Dose-Response columns published by Dr. Preskorn
Published in Journal
of Psychiatric Practice
(formerly the Journal of Practical Psychiatry and Behavioral
The rationale for and clinical implications of dose-response
- 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
This column discusses what is a dose-response curve,
how it is determined, and why it is clinically important.