment of chronic pain in patients with addiction. Journal of Pain & Palliative Care Pharmacotherapy 16(3):5–26, 2002.

Webster, L.R., and Webster, R.M. Predicting aberrant behaviors in opioid-treated patients: Preliminary validation of the opioid risk tool. Pain Medicine 6(6):432–442, 2005.

Wisconsin Medical Society Task Force on Pain Management. Guidelines for the assessment and management of chronic pain. Wisconsin Medical Journal 103(3):14–42, 2004.


--------------------------------------------------------------------------------

Ordering Information

To order additional copies of Substance Abuse in Brief Fact Sheet and the other SAMHSA products, contact:
SAMHSA’s National Clearinghouse for Alcohol and Drug Information
P.O. Box 2345
Rockville, MD 20847-2345
Phone: 800-729-6686, TDD: 800-487-4889
Fax: 240-221-4292
Web site: www.ncadi.samhsa.gov

Substance Abuse in Brief Fact Sheet is produced under contract number 270-04-7049 by JBS International, Inc., and The CDM Group, Inc., for the Center for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration (SAMHSA), U.S. Department of Health and Human Services (HHS). An electronic version of Substance Abuse in Brief Fact Sheet is available on line at www.kap.samhsa.gov under Products. If you wish to reference or reproduce this issue, citation of this publication is appreciated.

Recommended Citation: Center for Substance Abuse Treatment.Pain Management Without Psychological Dependence: A Guide for Healthcare Providers. Substance Abuse in Brief Fact Sheet Summer 2006, Volume 4, Issue 1.

Public Domain Notice: All material appearing in this report is in the public domain and may be reproduced or copied without permission. This publication may not be reproduced or distributed for a fee without the specific, written authorization of the Office of Communications, SAMHSA, HHS.

DHHS Publication No. (SMA) 06-4186
NCADI Publication No. MS993
Printed 2006


--------------------------------------------------------------------------------

1. Many pain management articles and discussions use the term addiction to refer to psychological dependence. This publication uses the term psychological dependence to avoid any possible pejorative connotations of the term addiction.

[Melis11577]

Miriam Z. Mintzer, Marc L. Copersino, and Maxine L. Stitzer. Opioid abuse and cognitive performance. Drug and Alcohol Dependence 78(2):225-230, May 2005.

Summary:
A few recent studies provide evidence for performance impairment in dependent opioid abusers enrolled in methadone maintenance programs. However, it is difficult to differentiate the effects of a history of long-term opioid (or multiple drug) abuse from the effects of methadone maintenance itself. This study addressed the issue by comparing the performance of a newly recruited group of 20 currently abstinent former opioid abusers retrospectively to two groups (18 methadone maintenance patients (MMP); 21 matched non-drug abusing controls), who were the subjects of a previous report from the authors' laboratory (Mintzer, M.Z. and Stitzer, M.L. Cognitive impairment in methadone maintenance patients. Drug and Alcohol Dependence 67, 41–51, 2002), using the same performance testing battery. The abstinent abusers were demographically similar to the MMP and matched controls, and reported histories of drug use similar to those of the MMP. Although conclusions are somewhat limited by the small sample size, performance of the abstinent abusers fell between that of the MMP and controls on a number of measures, suggesting that methadone maintenance may be associated with additional impairment over and above that associated with long-term abuse, and that recovery of functioning may occur during abstinence. The authors recommend further research to explore the factors underlying performance impairment in MMP and to determine the clinical significance of the observed impairments for daily performance in the natural environment.

[Melis11577]

Neonatal Abstinence Syndrome
What is neonatal abstinence syndrome?
Neonatal abstinence syndrome (NAS) is a term for a group of problems a baby experiences when withdrawing from exposure to narcotics. It is estimated that 3 to 50 percent of newborn babies have been exposed to maternal drug use, depending on the population and area of the country.

What causes neonatal abstinence syndrome?
Almost every drug passes from the mother's blood stream through the placenta to the fetus. Illicit substances that cause drug dependence and addiction in the mother also cause the fetus to become addicted. At birth, the baby's dependence on the substance continues. However, since the drug is no longer available, the baby's central nervous system becomes overstimulated causing the symptoms of withdrawal.

Some drugs are more likely to cause NAS than others, but nearly all have some effect on the baby. Opiates, such as heroin and methadone, cause withdrawal in over half of babies exposed prenatally. Cocaine may cause some withdrawal, but the main symptoms in the baby are due to the toxic effects of the drug itself. Other drugs such as amphetamines, barbiturates, and narcotics can also cause withdrawal. Alcohol use causes withdrawal in the baby, as well as a group of problems including birth defects called fetal alcohol syndrome.

Why is neonatal abstinence syndrome a concern?
When a mother uses illicit substances, she places her baby at risk for many problems. A mother using drugs may be less likely to seek prenatal care, which can increase the risks for her and her baby. In addition, women who use drugs are more likely to use more than one drug, which can complicate the treatment. The risk of contracting HIV and AIDS is also greater among intravenous (IV) drug users.

In addition to the specific difficulties of withdrawal after birth, problems in the baby may include, but are not limited to, the following:

poor intrauterine growth
premature birth
seizures
birth defects
Specific drugs often times cause specific problems in the baby and may include the following:

Heroin and other opiates, including methadone, can cause significant withdrawal in the baby, with some symptoms lasting as long as four to six months. Seizures may also occur and are more likely in babies born to methadone users.


Prenatal use of amphetamines is associated with low birthweight and premature birth, and may cause intracranial (in the head) bleeding in the baby.


A mother's prenatal cocaine use may be related to an increased risk of sudden infant death syndrome (SIDS).


Marijuana use is linked to lower birthweight and size of the baby.


Alcohol use in pregnancy also has significant effects on the fetus and the baby. Growth during pregnancy and after birth is slowed. Specific deformities of the head and face, heart defects, and mental retardation are seen with fetal alcohol syndrome. Withdrawal symptoms from alcohol may last up to 18 months.


Cigarette smoking has long been known for its effects on the fetus. Generally, smokers have smaller babies than non-smokers. Babies of smokers may also be at increased risk for premature birth and stillbirth.
What are the symptoms of neonatal abstinence syndrome?
Symptoms of NAS may vary depending on the type of substance used, the last time it was used, and whether the baby is full-term or premature. Symptoms of withdrawal may begin as early as 24 to 48 hours after birth, or as late as five to ten days. Alcohol withdrawal may begin within a few hours after birth.

The following are the most common symptoms of neonatal abstinence syndrome. However, each baby may experience symptoms differently. Symptoms of withdrawal in full-term babies may include:

tremors (trembling)
irritability (excessive crying)
sleep problems
high-pitched crying
tight muscle tone
hyperactive reflexes
seizures
yawning, stuffy nose, and sneezing
poor feeding and suck
vomiting
diarrhea
dehydration
sweating
fever or unstable temperature
Premature babies may not have the classic signs of withdrawal listed above, but more often experience the following symptoms:

tremors (trembling)
high-pitched crying
rapid breathing
poor feeding
The symptoms of NAS may resemble other conditions or medical problems. Always consult your baby's physician for a diagnosis.

How is neonatal abstinence syndrome diagnosed?
An accurate report of the mother's drug usage is important, including the time of the last drug taken. A neonatal abstinence scoring system may be used to help diagnose and grade the severity of the withdrawal. Using the scoring system, points are assigned for certain signs and symptoms and the severity of each. This scoring may also help in planning treatment.

