Dose-Response columns published by Dr. Preskorn
Published in Journal of Psychiatric Practice
(formerly the Journal of Practical Psychiatry and Behavioral Health)

The rationale for and clinical implications of dose-response curves

  • Nov. 1996 -- If Lack of Concentration Didn't Cause the Fall, What Did? - In the question and answer period following a lecture, I am frequently asked by a physician in the audience: "Why didn't my patient get better? I had him/her on the usually effective dose and even had therapeutic plasma drug levels." It is a tough but fair question. It emphasizes that physicians are less interested in what happens to the "usual" patient than in what happens to their specific patients. There is no single answer to this question; rather, a series of factors must be systematically explored.

    This column addresses these factors and our increasing ability to understand and make
    appropriate adjustments for the patient who falls off the dose-response curve despite being on the "usually effective" dose and achieving "usually effective" plasma drug levels. To provide the backdrop for this discussion, this column briefly reviews some points covered in more detail in earlier columns.

  • Sep. 1996 -- To Monitor or Not to Monitor, II: The Glass Is More Than Half Full - In law, there are several different levels of proof: probable cause, preponderance, clear and convincing, and beyond a reasonable doubt. In interpreting the results of therapeutic drug monitoring (TDM in most areas of medicine and certainly in psychiatry, we are generally at the level of clear and convincing for toxicity and at the level of preponderance for efficacy. In other words, the glass of evidence is somewhat more than half full when it comes to TDM and efficacy.

    This column, continues the discussion of the role of TDM in psychiatry to the issue of efficacy.

  • May 1996 -- To Monitor or Not to Monitor? - That is the question. When is it nobler and better patient care to use therapeutic drug monitoring (TDM) as opposed to the time honored approach of dose titration based on clinical assessment of response?

    This column discusses the primary goal of TDM -- to increase the safety of treatment by avoiding high concentrations that are associated with an increased risk of toxicity. The ultimate goal of TDM, and of good patient care in general, is to reduce the variance in response and make it more predictable.

  • Mar. 1996 -- Have You Phenotyped Your Patient Lately? - This column discusses why different patients respond differently to the same dose of the same drug. This column focuses on the role of TDM, which is a refinement of the standard dose-response strategy and involves measuring the concentration of the drug achieved in a specific patient on a specific dose. The concentration in plasma is typically used as a surrogate for the concentration at the site of action because it is relatively easy to obtain and is correlated with concentration in other body compartments (e.g., a specific receptor in the brain). The goal of TDM is typically to ensure that the patient is on a dose that will produce a plasma drug concentration within a range that provides a therapeutically desired response in the majority of patients without undue adverse effects. Advances such as TDM have been made possible by research in clinical pharmacology and pharmacogenetics. They can help clinicians detect the reasons behind the interindividual differences that determine much of the variance in response among patients receiving the same dose of the same drug.

  • Jan. 1996 -- Why Did Terry Fall Off the Dose-Response Curve? - This column addresses a frequent, vexing problem in clinical psychopharmacology: Why some patients do not respond optimally to the usually effective dose of a medication.

    Patients may fall off the standard dose-response curve in several ways: the patient who does not improve on the usually optimal dose (i.e., an insensitive benefit outlier) or who does not tolerate the usually optimal dose (i.e., a sensitive tolerance outlier). There is also the inverse of each of these categories: the patient who responds at a dose much smaller than is usually necessary (i.e., the sensitive benefit outlier) or who appears to tolerate a much higher dose than usual (i.e., an insensitive tolerance outlier). While the latter two types of patient typically cause less clinical concern, they are of equal scientific interest.

    This column discusses what is a dose-response curve, how it is determined, and why it is clinically important.


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