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Combined drug intoxication (CDI), or multiple drug intake (MDI), is a cause of death by drug overdose from poly drug use, often implicated in polysubstance dependence.

The CDI/MDI phenomenon seems to be becoming more common in recent years. In December 2007, according to Dr. John Mendelson, a pharmacologist at the California Pacific Medical Center Research Institute, deaths by combined drug intoxication were relatively "rare" ("one in several million"), though they appeared then to be "on the rise".[1] In July 2008, the Associated Press and CNN reported on a medical study showing that over two decades, from 1983 to 2004, such deaths have soared.[2] It has also become a prevalent risk for older patients.[3]

Risk factors[edit]

People who engage in polypharmacy and other hypochondriac behaviors are at an elevated risk of death from CDI. Other dangers of combining drugs include "brain damage, heart problems, seizures, stomach bleeding, liver damage/ liver failure, heatstroke, coma, suppressed breathing, and respiratory failure", along with many other complications. Disorders like depression and anxiety can also stem from polydrug use.[4] Elderly people are at the highest risk of CDI, because of having many age-related health problems requiring many medications combined with age-impaired judgment, leading to confusion in taking medications.[2][3] Elderly patients are often prescribed more than one drug within the same drug class, and doctors may treat the side effects of prescribed drugs with even more drugs, which can overwhelm the patient.[5]


In general, the simultaneous use of multiple drugs should be carefully monitored by a qualified individual such as board certified and licensed medical doctor, either an MD or DO. Close association between prescribing physicians and pharmacies, along with the computerization of prescriptions and patients' medical histories, aim to avoid the occurrence of dangerous drug interactions. Lists of contraindications for a drug are usually provided with it, either in monographs, package inserts (accompanying prescribed medications), or in warning labels (for OTC drugs). CDI/MDI might also be avoided by physicians requiring their patients to return any unused prescriptions. Patients should ask their doctors and pharmacists if there are any interactions between the drugs they are taking.

Common combinations[edit]

Acetaminophen/paracetamol deaths[edit]

On June 30, 2009, an FDA advisory panel recommended that Vicodin and another painkiller, Percocet, be removed from the market because they have allegedly caused over 400 deaths a year.[6] The problem is with paracetamol (acetaminophen/Tylenol for example) overdose and liver damage. These two drugs, in combination with other drugs like Nyquil and Theraflu, can cause death by multiple drug intake and/or drug overdose.


Alcohol can exacerbate the symptoms and may directly contribute to increased severity of symptoms. The reasons for toxicity vary depending on the mixture of drugs. Usually, most victims die after using two or more drugs in combination that suppress breathing, and the low blood oxygen level causes brain death.[7]

Celebrity deaths because of CDI/MDI[edit]

Many celebrities have died from CDI/MDI, including:

Anna Nicole Smith and Daniel Wayne Smith[edit]

On February 8, 2007, five months after her son Daniel Wayne Smith was found dead from CDI with methadone, sertraline, and escitalopram in his system,[10] Anna Nicole Smith also died from CDI/MDI. Her two autopsies detected more than 11 drugs in her bloodstream, including chloral hydrate, clonazepam, lorazepam, oxazepam, diazepam, diphenhydramine, topiramate, oseltamivir, ciprofloxacin, methocarbamol, carisoprodol and others. The deaths of Daniel Smith and Anna Nicole Smith were declared as Combined Drug Intoxication.[11][12]

Heath Ledger[edit]

Australian actor Heath Ledger was found dead on January 22, 2008, in his SoHo, New York City, apartment; the toxicology report concluded that the cause of death was "acute intoxication" resulting from "the combined effects of oxycodone, hydrocodone, diazepam, temazepam, alprazolam, and doxylamine" and "that the manner of [his] death" was "accident, resulting from the abuse of prescription medications or combined drug intoxication (CDI)."[2][13][14]

Speedball deaths[edit]

Some speedball deaths that are diagnosed as MDI/CDI might simply be drug overdose, which is a related but completely different phenomenon. The following list is for speedball CDI/MDI deaths only. Any combination of uppers and downers can be called a speedball death.

CDI-related legal cases[edit]

Karen Ann Quinlan[edit]

The right-to-die case of then-comatose Karen Ann Quinlan (March 29, 1954 – June 11, 1985) made legal history in 1975 and 1976, stimulating public scrutiny of ethical and moral implications of her case. In 1975, after drinking gin and tonics at a party and then taking diazepam, Quinlan collapsed, suffered respiratory failure and irreversible brain damage, and, after being taken to the hospital, lapsed into a persistent vegetative state. After she had been kept alive on a ventilator for several months without improvement, her parents requested that the hospital discontinue such active care and allow her to die. The hospital refused, and the subsequent legal battles made newspaper headlines and set significant precedents. After the New Jersey Supreme Court ruled in her parents' favor, Quinlan spent nine more years comatose in the hospital, before dying from pneumonia in 1985.