Treatment for neonatal abstinence syndrome:
Specific treatment for NAS will be determined by your baby's physician based on:

your baby's gestational age, overall health, and medical history
extent of the disease
your baby's tolerance for specific medications, procedures, or therapies
expectations for the course of the disease
your opinion or preference
Babies suffering from withdrawal are irritable and often have a difficult time being comforted. Swaddling, or snugly wrapping the baby in a blanket, may help comfort the baby. Babies also may need extra calories because of their increased activity and may need a higher calorie formula. Intravenous (IV) fluids are sometimes needed if the baby becomes dehydrated or has severe vomiting or diarrhea.

Some babies may need medications to treat severe withdrawal symptoms, especially for seizures. Specific drugs approved by the US Food and Drug Administration (FDA) for treating withdrawal include the following:

methadone for heroin and other opiate withdrawal
benzodiazepines (for alcohol withdrawal)
Other drugs are also being used to help relieve the discomfort and problems of withdrawal. The treatment drug is usually in the same class as the substance the baby is withdrawing from. Once the signs of withdrawal are controlled, the dosage is gradually decreased to help wean the baby off the drug. Consult your baby's physician to learn which treatments might be effective for your baby.

Prevention of neonatal abstinence syndrome:
Neonatal abstinence syndrome is a totally preventable problem. However, it requires that a mother stop using drugs before pregnancy, or as soon as she learns she is pregnant.

http://tinyurl.com/y9p3nn

[Melis11577]

FAST FACT AND CONCEPT #171 - Methadone for Neuropathic Pain Author: David E. Weissman, MD

Prescriptions for methadone have greatly increased in the past six years.1 The reason for this increase is likely related to two factors: reduced cost relative to other potent opioids and basic science data suggesting that methadone may be particularly useful in treating neuropathic pain. Two previous Fast Facts (#75, 86) reviewed methadone’s pharmacological properties. This Fast Fact examines the research base regarding methadone and neuropathic pain and reviews the rise in methadone-related deaths.

Historical Context

Prior to 1985, when long-acting morphine preparations were introduced, methadone was commonly prescribed for cancer-related pain as it had a longer duration of action than morphine. However, it was well appreciated that methadone had a higher risk of respiratory depression due to drug accumulation with chronic dosing---an effect not associated with other opioids, in which there is no drug accumulation in the setting of normal renal function.
Prior to 1990 there was a widespread belief that opioids were relatively ineffective in treating neuropathic pain. Since then, there been a much greater understanding that opioids are an effective part of neuropathic pain treatment.
Basic science data – Methadone inhibits reuptake of norepinephrine and serotonin in a similar manner to newer anti-depressants, some of which are effective against neuropathic pain (e.g., venlafaxine). Also, methadone binds to the NMDA receptor, a known modulator of neuropathic pain. Finally, methadone has demonstrated efficacy in animal models of neuropathic pain.1

Patient data - Small non-controlled case series and at least one small randomized study (methadone vs. placebo) have demonstrated that methadone can reduce neuropathic pain in both cancer and non-cancer patients.2-5 There is no data, for or against the proposition, that methadone is superior to other opioids for neuropathic pain. A 2004 Cochrane Collaborative review found, “there is no trial evidence to support the proposal that methadone has a particular role in neuropathic pain of malignant origin.”6 Furthermore, the review cautioned clinicians about the danger of methadone-induced respiratory depression due to its long terminal half-life.6

Methadone deaths - There is a growing awareness that the increased prescription of methadone is being paralleled by a similar increase in methadone-related deaths. Florida, Utah, North Carolina, Oregon, Indiana, Maryland, Alabama and West Virginia have all reported a spike in deaths related to methadone since 2000.7,8 The US Department of Health and Human Services convened an expert panel in 2003 to investigate the rise in methadone deaths and concluded that the rise was largely due to the increasing use of methadone as an analgesic.9 The Center for Disease Control published a report detailing data from Utah in 2005, suggesting that part of the problem was due to increased prescribing.10 The current data seem to suggest that the general increased supply of methadone, via legitimate prescribing, is leading to deaths due to accidental overdose through improper prescribing or illicit diversion/recreational use. In addition to concern about respiratory depression, there has been a relatively recent observation that methadone, unlike morphine or hydromorphone, can prolong the QTc interval and lead to serious cardiac conduction abnormalities. Note: the overall number of opioid-related deaths has increased, not just from methadone. Note: there are no data on untimely deaths related to methadone prescribing in hospice/palliative care patients.

Summary - the renewed interest in an old drug based on new science holds exciting promise of benefit for the many patients with neuropathic pain. However, clinical research has yet to confirm or deny a unique clinical role for methadone compared to other opioids. The risk of respiratory depression should give clinicians pause before prescribing methadone based solely on the theory that it is a superior opioid in neuropathic pain. Furthermore, given that diversion of legitimate opioid prescriptions to the illicit market can occur, even in the practice of hospice and palliative care, physicians and hospice agencies need to recognize they also have a larger social responsibility to the public welfare, and prescribe methadone with care and caution.


--------------------------------------------------------------------------------

References

Foley KM. Opioids and chronic neuropathic pain. NEJM 2003;348:1279-1281.
Morley JS et al. Low-dose methadone has an analgesic effect in neuropathic pain: a double-blind randomized controlled crossover trial. Pall Med 2003;17:576-587.
Altier N et al. Management of chronic neuropathic pain with methadone: a review of 13 cases. Clin J Pain 2005;21:364-369.
Gagnon B et al. Methadone in the treatment of neuropathic pain. Pain Res Manage 2003;8:149-154.
Moulin DE et al. Methadone in the management of intractable neuropathic non cancer pain. Can J Neuro Sci 2005;32:340-343.
Nichloson AB. Methadone for cancer pain: Review. Cochrane Database of systematic reviews. 2004;2:CD003971
Google Search; Methadone deaths.
Finn S and Tuckwiller S Feds act on methadone deaths . West Virginia Gazette, July 23 2006.
Increase in poisoning deaths caused by non-illicit drugs--- Utah, 1991-2003.MMWR Weekly; 2005; 54:33-36.
http://dpt.samhsa.gov/reports/methodone_mortality-05.htm

--------------------------------------------------------------------------------

Fast Facts are edited by David E. Weissman, MD; Palliative Care Center, Medical College of Wisconsin. For comments/questions write to: dweissma@mail.mcw.edu. The complete set of Fast Facts are available at EPERC: www.eperc.mcw.edu

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Weissman DE. Fast Fact and Concept #171. Methadone for neuropathic pain. December 2007. End-of-Life Physician Education Resource Center End-of-Life Palliative Education Resource Center www.eperc.mcw.edu.

Disclaimer: Fast Facts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.

