The Clinical Use of Antipsychotic Plasma Levels: Stahl's Handbooks Paperback – 30 September 2021

This is a very well written and informative textbook covering an area that may not be the sexiest in prescribing of medication, but sure matters in terms of helping patients get better outcomes, and should be a cornerstone textbook for specialists prescribing antipsychotic medications

Meyer and Stahl's book is well written, evidence-based and scientific. The authors compile and analyze the relevant literature regarding serum levels including threshold for response and point of futility. This is an indispensable resource particularly for anybody working with patients with severe and persistent mental illness

Es un libro muy recomendable para el médico que requiere manejar clozapina. Bien sea para el inicio, como el mantenimiento, el retiro y el abordaje de los efectos adversos.La versión recomendada es esta. La traducción al español es terrible e incluso muchas veces no se puede entender.

This book helps you treat complicated psychotic patients using state of the art methods of utilizing blood levels. You will leave understanding the why behind blood levels. Dr. Puder did an interview with him on Psychiatry & Psychotherapy Podcast. Would highly recommend this book to any serious mental health professional treating psychosis.

Therapeutic Drug Monitoring (TDM) emerged in the 1960s and 70s following improvements in drug assays, and the prescribing of some notable examples, such as phenytoin, digoxin, gentamicin, and lithium gained precision. Extension of TDM to tricyclic antidepressants and particularly to antipsychotics (neuroleptics) was more challenging, especially with phenothiazines (e.g. chlorpromazine). Success came when gas chromatography with the nickel-63 detector of Lovelock was applied to the problem, leading to the first report of instrumentalized chromatography being applied to tricyclic drugs. Chlorpromazine concentrations in patients were found to show a massive and variable “first-pass effect”, immense variations between patients considered to be achieving the maximum possible clinical effect, and lack of predictability of long-term “steady-state” concentrations - in the first six weeks of treatment with a fixed dose, after relatively high concentrations from early doses, daily mean concentrations of chlorpromazine declined, while clinical rating improved. Consequently, any attempts at TDM that disregarded time-dependent changes were destined to be difficult. The fact that the relationship between effect and concentration changed as the disease progressed, and as the effect developed, defied standard concepts of Pharmacology, and caused nightmares in scientists looking for simple concepts applicable across the board!The earliest scientific studies reported a low plasma threshold below which the chances of therapeutic success were minimal, and an upper level above which therapeutic failure was likely, presumably caused by chlorpromazine toxicity enhanced by the similarity of the signs of the disease and the central anticholinergic side effect syndrome common with tricyclic antipsychotics and antidepressants, defining the limits of a range between lower and upper points (the U-shaped clinical relationship) that is a major focus of this book. Meyer and Stahl have shown that the original observations concerning first-pass effects, the U-shaped clinical relationship (since extended to haloperidol and clozapine in particular, and to approximately 15 other drugs), great interpatient variation, and the pharmacokinetic justification for intramuscular dosing remain intact, and that they apply widely across the various antipsychotics, old and new. While the term “therapeutic threshold” is already widely used for the lower limit, Meyer and Stahl have labelled the upper limit of the therapeutic range as the “point of futility”.One of the issues that has particularly attracted the attention of Meyer and Stahl is the timing of samples, notably different and critical with the four early examples mentioned above (phenytoin etc.). These authors promote use of trough levels, which has become the standard of practice for much of TDM. However, scientific commonsense tells us that pharmacokinetic evaluations of overall exposure are sometimes needed and best made with mean, peak and trough concentrations, and/or pharmacokinetic areas under the curve, and it is notable that the early investigators of chlorpromazine recognized this. Their studies showed that means/peaks below 300 - 350 ng/ml were needed for control of toxicity. Also, that troughs below 100 ng/ml, but also above approximately 30 - 35 ng/ml, were compatible with successful treatment, and this has led to a serious non-trivial misunderstanding, highlighted by the work of Meyer and Stahl. Thus, chlorpromazine in plasma was mostly studied with pharmacokinetic evaluations of overall exposure until the literature on this drug ceased to carry new contributions around 1990. However, the objectives of modern TDM are different from the scientific objectives of the early chlorpromazine investigators. Contrasting with overall exposure, patient management demands the use of convenient “operational numbers”, and troughs provide those most easily. Operational numbers may serve the needs of clinical practice, but only rarely aid understanding of underlying science.The emphasis on the 300/350 figure, that has persisted dominantly into 21st century review literature, has failed to recognize that this is a random, not a trough, level. Meyer and Stahl have taken some of the early investigators, and the more recent data compilers, to task for perpetuating an idea of clinically acceptable trough plasma levels being up to 300/350 ng/ml in the case of chlorpromazine. It is unfortunate that after 50 years, we see this level quoted in data compilations, which have become prominent in the literature, without recognition of what it is. It is also unfortunate that Meyer and Stahl’s sentence in line 15 of their page 225 is wrong in using the expression “trough” plasma levels regarding levels of 300/350 ng/ml of chlorpromazine. The early scientific data is not in conflict with the now widely accepted idea that a suitable trough for avoiding toxicity is 100 ng/ml.From the mid-1970s to the present day the potential of antipsychotics to be aided in their success by TDM has been studied by literally thousands of investigators, and Meyer and Stahl have studied and summarized much of the published work of this community of medical scientists in commendable detail in this very welcome book, seemingly the first dedicated exclusively to TDM of drugs for schizophrenia. The TDM concept has now been tried with some thirty commonly used first and second-generation antipsychotics, with varying levels of success, such that there are no absolute rules, just a large body of heavily-nuanced recommendations. However, most psychiatric care communities nowadays work to some kind of manual codifying their standards of care, such as the one associated with the Maudsley Hospital in London, and most of these manuals refer to TDM. One of the reasons for this is that the advent and gradual acceptance of TDM in Psychiatry has accompanied a gradual reduction in individual dose, reflecting a very welcome change in prescribing philosophy from use of the maximum that the patient can tolerate to the minimum that induces a useful effect. At the same time there has been a gradual closure of the large public hospitals that catered for the psychiatrically ill in the middle of the 20thcentury; this has been greatly to the benefit of the patients concerned. TDM, at the least, has provided a critical component of the scientific underpinning of modern practice.Meyer and Stahl are to be congratulated and thanked for identifying a very real need, and having produced a handy and inexpensive book, packed with useful information, easy to read and use, and which should be on the personal bookshelf of anyone caring for patients with psychoses, especially the modern-day Psychiatric Pharmacists cropping up all over the world. The chlorpromazine peak and trough issues apart, admittedly with a near-obsolete drug but one that facilitated the pioneering of standards of care, this is an excellent book. It is particularly well-endowed with literature citations, and readers will be readily able to experiment with cross-checking the author conclusions with the original literature. The citations will also assist in development of an appropriate sense of history.Stephen H. Curry.Rochester, New York.