Presented by the author at the 2003 New England Forensic Sciences Conference   
   at Colby   
   College:   
      
   Polypharmacy: What Cost in Morbidity and Mortality?©   
      
   It is common practice in  Medicine to  put patients on combinations of drugs.    
   The vast   
   majority of these combinations of drugs (especially where 3 or more drugs are   
   involved)   
   have never  been studied at all, let alone in  double-blind trials ( with the   
   exception of   
   Oncology/AIDS treatment, where the toxicity of the drugs demands study);  yet   
   it is   
   frequent practice to prescribe these multiple-drug combinations.   
      
   It is well accepted in Pharmacology that it is scientifically impossible  to   
   accurately   
   predict the side effects or clinical effects of a combination of drugs without   
   studying   
   that particular  combination of drugs in test subjects. Knowledge of the   
   pharmacologic   
   profiles of the individual drugs in question does not in any way   
   assure accurate  prediction of the side effects of combinations of those   
   drugs, especially   
   when they have different mechanisms of action, which is very common because   
   polypharmacy   
   is most often prescribed to patients with "multiple illnesses".  More than   
   100,000   
   patients in this country die from identified adverse drug reactions (perhaps   
   the 4th to   
   6th leading cause of death in the U.S.)3  The number who die as a consequence   
   of   
   polypharmacy is, to my knowledge,  unknown.   
      
   The argument that the  prescribing of drugs is the "Art" of Medicine is not   
   valid in   
   defending polypharmacy, because drugs are developed (indications, dose and   
   administration,   
   etc.) and approved through a "scientific" process (double-blind,   
   placebo-controlled   
   studies).  The fact that the medicines are often prescribed for "different   
   conditions"  is   
   irrelevant (especially to the patient's physiology).  The idea that  " we are   
   doing the   
   best we can ", a frequent defense of Polypharmacy, does not in any way uphold   
   a scientific   
   argument in favor of it. (We are, indeed, trying the best we can, with tools   
   which do not   
   improve at the rate we would wish!)  The fact that "there is a limit to how   
   much research   
   can be done" in no way makes the research unnecessary in order to predict the   
   side effects   
   of specific combinations of drugs.   
      
   It has been said in the past that <30% of medical practice was backed by   
   controlled   
   studies ¹ · ². Has this changed?   How do we know?  Are we looking closely   
   enough at our   
   way of practicing Medicine?  Can the use of unstudied polypharmacy really be   
   considered   
   evidence-based, "scientific" Medicine? Can the Pathology community help   
   initiate   
   meaningful debate regarding this subject at a level that will produce more   
   widespread   
   awareness?   
      
   Charles Sullivan, D.O.   
   Oakland, ME   
      
      
   "Science progresses, funeral by funeral."  -  Max Planck   
      
   1.) Office of Technology Assessment: Assessing the efficacy and safety of   
   medical technologies. U.S. Government Printing Office, Washington, 1978   
   2.) Smith R: Where is the wisdom . . . ? the poverty of medical evidence.   
   BMJ 1991;303:798   
      
   3.) Incidence of Adverse Drug Reactions in Hospitalized Patients. JAMA.   
   1998;279:1200-1205   
      
   4. "...only about 15% of medical interventions are supported by solid   
   scientific evidence;   
   in other words, eighty-five percent are not."   
   Smith, R (editor of British Medical Journal), The ethics of ignorance, Journal   
   of Medical   
   Ethics, 1992;18:117   
      
   ==============================   
   Additional Refs:   
      
   Daubert v. Merrel Dow Pharmaceuticals 509 U.S. 579 (1993), 509,   
   579.   
      
   Goodstein, D. 2000. How Science Works. In U.S. Federal Judiciary   
   Reference Manual on Evidence, pp. 66–72.   
      
   Horrobin, D.F. 1990. The philosophical basis of peer review and the   
   suppression of innovation. J. Am. Med. Assoc. 263:1438–1441.   
      
