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Overdose

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Alcohol
Cannabis
Cocaine
Heroin
- Naloxone / Narcan and Opiate Overdose Reversal
Methadone
Methamphetamine
Prescription Opioid Analgesics
- Naloxone / Narcan and Opiate Overdose Reversal
The Bottom Line

Related Chapter:
Annual Causes of Death in the US

(Note: For an excellent training video and other materials regarding Naloxone and opiate overdose reversal, check out this resource from the Chicago Recovery Alliance, http://www.anypositivechange.org/menu.html.)

Alcohol

  1. (Alcohol Overdose) "Toxicity or overdose: In alcohol-naive people, a BAC of 300 to 400 mg/dL often causes unconsciousness, and a BAC ≥ 400 mg/dL may be fatal. Sudden death due to respiratory depression or arrhythmias may occur, especially when large quantities are drunk rapidly. This problem is emerging in US colleges but has been known in other countries where it is more common. Other common effects include hypotension and hypoglycemia.
    "The effect of a particular BAC varies widely; some chronic drinkers seem unaffected and appear to function normally with a BAC in the 300 to 400 mg/dL range, whereas nondrinkers and social drinkers are impaired at a BAC that is inconsequential in chronic drinkers."

    Source: 
    "Alcohol," The Merck Manual for Health Care Professionals, Special Subjects: Drug Use and Dependence, Alcohol (Merck & Co. Inc., last revised July 2008), last accessed August 28, 2013.
    http://www.merckmanuals.com/professional/special_subjects/drug_use_and_d...

  2. (Ethanol Poisoning) "Ethanol poisoning is caused by drinking too much alcohol."
    "Where Found: Alcohol beverages, including: beer, gin, vodka, wine, whiskey."
    "Symptoms:
    * Abdominal pain
    * Coma
    * Intestinal bleeding
    * Moving from side to side
    * Slowed breathing
    * Slurred speech
    * Stupor
    * Unable to walk normally
    * Vomiting
    "Home care: If you can wake an adult who has drank too much alcohol, move the person to a comfortable place to sleep off the effects. Make sure the person won't fall or get hurt.
    "Place the person on their side in case they throw up (vomit). DO NOT make the person throw up unless told to do so by a health care professional or Poison Control.
    "Check the person frequently to make sure their condition does not get worse.
    "If the person is not alert (unconscious) or only somewhat alert (semi-conscious), emergency assistance may be needed. When in doubt, call for medical help."
    "Survival over 24 hours past the drinking binge usually means the person will recover."

    Source: 
    "Ethanol Poisoning," MEDLINEplus Medical Encyclopedia, US National Library of Medicine (Bethesda, MD: American Accreditation HealthCare Commission, Feb. 3, 2009).
    http://www.nlm.nih.gov/medlineplus/ency/article/002644.htm

Cannabis

  1. "Tetrahydrocannabinol is a very safe drug. Laboratory animals (rats, mice, dogs, monkeys) can tolerate doses of up to 1,000 mg/kg (milligrams per kilogram). This would be equivalent to a 70 kg person swallowing 70 grams of the drug—about 5,000 times more than is required to produce a high. Despite the widespread illicit use of cannabis there are very few if any instances of people dying from an overdose. In Britain, official government statistics listed five deaths from cannabis in the period 1993-1995 but on closer examination these proved to have been deaths due to inhalation of vomit that could not be directly attributed to cannabis (House of Lords Report, 1998). By comparison with other commonly used recreational drugs these statistics are impressive."

    Source: 
    Iversen, Leslie L., PhD, FRS, "The Science of Marijuana" (London, England: Oxford University Press, 2000), p. 178, citing House of Lords, Select Committee on Science and Technology, "Cannabis — The Scientific and Medical Evidence" (London, England: The Stationery Office, Parliament, 1998).
    http://www.green215.com/sites/all/files/education_articles/Science%20Can...

  2. An exhaustive search of the literature finds no deaths induced by marijuana. The US Drug Abuse Warning Network (DAWN) records instances of drug mentions in medical examiners' reports, and though marijuana is mentioned, it is usually in combination with alcohol or other drugs. Marijuana alone has not been shown to cause an overdose death.

    Source: 
    Drug Abuse Warning Network (DAWN), available on the web at http://www.samhsa.gov/ ; also see Janet E. Joy, Stanley J. Watson, Jr., and John A. Benson, Jr., "Marijuana and Medicine: Assessing the Science Base," Division of Neuroscience and Behavioral Research, Institute of Medicine (Washington, DC: National Academy Press, 1999), available on the web at http://www.nap.edu/html/marimed/ ; and US Department of Justice, Drug Enforcement Administration, "In the Matter of Marijuana Rescheduling Petition" (Docket #86-22), September 6, 1988, p. 57.

Cocaine

  1. (Cocaine Toxicity or Overdose) "An overdose may cause severe anxiety, panic, agitation, aggression, sleeplessness, hallucinations, paranoid delusions, impaired judgment, tremors, seizures, and delirium. Mydriasis and diaphoresis are apparent, and heart rate and BP are increased. Death may result from MI or arrhythmias.
    "Severe overdose causes a syndrome of acute psychosis (eg, schizophrenic-like symptoms), hypertension, hyperthermia, rhabdomyolysis, coagulopathy, renal failure, and seizures. Patients with extreme clinical toxicity may, on a genetic basis, have decreased (atypical) serum cholinesterase, an enzyme needed for clearance of cocaine.
    "The concurrent use of cocaine and alcohol produces a condensation product, cocaethylene, which has stimulant properties and may contribute to toxicity."

    Source: 
    "Cocaine," The Merck Manual for Health Care Professionals, Special Subjects, Drug Use and Dependence, Cocaine (Merck & Co. Inc.: July 2008), last accessed Dec. 13, 2012.
    http://www.merckmanuals.com/professional/special_subjects/drug_use_and_d...

Heroin

(Note: For an excellent training video and other materials regarding Naloxone and overdose prevention, check out this resource from the Chicago Recovery Alliance, http://www.anypositivechange.org/menu.html.)

  1. (Heroin Toxicity or Overdose) "The main toxic effect is decreased respiratory rate and depth, which can progress to apnea. Other complications (eg, pulmonary edema, which usually develops within minutes to a few hours after opioid overdose) and death result primarily from hypoxia. Pupils are miotic. Delirium, hypotension, bradycardia, decreased body temperature, and urinary retention may also occur.
    "Normeperidine, a metabolite of meperidine, accumulates with repeated use (including therapeutic); it stimulates the CNS and may cause seizure activity."