Purpose: Self-Study Guide, Teaching

Audience(s)


Training: Fellows, 3rd/4th Year Medical Students, PGY1 (Interns), PGY2-6, Physicians in Practice


Specialty: Anesthesiology, Emergency Medicine, Family Medicine, General Internal Medicine, Geriatrics, Hematology/Oncology, Neurology, OB/GYN, Ophthalmology, Pulmonary/Critical Care, Pediatrics, Psychiatry, Surgery


Non-Physician: Nurses, Pharmacists/Clinical Pharmacists


ACGME Competencies: Medical Knowledge and Patient Care

Keyword(s): Pain
http://www.eperc.mcw.edu/fastFact/ff_171.htm

[Melis11577]

West J Med. 2000 January; 172(1): 11–14.
Copyright © Copyright 2000 BMJ publishing Group


Toxicology and pathology of deaths related to methadone: retrospective reviewSteven B Karch1 and Boyd G Stephens1

1 Office of the Medical Examiner, City and County of San Francisco, Hall of Justice, 850 Bryant Street, San Francisco, CA 94103

Correspondence to: Steven B Karch, fdaa@batnet.com


This article has been cited by other articles in PMC.
Abstract
Objectives To clarify the mechanisms and risk factors of methadone toxicity and to describe the findings of deaths related to methadone use Design Retrospective review of case notes in the records of the San Francisco Medical Examiner comparing the findings in cases where methadone was deemed the cause of death with findings in decedents where methadone was an incidental finding, and with 50 age-matched, disease and drug free, trauma victims. Results 38 cases out of the 3317 processed by our office during 1997-1998 were identified in which methadone had been detected. Cases were mostly male 28/38 (74%) and white, 28/38 (74%). In 17 of 38 cases death was deemed to have been caused by methadone toxicity. For the group the mean blood methadone concentration for all 38 patients, was 957 ng/ml SD =.681, SE =.14). The mean blood concentration of the main methadone metabolite (EDDP) was 253 ng/ml, SD = 529 ng/ml, SE =.089. The mean ratio of methadone in the blood to EDDP in the blood was 13.6:1 Values were not significantly different between cases in which methadone toxicity was the cause of death and in those in which it was an incidental finding. Cocaine, or the cocaine metabolite benzoylecgonine, was detected in the blood or urine of 16/38 cases (42%); morphine in one-third (13/3 and methamphetamine in only one. Pulmonary edema was evident in all cases, coronary artery disease in 9/38 (24%) and cirrhosis in 7/38 (18%) of the methadone users. Necrotizing fasciitis was the cause of death in 4 of the 38 methadone users (11%). Nationally, a sizeable percent of methadone deaths are from drugs diverted from treatment programs. Conclusions The presence of methadone is often an incidental finding during postmortem examination which is unrelated to the cause of death. Postmortem measurements of methadone or its metabolite, or both, cannot be used in isolation to identify which deaths are associated with methadone toxicity.


The Office on National Drug Control Policy is commited to making methadone treatment programs more widely available; deaths related to heroin use fall when where methadone replacement programs are available.1, 2, 3 Unfortunately, methadone is toxic. A total of 552 methadone-related deaths were reported to the government in 1996, making methadone the seventh most frequent cause of drug-related death in the United States (nearly 4000 deaths related to heroin were reported during that same period).4

Most deaths that are related to methadone occur during the first few weeks of maintenance treatment; they are often the result of the dosage having been increased so quickly that fatal respiratory depression occurs.5,6 The relative risk of fatal respiratory depression occurring during the first 2 weeks of methadone maintenance treatment is nearly seven times higher than that in untreated heroin addicts and 97.8 times higher than for patients who have been on methadone maintenance for more than 2 weeks.3,7

New opiate users who are using illicitly obtained methadone are also at risk. The amount of methadone diverted from treatment programs, and by inference the number of deaths occurring as a result, is limited because the number of heroin users actually enrolled in methadone programs is comparatively small. There are an estimated 810,000 heroin addicts in the United States but only 115,000 participate in maintenance programs.4 If methadone becomes more widely available opportunities for diversion from treatment programs will increase and so will the number of deaths.1 Some of these deaths might be prevented, especially if the underlying cause of death was better understood. Little is known about the pharmacokinetics of methadone in opiate users. The data that have been published are largely derived from studies of single doses given to healthy volunteers or intravenous doses given to patients with cancer. Whether such studies are relevant to the pharmacokinetics in chronic heroin users is not known. Furthermore, nearly all of these studies were undertaken before differences in the tissue distribution of methadone isomers were understood,8 before methadone metabolites could be routinely measured, before chiral (special chemical techniques used to separate dextro- from levo- isomers of the same molecule) separation of methadone isomers was possible 9 and before the problem of determining the redistribution of drugs after death was appreciated.10


MATERIALS AND METHODS
Records of the San Francisco Medical Examiner were reviewed to identify all cases in which methadone had been detected from the beginning of 1997 through the end of 1998. Positive screening tests were confirmed using gas chromatography with mass spectrometry. Blood samples were screened in cases for which no urine was available. Concentrations of methadone in the blood and concentrations of the methadone metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) were both measured using gas chromatography with nitrogenphosphorous detector detection. Chiral separation was not performed.

The cause and manner of death were reviewed to determine whether death was related to methadone toxicity (drug related) or whether methadone was merely an incidental finding. Death certificates cannot be used to make this distinction because in California and most other states, drug-related deaths are considered to be accidents. Drug-related deaths were defined as those in which a direct toxic effect of methadone caused or contributed to death. Findings in cases classed as being drug related were compared with findings from cases in which methadone was incidental and also with findings from a group of 50 controls in which toxicology screening was negative and who had died as a result of trauma.

Demographic findings
A total of 38 cases in which methadone had been detected were identified out of 3317 cases processed by our jurisdiction during that period. The decedents were predominantly male (28/38, SD = 9, SE = 2 or 74%). The mean age of the 21 cases whose deaths were deemed to have been drug related was 46.2 (7.9) years. The mean age of the 17 cases whose deaths were deemed not to have been drug related was 46.3 years (SD = 7.9, SE = 1.9). Decedents dying from methadone toxicity were almost all white (1/17, 95%); decedents where methadone toxicity was an incidental finding were racially mixed, with 57% white (12/21), 38% black (8/21), and one Asian.


Anatomical and medical findings
Table 1 shows the mean weight of the heart, lungs, liver, spleen, and brain of the 38 cases in which methadone was detected and in 50 controls. The weight of each organ was significantly increased in all cases. Table 2 shows the nine most commonly encountered physical findings in the 38 cases. Terminal aspiration and pneumonia occurred in 6/38 (16%) cases. Necrotizing fasciitis, a much less common complication of drug abuse, was the cause of death in four (11%) cases. Necrotizing fasciitis occurred in middle aged people (40, 44, 46, and 54 years old); two were white, one was black, and the race of one was impossible to determine.


Toxicological findings
The mean interval before the postmortem examination occurred was 17.1 hours. The interval did not differ significantly between those cases in which death was deemed to have been drug related and in those in which it was not (17.7 vs 17.6 hours). Blood was available for measurement for all cases and urine in 16/38 (42%) cases. The mean blood methadone concentration for all 38 patients, was 957 ng/ml (SD =.681, SE =.14). The mean blood concentration of the main methadone metabolite (EDDP) was 253 ng/ml (SD = 529 ng/ml, SE =.089). The mean ratio of the concentration ratio of methadone in the blood to EDDP in the blood was 13.6:1. Urine concentrations of methadone were similar between the group in which death was deemed to have been drug related and in that in which it was not (mean concentration of 5.2 mg/L, SD = 3.6 mg/L, in drug related deaths and 5.86 mg/L, SD = 6.4 mg/L in cases where methadone was an incidental finding (p=0.797). Concentrations of EDDP were not significantly different between the two groups either. The EDDP concentration for drug related deaths was 6.55 mg/L (SD = 5.6 mg/L) vs 11.8 mg/L (SD = 16.7 mg/L, p =.3480).
The methadone/ EDDP ratio for the 38 cases was 13.58 (SD = 17.4, SE = 3.35 ; range 0.572 to 60). Cocaine or the cocaine metabolite benzoylecgonine, or both, was detected in 16/38 (42%) cases. Six of the 16 (38%) who had used cocaine also had detectable concentrations of morphine. Morphine was detected in nearly one-third (12/3 of the cases; concentrations ranged from 40 to 1728 ng/ml. Fentanyl was also detected in the case that also had the highest concentration of morphine. If the case with the highest concentration was excluded, the mean concentration of morphine in all 38 methadone users who were also taking morphine (presumably as heroin) was 345 ng/ml (SD = 325, SE =.09 ng/ml). Ethanol was present in 10 of 38 cases (26%) in a mean concentration 0.113 mg/dl (range 0.020-0.340, SD =.073, SE =.012). Other prescription drugs identified, which were generally present in subtherapeutic or therapeutic concentrations, are listed in table 3.