   Horrobin, D.F. 1996. Peer review of grant applications: A harbinger   
   for mediocrity in clinical research? Lancet 348:1293-1295.   
      
   Horrobin, D.F. 1981-1982. Peer review: Is the good the enemy of the   
   best? J. Res. Commun. Stud. 3:327–334.   
      
   Rothwell, P.M. and Martyn, C.N. 2000. Reproducibility of peer   
   review in clinical neuroscience: Is agreement between reviewers any   
   greater than would be expected by chance alone? Brain   
   123:1964–1969.   
      
   Horrobin, D.F. 2000. Innovation in the pharmaceutical industry. J.   
   R. Soc. Med. 93:341–345.   
      
    Abstracts   
      
      
   David A. Flockhart, and Jose E. Tanus-Santos Implications of Cytochrome P450   
   Interactions   
   When Prescribing Medication for Hypertension   
   Archives of Internal Medicine 162: 405-412.   
      
   Kathryn A. Phillips, David L. Veenstra, Eyal Oren, Jane K. Lee, and Wolfgang   
   Sadee   
   Potential Role of Pharmacogenomics in Reducing Adverse Drug Reactions: A   
   Systematic Review   
   JAMA 286: 2270-2279.   
      
   Just Ebbesen, Ingebjørg Buajordet, Jan Erikssen, Odd Brørs, Thor Hilberg,   
   Helge Svaar, and   
   Leiv Sandvik Drug-Related Deaths in a Department of Internal Medicine   
   Archives of Internal Medicine 161: 2317-2323.   
      
   Jeffrey M. Rothschild, Frank A. Federico, Tejal K. Gandhi, Rainu Kaushal,   
   Deborah H.   
   Williams, and David W. Bates Analysis of Medication-Related Malpractice   
   Claims: Causes,   
   Preventability, and Costs   
   Archives of Internal Medicine 162: 2414-2420.   
      
   Mark T. Holdsworth, Richard E. Fichtl, Maryam Behta, Dennis W. Raisch, Elena   
   Mendez-Rico,   
   Alexa Adams, Melanie Greifer, Susan Bostwick, and Bruce M. Greenwald Incidence   
   and Impact   
   of Adverse Drug Events in Pediatric Inpatients   
   Arch Pediatr Adolesc Med 157: 60-65.   
      
   David N. Juurlink, Muhammad Mamdani, Alexander Kopp, Andreas Laupacis, and   
   Donald A.   
   Redelmeier Drug-Drug Interactions Among Elderly Patients Hospitalized for Drug   
   Toxicity   
   JAMA 289: 1652-1658.   
      
   Jason Lazarou, Bruce H. Pomeranz, and Paul N. Corey Incidence of Adverse Drug   
   Reactions in   
   Hospitalized Patients: A Meta-analysis of Prospective Studies   
   JAMA 279: 1200-1205.   
      
   Karen E. Lasser, Paul D. Allen, Steffie J. Woolhandler, David U. Himmelstein,   
   Sidney M.   
   Wolfe, and David H. Bor Timing of New Black Box Warnings and Withdrawals for   
   Prescription   
   Medications   
   JAMA 287: 2215-2220.   
      
   Abstract 1 of 8   
   Implications of Cytochrome P450 Interactions When Prescribing Medication for   
   Hypertension   
   David A. Flockhart, MD, PhD and Jose E. Tanus-Santos, MD, PhD   
      
   Arch Intern Med. 2002;162:405-412.   
   Many of the estimated 50 million Americans with high blood pressure receive   
   medications   
   for hypertension and for other conditions, placing them at risk for adverse   
   drug   
   interactions. The risk for hypertension and for adverse drug reactions is   
   highest in the   
   elderly, who have the greatest need for pharmacologic therapy. The most   
   important class of   
      
   [continued in next message]   
      
   --- SoupGate-Win32 v1.05   
    * Origin: you cannot sedate... all the things you hate (1:229/2)