    Source: 
    "Opioids," The Merck Manual for Health Care Professionals, Special Subjects: Drug Use and Dependence, Opioids (Merck & Co. Inc., last revised July 2008), last accessed Feb. 16, 2013.
    http://www.merckmanuals.com/professional/special_subjects/drug_use_and_d...

  2. "A striking finding from the toxicological data was the relatively small number of subjects in whom morphine only was detected. Most died with more drugs than heroin alone 'on board', with alcohol detected in 45% of subjects and benzodiazepines in just over a quarter. Both of these drugs act as central nervous system depressants and can enhance and prolong the depressant effects of heroin."

    Source: 
    Zador, Deborah, Sunjic, Sandra, and Darke, Shane, "Heroin-related deaths in New South Wales, 1992: toxicological findings and circumstances," The Medical Journal of Australia, 1996; 164 (4): 204-207.
    https://www.mja.com.au/journal/1996/164/4/heroin-related-deaths-new-sout...

  3. (Adulterants) "If it is not pure drugs that kill, but impure drugs and the mixture of drugs, then the myth of the heroin overdose can be dangerous. If users had a guaranteed pure supply of heroin which they relied on, there would be little more likelihood of toxic doses than occur with narcotics administered in a hospital.
    "But when people take whatever they can off the street, they have no way of knowing how the drug is adulterated. And when they decide to augment heroin's effects, possibly because they do not want to take too much heroin, they may place themselves in the greatest danger."

    Source: 
    Peele, Stanton, MD, (1998), "The persistent, dangerous myth of heroin overdose." Last accessed Jan. 12, 2013.
    http://lifeprocessprogram.com/lp-blog/library/the-persistent-dangerous-m...

  4. (Naloxone and Overdose Prevention in the EU) "In 2011, two thirds of European countries reported that ambulance personnel are trained in naloxone use; in just over half of these countries, naloxone is reported to be one of the standard medications carried in ambulances. Only Italy, Romania and the United Kingdom report the existence of community-based harm-reduction programmes that provide take-home naloxone to opioid users, their family members and carers. Legal barriers remain in place in other European countries, including Estonia, which has the highest drug-related mortality rate among adults (15–64) in the European Union. However, it was demonstrated in the United Kingdom that, with minimal training, healthcare professionals, including drug workers, can increase their knowledge, skills and confidence for managing an opioid overdose and administering naloxone (Mayet at al., 2011)."

    Source: 
    European Monitoring Centre for Drugs and Drug Addiction, "Annual report 2012: the state of the drugs problem in Europe" (Luxembourg: Publications Office of the European Union, November 2012), Catalog No. TDAC12001ENC, doi:10.2810/64775, p. 87.
    http://www.emcdda.europa.eu/publications/annual-report/2012
    http://www.emcdda.europa.eu/attachements.cfm/att_190854_EN_TDAC12001ENC_...

  5. Opiate Overdose Prevention and Treatment: Naloxone

    (Note: For an excellent training video and other materials regarding Naloxone and overdose prevention, check out this resource from the Chicago Recovery Alliance, http://www.anypositivechange.org/menu.html.)

    (Naloxone As Overdose Prevention) "The heart of the challenge is the possibility that things could be different: overdose is a public health problem that can be solved. Unlike many of the other leading causes of death, death from opioid overdose is almost entirely preventable,21 and preventable at a low cost.22 Opioids kill by depressing respiration, a slow mode of death that leaves plenty of time for effective medical intervention.23 Overdose is rapidly reversed by the administration of a safe and inexpensive drug called naloxone. Naloxone strips clean the brain’s opioid receptors and reverses the respiratory depression causing almost immediate withdrawal.24 A growing number of harm reduction organizations in the United States are offering overdose prevention programs that provide injection drug users with resuscitation training and take-home doses of naloxone.25"

    Source: 
    Burris, Scott; Beletsky, Leo; Castagna, Carolyn; Coyle, Casey; Crowe, Colin; and McLaughlin, Jennie Maura, "Stopping an Invisible Epidemic: Legal Issues in the Provision of Naloxone to Prevent Opioid Overdose," Drexel Law Review (Philadelphia, PA: Earle Mack School of Law, Spring 2009), Vol. 1, Number 2, p. 277.
    http://prescribetoprevent.org/wp-content/uploads/2012/11/burris_stopping...

  6. (Effectiveness of Naloxone Against Overdoses) "Treatment with naloxone can reverse respiratory failure within a few minutes (Darke and Hall, 1997; Physician’s Desk Reference, 2000). Naloxone is an opiate antagonist, and is thought to displace heroin at the Mu2 receptors. Physicians and emergency personnel treat patients suspected of heroin overdose by administering an initial dose of naloxone parenterally. While 2 mg are almost always sufficient to revive a patient, additional doses can be administered if the desired improvement does not occur, and smaller doses are often used to minimize the discomfort of sudden heroin withdrawal (Physician’s Desk Reference, 2000). In adults, naloxone has a half-life of between 30 and 81 minutes (Physician’s Desk Reference, 2000). Therefore, repeated administration could be necessary to reverse the effect of particularly large or long-lasting doses of heroin. (Sporer, 1999; Physician’s Desk Reference, 2000). In practice, however, a single 2 mg does is almost always sufficient. If a patient has not taken opioids, naloxone has no pharmacological effect (Darke and Hall, 1997).
    "While administration of naloxone may produce acute withdrawal symptoms in patients with heroin dependence (Physician’s Desk Reference, 2000), the drug does not have long-term or life threatening adverse effects when it is administered at therapeutic doses (Strang, et al, 1996). Naloxone has been associated with complications such as seizures and arrhythmia, (Physician’s Desk Reference, 2000) but more recent research suggests that complications are exceedingly rare, that past reports of complications may have been erroneous (Goldfrank and Hoffman, 1995), or that complications occur, if at all, in patients with pre-existing heart disease (Goldfrank and Hoffman, 1995). Naloxone is not addictive, and has no psycho-pharmacological effects."

    Source: 
    Burris, Scott; Norland, Joanna; and Edlin, Brian, "Legal Aspects of Providing Naloxone to Heroin Users in the United States," International Journal of Drug Policy, 2001, Vol. 12, pp. 237-48.
    http://papers.ssrn.com/sol3/papers.cfm?abstract_id=286850

  7. (Feasibility of Naloxone Distribution to Injection Drug Users (IDUs)) "This pilot trial is the first in North America to prospectively evaluate a program of naloxone distribution to IDUs to prevent heroin overdose death. After an 8-hour training, our study participants' knowledge of heroin overdose prevention and management increased, and they reported successful resuscitations during 20 heroin overdose events. All victims were reported to have been unresponsive, cyanotic, or not breathing, but all survived. These findings suggest that IDUs can be trained to respond to heroin overdose by using CPR and naloxone, as others have reported. Moreover, we found no evidence of increases in drug use or heroin overdose in study participants. These data corroborate the findings of several feasibility studies recommending the prescription and distribution of naloxone to drug users to prevent fatal heroin overdose."