DISCUSSION
A redistribution of drugs through the body occurs after death making it impossible to estimate the true concentration of methadone or any other basic drug, such as a mild alkali in the period just before death until autopsy.14 Therapeutic monitoring of people on methadone maintenance is problematic. Dosages are estimated based on pharmacokinetic measurements made in healthy volunteers not addicts. These estimates have proven to be extremely inaccurate suggest a falsely short terminal half-life and a falsely low volume of distribution in addicts.12,13

The S- form (S, Latin for sinister) of methadone exerts little narcotic effect but pure R- isomer is expensive to manufacture, so a racemic mixture of the D and S forms (or right and left) mirror images of the methadone is widely used. The isomers have different volumes of distribution (defined as the amount of drug in the body divided by the blood concentration at equilibrium) is much greater for the S form than for the R form, while the R form is cleared from the system (has a shorter half-life, much more quickly than the S form. At at equilibrium, more of the inactive S- form than the active R-form can be found in the bloodstream.14, 15, 16, 17 Chiral interaction can probably be used to explain why postmortem concentrations of methadone overlap among patients whose death is drug related and those whose death is not. The active R-isomer has a smaller volume of distribution than the inactive S- isomer, which means that more of the active drug, R-methadone, is found in the bloodstream than in the tissue. If only a small percentage of the S- isomer is released from tissue back into the bloodstream, measured concentrations will be falsely raised.

The conversion of methadone to the metabolite EDDP is mediated by liver microsomes, mainly CYP3A4 and possibly CYP2C9 and CYP2C19.18 Methadone induces hepatic production of these microsomal enzymes, accelerating the metabolism of methadone in chronic users. These enzyme systems will not have been induced in new opiate users who will thus take longer to clear methadone from their bodies, placing them at greater risk of overdose. If other drugs are misused, or if prescription drugs are taken, the picture is further complicated since these drugs can induce, inhibit or compete for the same microsomal enzymes. The interactions between methadone and certain antiviral drugs are a recognized complication of treatment for HIV infection.19

In a recent study, antibodies to methadone were detected in more than half of the 46 heroin addicts who were tested.20 Antibodies were detected in nearly all of the cases with HIV, and concentrations of methadone in the blood were higher in patients who were infected with HIV than in those who were not (398 ng/ml vs 265 ng/ml). Thus, it is impossible to draw conclusions about the toxicity of a given dose of methadone or of a particular concentration of methadone in the blood without the use of chiral separation and without additional clinical information and information about the patient's history.


Medical consequences
Most of the findings made during the postmortem examination, such as the terminal aspiration and pneumonia that occurred in 16% of cases, are recognized complications of intravenous opiate use. However, necrotizing fasciitis is a much less common complication, and it is not clear why four members of this cohort died from it. Necrotizing fasciitis is characterized by a rapid and progressive course, and unrecognized infection spreads along fascial planes. It is usually caused by group A β hemolytic streptococci but other Gram negative bacilli, alone or in combination with hemolytic streptococci, may also be responsible.21 Usually there is also a history of alcoholism, diabetes mellitus, intravenous drug use, or some other disorder that impairs resistance.22
There was evidence of prior intravenous drug use in only one of the four cases of necrotizing fasciitis described here. In two of the cases complete toxicology testing identified the presence of methadone only. In the other two cases, cocaine and cocaine metabolite were found in both blood and urine samples. A link between cocaine use and necrotizing skin infection has previously been reported.23

The incidence of necrotizing fasciitis among intravenous drug users is clearly increasing in San Francisco, and these four cases may reflect the increased prevalence of this disorder in our jurisdiction.24 But the occurrence of this disorder in those who may have been in methadone maintenance programs is particularly worrisome because methadone is supposed to help normalize immune responses, even in those drug users not infected with HIV.25

Summary points

Isolated postmortem measurements of blood concentrations of methadone or its metabolite cannot reliably be used to discriminate between cases who have died from methadone toxicity and cases in which the presence of the drug is an incidental finding
In nearly half of the cases in which death was related to methadone, cocaine was also found to have been used
New opiate users take longer to clear methadone from their bodies, placing them at greater risk of overdose
Necrotizing fasciitis occurring in methadone users seems to be more common than had previously been recognized; methadone may not be able to normalize the functioning of the immune system






