Source: Los Angeles Times (CA) Contact: http://www.latimes.com/ Pubdate: Tue, 14 Apr 1998 Author: Terence Monmaney MEDICATIONS KILL 100,000 ANNUALLY, STUDY SAYS Health: Adverse reactions to prescribed drugs are found to be far more common than previously thought. But some question research methods. Properly prescribed medications may kill more than 100,000 people a year, taking more lives than diabetes or pneumonia, according to a new analysis that suggests prescription medications cause more harm than previously believed. The study, appearing today in the Journal of the American Medical Assn., estimates that 76,000 to 137,000 people died in 1994 from such treatments. That would make so-called adverse drug reactions between the sixth and fourth leading cause of death in the United States. Moreover, of the 33 million hospitalized patients in 1994, some 2.2 million had a nonfatal reaction serious enough to require medical attention, the researchers say. Although some experts questioned the study's methods, the new estimates put the problem in the most dramatic light yet. The study ''puts into clear perspective that adverse drug reactions are a major form of death and injury that can be prevented,'' said Dr. Sidney Wolfe, director of the Public Citizen Health Research Group. He said the injuries and deaths detailed in the study are nearly twice as high as estimates recently done by his consumer group. The findings should not encourage people to abandon vital medications, said the study's leader, Dr. Bruce Pomeranz of the University of Toronto, who said he was surprised by the death toll. ''What's needed is more awareness of the potential problems with taking some drugs. Before you take a medication you should know about its risk-benefit ratio,'' he said. In addition, Pomeranz and other researchers say that the new findings should spur hospitals and doctors to monitor patients more closely to reduce potential toxic drug reactions. The Pharmaceutical Research and Manufacturers of America, an drug industry group, cautioned patients not to panic. ''Prescription medicines are safe and effective when used properly,'' president Alan Holmer said in a statement. The analysis did not specify which drugs were most risky or what diseases patients had when the adverse reactions occurred. But other studies have found that the drug types causing the most serious medical problems in hospitalized patients are painkillersfrom narcotics that halt breathing to aspirin pills that induce stomach bleeding; antibiotics and antiviral drugs, which can cause severe diarrhea, and cardiovascular and anticoagulant drugs, which can cause a range of problems including internal bleeding. In addition, some people are allergic or sensitive to particular drugs, while other bad reactions happen when two or more drugs are combined. For instance, the widely prescribed allergy drug terfenidine, or Seldane, was withdrawn from the market this year after reports that it triggered heart rhythm problems in people also taking the commonly administered antibiotic erythromycin. Adverse drug reactions especially trouble the elderly, experts say, because they are more likely to have multiple underlying health problems and also tend to have a weakened liver and kidneys, the organs that break down and eliminate medications. Medical researchers believe that adverse drug reactions have been underestimated for years. That is chiefly because hospitals and physicians seldom report such reactions, dismiss them as unavoidable or mistake them for disease symptoms. The U.S. Health Care Financing Administration last fall proposed new federal regulations requiring hospitals to step up drug-reaction monitoring. But some physicians have criticized the proposed monitoring system, which would involve periodic reviews of patient charts, as intrusive and costly. In their study, the Toronto researchers pooled and analyzed data from 39 U.S. studies on adverse drug reactions published between 1964 and 1996. They looked at two groups: Patients who underwent an adverse drug reaction while in the hospital that was at least serious enough to prolong their stay, and also outpatients who had a drug reaction bad enough to hospitalize them. While other studies have looked at those two groups separately, this was the first to combine them, leading to the ''extremely high'' prevalence of drug reactions, as the researchers called it. Between the upper and lower fatality estimates is the midpoint of 106,000 drug-induced deaths. That means that in 1994 - which the researchers chose as a representative year - 0.32% of patients on a prescription drug, or three out of every thousand, had a fatal reaction. Their approach was ''conservative,'' the researchers said, in that they focused only on correctly prescribed drugs. Their analysis did not consider other sources of prescription drug problems, such as patient compliance errors, intentional overdoses, narcotic abuse and accidental poisonings. Nor did the researchers consider the presumably large number of people with bad drug reactions who were not subsequently hospitalized. ''The truth is we missed a lot of people,'' Pomeranz says, including those who ''died at home.'' Still, other researchers questioned aspects of the study because it is a ''meta-analysis,'' which involves statistically analyzing data pooled from other studies, rather than studying real people. It is often difficult to establish that a very sick person died from a drug reaction rather than an underlying illness, said Dr. John Burke, a medical epidemiologist at LDS Hospital in Salt Lake City, who has studied adverse drug reactions. He urged caution in accepting the study as fact, but also praised it as a ''spur to action'' in attacking the problem of adverse drug reactions. At LDS Hospital, which has one of the nation's few computer systems for linking drug reactions and patient records, doctors have reduced adverse events by 50%. Dr. David Bates of the Brigham and Women's Hospital in Boston, who has studied hospital reporting of adverse drug reactions, said ''even if the true incidence of [adverse drug reactions] is somewhat lower'' than the Toronto researchers say ''. . . it is still high, and much higher than generally recognized.'' Wolfe, co-author of the book ''Worst Pills, Best Pills,'' said the analysis underscored that the United States is ''an over-medicated society.'' Patients being prescribed a drug should ask if it is absolutely necessary, he said, and should also be sure to tell doctors of any other drugs they may already be taking.