    Source: 
    Seal, Karen H., Robert Thawley, Lauren Gee, Joshua Bamberger, Alex H. Kral, Dan Ciccarone, Moher Downing, and Brian R. Edlin, "Naloxone Distribution and Cardiopulmonary Resuscitation Training for Injection Drug Users to Prevent Heroin Overdose Death: A Pilot Intervention Study," Journal of Urban Medicine (New York, NY: New York Academy of Medicine, 2005), Vol. 82, No. 2, p. 308.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570543/pdf/nihms67318.pdf

  8. (Cost-Effectiveness of Naloxone Distribution) "Naloxone distribution was cost-effective in our base-case and all sensitivity analyses, with incremental costs per QALY [Quality-Adjusted Life-Year] gained much less than $50 000 (Table 2 and Appendix Figure 3, available at www.annals.org; see Appendix Table 3, available at www.annals.org, for detailed results of selected analyses). Cost-effectiveness was similar at starting ages of 21, 31, and 41 years; the greater QALY gains of younger persons were roughly matched by higher costs. In scenarios where naloxone administration reduced reliance on EMS, naloxone distribution was cost-saving and dominated (that is, less costly and more effective than) the no-distribution comparison. Cost-effectiveness was somewhat sensitive to the efficacy of lay-administered naloxone and the cost of naloxone but was relatively insensitive to the breadth of naloxone distribution, rates of overdose and other drug-related death, rates of abstinence and relapse, utilities, or the absolute cost of medical services. Naloxone was no longer cost-effective if the relative increase in survival was less than 0.05%, if 1 distributed kit cost more than $4480, or if average emergency care costs (as a proxy for downstream health costs) exceeded $1.1 million. A worst-case scenario, in which the likelihood of an overdose being witnessed, the effectiveness of naloxone, and the likelihood of naloxone being used were minimized and the cost of naloxone was maximized, resulted in an incremental cost of $14,000 per QALY gained. A best-case scenario, in which naloxone distribution reduced the risk for overdose, was dominant."

    Source: 
    Coffin, Phillip O., MD, and Sullivan, Sean D. PhD, "Cost-Effectiveness of Distributing Naloxone to Heroin Users for Lay Overdose Reversal," Annals of Internal Medicine 2013 Jan 1;158(1):1-9. doi: 10.7326/0003-4819-158-1-201301010-00003.
    http://www.ncbi.nlm.nih.gov/pubmed/23277895

  9. (Benefits from Naloxone Distribution) "Naloxone distribution to heroin users would be expected to reduce mortality and be cost-effective even under markedly conservative assumptions of use, effectiveness, and cost. Although the absence of randomized trial data on naloxone distribution and reliance on epidemiologic data increase the uncertainty of results, there are few or no scenarios in which naloxone would not be expected to increase QALYs [Quality-Adjusted Life-Years] at a cost much less than the standard threshold for cost-effective health care interventions. Ecological data, in fact, suggest that naloxone distribution may have far greater benefits than those forecast in this model: Reductions in community-level overdose mortality from 37% to 90% have been seen concordant with expanded naloxone distribution in Massachusetts (7), New York City (11), Chicago (10), San Francisco (9, 67, 68), and Scotland (69). Such a result is approached in this model only by maximizing the likelihood of naloxone use or by assuming that naloxone distribution reduces the risk for any overdose. Preliminary data showing that naloxone distribution is associated with empowerment and reduced HIV risk behaviors (70, 71) suggest that future research is needed to test these hypotheses."

    Source: 
    Coffin, Phillip O., MD, and Sullivan, Sean D. PhD, "Cost-Effectiveness of Distributing Naloxone to Heroin Users for Lay Overdose Reversal," Annals of Internal Medicine 2013 Jan 1;158(1):1-9. doi: 10.7326/0003-4819-158-1-201301010-00003.
    http://www.ncbi.nlm.nih.gov/pubmed/23277895

  10. (Naloxone Availability and Use in the US) "Opioid overdose, a major source of morbidity and mortality worldwide, accounts for half of the mortality among heroin users (1) and is a leading cause of death among adults in the United States (2). Naloxone is a safe, effective, short-acting opioid antagonist for intravenous, intramuscular, subcutaneous, or intranasal administration by medical personnel and—since the late 1990s—laypersons to reverse opioid overdose. (3). Naloxone distribution is endorsed by the American Medical Association, generally integrated into preexisting services, and targeted at anyone at risk for witnessing or having an opioid overdose. Naloxone “kits” are usually wallet-sized packets containing 2 doses of naloxone and other items, including syringes, brochures, simple rescue breathing masks, and brief educational materials about overdose risks and management. As of 2010, a total of 188 U.S. programs distributing naloxone reported training 53,032 persons and recording 10,171 reversals (3)."

    Source: 
    Coffin, Phillip O., MD, and Sullivan, Sean D. PhD, "Cost-Effectiveness of Distributing Naloxone to Heroin Users for Lay Overdose Reversal," Annals of Internal Medicine 2013 Jan 1;158(1):1-9. doi: 10.7326/0003-4819-158-1-201301010-00003.
    http://www.ncbi.nlm.nih.gov/pubmed/23277895

  11. (Rapid Effect)"Heroin is particularly toxic because of high lipid solubility, which allows it to cross the blood–brain barrier within seconds and achieve high brain levels.10
    "Naloxone is also lipid soluble and enters the brain rapidly. Reversal of respiratory depression is evident 3–4 minutes after IV and 5–6 minutes after subcutaneous administration.11"

    Source: 
    Etherington, Jeremy; Christenson, James; Innes, Grant; Grafstein, Eric; Pennington, Sarah; Spinelli, John J.; Gao, Min; Lahiffe, Brian; Wanger, Karen; Fernandes, Christopher, "Is early discharge safe after naloxone reversal of presumed opioid overdose?" Canadian Journal of Emergency Medicine (Ottawa, ON: Canadian Association of Emergency Physicians, July 2000), p. 160.
    http://www.cjem-online.ca/sites/default/files/pg156.pdf

  12. (Barriers to Naloxone Access) "A more prosaic, but no less important, legal barrier to widespread naloxone access is the Food and Drug Administration’s (FDA) classification of naloxone as a prescription drug. This means that public health and harm reduction agencies cannot distribute naloxone like condoms or sterile syringes. Instead, naloxone must be prescribed by a properly licensed health care provider after an individualized evaluation of the patient. Because health care providers have to be involved, naloxone programs must deal with concerns about liability, which among doctors can be powerful even when they are not wellfounded in fact.31 The prescription status raises the cost of naloxone distribution and makes it illegal to give naloxone to lay people willing to administer the drug to others suffering an overdose."

