Roger S. McIntyre, MD: GLP-1 agonists for psychiatry?

GLP-1/GIP receptor agonists, including semaglutide (Ozempic) and the investigational retatrutide, represent a seismic shift in cardiometabolic and comorbidity treatment. Over the past decade, the emerging drug class has been robustly shown to effectively treat type 2 diabetes, as well as persistent comorbidities such as cardiovascular events, chronic kidney disease, fatty liver disease, and clinical obesity, among other results.

Perhaps unsurprisingly, they may have a role to play in psychiatric treatment.

In an interview with HCPLive During the American Psychiatric Association (APA) 2024 Annual Meeting in New York, NY this week, Roger S. McIntyre, MD, professor of psychiatry and pharmacology at the University of Toronto, discussed his presentation topic assessing the perspective of GLP-1 receptor agonists in the treatment of psychiatric disorders.

As McIntyre explained, the potential benefit with the dynamic drug class would be threefold.

We now have reason to believe that the mechanistic steps leading to symptom relief in many mental disorders include the activation of molecular and cellular systems in the brain relevant to neuroplasticity, neuroprotection, and so-called anti-apoptosis by keep cells alive. This is a mechanism shared by antidepressants, shared by neurostimulation such as transcranial magnetic stimulation, as well as psychotherapy, McIntyre said. What’s interesting about GLP and GIP is similar to what I just described, they also activate molecular and cellular systems relevant to neuroplasticity, neuroprotection, anti-apoptosis.

McIntyre said that GLP-1 and GIP receptor agonists may provide some specific preventive effects in psychiatry similar to their effect in various chronic conditions. The potential would be to address patients’ conditions with mechanistically informed therapy.

We prefer treatments that can target the key mechanisms responsible for these syndromes that we have in the DSM, he said. We would also like to have treatments that not only suppress the symptoms, but hopefully modify the disease. It may be modifying the course of the disease.

McIntyre identified neurocognitive disorders such as Parkinson’s and Alzheimer’s disease as viable clinical targets for the drug class; in the first condition, researchers have found evidence to suggest that it can slow down some of the progression of the motor problems so cardinal to this disease. In addition, he believes there may be opportunities to treat conditions such as alcohol use disorder, among other substance problems.

The prevailing view in obesity research today is that a key mechanism mediating decreased food consumption with obesity is modulating what we call reward salience. McIntyre said there is too much over-reward for a signal in the environment. So people are looking at this opportunity to be GLP-1 to treat these types of other addictive disorders.

Other conditions appropriate for GLP-1/GIP receptor agonists may include traumatic brain injury, stroke-related diseases and depressive disorders, McIntyre said.

Finally, McIntyre discussed the well-regarded clinical efficacy of the drug class on weight loss outcome that may hold particular promise for addressing the common antipsychotic treatment effect of uncontrolled weight gain.

And now we have the beginnings of an evidence base showing that GLP-1s could be extremely effective in helping not only the weight gain that has been imparted by the underlying drugs, but weight gain as well. as part of the disease, helping not only the weight, but also the metabolism (conditions). ) and also helps with blood pressure, McIntyre said.

^{McIntyre has received research grants from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; Speaker/consulting fees from Lundbeck, Janssen, All Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Neurawell, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi , Esisai , Intra-C NewBridge Pharmaceuticals, Viatris, Abbie and Atai Life Sciences.}