Polypharmacology columns published by Dr. Preskorn
Published in Journal
of Psychiatric Practice
(formerly the Journal of Practical Psychiatry and Behavioral
The polypharmacology section
The columns in this section are concerned with the patient
who is on more than one medication. This section begins with
a discussion of basic principles of pharmacology that are
particularly important to consider when treating such patients.
Subsequent columns present cases which illustrate the application
of these principles to clinical practice. Many of these case-based
columns are structured so the case is presented first allowing
the reader to take a moment to formulate how they might have
managed the patient. The column then proceeds to review what
was done followed by a discussion of the clinically important
- Jul. 2003 -- Relating
Clinical Trials to Psychiatric Practice: Part I: The Case
of a 13-Year Old on Aripiprazole and Fluoxetine
- Nov. 2003 -- Relating
Clinical Trials To Psychiatric Practice: Part II: The Gap
Between the Usual Patient in Registration Trials and in
- Mar. 2002 -- Physician
Perceptions of Drug-Drug Interactions and How to Avoid Them
-- This article discusses a presentation made at a Veterans
Administration (VA) Medical Center to a group composed mainly
of primary care physicians. The primary focus of the presentation
was to review the findings from a study of the nature and
frequency of polypharmacy in the VA.
Based on feedback from the audience, physicians are aware
of the problems inherent in the practice of polypharmacy,
but their dissatisfaction with their ability to understand
and avoid DDIs is realistic given the sheer number of potential
drug combinations that can occur in clinical practice and
the limitations of existing DDI alert systems.
- Jan. 2002 -- Drug
Approvals and Withdrawals Over the Last 60 Years
-- The human genome project and the increased understanding
of brain-specific regulatory proteins has led to a vast
increase in the number of CNS drugs brought to market as
well as the number of new indications for drugs. To put
these advances in perspective, this column will review the
number of drugs approved and withdrawn per year in the United
States during the second half of the 20th century. In addition,
this column will also discuss the limitations of the drug
development and approval process.
- Jan. 1998 -- Do
you feel lucky? - This column presents data on how
often polypharmacy is encountered in patients on antidepressants
in different clinical settings ranging from primary care
to special populations. It uses analogies to movies to make
specific take-home points. For example, what does Clint
Eastwood have to do with clinical psychopharmacology? As
the character, Dirty Harry, in the 1972 movie, he asked
the question: "Do you feel lucky?" That question
is relevant to the use of multiple drugs in a patient.
'The Good, the Bad, and the Ugly' is another title from
a Clint Eastwood movie and is also relevant to the use
of multiple medications. The consequences of using drugs
in combination can range from good to bad to downright
ugly. The question is how to achieve the good and avoid
the bad or ugly outcomes. The problem is the odds posed
by the practice of polypharmacy are substantial - over
642 billion. This column explains how these odds were
calculated and their implications for patient care.
- Jul. 1995 -- Polypharmacy:
When is it rational? - This article discusses what
principles to consider when deciding to use more than one
medication at the same time. A brief history of the use
of polypharmacy in psychiatry is discussed, along with how
new discoveries in psychotropic drug development are making
polypharmacy an increasingly important topic today. A list
of 10 criteria is provided to guide the clinician in rational
use of psychotropic polypharmacy. Each criteria is explained
in detail with examples drawn from clinical practice.
- Jan. 2001 -- Multiple
Medications, Multiple Considerations - This column
then is another in the clinical pharmacology case conference
(CPC) series, and examines issues related to the fact that
depressed patients are often in multiple medications. This
manuscript summarizes a review of current prescription data
that were extracted from the computerized pharmacy database
on 4,857 patients selected at random and 2,779 patients
selected solely based on the fact that they were taking
at least one antidepressant. Findings of this review showed
that those individuals not taking an antidepressant was
on average taking four systemically administered prescription
drugs, whereas the group taking an antidepressant was on
average taking five medications. This result, along with
other findings makes it clear that being on an antidepressant
appears to be a risk factor for being on a larger number
of medications. This column reviews the issues, including
the potential for drug-drug interactions (DDIs) given that
individuals with depression are often on multiple medications.
- Jan. 1999 -- The
slippery slide - This column shows how easy it is
to go from having the patient on one medication to multiple
medications. It discusses the importance of disciplined
empirical trials and of deciding a trial has failed.