    Source: 
    Burris, Scott; Beletsky, Leo; Castagna, Carolyn; Coyle, Casey; Crowe, Colin; and McLaughlin, Jennie Maura, "Stopping an Invisible Epidemic: Legal Issues in the Provision of Naloxone to Prevent Opioid Overdose," Drexel Law Review (Philadelphia, PA: Earle Mack School of Law, Spring 2009), Vol. 1, Number 2, p. 278.
    http://prescribetoprevent.org/wp-content/uploads/2012/11/burris_stopping...

  13. (Support for Distribution of Naloxone) "Our findings that an ambulance was called while the subject was still alive in only 10% of cases, and that a substantial minority of heroin users died alone, strongly suggest that education campaigns should also emphasise that it is safer to inject heroin in the company of others, and important to call for an ambulance early in the event of an overdose. Consideration should also be given to trialling the distribution of the opioid antagonist naloxone to users to reduce mortality from heroin use."

    Source: 
    Zador, Deborah, Sunjic, Sandra, and Darke, Shane, "Heroin-related deaths in New South Wales, 1992: toxicological findings and circumstances," The Medical Journal of Australia, 1996; 164 (4): 204-207.
    https://www.mja.com.au/journal/1996/164/4/heroin-related-deaths-new-sout...

  14. "The disadvantage of continuing to describe heroin-related fatalities as 'overdoses' is that it attributes the cause of death solely to heroin and detracts attention from the contribution of other drugs to the cause of death. Heroin users need to be educated about the potentially dangerous practice of concurrent polydrug and heroin use."

    Source: 
    Zador, Deborah, Sunjic, Sandra, and Darke, Shane, "Heroin-related deaths in New South Wales, 1992: toxicological findings and circumstances," The Medical Journal of Australia, 1996; 164 (4): 204-207.
    https://www.mja.com.au/journal/1996/164/4/heroin-related-deaths-new-sout...

  15. (Overdose Prevention a Priority) "A first priority for prevention must be to reduce the frequency of drug overdoses. We should inform heroin users about the risks of combining heroin with alcohol and other depressant drugs. Not all users will act on such information, but if there are similar behavioral changes to those that occurred with needle-sharing overdose deaths could be substantially reduced. Heroin users should also be discouraged from injecting alone and thereby denying themselves assistance in the event of an overdose."

    Source: 
    Dr. W.D. Hall, "How can we reduce heroin 'overdose' deaths?" The Medical Journal of Australia (MJA 1996; 164:197).
    https://www.mja.com.au/journal/1996/164/4/how-can-we-reduce-heroin-overd...

Methadone

  1. (Factors Influencing Methadone-Related Mortality) "Still, methadone is a potent drug; fatal overdoses have been reported over the years (Baden, 1970; Gardner, 1970; Clark, et al., 1995; Drummer, et al., 1992). As with most other opioids, the primary toxic effect of excessive methadone is respiratory depression and hypoxia, sometimes accompanied by pulmonary edema and/or aspiration pneumonia (White and Irvine, 1999; Harding-Pink, 1993). Among patients in addiction treatment, the largest proportion of methadone-associated deaths have occurred during the drug's induction phase, usually when (1) treatment personnel overestimate a patient's degree of tolerance to opioids, or (2) a patient uses opioids or other central nervous system (CNS) depressant drugs in addition to the prescribed methadone (Karch and Stephens, 2000; Caplehorn, 1998; Harding-Pink, 1991; Davoli, et al., 1993). In fact, when deaths occur during later stages of treatment, other drugs usually are detected at postmortem examination (Appel, et al., 2000). In particular, researchers have called attention to the 'poison cocktail' resulting from the intake of multiple psychotropic drugs (Borron, et al., 2001; Haberman, et al., 1995) such as alcohol, benzodiazepines, and other opioids. When used alone, many of these substances are relatively moderate respiratory depressants; however, when combined with methadone, their additive or synergistic effects can be lethal (Kramer, 2003; Payte and Zweben, 1998).
    "It is important to note that postmortem blood concentrations of methadone do not appear to reliably distinguish between individuals who have died from methadone toxicity and those in whom the presence of methadone is purely coincidental (Drummer, 1997; Caplan, et al., 1983)."

    Source: 
    Center for Substance Abuse Treatment, "Methadone-Associated Mortality: Report of a National Assessment, May 8-9, 2003," CSAT Publication No. 28-03 (Rockville, MD: Center for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration, 2004), p. 11.
    http://www.atforum.com/SiteRoot/pages/addiction_resources/CSAT-MAM_Final...

  2. "Three primary scenarios characterize current reports of methadone-associated mortality:

    1. "In the context of legitimate patient care, methadone accumulates to harmful serum levels during the first few days of treatment for addiction or pain (that is, the induction period before methadone steady state is achieved or tolerance develops).
    2. "Illicitly obtained methadone is used by some individuals who have diminished or no tolerance to opioids and who may use excessive and/or repetitive doses in an attempt to achieve euphoric effects.
    3. "Methadone - either licitly administered or illicitly obtained - is used in combination with other CNS depressant agents (such as benzodiazepines, alcohol, or other opioids)."
     
    Source: 
    Center for Substance Abuse Treatment, "Methadone-Associated Mortality: Report of a National Assessment, May 8-9, 2003," CSAT Publication No. 28-03 (Rockville, MD: Center for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration, 2004), pp. 28-29.
    http://www.atforum.com/SiteRoot/pages/addiction_resources/CSAT-MAM_Final...

Methamphetamine

  1. (Methamphetamine Overdose) "Toxicity or overdose: Tachycardia, arrhythmias, chest pain, hypertension, dizziness, nausea, vomiting, and diarrhea can occur. CNS effects include acute delirium and toxic psychosis. Overdose can also cause stroke (usually hemorrhagic), seizures, muscle rigidity, and hyperthermia (> 40° C); all of these effects may precipitate rhabdomyolysis, which can lead to renal failure."

    Source: 
    "Amphetamines," The Merck Manual for Health Care Professionals, Special Subjects: Drug Use and Dependence: Amphetamines, Merck & Co. Inc. (July 2008).
    http://www.merckmanuals.com/professional/special_subjects/drug_use_and_d...