References
References1.NIH consensus panel recommends expanding access to and improving methadone treatment programs for heroin addiction. Eur Addict Res 1999;5:50-51. [PubMed].
2.Gronbladh L, Ohlund LS, Gunne LM. Mortality in heroin addiction: impact of methadone treatment. Acta Psychiatr Scand 1990;82:223-227. [PubMed].
3.Caplehorn JR, Drummer OH. Mortality associated with New South Wales methadone programs in 1994: lives lost and saved. Med J Aust 1999;170:104-109. [PubMed].
4.Substance Abuse and Mental Health Services Administration Drug Abuse Warning Network. Annual Medical Examiner Data, 1995. Office of Applied Studies, DHHS Publication No. (SMA) 97-3126, Rockville, MD, 1997.
5.Drummer OH, Opeskin K, Syrjanen M, et al. Methadone toxicity causing death in ten subjects starting on a methadone maintenance program. Am J Forensic Med Pathol 1992;13:346-350. [PubMed].
6.Coleridge J, Cameron PA, Drummer OH, et al. Survey of drug-related deaths in Victoria. Med J Aust 1992;157:459-462. [PubMed].
7.Wu CH, Henry JA. Deaths of heroin addicts starting on methadone maintenance. Lancet 1990;335:424.
8.Lanz M, Thormann W. Characterization of the stereoselective metabolism of methadone and its primary metabolite via cyclodextrin capillary electrophoretic determination of their urinary enantiomers. Electrophoresis 1996;17:1945-1949. [PubMed].
9.Frost M, Kohler H, Blaschke G. Enantioselective determination of methadone and its main metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in serum, urine and hair by capillary electrophoresis. Electrophoresis 1997;18:1026-1034. [PubMed].
10.Levine B, Wu SC, Dixon A, et al. Site dependence of postmortem blood methadone concentrations. Am J Forensic Med Pathol 1995;16:97-100. [PubMed].
11.Pounder DJ, Jones GR. Post-mortem drug redistribution-a toxicological nightmare. Forensic Sci Int 1990;45:253-263. [PubMed].
12.Kristensen K, Blemmer T, Angelo HR, et al. Stereoselective pharmacokinetics of methadone in chronic pain patients. Ther Drug Monit 1996;18:221-227. [PubMed].
13.Wolff K, Rostami-Hodjegan A, Shires S, et al. The pharmacokinetics of methadone in healthy subjects and opiate users. Br J Clin Pharmacol 1997;44:325-334. [PubMed].
14.Eap C, Finkbeiner T, Gastpar M, et al. Replacement of (R)-methadone by a double dose of (R,S)-methadone in addicts: interindividual variability of the (R)/(S) ratios and evidence of adaptive changes in methadone pharmacokinetics. Eur J Clin Pharmacol 1996;50:385-389. [PubMed].
15.Rostami-Hodjegan A, Wolff K, Hay AW, et al. Population pharmacokinetics of methadone in opiate users: characterization of time-dependent changes. Br J Clin Pharmacol 1999;48:43-52. [PubMed].
16.Garrido MJ, Valle M, Calvo R, et al. Altered plasma and brain disposition and pharmacodynamics of methadone in abstinent rats. J Pharmacol Exp Ther 1999;288:179-187. [PubMed].
17.Dyer KR, Foster DJ, White JM, et al. Steady-state pharmacokinetics and pharmacodynamics in methadone maintenance patients: comparison of those who do and do not experience withdrawal and concentration-effect relationships. Clin Pharmacol Ther 1999;65:685-694. [PubMed].
18.Foster DJ, Somogyi AA, Bochner F. Methadone N-demethylation in human liver microsomes: lack of stereoselectivity and involvement of CYP3A4. Br J Clin Pharmacol 1999;47:403-412. [PubMed].
19.Altice FL, Friedland GH, Cooney EL. Nevirapine induced opiate withdrawal among injection drug users with HIV infection receiving methadone. AIDS 1999;13:957-962. [PubMed].
20.Gamaleya N, Dmitrieva I, Borg S, et al. Induction of antibodies to methadone during methadone maintenance treatment of heroin addicts and its possible clinical implications. Eur J Pharmacol 1999;369:357-364. [PubMed].
21.Haywood CT, McGeer A, Low DE. Clinical experience with 20 cases of group A streptococcus necrotizing fasciitis and myonecrosis: 1995 to 1997. Plast Reconstr Surg 1999;103:1567-1573. [PubMed].
22.Stevens DL. The flesh-eating bacterium: what's next? J Infect Dis 1999;179(suppl 2):366-374S.
23.Hoeger PH, Haupt G, Hoelzle E. Acute multifocal skin necrosis: synergism between invasive streptococcal infection and cocaine-induced tissue ischaemia? Acta Derm Venereol 1996;76:239-241. [PubMed].
24.`Flesh-eating' disease kills 2nd S.F. woman-four victims in S.F. contracted disease after injecting drugs.San Francisco Chronicle 1999:A1.
25.Novick D, Ochshorn M, Ghali V, et al. Natural killer cell activity and lymphocyte subsets in parenteral heroin abusers and long-term methadone maintenance patients. J Pharm Exp Ther 1989;250:606-610.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1070708

[Melis11577]

Is methadone too dangerous for opiate addiction?
The case for using a safer alternative, buprenorphine, is strong


Methadone is an effective treatment for heroin addiction, and it remains the mainstay of drug treatment for opiate dependence in the United Kingdom.1 The lethal dose of methadone is estimated at 50 mg for an opiate-naive adult.2 Nevertheless, many authorities recommend that methadone doses should be gradually increased to maintenance doses of 80-120 mg1—that is, twice the lethal dose for non-users. The greatly increased risk to users from methadone, particularly black market methadone, thus remains a major concern. Buprenorphine is a partial agonist that has a lower potential for causing respiratory depression than many other opioids, including methadone and heroin.3 It is increasingly used in the United Kingdom to treat opiate dependence, with guidelines for clinical management in primary and secondary care summarised by Ford et al4 and Taikato et al.5 It is time it replaced methadone as the mainstay of drug treatment for opiate dependence.

A long running debate continues between proponents of long term maintenance treatment with methadone and the proponents of detoxification (in which the dose of a substitute drug is reduced over time to achieve abstinence from all agents). An expert US panel concluded, "although the drug free state represents an optimal treatment goal, research has demonstrated that the state cannot be achieved or sustained by the majority of persons dependent on opiates."6 Without digressing further into this debate, we point out that that buprenorphine is at least as effective as methadone in both maintenance and detoxification.7-9

One mechanism to reduce the diversion of methadone on to the black market is to insist that these drugs are taken in the presence of a pharmacist rather than being given "to take away." Repeated advice to this effect is provided by the UK Department of Health and the Home Office.1 10 We have recently contacted 120 of the 140 community drug teams in England and Wales to ask what proportion of new patients on methadone undergo supervised consumption. We found that at least 25% of people who start prescriptions for methadone are still prescribed methadone to take away. This proportion is likely to be much higher in people who remain on methadone in the long term. Historical practice, and the reluctance of many pharmacies to provide supervised consumption facilities, make routine supervised consumption of methadone difficult to provide.

In 2003 there were 167 drug related deaths in Britain where methadone was solely or partly involved.2 Just over half of these deaths were due to diverted methadone—that is, methadone that had been sold to the victim on the black market. A total of 1 486 800 prescriptions for methadone were issued in 2003 (www.ppa.org.uk). This translates into an annual death rate of 112 deaths per million methadone prescriptions. In contrast, the risk of death from overdose of tricyclic antidepressants is estimated at 30 per million prescriptions.11 Clearly, opiate dependent people are likely to have much higher levels of risk taking behaviour than recipients of antidepressants, but these figures indicate the relative risk of methadone compared with other drugs that are regularly cited in fatal overdose.

In 2003 310 700 prescriptions were issued for buprenorphine (www.ppa.org.uk). Buprenorphine has not been cited in any drug related deaths reported to coroners in England and Wales since it was licensed for the treatment of opiate dependence in 1999. The Medicines Control Agency adverse drug reactions database has received reports of seven deaths involving buprenorphine, (www.mca.gov.uk), although to what extent these cases were related to buprenorphine or to other factors (such as intercurrent cardiac illness or continued illicit drug use) is unknown.

The maximum licensed dose of buprenorphine is 32 mg, with a suggested maintenance dose of 16 mg/day. Trials have shown that even opiate-naive individuals can tolerate doses of 32 mg of buprenorphine while "experiments on rhesus monkeys proved that buprenorphine does not cause any respiratory depression that requires intervention, even at very high doses (10 mg/kg)."3 Pirnay et al reported a series of 34 deaths involving buprenorphine in France,12 but buprenorphine was "clearly" responsible for only four of these; most deaths involved its intake with other drugs, especially benzodiazepines and antipsychotics.

Buprenorphine is as prone as methadone to diversion to the black market and it may have a higher propensity to be injected than oral methadone.5 8 This is probably the main reason for the reluctance to use this drug in preference to methadone in some areas. Cost may be another reason; although buprenorphine has clearly been shown to be cost effective,13 it is about four times more expensive than methadone (www.BNF.org). Nevertheless, the safety of buprenorphine in overdose is a significant advantage over methadone, especially considering the continued failure to prevent diversion of these agents on to the black market.

