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Life-Threatening Effects of Antipsychotic DrugsReview - Life-Threatening Effects of Antipsychotic Drugs
by Peter Manu, Robert J. Flanagan, Kathlyn J. Ronaldson (Editors)
Academic Press, 2016
Review by Sandra Steingard, M.D.
Nov 22nd 2016 (Volume 20, Issue 47)

Antipsychotic drugs, initially promoted primarily to treat people diagnosed with schizophrenia, have become widely prescribed in the past two decades. They are increasingly used in the contexts of mood disorders, a more common diagnostic category than schizophrenia, and for children experiencing an array of behavioral problems. While there are many controversies regarding this burgeoning use, it remains crucial, whether one considers them overused or critical to good care, to understand their broad effects beyond the impacts they may have on psychiatric symptoms.  This academic text addresses the needs of all clinicians who prescribe them as well as those who may be called upon to treat people suffering from their deleterious effects.

The book is organized primarily by systems. Sections detail cardiovascular, hematological, digestive, neurological, and metabolic effects.  The cardiovascular section includes chapters on sudden death, myocarditis, pulmonary embolism, and hypotension. The digestive section encompasses chapters on hypomotility, liver failure, and pancreatitis. Chapters in the neurological section address seizures, neuroleptic malignant syndrome, and heat stroke. There are also chapters on interstitial nephritis and interstitial lung disease. These sections are exhaustive and include reviews of basic physiology as well as the myriad ways in which this class of drugs can result in pathophysiologic changes. This exhaustive reference book will find its useful place on many book shelves and serve as a handy source of information on this complex and broad topic.

After even a cursory review of the book, one might wonder if these drugs are worth the tremendous burden of morbidity they carry. Later chapters in the text address the benefits of the drugs, strategies for reducing risk, and forensic investigations of antipsychotic-related deaths. These chapters were instructive but disappointing. They were useful in that they offer a view of standard, accepted practice in the field. In the chapter on drug benefits, the author frames schizophrenia as a chronic illness with severe morbidity of its own.  He then reviews studies on short-term use of antipsychotic drugs, which demonstrate a robust reduction of psychotic symptoms. This is followed by reviews of the so-called relapse studies in which those stabilized on the drug are assigned randomly either to continue or to stop the drugs and are then followed for two years. Such investigations also find robust reductions of relapse risks over this time frame. In that context, the recommendation that these drugs are necessary and required for long-term use seems self-evident. However, there is a counter narrative that has emerged in recent years.  First of all, the conceptualization of schizophrenia as a condition that is invariably chronic is based on old data that have been called into question (1).  Secondly, the validity of the studies referenced has also been challenged. There is bias associated with drugs studies performed by companies that manufacture and market the drugs under investigation (2), and such bias is never acknowledged in this chapter.  That bias can account for an overly optimistic account of drug benefits in meta-analyses that include these studies. Finally, the relapse studies follow people for two years at most. There are emerging data that reveal that outcomes ascertained over longer time frames favor those who are on low doses or no antipsychotic drugs at all.  A text devoted to the topic of life-threatening outcomes of treatment with these drugs is inadequate without a discussion of the possibility of mitigating risk by lowering doses or even stopping the drugs and pursuing alternative approaches. The chapter on reducing risk focuses on enforcing adherence to drug regimens with assertive community outreach. The risk mitigation involves using this same assertive approach to improve adherence to treatments for the illnesses induced by the drugs. While these approaches have value, the absence of alternative strategies is not only disappointing; it limits the value of the text as a whole since it will not lead to what may be the best way to reduce life-threatening consequences of these drugs: limiting exposure to them.

With that serious caveat, this book is a useful resource.


1.    Harding C, Brooks, GW, Ashikaga, T et al “The Vermont Longitudinal Study of Persons With Severe Mental Illness, I Methodology, Study Sample, and Overall Status 32 Years Later.” Am J Psychiatry 1987;144;718-726.

2.    Gotzsche Peter Deadly Medicine and Organized Crime: How Big Pharma Has Corrupted Healthcare. Radcliffe Publishing, 2013.


© 2016 Sandra Steingard


Sandra Steingard, M.D., Chief Medical Officer, Howard Center, Burlington, Vermont



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