Pseudospecific and Transdiagnostic Symptom Targeting in Clinical Trials

CONFERENCE REPORTER

In this Mental Health Minute, Joseph F. Goldberg, MD, joins Psychiatric Times® live from the 2024 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting and gives us a preview of his upcoming panel presentation, “Pseudospecific Versus Transdiagnostic Symptom Targeting in Pharmacotherapy Trials: Agitation, Attention, Anhedonia, and Mood Instability.” The full transcript is below.

Hi, I am Dr Joseph Goldberg. I am a clinical professor of psychiatry at The Icahn School of Medicine at Mount Sinai in New York. And I am also the president of the ASCP.

As part of the ASCP Annual Meeting, on Thursday, I am involved in a presentation about transdiagnostic vs pseudospecific features of psychopathology. Along with my colleagues, Drs Roger McIntyre, Manpreet Singh, and Justin Faden, as well as Dr Tiffany Farchioni from the FDA, will be talking about the ways in which certain target symptoms in clinical trials might represent either phenomena that cut across different diagnostic spectra and may not have pathognomonic or diagnosis-specific importance, but rather reflect broader underlying neural circuitry processes.

We will then tease apart the ways in which some of those common psychopathology features may or may not reflect true, independent targets of treatment themselves, as opposed to the term pseudospecific phenomena.

Let me give an example. Let’s suppose you have pneumonia, and you are coughing quite a bit, and I target your cough with an antitussive medication. I help your cough, but I have not really treated your pneumonia. If we concluded that Robitussin was helpful, we would say it was pseudospecifically helpful in treating your cough. But that does not mean that every time you have a cough from any and all causes like allergies or airway obstructions, let’s use Robitussin. That would be an instance where we have a transdiagnostic symptom. Coughing happens in lots of different elements, but the treatments may differ depending on the etiology. So, that is where the pseudospecificity and the transdiagnostic features come into play.

This Thursday, at our presentation, we are going to be talking about 4 particular kinds of either transdiagnostic or pseudospecific features:

• Anhedonia—the loss of the ability to feel pleasure
• Cognition—cognitive processing, attentional processing, executive functioning, mood instability (that is, variations in mood from moment to moment. It is a term that we do not really formally identify in clinical trials, but it is something that, on a day-to-day basis, we often talk about with patients)
• Variations in mood—consistency of mood provocation and of mood changes, and the extent to which our interventions specifically target mood instability
• Agitation, which is a very ubiquitous phenomenon, again, cutting across many disorders, from psychotic disorders, mania, and posttraumatic stress disorders to substance use disorders

What can we learn about agitation in the context in which it arises? To what extent might there be particular interventions that we could call anti-agitation treatments that might work better in the context of psychosis, or that might work better in the context of a mood disorder or in the context of a substance use disorder? And how much should the clinician or the investigator or the practitioner really be thinking about what is the underlying etiology of 1 of these 4 symptoms—anhedonia, cognitive dysfunction, agitation, and mood instability? Because they are nonspecific, they do cut across diagnoses.

What we are really going to, in a panel fashion, is talk about the ways in which different manifestations of these phenomena may come up in these different contexts, and how some treatments may cut across broadly. There are certain classes of medicine that might be very broad treatments for mood instability, regardless of the diagnosis, and maybe others that are a little more specifically helpful when 1 of these core transdiagnostic symptoms occurs in a particular diagnostic setting.

So, the “stay tuned” portion of my presentation to you here is to hear more about the ways in which these kinds of symptoms present may reflect underlying neural circuitry disorders and cut across diagnoses. That is really the thrust of our presentation, and we hope to share information that will shed light on how to better treat patients with these kinds of transdiagnostic symptoms.

Maybe as a final thought, let me just leave you with this notion. One of the things that ASCP is really committed to, as an organization, is not just identifying cutting-edge treatments and new technologies, but really understanding what it is we are treating when we approach psychopathology and different disorders. That goes beyond the DSM-5 categorization of disorders. It really brings us more toward understanding what we think is going on in the brain disorders of neural circuitry that involve mood regulation, attentional processing, executive functioning, impulse control, and aggression.

These are all examples of brain circuitry gone awry, so this really is an opportunity to invite broader thinking about not just on-label uses of drugs for disorders, but targeting specific symptoms within certain contexts that we think is really getting more specifically what the underlying brain processes are. Hopefully we will be advancing knowledge in our clinical and critical thinking about brain disorders with examples such as this one from transdiagnostic and pseudospecific treatment targets.

Dr Goldberg is a clinical professor of psychiatry at The Mount Sinai School of Medicine and president of the ASCP.

Follow the Psychiatric Times coverage of the 2024 ASCP Annual Meeting, and stay up-to-date on news related to research on promising new interventions and developments in the treatment of a wide variety of psychiatric disorders, at psychiatrictimes.com.