HCPLive Five at APA 2024

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From the prospect of semaglutide and MDMA for substance use disorder to evolving research around personality disorders and OCD, here are 5 key topics from the annual psychiatric meeting.

Top #5

0:11 Roger S. McIntyre, MD on GLP-1 agonists for psychiatry

1:10 John M. Oldham, MD, MS on new guidelines for personality disorders

2:21 Brian Barnett, MD on psychedelics for substance use disorders

3:21 Katharine Phillips, MD on differentiating between OCD and body dysmorphic disorder

4:33 Davangere P. Devanand, MD on the value of lecanemab and other dementia therapies

Clinical psychiatry is nearing a convergence of fascinating drug development with refined disease definition and diagnostics. With the late-stage progression of agents like cognition- and dementia-targeting therapies as well as psychedelics and antidepressants for depressive and mood disorders, clinicians are re-evaluating their capability to treat once improbably targets of the human psyche and cognition. All the while, the intricate pathophysiology and manifestation of psychiatric conditions are increasingly understood; the paired developments could give hope toward more individualized care in psychiatry and its neighboring fields.

Few events capture this approaching convergence as well as the American Psychiatric Association (APA) Annual Meeting, which convened in New York, NY, this month to host a bevy of sessions, discourse and new data in every subspecialty of psychiatry.

Highlighted in this latest episode of the HCPLive 5 are the biggest topics covered by HCPLive at APA 2024, featuring leading experts on the subject. Here’s the list.

5. Research on GLP-1 Receptor Agonists for Psychiatry

While the world remains arrested by the robust clinical efficacy of semaglutide (Ozempic) and other GLP-1 receptor agonists in the treatment of obesity-related weight loss and related cardio metabolic outcomes,1 psychiatrists like Roger S. McIntyre, MD, have become invested in the potential of the drug class for conditions including major depressive disorder and substance user disorders.

As McIntyre, professor of psychiatry and pharmacology at the University of Toronto, explained in his interview with HCPLive, there’s reason to believe that the provided symptom relief of mental disorders via antidepressants—as they relate to neuroplasticity, neuroprotection and anti-apoptosis—may also be capable of GLP-1 agonists.2

“What’s really caught our eye is there has been some recent data showing that when people in fact take GLP-1s—let’s say for diabetes…they have a much lower risk of developing depression,” McIntyre said. “They have a much lower risk of developing cognitive problems.”

McIntyre further discussed the potentially preventive nature of GLP-1 agonists, as well as what he would find most viable in a phase 3 trial assessing an agent like semaglutide for psychiatric disease, in his interview with HCPLive.

4. New Guidelines Coming for Personality Disorders

The first US guideline recommendations for the management of personality disorders were published in 2001, penned by a workshop committee chaired by John M. Oldham, MD, MS, distinguished emeritus professor at the Menninger Department of Psychiatry and Behavioral Sciences at Baylor College of Medicine.3 As Oldham told HCPLive at APA 2024, a long-awaited update to that original guideline is anticipated for publication in September this year.4

“It's time for an update, and it's been time for an update for quite a while,” Oldham said.

Oldham reviewed the conceptualization of the 2001 guideline and what he and his peers strove to update or refine, based on newly available research, in the latest recommendations. A key highlight to the updates will be the shift in interpreting personality disorder pathology as a more dimensional condition than was previously appreciated by psychiatrists.

“Our recommendation is that we move to a more systemic definition of personality disorders—moving away from the individual labels and defining the disorder in a very personalized way,” Oldham said. “So, if there is moderate or greater impairment, then the pathological personality traits (help) characterize your particular patient, or how you fill in the colors of your particular patient.”

Oldham additionally highlighted the concept of the current “alternative modeling” for personality disorder that was not included in the DSM-5 that deviates from medically-based categorization.

3. The Prospect of Psychedelics for Substance Use Disorders

While psychedelic therapy is on track to potentially reach the US market by way of indications such as Lykos Therapeutics’ MDMA for the treatment of PTSD—a US Food and Drug Administration (FDA) decision anticipated for later this summer5—the much-discussed drug class’ utility in other psychiatric fields remains a little more prospective.

One interesting approach is in the treatment of substance use disorders, as highlighted by Brian Barnett, MD, from the Center for Behavioral Health, Neurological Institute at Cleveland Clinic, to HCPLive at APA 2024.6

“One of the biggest questions would be, can we give someone who already has a substance use disorder a psychoactive substance to treat that, that also has misuse potential?” Barnett said.

Barnett highlighted that, despite the stigma surrounding psychedelics, they are known to have the lowest misuse potential by consumers among all psychoactive drugs. Among the reasons for that is the non-euphoric effect of psychedelics, as well as the “built-in protective feature” of tachyphylaxis and the reduced dopamine levels in patients’ reward pathways.

