Multiple Medicines a slippery slope

The use of multiple medications that, taken in combination, can cause adverse effects for patients is an emerging problem as Americans live longer and seek treatments for a variety of ills. Some health experts say the problem of polypharmacy is increased by direct-to-consumer advertising that prompts patients to ask their doctors for the drugs being promoted.

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 ’ · ”. 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.
15 Evergreen Dr
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,

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

Horrobin, D.F. 2000. Innovation in the pharmaceutical industry. J.
R. Soc. Med. 93:341–345.


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.

Share with Others

Leave A Reply

Your email address will not be published.

This site uses Akismet to reduce spam. Learn how your comment data is processed.