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Louis Lasagna, M.D.; Henry K. Beecher, M.D.
JAMA. 1954;156(3):230-234. doi:10.1001/jama.1954.02950030022008.
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The optimal dose of a drug may be defined as that dose that provides the desired therapeutic effects with a minimum of undesirable side-effects. The ease and safety with which a drug is administered is frequently related to the precision with which one can define an optimal dose for a majority of patients requiring the drug. In regard to morphine specifically, there are important reasons why its optimal dose should be carefully defined. First, it is usually employed in the treatment of acute pain when there is a premium on rapid and effective relief and little opportunity for leisurely trial and error individualization. Second, morphine can produce unpleasant and even dangerous side-effects, so that the flexibility in dosage is not as great as is permissible with a drug like penicillin, for example. Third, in regard to the risk of addiction, the view has been expressed that the use of minimal effective doses of morphine reduces the incidence of euphoria,1 and evidence has been presented that the development of physical dependence is directly related to the size of the dose administered. Fourth, it is customary for investigators to compare old and new analgesics with morphine as a standard of reference; the optimal dose of the latter drug is particularly appropriate as such a standard.


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