Of course, interpretation of adverse events including suicidal ideation, psychosis and bipolar disorder-related mania needs to be fully enveloped in clinical research before such an application was ready for FDA consideration.

2. Efforts to Differentiate OCD and Body Dysmorphic Disorder

The DSM-5 groups conditions including obsessive-compulsive disorder (OCD), body dysmorphic disorder and trichotillomania (compulsive hair-pulling) into the same spectrum of condition. However, as Katharine Phillips, MD, professor of psychiatry at Weill Cornell Medical College, explained to HCPLive, it remains critical to differentiate the signs and symptoms of each into unique diagnoses.7

Though they may present similarly, the rationale behind the 3 conditions can differentiate—showing the necessity of seeking and logging patient behavior history and other context.

“Body dysmorphic disorder is characterized by repetitive thoughts, obsessions, preoccupations—but it’s about appearance,” Phillips said. “It’s thinking, ‘I look ugly, I don’t look right.’ Some even think they look monstrous. The repetitive thoughts trigger repetitive behaviors that are different from OCD, like obsessive mirror-checking or grooming.”

It also doesn’t help that pathophysiologic research has further tied the conditions together. Phillips cited twin studies showing body dysmorphia and OCD are genetically related, but they also have disorder-specific genes. For instance, body dysmorphic disorder shares some genes with OCD, but trichotillomania has specific genes.

Other symptoms, including visual processing in patients with body dysmorphic disorder, may help differentiate the conditions.

1. Setting Value to Lecanemab and Other Dementia Therapies

After making headlines as one of the first drugs approved by the FDA to treat Alzheimer disease in decades last July, lecanemab (Leqembi) has settled into a clear role in the armamentarium of dementia-treating therapies among clinicians.8 Davangere P. Devanand, MD, director of geriatric psychiatry at Columbia University Medical Center, explained to HCPLive at APA 2024 that the anti-amyloid monoclonal antibody is now appreciated as a disease-modifying therapy for Alzheimer.9

“While it doesn't improve patients, it changes the trajectory so instead of going downhill at a steep slope, they go at a moderate slope,” Devanand said. “So in terms of diagnosis, understanding the pathophysiology and management, there have been improvements in all these areas, although we are a long way from curing the disease.”

While previously indicated dementia therapies like cholinesterase inhibitors have been shown to provide short-term cognitive symptom improvement, lecanemab is now better understood to delay the progression of cognitive loss that burdens patients with Alzheimer. Devanand highlighted some other viable treatments that could benefit patients with progressing dementia in a complementary way, as well as how the development and approval of lecanemab may shape the future of Alzheimer drug research.

References

  1. Campbell P. Semaglutide: The Drug of Today and a Steppingstone to Tomorrow. HCPLive. Published December 6, 2023. https://www.hcplive.com/view/semaglutide-drug-today-steppingstone-tomorrow
  2. Kunzmann K. Roger S. McIntyre, MD: GLP-1 Agonists for Psychiatry? HCPLive. Published May 5, 2024. https://www.hcplive.com/view/roger-mcintyre-md-glp-1-agonists-for-psychiatry
  3. American Psychiatric Association Practice Guidelines. Practice guideline for the treatment of patients with borderline personality disorder. American Psychiatric Association. Am J Psychiatry. 2001;158(10 Suppl):1-52.
  4. Kunzmann K. John M. Oldham, MD: A History of Personality Disorder Pathology. HCPLive. Published May 13, 2024. https://www.hcplive.com/view/john-oldham-md-history-personality-disorder-pathology
  5. Kunzmann K. FDA Advisory Committee Meeting to Review MDMA-Assisted Therapy for PTSD. HCPLive. Published May 6, 2024. https://www.hcplive.com/view/fda-advisory-committee-meeting-review-mdma-assisted-therapy-ptsd
  6. Derman C. Brian Barnett, MD: Psychedelics Fitting into the SUDs Treatment Paradigm. HCPLive. Published May 9, 2024. https://www.hcplive.com/view/brian-barnett-md-psychedelics-fitting-into-the-suds-treatment-paradigm
  7. Derman C. Katharine Phillips, MD: Various Treatments for Obsessive-Compulsive Disorders. HCPLive. Published May 11, 2024. https://www.hcplive.com/view/katharine-phillips-md-various-treatments-for-obsessive-compulsive-disorders
  8. Meglio M. FDA Grants Traditional Approval to Lecanemab as Therapy for Early-Stage Alzheimer Disease. NeurologyLive. Published July 6, 2023. https://www.neurologylive.com/view/fda-grants-traditional-approval-lecanemab-as-therapy-for-early-stage-alzheimer-disease
  9. Kunzmann K. Davangere Devanand, MD: The State of Dementia Drug Development. HCPLive. Published May 5, 2024. https://www.hcplive.com/view/davangere-devanand-dementia-drug-development
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