Surveillance of Prescription Drug-Related Mortality Using Death Certificate Data

AbstractBackground: The prescription drugs or drug classes that are most frequently associated with death in the US might be identifiable from death certificate data. Objective: To identify the drugs/drug classes associated with the greatest numbers of deaths in the US that might be considered as possible targets for prevention. Study design: US vital statistics data were accessed in order to identify International Classification of Diseases (10th Revision) [ICD-10] codes indicating that prescription drugs had caused or contributed to death and diseases with significant drug-related mortality. Main outcome measure: ICD-10 codes for primarily prescription drugs that were listed as the underlying cause or as ‘total mentions’ on death certificates and were implicated in ≥1000 deaths in any one year were selected. The annual number of deaths by ICD-10 code was obtained from the Division of Vital Statistics, National Center for Health Statistics. Codes for diseases with significant drug-related aetiologies and involvement in ≥1000 deaths in any one year were also identified and analysed separately. Results: For the selected ICD-10 codes, a total of 25 031 deaths were listed as having a prescription drug as the underlying cause in 2003, compared with 16 135 in 1999, a 55% increase. Total mentions of these codes increased from 46 523 in 1999 to 72 080 in 2003, also a 55% increase. Most codes involved ‘poisonings’ (overdose or the wrong substance given or taken in error that is accidental, intentional or with undetermined intent). Drugs associated with poisoning deaths had central nervous system effects. Among the codes associated with specified drug classes, poisonings and accidental poisonings involving narcotics, hallucinogens, psychoactive substances and opioids (other than opium and heroin) were associated with the largest numbers of deaths. Drug-related codes associated with the largest percentage increases in deaths between 1999 and 2003 included poisoning due to methadone (275%); poisoning by other and unspecified antidepressants (primarily selective serotonin reuptake inhibitors) [130%]; and poisoning by psychostimulants with potential for abuse (amfetamines and drugs for attention deficit hyperactivity disorder) [117%]. Anticoagulants were associated with the largest numbers of deaths with codes involving “adverse effects in therapeutic use”. Among diseases with significant drug-related aetiologies, Clostridium difficile enterocolitis (associated primarily with antibacterials) had the largest percentage increase in total mentions, with a 203% rise between 1999 and 2003. Conclusions: Deaths due to overdoses are the most prominent cause of drug-related mortality in death certificate data. Certain drugs and drug classes, especially the opioids (e.g. narcotics, methadone), psychoactive drugs (e.g. antidepressants, amfetamines), anticoagulants and antibacterials (which cause or contribute to C. difficile enterocolitis) are associated with large and increasing numbers of deaths and preventive strategies should be considered.

[1]  S. Shapiro,et al.  Agranulocytosis in Bangkok, Thailand: a predominantly drug-induced disease with an unusually low incidence. Aplastic Anemia Study Group. , 1999, The American journal of tropical medicine and hygiene.

[2]  D. Wysowski,et al.  Reports of Death with Use of Propofol (Diprivan) for Nonprocedural (Long-term) Sedation and Literature Review , 2006, Anesthesiology.

[3]  S. Glazier,et al.  Metabolic acidosis, rhabdomyolysis, and cardiovascular collapse after prolonged propofol infusion. , 2001, Journal of neurosurgery.

[4]  D. Wysowski Increase in deaths related to enterocolitis due to Clostridium difficile in the United States, 1999-2002. , 2006, Public health reports.

[5]  R. Hoffman,et al.  The fentanyl tea bag. , 2004, Veterinary and human toxicology.

[6]  Yongli Xi,et al.  Increasing deaths from opioid analgesics in the United States , 2006, Pharmacoepidemiology and drug safety.

[7]  G. Woody,et al.  Prescribing methadone as an analgesic. , 2005, Annals of internal medicine.

[8]  T. Gross,et al.  Myopathy and rhabdomyolysis associated with lovastatin-gemfibrozil combination therapy. , 1990, JAMA.

[9]  J. Bartlett,et al.  The new Clostridium difficile--what does it mean? , 2005, The New England journal of medicine.

[10]  G. Melli,et al.  Rhabdomyolysis: An Evaluation of 475 Hospitalized Patients , 2005, Medicine.

[11]  M. Meadows Proper use of fentanyl pain patches. , 2006, FDA consumer.

[12]  Mark R. Mueller,et al.  Unintentional prescription drug overdose deaths in New Mexico, 1994-2003. , 2006, American journal of preventive medicine.

[13]  D. Wysowski,et al.  Adverse drug event surveillance and drug withdrawals in the United States, 1969-2002: the importance of reporting suspected reactions. , 2005, Archives of internal medicine.

[14]  J. Inciardi,et al.  Diversion and abuse of methadone prescribed for pain management. , 2005, JAMA.

[15]  Ruth E. Winecker,et al.  Fatal intravenous fentanyl abuse: four cases involving extraction of fentanyl from transdermal patches. , 2004, The American journal of forensic medicine and pathology.

[16]  T. Scalea,et al.  Exercise-induced rhabdomyolysis. , 1994, Annals of emergency medicine.

[17]  X. Vidal,et al.  Population-based drug-induced agranulocytosis. , 2005, Archives of internal medicine.

[18]  D. Spyker,et al.  Oxycodone involvement in drug abuse deaths: a DAWN-based classification scheme applied to an oxycodone postmortem database containing over 1000 cases. , 2003, Journal of analytical toxicology.

[19]  Louis Valiquette,et al.  Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity , 2004, Canadian Medical Association Journal.

[20]  W. Schaffner,et al.  Nonsteroidal anti-inflammatory drug use and death from peptic ulcer in elderly persons. , 1988, Annals of internal medicine.

[21]  Ken Dewar,et al.  A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. , 2005, The New England journal of medicine.

[22]  Analyzing Prescription Drugs as Causes of Death on Death Certificates , 2004, Public health reports.

[23]  Richard Platt,et al.  Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. , 2004, JAMA.

[24]  J. Hallas,et al.  Complicated and Uncomplicated Peptic Ulcers in a Danish County 1993–2002: A Population-Based Cohort Study , 2006, The American Journal of Gastroenterology.