Jason Luty, honorary consultant psychiatrist in the addictions

(sl006h3607@blueyonder.co.uk)
Cambridge and Peterborough Mental Health NHS Trust, Taylor Centre, Southend on Sea, Essex SS4 1RB

Colin O'Gara, clinical research fellow in the addictions

National Addiction Centre, Institute of Psychiatry, London, SE5 8BB

Mohammed Sessay, staff grade in addiction psychiatry

Merton Community Drug Team, Department of Addictive Behaviour, St George's Hospital Medical School, London SW17 0RE




--------------------------------------------------------------------------------
Competing interests: None declared. None of the authors have received grants, hospitality, financial support, or any other incentives by the manufacturers of buprenorphine; nor do we write this article in the expectation of such incentives.
References


Department of Health. Drug misuse and dependence: guidelines for clinical management. London: Stationery Office, 1999.
Ghodse H, Schizfano F, Oyefeso A, Bannister D, Cobain K, Dryden R, et al. Drug-related deaths as reported by participating Procurator Fiscal and Coroners. London: St George's Hospital Medical School, 2004 (International Centre for Drug Policy Report 13).
Davids E, Gastpar M. Buprenorphine in the treatment of opioid dependence. Eur Neuropsychopharm 2004;14: 209-16.[CrossRef][ISI][Medline]
Ford C, Morton S, Lintzeris N, Bury J, Gerada C. Guidance for the use of burprenorphine for the treatment of opioid dependence in primary care. London: Royal College of General Practitioners, 2003.
Taikato M, Kidd B, Baldacchino A. What every psychiatrist should know about buprenorphine in substance misuse. Psychiatric Bull 2005;29: 225-7.[CrossRef]
National Consensus Development Panel. Effective medical treatment of opiate addiction. JAMA 1998;280: 1936-43.[Abstract/Free Full Text]
Ling W, Wesson DR, Charuvastra C, Klett CJ. A controlled trial comparing buprenorphine and methadone maintenance in opioid dependence. Arch Gen Psych 1996;53: 401-7.[Abstract]
Gowing L, Ali R, White J. Buprenorphine for the management of opioid withdrawal. Cochrane Database Syst Rev 2004;4: CD004417.[Medline]
Simoens, S, Matheson, C, Bond, C, Inkster K, Ludbrook A. The effectiveness of community maintenance with methadone or buprenorphine for treating opiate dependence. Br J Gen Pract 2005;55: 139-46.[ISI][Medline]
Advisory Council on the Misuse of Drugs. Home Office Report: Reducing Drug Related Deaths. London: The Stationery Office, 2000.
Nutt D. Death by tricyclic. J Psychopharm 2005;19(2): 123-34.[Free Full Text]
Pirnay S, Borron SW, Giudicelli CP, Tourneau J, Baud FJ, Ricordel I. A critical review of the causes of death among post-mortem toxicological investigations: analysis of 34 buprenorphine-associated and 35 methadone-associated deaths. Addiction 2004;99(: 978-88.[CrossRef][ISI][Medline]
Doran CM, Shanahan M, Mattick RP, Ali R, White J, Bell J. Buprenorphine versus methadone maintenance: a cost effectiveness analysis. Drug Alcohol Depend 2003;71: 295-302.[CrossRef][ISI][Medline]

http://www.bmj.com/cgi/content/full/331/7529/1352

[Melis11577]

EFFECT OF CHRONIC METHADONE ADMINISTRATION ON PREGNANT RATS AND THEIR OFFSPRING Doris Buchenauer 1 , Marilyn Turnbow 1 , and Marvin A. Peters 1
1 Department of Pharmacology, School of Medicine, Loma Linda University, Loma Linda, California



Chronic administration of methadone to pregnant rats is associated with an increase in mortality compared with either nontreated pregnant rats or treated nonpregnant rats. These observations would suggest some interaction between pregnancy and methadone administration. Treatment of the female during pregancy resulted in a decreased number of live offspring per litter, an increase in the percentage of stillborn pups, an increase in infant mortality and a retardation of growth of the pups nursing treated mothers. There was a dose-response relationship in most parameters at the lower doses used but at higher dose levels the dose-response was not as obvious. The overall effect of methadone on reproduction was seen as an increase in the number of maternal deaths, a decrease in the number of pups born per litter and a decrease in the number of pups weaned. One hundred and forty-eight pups were weaned from 20 control animals while 20 animals in each of the three treated groups, 2.5, 5 and 7.5 mg/kg of methadone, raised 78, 42 and 41 pups, respectively, to weaning age.

Submitted on May 24, 1973
Accepted on December 10, 1973

[Melis11577]

Methadone Withdrawl
Please do not attempt to contact DPEG directly about methadone or other treatment questions

If you wish to discuss methadone or other treatment questions, you may only contact Dr. David Arneson at thesourcenmc@msn.com.

The following statement is provided for information purposes only. Presentation of this material on DPEG's website does not constitute an endorsement of any kind.

THE FOLLOWING INFORMATION IS PRESENTED AS A PUBLIC SERVICE AND EDUCATION RESOURCE BY DRUG POLICY EDUCATION GROUP, INC. Please contact Dr. Arneson directly if you have questions about any of the material presented below.

Methadone/Opiate withdrawal

Dr. David Arneson, NMD

thesourcenmc@msn.com

‘There is no free lunch.’

Last updated 3/21/05



I believe in the search for truth…the following monograph is what I know to be true about the use and withdrawal from methadone. I also understand that in life, the truth is constantly evolving. My 18 years on the road to recovery probably taints my judgment somewhat…but friends—I know recovery from the bottom rung. I’ve written countless e-mail replies to those of you who wish to discontinue methadone. In order to save myself time I’ve decided to write as much as I can on one, or two, pages…the truth as I see it…to assist you in your endeavor. I will be adding and subtracting as more information is made available. Certainly, you may perceive your truth to be different. If you think that going to the methadone clinic every morning to get your dose for the rest of your life…gives you quality of life…then read no further and God bless you. I assure you, the standard medical establishment does not have an answer for withdrawal. In fact, the new way of thinking is that many of you will have to be on methadone for the rest of your lives. Nothing could be farther from the truth. They will try and convince you that sudden withdrawal will cause your untimely demise. Another falsehood, although the truth is you may feel like you’re dying. I consistently work with people stopping cold turkey and have better luck than lowering the dose over time., I’ve NEVER had an in-house methadone withdrawal case leave the program early…all have gone cold turkey from 60-150 mg per day…Many do this without the aid of other mind-altering prescriptive drugs…even though I’m licensed to prescribe these drugs. There are exceptions, for those that I detox out-patient, and for those that are on other medications when they come in for treatment…I’ll cover those medications in the following paragraphs. Personally, I urge all to consider in-house Detox for methadone…especially if going cold turkey. Although in my personal experience I’ve never seen any advantage in lowering the dose over time. Especially, if one is at 45 mg or less per day. Methadone Detox can normally be accomplished in 3-5 weeks. For information on natural methadone detox, in-patient, please visit http://www.theriversource.org



The most important issue in treatment for withdrawal is not so much treating the disease state but treating the individual. One specific protocol designed to treat a disease is standard medicine’s answer to all disease states. This is mechanistic medicine. It does not take into account our genetic variability…we respond to treatment in different ways…not just through biochemistry, but also on the emotional and spiritual levels. For the last 4 years I’ve been using nutrition—Intravenous and oral—to rebuild and repair the biochemistry pathways in the body and mind. Over four years experience —this includes heroin, and all other street drugs, alcohol, and prescription medications--has taught me that natural detox works 100 times better than detox formulated and predicated by the use of other mind altering chemicals. It is also important to recognize that there are many of you that were prescribed methadone for chronic pain. Yet one must recognize that the end result is the same—and therefore the remedies for withdrawal are the same.



One more important point is that emotional and spiritual supports are necessary in this journey back to health. It would be rare that a person is not stretched to the absolute limit—body, mind, and spirit--in the process of withdrawing from methadone. Those who chose to do this alone, rarely succeed. The support of family, friends, or even the 12-step programs are important adjuncts to this journey.