  2. (Treatment for Amphetamine Overdose) "When significant oral toxicity is recent (eg, < 1 to 2 h), activated charcoal may be given to limit absorption, although this intervention has not been shown to reduce morbidity or mortality. Urinary acidification hastens amphetamine excretion, but it may worsen myoglobin precipitation in the renal tubules and thus is not recommended.
    "Benzodiazepines are the preferred initial treatment for CNS excitation, seizures, tachycardia, and hypertension. Lorazepam 2 to 3 mg IV q 5 min titrated to effect may be used. High doses or a continuous infusion may be required. Propofol, with mechanical ventilation, may be required for severe agitation. Hypertension that does not respond to benzodiazepines is treated with nitrates (occasionally nitroprusside or other antihypertensives as needed, depending on the severity of the hypertension. β-Blockers (eg, metoprolol 2 to 5 mg IV) may be used for severe ventricular arrhythmias or tachycardia.
    "Hyperthermia can be life threatening and should be managed aggressively with sedation plus evaporative cooling, ice packs, and maintenance of intravascular volume and urine flow with IV normal saline solution."

    Source: 
    "Amphetamines," The Merck Manual for Health Care Professionals, Special Subjects: Drug Use and Dependence: Amphetamines, Merck & Co. Inc. (July 2008).
    http://www.merckmanuals.com/professional/special_subjects/drug_use_and_d...

  3. (Effects of Amphetamine Use) "A paranoid psychosis may result from long-term use; rarely, the psychosis is precipitated by a single high dose or by repeated moderate doses. Typical features include delusions of persecution, ideas of reference (notions that everyday occurrences have special meaning or significance personally meant for or directed to the patient), and feelings of omnipotence. Some users experience a prolonged depression, during which suicide is possible. Recovery from even prolonged amphetamine psychosis is usual but is slow. The more florid symptoms fade within a few days or weeks, but some confusion, memory loss, and delusional ideas commonly persist for months."

    Source: 
    "Amphetamines," The Merck Manual for Health Care Professionals, Special Subjects: Drug Use and Dependence: Amphetamines, Merck & Co. Inc. (July 2008).
    http://www.merckmanuals.com/professional/special_subjects/drug_use_and_d...

Prescription Analgesics

  1. (Medical Cannabis Laws and Opioid Overdose Mortality Rates) "In an analysis of death certificate data from 1999 to 2010, we found that states with medical cannabis laws had lower mean opioid analgesic overdose mortality rates compared with states without such laws. This finding persisted when excluding intentional overdose deaths (ie, suicide), suggesting that medical cannabis laws are associated with lower opioid analgesic overdose mortality among individuals using opioid analgesics for medical indications. Similarly, the association between medical cannabis laws and lower opioid analgesic overdose mortality rates persisted when including all deaths related to heroin, even if no opioid analgesic was present, indicating that lower rates of opioid analgesic overdose mortality were not offset by higher rates of heroin overdose mortality. Although the exact mechanism is unclear, our results suggest a link between medical cannabis laws and lower opioid analgesic overdose mortality."

    Source: 
    Bacchuber, Marcus A., MD; Saloner, Brendan, PhD; Cunningham, Chinazo O., MD, MS; and Barry, Colleen L., PhD, MPP. "Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999-2010." JAMA Intern Med. doi:10.1001/jamainternmed.2014.4005. Published online August 25, 2014.
    http://archinte.jamanetwork.com/article.aspx?articleid=1898878

  2. (Opioid Overdose Mortality Rates In States With Medical Cannabis Laws) "Although the mean annual opioid analgesic overdose mortality rate was lower in states with medical cannabis laws compared with states without such laws, the findings of our secondary analyses deserve further consideration. State-specific characteristics, such as trends in attitudes or health behaviors, may explain variation in medical cannabis laws and opioid analgesic overdose mortality, and we found some evidence that differences in these characteristics contributed to our findings. When including state-specific linear time trends in regression models, which are used to adjust for hard-to-measure confounders that change over time, the association between laws and opioid analgesic overdose mortality weakened. In contrast, we did not find evidence that states that passed medical cannabis laws had different overdose mortality rates in years prior to law passage, providing a temporal link between laws and changes in opioid analgesic overdose mortality. In addition, we did not find evidence that laws were associated with differences in mortality rates for unrelated conditions (heart disease and septicemia), suggesting that differences in opioid analgesic overdose mortality cannot be explained by broader changes in health. In summary, although we found a lower mean annual rate of opioid analgesic mortality in states with medical cannabis laws, a direct causal link cannot be established."

    Source: 
    Bacchuber, Marcus A., MD; Saloner, Brendan, PhD; Cunningham, Chinazo O., MD, MS; and Barry, Colleen L., PhD, MPP. "Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999-2010." JAMA Intern Med. doi:10.1001/jamainternmed.2014.4005. Published online August 25, 2014.
    http://archinte.jamanetwork.com/article.aspx?articleid=1898878

  3. (Prescription Opioid Overdose) "Among patients who are prescribed opioids, an estimated 80% are prescribed low doses (<100 mg morphine equivalent dose per day) by a single practitioner (7,8), and these patients account for an estimated 20% of all prescription drug overdoses (Figure 3). Another 10% of patients are prescribed high doses (≥100 mg morphine equivalent dose per day) of opioids by single prescribers and account for an estimated 40% of prescription opioid overdoses (9,10). The remaining 10% of patients are of greatest concern. These are patients who seek care from multiple doctors and are prescribed high daily doses, and account for another 40% of opioid overdoses (11). Persons in this third group not only are at high risk for overdose themselves but are likely diverting or providing drugs to others who are using them without prescriptions. In fact, 76% of nonmedical users report getting drugs that had been prescribed to someone else, and only 20% report that they acquired the drug from their own doctor (4). Furthermore, among persons who died of opioid overdoses, a significant proportion did not have a prescription in their records for the opioid that killed them; in West Virginia, Utah, and Ohio, 25%–66% of those who died of pharmaceutical overdoses used opioids originally prescribed to someone else (11–13). These data suggest that prevention of opioid overdose deaths should focus on strategies that target 1) high-dosage medical users and 2) persons who seek care from multiple doctors, receive high doses, and likely are involved in drug diversion."