- Nov. 1998 -- What Happened
to Tommy? -- This article illustrates two key pharmacological
principles. First, dosing rate and clearance of medications
are equally important to patient outcome because they determine
drug concentration. Second drug concentration is important
because it determines which site(s) of action will be engage
by the drug and to what extent.
- Jul. 2002 -- Fatal Drug-Drug
Interaction As a Differential Consideration in Apparent
Suicides -- This article presents a real life case
to illustrate clinical pharmacological principles. The topic
is drug drug interactions as a possible mechanism contributing
to death in drug overdoses or even as the cause of a false
positive diagnosis of suicide.
- Sep. 2002 -- Clinical
Pharmacology Case Conference: A Suicide Attempt?
-- This column is another in the series illustrating basic
clinical pharmacology principles. For this column, a case
report documenting the serious patient morbidity that can
result from CYP-enzyme-mediated drug-drug interactions,
and the hidden cost associated with such interactions will
be presented and discussed.
- Nov. 2002 -- Polypharmacy
in a Patient with Refractory Major Depression: Part I: The
Case - The goal of this column, as of all of the
columns in this series, is to provide real life examples
of such basic principles on the premise that much can be
learned from such untoward outcomes that will help prevent
future bad outcomes.
This column is another in the clinical pharmacological
case series, illustrating basic principles relevant to
the daily practice of clinical psychopharmacology. In
this first column (Part I), the case is presented followed
by a series of questions for the reader to consider. The
first and most immediate questions are then discussed.
- Jan. 2003 -- Polypharmacy
in a Case of Refractory Major Depression: Part II: Implications
for Clinical Management - This column, as part of
the clinical pharmacological case series, illustrates basic
principles relevant to the daily practice of clinical psychopharmacology.
This column continues the discussion of the clinical pharmacology
case started in Part I,
with a consideration of the remaining questions and the
implications of the case for clinical management. The brief
summary that follows and the information presented should
allow the reader to follow the discussion in this column.
Nevertheless, some may wish to read Part
I in the previous issue of the journal.
- Sep. 1997 -- "I
don't see 'em!" - "That has sometimes
been said about pharmacokinetically mediated drug-drug interactions.
However, "not seeing" does not equal "not
occurring." What makes this type of interaction problematic
is that the consequences can be "seen" but not
the cause. To illustrate this point, this column discusses
just such a case of "seeing" but not "recognizing."
- Jul. 1998 -- A message
from Titanic - The story of the Titanic has become
a common cultural experience around the world. Most of us
have vicariously experienced the horror of the crew in the
crow's nest and on the bridge as they see the iceberg dead
ahead in their path. Despite orders to reverse the engines
and turn hard to port, Titanic remains on her fatal collision
course. Why didn't the ship turn in time? Inherent in the
answer to this question and others about the Titanic is
a message for every clinician who prescribes medications.
This column, utilizes an actual case to illustrate the
Titanic's message including:
The fact that the consequences of a drug-drug interaction
can be seen but the cause missed.
Another message is how physicians, by thinking about
pharmacokinetics, and biological variance, can more safely
and effectively treat their patients whether they are
using a single medication or a combination of medications.
The fact that some medications take a long time to fully
accumulate and clear is neither good nor bad, in and of
itself. The clinically relevant issue is that physicians
need to be aware of the time course of medications and
take it into account when making treatment selections
and interpreting the patient's response to treatment.
- Mar. 1997 -- Do
you believe in magic? - We are all susceptible to
wanting to believe in magic, particularly when circumstances
seem hopeless without it. Sometimes, we are aware that we
are counting on a magical solution. At other times, we are
not. That can be the case when the clinician succumbs to
the use of "psychopharmacological magic." Unfortunately,
this practice can lead to convoluted cases of polypsychopharmacy
with adverse consequences. This subject is explored in this
column with a case-study used to illustrate some of the
- May 1999 -- A tale
of two patients - This column focuses on two frequent
dilemmas: 1) the patient who does not optimally benefit
from a drug even at its
maximum recommended dose, and 2) the patient who responds
at a dose below
the usually effective dose. Two real life case vignettes
are used to illustrate
these situations in the context of the basic principles