One final point needs to made about the use of methadone. There are those that were put on methadone for pain management. This occurs because opiates in general—while good acute therapy—are not good choices for chronic long-term pain. The body adjusts to opiate therapy by down regulating opiate receptors and the patient will eventually build a tolerance to the standard opiates like vicodin, percocet, or oxycontin just to name a few. Methadone is the last ditch effort to control pain…unfortunately, the use of methadone usually creates more long-term health problems. The other unfortunate aspect of taking someone off methadone—those that have been using it to treat chronic pain—is what will be used to control pain in the future. There has been some movement in treating pain with anti-depressants with poor results. Furthermore, long term opiate use eventually create what is termed the opiate pain syndrome…which simply is the fact that the receptors are so down regulated that the opiate have nothing to act on…and that’s why opiate therapy doesn’t work over the long term…For many of those with chronic pain, choices have to be made…and the withdrawal from methadone will be especially trying…but it can be done following the protocols listed below…as your body heals and the receptors are synthesized in the body your own enkephlins and endorphins (natural body opiates) will start to be interactive in pain management…this may not be enough…yet many cases of chronic pain will subside if serotonin levels in the brain can be increased—the reason for doing amino acid therapy is to increase these levels. Anti-depressants don’t increase the production of anything over the long term…in fact it is well known that in the long term they decrease levels of neurotransmitters such as serotonin. Amino acids therapies work well on most cases of fibromyalgia even though many of these patients will fall victim to the use of methadone which just creates more problems. The good news is that if a fibromyalgia patient will start the following protocols to get off methadone…these are the same basic protocols for treating Fibromyalgia…



1) Most Methadone clinics are for profit, private enterprises, do you really think they want you off the methadone. The cost of a dose of methadone is about $1.00…what are they charging you?

2) Since all associated therapists and counselors that work the methadone clinics are trained and get their information from the standard medical establishment…do you really think they know the truth…no one is saying that they are not caring individuals--but they don’t know the truth anymore than the people who prescribe the medication to you. If fact most of them think we’re idiots because we doubt and ask questions. The fact is that we do not know the long range effects of methadone on the human body and mind…many are now thinking that the longer you are on the methadone the more profound, and possibly irreversible these changes may be…In fact we don’t know the exact mechanism of action of many psychotropic drugs—just review the Physicians Desk Reference on Prozac…along with the countless other caustic chemicals we insist on putting in the human body.

3) Methadone is one of the most physically dependent medications invented in the 20th century. The reason for this is a) its long half-life (24-36 hours)…b) it is a synthetic morphine, c) the diabolic symptomology associated with withdrawal and the length of the withdrawal symptoms. Methadone, like all opioids creates profound changes to gastrointestinal function… In layman’s terms this means that regardless of the food you eat--absorption of the vital nutrients is impaired. If nutrients cannot be absorbed in sufficient quantities and associated quality…all biochemical pathways in the body are affected negatively. Chronic fatigue, sleeplessness, aches and pains, depression, anxiety, are all signs and symptoms of these deficiencies. Methadone also has profound effects on brain neurotransmitter production and function. It is also known that it creates havoc in what is called the hypothalamic-pituitary-adrenal axis…which accounts for the chronic fatigue. And like all opiates, methadone down-regulates opiate receptors in the human body thus the long lasting aches and pains associated with withdrawal. Methadone withdrawal is particularly insidious because, left untreated; these symptoms can last literally for months. Also the longer you are on methadone the more profound these changes in body and mind function.

4) Regardless of the level you decrease the dose before quitting…you will suffer some level of withdrawal…Frankly, I’ve never been able to discern much difference in the withdrawal intensity between 1 mg or 80 mg…it’s always difficult. The withdrawal is unique to each individual…I’ve had some come off 65 mg or more, and while uncomfortable, hardly seem to break a sweat. Others coming off low doses and be in pure agony. One must treat the individual, not the disease.



Nutritional treatment is essential in the recovery and withdrawal phase of any type of drug or alcohol dependency. To clarify nutritional treatment, consider the following statement:

The body on methadone, or any other mind altering drug or alcohol, is like the house that has been damaged in a storm. If you were repairing the house what building materials would you need? You would need lumber, sheet rock, shingles, and etc for the major supplies…these are the equivalent of the bodies need for protein, carbohydrates, and fats. How would you hold everything together?…nuts and bolts, nails, and screws—these are the equivalent of the bodies need for vitamins and minerals. To make the repairs we need the proper tools to cut the lumber and fit it into place…one would need the saws, the equivalent of the bodies production of enzymes…these are made from the proteins we eat…one can draw analogy after analogy to explain the necessity for nutritional treatment to facilitate one back to health…only one thing needs to be clearly understood…you put back into the body the things it needs to come back to health.

Any nutritional therapy should be adhered to for at least 90 to 180 days regardless of how you feel. Just like it takes time to alter profoundly the body’s biochemistry with drugs…it takes time to repair with proper nutrition. Oral nutrition is best but often is difficult for those in their first week of detox and recovery. Proteins, complex carbs, and essential fatty acids are necessary building blocks for repair and return of proper function of organ systems and brain neurochemistry. Vitamins and minerals are “co-factors and co-enzymes” which work on the building blocks to do repair and rebuilding. Additionally, it is always counter-productive to move from the complex to the simple…my philosophy is to start simple and move to the level of complexity that works for you…remember all patients are unique in the way they process nutrients and in their ability to maximize therapy. For more information on these necessary supplements go to www.happydestinysupplements.com

The following I suggest for those who wish to detox out-patient:



1) Pharmaceuticals: Clonidine 0.1, or 0.2 mg, twice to three times per day. Clonidine is an anti-hypertensive medication that is commonly utilized in opiate withdrawal syndromes. You must come off this medicine slowly—rebound hypertension may occur…especially if you already have high blood pressure…this medication is non-addicting; Vistaril 50-100mg…three times daily…this is a sedating antihistamine which helps with anxiety and sleep…down side is that after 10 days or so it loses its therapeutic efficacy; phenergan 25 mg tab…one every 6 hours for nausea and cramps. I may use these medications on my out/in-patient clients depending on the severity of symptoms. Imodium A/D works well for diarrhea.

2) Intra-Venous Nutritional therapy: In patient or out-patient…typically every day for the first 5-6 days, than every other day until the symptomology has subsided. These nutrient bags can contain proteins, vitamins, electrolytes, and other elements necessary for the body-mind to heal. The advantage of IV therapy is that all essential cofactors bypass compromised gut function. Only when the healing occurs will the symptoms of withdrawal disappear totally. Diarrhea is uncommon in those that receive IV nutrient therapy…but for those not so fortunate, Imodium A-D seems to work well in most. If your are a medical professional and wish I.V. treatment protocols contact me at thesourcenmc@msn.com

3) Oral nutrition: Increase the right proteins!!!! Proteins are the building blocks for neurotransmitters and neurotransmitter receptors…as well as the building blocks for your natural opiate receptors

· For 3 weeks you must remove all red meats from your diet. Red meat has chemical components that increase inflammation and pain. Fish, chicken, eggs are good sources of protein. If you are having a hard time taking in solid foods go to a health food store and buy protein powders that can be made into smoothies or drinks. You absolutely must have increased protein intake…proteins are the building blocks for all enzymes, neurotransmitters, and enzyme receptors in the body. No chemical works in the body without receptors. Just like opioids have to have opioid receptors—which are down regulated during methadone use—this is the reason people have long-lasting pain and aggravation coming off methadone…this isn’t much of a problem with heroin use because of it’s short half-life…proteins are essential for the repair work in recovery…I now use a formulation made by Neuroresearch…their Neuroreplete/D-5 protein formulas works well for those coming off of methadone, methamphetamines and benzodiazepines or any drug for that matter…for more information on this product go to www.neuroresearch.com or www.neuroreplete.com and try to find a doctor close to you that will help you get his product…in fact I treat all my methadone withdrawal patients with this formula