    Source: 
    Kanny, Dafna; Garvin, William S.; and Balluz, Lina, "Vital Signs: Binge Drinking Prevalence, Frequency, and Intensity Among Adults — United States, 2010," Morbidity and Mortality Weekly Report (Atlanta, GA: Centers for Disease Control and Prevention, January 13, 2012) Vol. 61, No. 1, p. 10.
    http://www.cdc.gov/mmwr/pdf/wk/mm6101.pdf

  4. (Polydrug Involvement in Pharmaceutical Overdose Deaths in the US, 2010) "Opioids were frequently implicated in overdose deaths involving other pharmaceuticals. They were involved in the majority of deaths involving benzodiazepines (77.2%), antiepileptic and antiparkinsonism drugs (65.5%), antipsychotic and neuroleptic drugs (58.0%), antidepressants (57.6%), other analgesics, antipyretics, and antirheumatics (56.5%), and other psychotropic drugs (54.2%). Among overdose deaths due to psychotherapeutic and central nervous system pharmaceuticals, the proportion involving only a single class of such drugs was highest for opioids (4903/16 651; 29.4%) and lowest for benzodiazepines (239/6497; 3.7%)."

    Source: 
    Christopher M. Jones, PharmD, Karin A. Mack, PhD, and Leonard J. Paulozzi, MD, "Pharmaceutical Overdose Deaths, United States, 2010," Journal of the American Medical Association, February 20, 2013, Vol 309, No. 7, p. 658.
    http://jama.jamanetwork.com/article.aspx?articleid=1653518

  5. (Drug Overdose Deaths and Pharmaceutical Drugs, 2010) "In 2010, there were 38,329 drug overdose deaths in the United States; most (22 134; 57.7%) involved pharmaceuticals; 9429 (24.6%) involved only unspecified drugs. Of the pharmaceutical-related overdose deaths, 16,451 (74.3%) were unintentional, 3780 (17.1%) were suicides, and 1868 (8.4%) were of undetermined intent. Opioids (16,651; 75.2%), benzodiazepines (6497; 29.4%), antidepressants (3889; 17.6%), and antiepileptic and antiparkinsonism drugs (1717; 7.8%) were the pharmaceuticals (alone or in combination with other drugs) most commonly involved in pharmaceutical overdose deaths. Among overdose deaths involving opioid analgesics, the pharmaceuticals most often also involved in these deaths were benzodiazepines (5017; 30.1%), antidepressants (2239; 13.4%), antiepileptic and antiparkinsonism drugs (1125; 6.8%), and antipsychotics and neuroleptics (783; 4.7%)."

    Source: 
    Christopher M. Jones, PharmD, Karin A. Mack, PhD, and Leonard J. Paulozzi, MD, "Pharmaceutical Overdose Deaths, United States, 2010," Journal of the American Medical Association, February 20, 2013, Vol 309, No. 7, p. 658.
    http://jama.jamanetwork.com/article.aspx?articleid=1653518

  6. (Overdose Risk Based on Prescription Type) "Dunn et al4 found that risk of drug-related adverse events among individuals treated for chronic noncancer pain with opioids was increased at opioid doses equivalent to 50 mg/d or more of morphine. Our analyses similarly found that the risk of opioid overdose increased when opioid dose was equivalent to 50 mg/d or more of morphine.
    "The present study also extended prior research in several important ways. We used a large, national sample of individuals and focused exclusively on opioid overdose deaths. Because the circumstances that lead to overdose death may vary by the condition for which the opioid is prescribed and substance use disorder status, we conducted analyses for subgroups of patients, including those with cancer, acute pain, and substance use disorders.
    "The present study also extended the prior research by exploring a novel risk factor, ie, concurrent prescriptions of regularly scheduled and as-needed opioids. We found that those patients who were simultaneously treated with as-needed and regularly scheduled opioids, a strategy for treating pain exacerbations,7,8 did not have a statistically significant increased risk of opioid overdose in adjusted models. Recent treatment guidelines have indicated that the long-term safety of this strategy for pain exacerbation has not been established,5,9 and in the present study we did not find evidence of greater overdose risk associated with this treatment practice after accounting for maximum daily dose and patient characteristics."

    Source: 
    Bohnert, Amy S.B., et al., "Association Between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths," Journal of the American Medical Association, April 6, 2011, Vol 305, No. 13, pp. 1319-1320.
    http://jama.jamanetwork.com/article.aspx?articleid=896182

  7. (Overdose Risk Based on Prescription Type) "Dunn et al4 found that risk of drug-related adverse events among individuals treated for chronic noncancer pain with opioids was increased at opioid doses equivalent to 50 mg/d or more of morphine. Our analyses similarly found that the risk of opioid overdose increased when opioid dose was equivalent to 50 mg/d or more of morphine.
    "The present study also extended prior research in several important ways. We used a large, national sample of individuals and focused exclusively on opioid overdose deaths. Because the circumstances that lead to overdose death may vary by the condition for which the opioid is prescribed and substance use disorder status, we conducted analyses for subgroups of patients, including those with cancer, acute pain, and substance use disorders.
    "The present study also extended the prior research by exploring a novel risk factor, ie, concurrent prescriptions of regularly scheduled and as-needed opioids. We found that those patients who were simultaneously treated with as-needed and regularly scheduled opioids, a strategy for treating pain exacerbations,7,8 did not have a statistically significant increased risk of opioid overdose in adjusted models. Recent treatment guidelines have indicated that the long-term safety of this strategy for pain exacerbation has not been established,5,9 and in the present study we did not find evidence of greater overdose risk associated with this treatment practice after accounting for maximum daily dose and patient characteristics."

    Source: 
    Bohnert, Amy S.B., et al., "Association Between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths," Journal of the American Medical Association, April 6, 2011, Vol 305, No. 13, pp. 1319-1320.
    http://jama.jamanetwork.com/article.aspx?articleid=896182

  8. (Prescribing Patterns and Opioid Overdose-Related Deaths) "There is some evidence that higher prescribed doses increase the risk of drug overdose among individuals treated with opioids for chronic non-cancer pain.4 Specifically, the risk of drug-related adverse events is higher among individuals prescribed opioids at doses equal to 50 mg/d or more of morphine. The association of opioid prescribing patterns with risk of over-dose may vary across groups of patients; opioid treatment recommendations for pain are typically specific to particular subgroups such as those with chronic noncancer pain,5 cancer-related pain, and substance use disorders.6 However, potential subgroup differences in opioid prescribing have not been examined."

