Dose discrepancies between the Physicians' Desk Reference and the medical literature, and their possible role in the high incidence of dose-related adverse drug events

Arch Intern Med. 2001 Apr 9;161(7):957-64. doi: 10.1001/archinte.161.7.957.


Background: Adverse drug events (ADEs) are a major cause of morbidity and mortality, and even minor ADEs may adversely affect patients' compliance with treatment. Because most ADEs are dose-related phenomena, adjusting drug dosages to account for individual patients' needs and tolerances is fundamental to good therapeutics.

Objective: To determine whether the Physicians' Desk Reference (PDR), the leading source of drug information for physicians, provides the full range of effective drug doses, especially the lowest, least ADE-prone doses of medications, for physicians to consider in treating patients.

Methods: Review of dosage guidelines and dose-response information in the PDR. Comparison with dose-response data obtained from articles listed in MEDLINE from 1966 to 2000.

Results: For many types of medications, physicians are frequently advised to use the lowest effective doses of drugs, especially initially. Yet, effective low doses determined in prerelease studies or in postrelease work are often omitted from the PDR, even when they have been recommended by expert panels.

Conclusions: Optimal therapeutics depends on the availability of comprehensive information. However, the PDR contains only the limited dose information from package inserts. Because the PDR was originally developed as a promotional device, there is no mechanism by which all clinically relevant dose-response data or important postrelease discoveries are regularly and rapidly incorporated into it. Thus, a gap exists in the availability of current and comprehensive dose information for physicians. This article provides information on lower, effective doses for 48 major medications, with an extensive reference list-a compilation of low-dose information not previously published, to our knowledge, in the medical literature. Physicians must have a readily accessible source of current and complete dose-response information to individualize drug therapy and minimize the risks of ADEs.

Publication types

  • Validation Study

MeSH terms

  • Adverse Drug Reaction Reporting Systems / standards*
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / adverse effects
  • Bias
  • Dose-Response Relationship, Drug
  • Drug Industry
  • Drug Information Services / standards*
  • Estrogens, Conjugated (USP) / administration & dosage
  • Estrogens, Conjugated (USP) / adverse effects
  • Humans
  • Needs Assessment
  • Pharmacopoeias as Topic / standards*
  • Practice Guidelines as Topic / standards*
  • Review Literature as Topic


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antihypertensive Agents
  • Estrogens, Conjugated (USP)