Novel Depression Treatments Focus of Psych Congress Regionals Q&A Session

During the July 2023 Psych Congress Regionals virtual meeting, Rakesh Jain, MD, and Greg Mattingly, MD, answered audience questions regarding the potential of GABA and glutamate modulation in understanding and treating the psychological impact of traumatic brain injury (TBI) in the frontal lobe, as well as positive insights on the newer depression treatment options available and the flexibility of those approaches. 

The live Q&A session, moderated by Saundra Jain, PsyD, bookended the virtual session titled "Evolving Perspectives on Depression: Chronic Vs. Episodic Treatment in MDD and the Role of the GABA System."

Dr Mattingly, a seasoned professional in sports medicine, emphasized the importance of neuroplasticity in addressing mental health disorders resulting from prolonged brain stress.

"There are some experimental studies showing… that if you turn on this GABA glutamate junction, you can help with neuroplasticity in animals that have had traumatic brain injury. As we get these models, then testing that in adults is going to be a fascinating area," Dr Mattingly said.

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Dr Rakesh Jain then highlighted the environmental-induced damage to neural connections—from psychological trauma and/or physical trauma—and advocated for a comprehensive approach beyond monoamines, emphasizing the significance of glutamatergic and GABAergic interventions. 

New treatment paradigms, Dr Mattingly suggested in support of Dr Jain’s point, differ from chronic treatment paradigms where the plan is to continuously elevate patients’ serotonin, norepinephrine, and dopamine levels. "We're talking about resetting the thermostat to help [patients] get out of an [depressive] episode and prevent future episodes," he said. Clinicians may need to "reset that thermostat more than once…and may need to give them down the road when needed but spaced out for when the patient needs them."

An audience question shifted the conversation to insights on newer medications available for depression, as discussed during the session. The new medications can either be combined with other antidepressants or given as monotherapy, depending on the patient and situation, said Dr Jain. Some patients coming off monoaminergic medication who have comorbid conditions alongside MDD would benefit from combination treatments, he recommended.

Zuranalone, for example, has a robust database supporting its efficacy, and "both pathways are appropriate now with esketamine." Esketamine, Dr Jain said, is not given as monotherapy "quite simply because it has never been studied that way, but that does not negate the fact that in many people, an NMDA(N-methyl-D-aspartate) antagonist as monotherapy may be sufficient."

In the session preceding the Q&A, Dr Jain expressed, "Major depression is a common and "hugely disabling condition," and current therapies of MDD are associated with low response and remission rates with a substantial burden of acute and chronic side effects. "The hopeful message I have for you," he said, "is…rapid response and remission are a clinical necessity, and episodic treatment of MDD is an exciting, emergent concept."

Additional key points regarding new treatments for depression included:

• GABA tone modulates neural firing and neural networks;
• Neural active steroids (NAS) have the potential to recalibrate GABA/Glutamate tone within the brain;
• Allopregnalone IV is currently FDA-approved for postpartum depression; and
• Zuranalone and other NAS are currently in development for a variety mental health conditions.

Reference

Jain R, Jain S, Mattingly G, Baig A, Meier. Evolving Perspectives on Depression: Chronic Vs. Episodic Treatment in MDD and the Role of the GABA System. Presented at Psych Congress Regionals. Virtual; July 27, 2023.