    Source: 
    Bohnert, Amy S.B., et al., "Association Between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths," Journal of the American Medical Association, April 6, 2011, Vol 305, No. 13, p. 1315.
    http://jama.jamanetwork.com/article.aspx?articleid=896182

The Bottom Line

  1. (Medical Cannabis Laws and Opioid Overdose Mortality Rates) "In an analysis of death certificate data from 1999 to 2010, we found that states with medical cannabis laws had lower mean opioid analgesic overdose mortality rates compared with states without such laws. This finding persisted when excluding intentional overdose deaths (ie, suicide), suggesting that medical cannabis laws are associated with lower opioid analgesic overdose mortality among individuals using opioid analgesics for medical indications. Similarly, the association between medical cannabis laws and lower opioid analgesic overdose mortality rates persisted when including all deaths related to heroin, even if no opioid analgesic was present, indicating that lower rates of opioid analgesic overdose mortality were not offset by higher rates of heroin overdose mortality. Although the exact mechanism is unclear, our results suggest a link between medical cannabis laws and lower opioid analgesic overdose mortality."

    Source: 
    Bacchuber, Marcus A., MD; Saloner, Brendan, PhD; Cunningham, Chinazo O., MD, MS; and Barry, Colleen L., PhD, MPP. "Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999-2010." JAMA Intern Med. doi:10.1001/jamainternmed.2014.4005. Published online August 25, 2014.
    http://archinte.jamanetwork.com/article.aspx?articleid=1898878

  2. (Opioid Overdose Mortality Rates In States With Medical Cannabis Laws) "Although the mean annual opioid analgesic overdose mortality rate was lower in states with medical cannabis laws compared with states without such laws, the findings of our secondary analyses deserve further consideration. State-specific characteristics, such as trends in attitudes or health behaviors, may explain variation in medical cannabis laws and opioid analgesic overdose mortality, and we found some evidence that differences in these characteristics contributed to our findings. When including state-specific linear time trends in regression models, which are used to adjust for hard-to-measure confounders that change over time, the association between laws and opioid analgesic overdose mortality weakened. In contrast, we did not find evidence that states that passed medical cannabis laws had different overdose mortality rates in years prior to law passage, providing a temporal link between laws and changes in opioid analgesic overdose mortality. In addition, we did not find evidence that laws were associated with differences in mortality rates for unrelated conditions (heart disease and septicemia), suggesting that differences in opioid analgesic overdose mortality cannot be explained by broader changes in health. In summary, although we found a lower mean annual rate of opioid analgesic mortality in states with medical cannabis laws, a direct causal link cannot be established."

    Source: 
    Bacchuber, Marcus A., MD; Saloner, Brendan, PhD; Cunningham, Chinazo O., MD, MS; and Barry, Colleen L., PhD, MPP. "Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999-2010." JAMA Intern Med. doi:10.1001/jamainternmed.2014.4005. Published online August 25, 2014.
    http://archinte.jamanetwork.com/article.aspx?articleid=1898878

  3. (Prescription Opioid Overdose) "Among patients who are prescribed opioids, an estimated 80% are prescribed low doses (<100 mg morphine equivalent dose per day) by a single practitioner (7,8), and these patients account for an estimated 20% of all prescription drug overdoses (Figure 3). Another 10% of patients are prescribed high doses (≥100 mg morphine equivalent dose per day) of opioids by single prescribers and account for an estimated 40% of prescription opioid overdoses (9,10). The remaining 10% of patients are of greatest concern. These are patients who seek care from multiple doctors and are prescribed high daily doses, and account for another 40% of opioid overdoses (11). Persons in this third group not only are at high risk for overdose themselves but are likely diverting or providing drugs to others who are using them without prescriptions. In fact, 76% of nonmedical users report getting drugs that had been prescribed to someone else, and only 20% report that they acquired the drug from their own doctor (4). Furthermore, among persons who died of opioid overdoses, a significant proportion did not have a prescription in their records for the opioid that killed them; in West Virginia, Utah, and Ohio, 25%–66% of those who died of pharmaceutical overdoses used opioids originally prescribed to someone else (11–13). These data suggest that prevention of opioid overdose deaths should focus on strategies that target 1) high-dosage medical users and 2) persons who seek care from multiple doctors, receive high doses, and likely are involved in drug diversion."

    Source: 
    Kanny, Dafna; Garvin, William S.; and Balluz, Lina, "Vital Signs: Binge Drinking Prevalence, Frequency, and Intensity Among Adults — United States, 2010," Morbidity and Mortality Weekly Report (Atlanta, GA: Centers for Disease Control and Prevention, January 13, 2012) Vol. 61, No. 1, p. 10.
    http://www.cdc.gov/mmwr/pdf/wk/mm6101.pdf

  4. "In 2009, 1.2 million emergency department (ED) visits (an increase of 98.4% since 2004) were related to misuse or abuse of pharmaceuticals, compared with 1.0 million ED visits related to use of illicit drugs such as heroin and cocaine (3)."

    Source: 
    Centers for Disease Control and Prevention, "Vital Signs: Overdoses of Prescription Opioid Pain Relievers — United States, 1999–2008," Morbidity and Mortality Weekly Report (Atlanta, GA: 2011), Vol. 60, No. 43, p. 1487.
    http://www.cdc.gov/mmwr/pdf/wk/mm6043.pdf

  5. (Polydrug Involvement in Pharmaceutical Overdose Deaths in the US, 2010) "Opioids were frequently implicated in overdose deaths involving other pharmaceuticals. They were involved in the majority of deaths involving benzodiazepines (77.2%), antiepileptic and antiparkinsonism drugs (65.5%), antipsychotic and neuroleptic drugs (58.0%), antidepressants (57.6%), other analgesics, antipyretics, and antirheumatics (56.5%), and other psychotropic drugs (54.2%). Among overdose deaths due to psychotherapeutic and central nervous system pharmaceuticals, the proportion involving only a single class of such drugs was highest for opioids (4903/16 651; 29.4%) and lowest for benzodiazepines (239/6497; 3.7%)."

    Source: 
    Christopher M. Jones, PharmD, Karin A. Mack, PhD, and Leonard J. Paulozzi, MD, "Pharmaceutical Overdose Deaths, United States, 2010," Journal of the American Medical Association, February 20, 2013, Vol 309, No. 7, p. 658.
    http://jama.jamanetwork.com/article.aspx?articleid=1653518

  6. (Drug Overdose Deaths and Pharmaceutical Drugs, 2010) "In 2010, there were 38,329 drug overdose deaths in the United States; most (22 134; 57.7%) involved pharmaceuticals; 9429 (24.6%) involved only unspecified drugs. Of the pharmaceutical-related overdose deaths, 16,451 (74.3%) were unintentional, 3780 (17.1%) were suicides, and 1868 (8.4%) were of undetermined intent. Opioids (16,651; 75.2%), benzodiazepines (6497; 29.4%), antidepressants (3889; 17.6%), and antiepileptic and antiparkinsonism drugs (1717; 7.8%) were the pharmaceuticals (alone or in combination with other drugs) most commonly involved in pharmaceutical overdose deaths. Among overdose deaths involving opioid analgesics, the pharmaceuticals most often also involved in these deaths were benzodiazepines (5017; 30.1%), antidepressants (2239; 13.4%), antiepileptic and antiparkinsonism drugs (1125; 6.8%), and antipsychotics and neuroleptics (783; 4.7%)."