· L-Methionine—a sulfur bearing amino acid…necessary for the production of S-Adenosyl-methionine (SAM-e)…SAM-e is a necessary cofactor in the production of the master neurotransmitters—serotonin, dopamine, adrenalin, and nor-adrenalin…this must be added to any amino acid therapy directed at rebuilding neurotransmitter production and function…500 mg—two twice per day

· Increase your intake of raw fruits and vegetables…you get little or nothing from canned foods…fresh fruits and veges are loaded with fiber which help bind and remove toxins from your body…they also normalize gut function

· Stay off candy, and other sugar heavy foods

· Drink lots of good water, green teas are good for the antioxidants and anti-inflammatory properties…no cokes or soda waters for three weeks

· When capable you must start exercising…swimming is best because it is low impact exercise…yoga…tai chi…walking daily…detoxing or otherwise…exercise is a normal component of good health

Supplements: Some need less and some more…remember the efficacy of all nutrition and supplement use is ultimately guided by your genetics…and we are all different to some degree…This is the value of seeing a good Naturopathic physician in the state you are in…The fact is that very few Medical Doctors know anything about nutrition…70%-75% of the standard medical schools in this country have absolutely no nutritional classes what-so-ever…in the other 25 %--nutrition is often a 14-20 hour block of education and this is commonly an elective…Naturopathic physicians that are educated in a medical school environment are taught nutrition extensively with the associated biochemistry.

· I use the following with all types of drug and alcohol recovery….

· Multivitamin with a strong mineral component: in gel caps only…an excellent quality multivitamin is absolutely necessary…remember that vitamins and minerals are cofactors/coenzymes for repair, healing, and normal function of the body…most times I have patients double up on multivitamins for the first 3-4 weeks

· Mineral complex: see above

· Fish oils, or flax seed oil.: necessary for repair and proper function of cellular membranes…anti-inflammatory…these need to be mixed omega 3, omega 6, omega 9 oils—4000 to 6000 mg per day in split doses…although some can be purchased as liguids and mixed with your smoothies.

· If you don’t do the drinks…get proteins as free amino acids…double up

· L-Glutamine 500mg caps…at least 2000-3000 mg per day…split the dose so that your doing it at least twice per day…helps heal the gut and the building block for GABA…the primary inhibitory neurotransmitter…helps slow things down…Do not take GABA as a supplement…GABA is make in the brain…when out side the brain the molecule is to large to cross the blood brain barrier…the building block for GABA is L-Glutamine or Glutamic acid…these building blocks readily cross the blood brain barrier.

· Valarian Root 450 mg: Botanical that reduces anxiety and helps one to sleep…Kava, Jamaican Dog Wood, Lemon Balm, Avena are all nervine botanicals which can be used together or by self…I find the doses for each individual varies but typically 1000 to 1500 mg every 4 hours.

· Melatonin…dosages vary…this is a hormone released from the pinal gland in the human body at night time for sleep…this is essential for those coming off opioids…in my experience as little as 1 mg to 30 mg has been effective…do what you have to do…I’ve had addicts coming off $100.00 a day habits sleep 4 hours the first night…start low and add 3-5 mg every half-hour till sleep…research on healthy volunteers using up to 100 mg of melatonin in a single dose shows little side effects…Melatonin is also known as a very strong antioxidant with 1000 times the potency as Vit E…Take only at night when you would be going to bed at the regular time…the room must be dark…that’s the way this hormone is released in the natural state…

· Full Spectrum antioxidants: relieves inflammation and helps normalize inflammatory pathways and reduces damaging molecules (free radicals) present in the system while detoxing

· Vitamin C: 2000-3000 mg per day divided doses…

· Reduced L-Glutathione 300mg per day: Helps liver detox metabolites of methadone…Detoxing agents can be found in many products…most in combinations…

· Adrenal Support: Research has shown that methadone, and drug use in general, has profound effects on the adrenal glands. In fact, research shows that there is a profound negative effect by methadone on the hypothalamic-pituitary-adrenal axis. This is why those that withdraw from methadone have protracted fatigue and problems with anxiety and insomnia. I often use freeze dried adrenal extracts in treatment with fairly good results. You’ll find these products listed under names such as Adrenal Plus, or Adrenplus…the starting dose is around 1000 mg per day in split doses.

· Milk Thistle with alpha-Lipoic Acid is one combination that I use extensively---for liver repair and detoxification…1200 to 1500 mg of milk thistle and 400 mg of lipoic acid per day in split doses

This is the basics. There is absolutely no way to eliminate all the problems associated with withdrawal from methadone...one must have a supportive environment and often with daily visits from a compassionate health care provider…This will not kill you…it will be a miserable event…what kills most is the movement back to street drugs to ward off the side effects of withdrawal. If fact, cold turkey deaths coming off opioids and methadone are rare and usually associated with other health problems, or overdosing on prescription medications…withdrawal from methadone is much less of a risk than total withdrawal from alcohol. I wish you all luck on this endeavor…My compassion and empathy goes out to you…Ultimately, I know that you can do this…after all…it has to be done.



CURRICULUM VITAE

David Arneson was born on September 22, 1949 in Sidney, Montana. He graduated from Philomath High School in Philomath, Oregon in 1967. He entered the U. S. Army in 1968 and was honorably discharged in 1970. After his Army service, he went to Oregon State University for one year where he majored in Liberal Studies. In 1971 he moved to El Paso and worked for several years in the customer service industry. In 1976 he started his own contracting business to which he sold majority interest in 1992 and the remaining limited interest in 1996. In 1988 he took the opportunity to return to school and entered the University of Texas at El Paso where he received his Bachelor of Science degree in 1992 with a double major in Biology and Psychology, graduating with Honors. From 1994 to 1996, he continued his education at the University of Texas at El Paso and the El Paso Community College. In 1994 he received the necessary training to be certified by the American Board of Hypnotherapy in clinical and regression hypnotherapy. In 1996 he entered into his medical training at the Southwest College of Naturopathic Medicine where he received his Doctorate in Naturopathic Medicine in August 2000. From 1988, he has worked in both the volunteer and employee capacity in the field of addiction, as well as with the seriously mentally ill, working extensively with both adult and adolescent populations. Since October of 2000, to July 2002, he served in the capacity of Clinical/Medical Director at the Naturopathic Detox Program, a non-profit 14-28 day residential naturopathic drug and alcohol detoxification facility. Presently, he is Medical Director of The River Source Naturopathic Detox and Treatment Program in Mesa, Arizona. He is currently a part time Clinical Instructor of Naturopathic Medicine at the Southwest College of Naturopathic Medicine and Health Sciences where he supervises and trains student doctors in clinical settings. He also maintains a private practice, focusing on treatment of alcoholism, drug dependency, and chronic disease.

Subject: Methadone Treatment from the other side.

If you wish to discuss methadone or other treatment questions, you may only contact Dr. David Arneson at thesourcenmc@msn.com.

Please do not attempt to contact DPEG directly about methadone or other treatment questions

http://www.dpeg.org/treatment/methadone_withdrawal.htm