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

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 take-home points.

  • 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 Practice

  • 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 To put these advances in perspective, this column will review the number of drugs approved and withdrawn per year in the United States during the second half of the 20th century.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 pharmacodynamics,
    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 major points.

  • May 1999 -- A tale of two patients - This column focuses on two frequent clinical
    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 of clinical


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