The interaction index: a measure of drug synergism

Pain. 2002 Jul;98(1-2):163-8. doi: 10.1016/s0304-3959(02)00041-6.


Two drugs used in combination may produce enhanced or reduced effects. The degree of enhancement or reduction is measured from the interaction index (gamma), a quantity that indicates the changed potency of the combination. The index is therefore a quantitative marker for the drug combination and effect metric used. Methodology for measuring the interaction index utilizes the combination and individual drug dose-effect data suitably modeled by regression techniques that most often produce linear plots of effect on log dose from which isobolar analysis is employed. The isobologram provides a simple and convenient graphical assessment of the interaction index but an independent statistical analysis is needed to assess its precision. In some cases, the relative potency of the constituent drugs is the same at all effect levels. When this is so, it is shown that the interaction index can be measured by either an isobolar or an alternate method that is illustrated here. These calculations demonstrate that these different methods of analysis yield the same value of gamma, and do so with comparable precision.

MeSH terms

  • Analgesics / pharmacology
  • Analgesics, Opioid / pharmacology
  • Animals
  • Clonidine / pharmacology
  • Drug Synergism*
  • Models, Theoretical*
  • Morphine / pharmacology
  • Pharmacology / methods*


  • Analgesics
  • Analgesics, Opioid
  • Morphine
  • Clonidine