Response to Commentary Titled “Conflation of Delirium and Coma as Acute Encephalopathy”

We sincerely appreciate and share the passion for delirium Trzepacz and Franco have expressed in their recent commentary (1). We would like to review areas of mutual agreement and address a key difference of opinion. Recognizing that interest in delirium has expanded to many specialties outside psychiatry, we emphasize that the spirit of our original article (2) was to present an interdisciplinary dialogue on delirium that engages with different perspectives and terminology, while reaffirming delirium as the unifying centerpiece.

We are in full agreement with this commentary’s primary message (1), namely, that acute encephalopathy is not an umbrella term. Encephalopathy should not be conflated for delirium. Indeed, the title of our article features delirium, not encephalopathy. When we describe acute encephalopathy as a “broader construct than delirium” (2) we do not propose it as an encompassing term. Rather, we characterize it as broad and uninformatively non-specific, stating it “lacks operationalized criteria, making it impossible to identify reliably.” Further, acute encephalopathy describes only the underlying pathobiology and “is not recommended as a descriptor of clinical features that can be observed at the bedside.”

We share the concerns that Trzepacz and Franco outline regarding the lack of diagnostic clarity and utility offered by the concept of acute encephalopathy. Nevertheless, we used the term in interdisciplinary dialogue to build bridges within the broader medical community. We also recognize that the term has been used consistently for decades and is favored nearly exclusively by many medical sub-communities (e.g., many in the neurosciences and those devoted to conditions with “encephalopathy” in their names, including uremic encephalopathy, hepatic encephalopathy, and septic encephalopathy) (3).

By considering acute encephalopathy within the broader construct of delirium, we intend to contextualize it rather than to promote it. As detailed in a recent publication on this topic, a delirium diagnosis subsumes the underlying encephalopathy, not the other way around (4). This is crucial because it reveals the reimbursement disparity favoring toxic and metabolic encephalopathy to be conceptually indefensible (5). It is possible to describe delirium without recourse to the term encephalopathy, substituting the term pathophysiology or something similar, though a wholesale avoidance of the term encephalopathy could risk furthering the segregation of literatures.

As another point of firm agreement, we applaud the authors for emphasizing the importance of a detailed mental status examination. This is essential, and also where the psychiatrist brings a unique clinical expertise to delirium practice at the bedside. Emphasizing the mental status ensures that the patient is at the center of clinical care, where they belong. This reason alone is why clinicians should unanimously prefer delirium to acute encephalopathy.

Trzepacz and Franco disagree with our article concerning the verbal distinction between the phenotype and disorder of delirium, which they regard as one and the same. Readers are referred to the reasons we provided for proposing this distinction, as well as previous articles on the model of delirium disorder we cited. Here we will highlight a central reason for proposing this distinction: it calls attention to and challenges the widespread use of the overarching term “delirium” to refer to a kind of “all-cause delirium” that ignores physiological distinctions that occur in and across clinical settings and populations.

Although many delirium scholars, including Trzepacz and Franco, do appreciate the physiological heterogeneity that can give rise to delirium, it is commonplace for clinicians and researchers to talk and think about delirium in the singular: “Delirium predicts poor outcomes.” “Delirium is associated with elevated inflammatory markers.” “Should we use antipsychotics to treat delirium?” Each of these is often understood to imply pathophysiological homogeneity. Yet, not all pathobiology underlying the delirium phenotype is the same: Some delirium is of no lasting consequence. Some delirium is not associated with inflammatory markers. One does not simply reverse delirium with antipsychotics.

We lament that the clinical practice of delirium remains largely unchanged since Lipowski wrote his seminal monographs decades ago, and the tremendous variance across delirium studies likely belies physiological types that are being lumped together. Making an explicit verbal distinction between delirium phenotype and physiology does not imply mind–body dualism any more than the terms “mind” and “body” do themselves, yet this distinction can provide for greater conceptual and descriptive clarity. The goal of a broader terminology is to be both generative and integrative, building on the collective insights of a full range of scholars as well as drawing together interdisciplinary teams for a unified understanding of this condition that is critically important to a broad diversity of clinicians and scientists.