Drug-Induced Dementia

The Perfect Crime:  Murder on the Orient Express + Michael Clayton

Murder on the Orient Express:  The Challenge of Multiple Suspects

In the Agatha Christie novel and film, Murder on the Orient Express, a group of co-conspirators board the famous trans-European railway with the goal of killing a fellow passenger.   As the plot unfolds, Christie’s famous protagonist – a Belgian sleuth by the name of Hercule Poirot – must sort through a collection of confusing and seemingly excessive clues.  Although the story ultimately leads to two possible endings, one of them is germane to the field of psychiatry.  The problem for Poirot is not the fact that he lacks suspects for the murder.  Rather, the problem is that he discovers evidence and motives which implicate not one, but twelve different individuals who have all participated in the crime.

In clinical practice, physicians face a similar Poirot-like challenge in terms of sorting through an assortment of clues and suspects.  In this case, the “crime” is drug-induced dementia (with or without immediate death).  The “clues” include a variety of neuropsychiatric symptoms:  movement abnormalities, seizures, mania, depression, anxiety, hallucinations, delusions, and cognitive decline.   The “suspects” include a vast array of potential weapons (antidepressants, antipsychotics, anticonvulsants, sedatives/hypnotics, and stimulants) and the agents who mandate or encourage their use: judges, lawyers, educators, journalists, “key opinion leaders,” and many more.

Michael Clayton – “Make It Look Like An Accident”

In the Academy Award nominated movie, Michael Clayton, one of the heroes of the film is eliminated by hit men in an effort to protect the commercial interests of a chemical manufacturer.   Notwithstanding the substantive relevance of the plot to the theme of this book, the point to be made here is how the pivotal assassination in the film is cleverly conceived and executed so that it looks like an accident.

First, the hero is knocked unconscious with a stun gun.  Next, pills are forced down the back of his throat in order to create the illusion of intentional drug overdose.   Finally, the victim is injected between the web of two toes with an unidentified, untraceable, and rapidly lethal substance (presumably, potassium or another electrolyte which results in a brief convulsion, the cessation of breathing, and sudden cardiac death).   The hit men  achieve the perfect crime because – to the unwary characters in the screenplay – the murder is initially misinterpreted as a suicide.

What possible relevance could these movie events have for physicians and patients?

The answer to this question lies outside of medicine.  Within the profession of toxicology, scientists study the “mechanisms and modes of action by which chemicals produce adverse effects in biological systems.” ³⁰  When a substance is absorbed and distributed in the human body, toxicologists refer to the location where it produces damage as the target organ.   In sum, toxicology – as a field of scholarly and applied endeavor – is dedicated to the identification, prevention, and mitigation of target organ toxicity.³¹  Unfortunately for patients, though, the profession of medicine is not.  This discrepancy – especially when toxicity concerns the intended target of treatment – is the basis of how and why the effects of America’s health care system are, at this moment, frequently analogous to a murder mystery.

Target organ toxicity is often undetected when there are too many suspects.

To return to the case involving rivastigmine (Case #2), the patient was receiving ten different neuropsychiatric drugs at the time of hospitalization.  Ironically, it was this combination of agents which created confusion, resulting in the delayed (and only partial) recognition of medications as the cause of the patient’s distress.  For example, neither lamotrigine, nor memantine, nor dextroamphetamine, nor the two antidepressant drugs were ever suspected as contributing or determining causes of dystonia, because the treating physicians focused only upon the cholinesterase inhibitor (rivastigmine) and two antipsychotic drugs.^32-33

Target organ toxicity is not suspected by physicians when an event “looks like an accident.”

Throughout their training and throughout the practice of their various clinical specialties, physicians a