    Source: 
    Christopher M. Jones, PharmD, Karin A. Mack, PhD, and Leonard J. Paulozzi, MD, "Pharmaceutical Overdose Deaths, United States, 2010," Journal of the American Medical Association, February 20, 2013, Vol 309, No. 7, p. 658.
    http://jama.jamanetwork.com/article.aspx?articleid=1653518

  7. (Overdose Risk Based on Prescription Type) "Dunn et al4 found that risk of drug-related adverse events among individuals treated for chronic noncancer pain with opioids was increased at opioid doses equivalent to 50 mg/d or more of morphine. Our analyses similarly found that the risk of opioid overdose increased when opioid dose was equivalent to 50 mg/d or more of morphine.
    "The present study also extended prior research in several important ways. We used a large, national sample of individuals and focused exclusively on opioid overdose deaths. Because the circumstances that lead to overdose death may vary by the condition for which the opioid is prescribed and substance use disorder status, we conducted analyses for subgroups of patients, including those with cancer, acute pain, and substance use disorders.
    "The present study also extended the prior research by exploring a novel risk factor, ie, concurrent prescriptions of regularly scheduled and as-needed opioids. We found that those patients who were simultaneously treated with as-needed and regularly scheduled opioids, a strategy for treating pain exacerbations,7,8 did not have a statistically significant increased risk of opioid overdose in adjusted models. Recent treatment guidelines have indicated that the long-term safety of this strategy for pain exacerbation has not been established,5,9 and in the present study we did not find evidence of greater overdose risk associated with this treatment practice after accounting for maximum daily dose and patient characteristics."

    Source: 
    Bohnert, Amy S.B., et al., "Association Between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths," Journal of the American Medical Association, April 6, 2011, Vol 305, No. 13, pp. 1319-1320.
    http://jama.jamanetwork.com/article.aspx?articleid=896182

  8. "DAWN accepts reports of illicit drugs, alcohol, prescription and over-the-counter pharmaceuticals, dietary supplements, and non-pharmaceutical inhalants. Multiple substances (as many as 6) can be reported for a single case. In 2003, the typical DAWN case involved between 2 and 3 drugs. Multiple drugs were as common in drug misuse deaths as in drug-related suicide cases; each averaged 2.7 drugs per case.
    "When multiple drugs are involved in a single case, the cause of death often cannot be attributed to any one substance. Instead, the cause may be attributed to 'combined effects' of multiple drugs. To illustrate this important concept, the area profiles in this publication differentiate the number of deaths that involved only one drug (termed 'single-drug' deaths) from all deaths. On average, participating metropolitan areas reported only 24% of drug misuse deaths (range 2% to 50%) and 19% of drug-related suicides (range 0% to 50%) with a single drug. Similarly, in the 6 States 24% of misuse deaths (range 7% to 35%) and 27% of drug-related suicides (range 10% to 57%) involved a single drug."
    "Across the metropolitan areas, the most common single-drug deaths involved opiates/opioids alone, followed by cocaine and stimulants. The most frequent multiple-drug deaths involved various combinations of opiates/opioids, cocaine, and alcohol. In new DAWN, alcohol is reported in combination with other drugs and, for individuals under age 21, alcohol is reported even when no other drugs are present. Across the 32 metropolitan areas, the most common unique combinations were: Cocaine with opiates/opioids, Alcohol with opiates/opioids, Alcohol with cocaine and opiates/opioids, and Alcohol with cocaine."

    Source: 
    Source: Substance Abuse and Mental Health Services Administration, Office of Applied Studies "Drug Abuse Warning Network, 2003: Area Profiles of Drug-Related Mortality," DAWN Series D-27, DHHS Publication No. (SMA) 05-4023. Rockville, MD, 2005, p. 17.
    http://www.samhsa.gov/data/DAWN/files/ME2003/ME03FullReport.pdf

  9. (Overdose Risk Based on Prescription Type) "Dunn et al4 found that risk of drug-related adverse events among individuals treated for chronic noncancer pain with opioids was increased at opioid doses equivalent to 50 mg/d or more of morphine. Our analyses similarly found that the risk of opioid overdose increased when opioid dose was equivalent to 50 mg/d or more of morphine.
    "The present study also extended prior research in several important ways. We used a large, national sample of individuals and focused exclusively on opioid overdose deaths. Because the circumstances that lead to overdose death may vary by the condition for which the opioid is prescribed and substance use disorder status, we conducted analyses for subgroups of patients, including those with cancer, acute pain, and substance use disorders.
    "The present study also extended the prior research by exploring a novel risk factor, ie, concurrent prescriptions of regularly scheduled and as-needed opioids. We found that those patients who were simultaneously treated with as-needed and regularly scheduled opioids, a strategy for treating pain exacerbations,7,8 did not have a statistically significant increased risk of opioid overdose in adjusted models. Recent treatment guidelines have indicated that the long-term safety of this strategy for pain exacerbation has not been established,5,9 and in the present study we did not find evidence of greater overdose risk associated with this treatment practice after accounting for maximum daily dose and patient characteristics."

    Source: 
    Bohnert, Amy S.B., et al., "Association Between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths," Journal of the American Medical Association, April 6, 2011, Vol 305, No. 13, pp. 1319-1320.
    http://jama.jamanetwork.com/article.aspx?articleid=896182

  10. (Prescribing Patterns and Opioid Overdose-Related Deaths) "There is some evidence that higher prescribed doses increase the risk of drug overdose among individuals treated with opioids for chronic non-cancer pain.4 Specifically, the risk of drug-related adverse events is higher among individuals prescribed opioids at doses equal to 50 mg/d or more of morphine. The association of opioid prescribing patterns with risk of over-dose may vary across groups of patients; opioid treatment recommendations for pain are typically specific to particular subgroups such as those with chronic noncancer pain,5 cancer-related pain, and substance use disorders.6 However, potential subgroup differences in opioid prescribing have not been examined."

    Source: 
    Bohnert, Amy S.B., et al., "Association Between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths," Journal of the American Medical Association, April 6, 2011, Vol 305, No. 13, p. 1315.
    http://jama.jamanetwork.com/article.aspx?articleid=896182