Michael Jackson[edit]

The CDI/MDI death of Michael Jackson led to the trial of Conrad Murray, whose license was revoked in four states and who was sentenced to serve four years in a California prison.[15][16][17][18][19]

See also[edit]


  1. ^ a b James Montgomery (June 21, 2007). "Hawthorne Heights Guitarist Casey Calvert's Fatal Drug Interaction Was Rare, Experts Say: Number of Accidental-Interaction Deaths Still Remains Relatively Low, Although Such Incidents Are on the Rise". MTV. Retrieved August 4, 2008.
  2. ^ a b c "Home deaths from Drug Errors Soar". CNN. (Associated Press). July 28, 2008. Archived from the original on March 22, 2014. Retrieved 2008-08-04. Deaths from medication mistakes at home, such as actor Heath Ledger's accidental overdose, rose dramatically during the past two decades, an analysis of U.S. death certificates finds. ... Prescription drug abuse plays a role in the rise in fatalities, but it's unclear how much, researchers said. ... The authors blame soaring home use of prescription painkillers and other potent drugs, which 25 years ago were given mainly inside hospitals. ... 'The amount of medical supervision is going down and the amount of responsibility put on the patient's shoulders is going up,' said lead author David P. Phillips of the University of California, San Diego. ... The findings, based on nearly 50 million U.S. death certificates, are published in Monday's Archives of Internal Medicine. Of those, more than 224,000 involved fatal medication errors, including overdoses and mixing prescription drugs with alcohol or street drugs. ... Deaths from medication mistakes at home increased from 1,132 deaths in 1983 to 12,426 in 2004. Adjusted for population growth, that amounts to an increase of more than 700 percent during that time.
  3. ^ a b Rubin, Rita (December 23, 2008). "Mixing Drugs Puts More Older Patients at Risk" (Web). USA Today. Gannett Corporation. Retrieved December 24, 2008.
  4. ^ "Polydrug Abuse - Dangerous Drug Combinations". AddictionCenter. Retrieved March 28, 2019.
  5. ^ Gujjarlamudi, Hima (2016). "Polytherapy and drug interactions in elderly". Journal of Mid-Life Health. 7 (3): 105–107. doi:10.4103/0976-7800.191021. PMC 5051228. PMID 27721636.
  6. ^ Harris, Gardiner (June 30, 2009). "Ban Is Advised on 2 Top Pills for Pain Relief". New York Times. Retrieved October 10, 2019.
  7. ^ "Combined Drug Intoxication". American Outreach. (March 22, 2010).
  8. ^ "Boogaard death from alcohol, oxycodone toxicity". Archived from the original on August 15, 2011. Retrieved May 20, 2011.
  9. ^ Christina Fuoco-Karasinski (LiveDaily Contributor) (October 9, 2008). "Hawthorne Heights Stay Positive After a Rough Year". LiveDaily. Ticketmaster. Archived from the original (Web) on October 10, 2008. Retrieved December 24, 2008.
  10. ^ "Doctor: Drug Combo Killed Anna Nicole's Son: 20-year-old Mixed Methadone and Antidepressants, Pathologist Testifies". MSNBC News. (MSNBC). Archived from the original on December 12, 2007. Retrieved August 4, 2008.
  11. ^ Dan Whitcomb (Los Angeles) (April 6, 2007). "Anna Nicole Smith's Doctor in Drug Probe". The Age. Melbourne: (The Age Company Ltd.). Retrieved August 4, 2008.
  12. ^ "The Law: Drugs: Anna Nicole's Son Died From Lethal Drug Combo, Pathologist Says: Star's Son Killed by Combination of Pain Killer, Antidepressants, Pathologist Testifies". ABC News (Associated Press). December 10, 2007. Retrieved August 4, 2008.
  13. ^ Sewell Chan and James Barron (contributing) (February 6, 2008). "City Room: Heath Ledger's Death Is Ruled an Accident". The New York Times. Retrieved February 6, 2008.
  14. ^ "Ledger's Death Caused by Accidental Overdose" (Web). CNN. February 6, 2008. Retrieved February 7, 2008.
  15. ^ "Karen Ann Quinlan (Medical patient)" (Web). Who2, LLC. 2008. Retrieved December 24, 2008.
  16. ^ Lauren Marmaduke (October 21, 2011). "Music's Top 5 Dubious 'Dr. Feelgoods'". Houston Press.
  17. ^ David Batty (June 27, 2009). "In the public eye – feelgood physicians". The Guardian.
  18. ^ Steven Mikulan (November 16, 2009). "Dr. Feelgoods and Their Celeb Patients: Who Needs Who? (PART 2: Hollywood's history of addicted stars and the doctors who supply them". The Wrap.
  19. ^ Steven Mikulan. "Jailing Dr. Feelgood: Prescriptions-on-Demand Gets Riskier (First of 2 Parts:Prosecutors are targeting celeb-friendly docs, but making charges stick is tough". The Wrap.

External links[edit]

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