Exploring the Role of GABA in Psychiatric Treatment

SAN DIEGO—Charles F. Zorumski, MD, has been studying the complex neurotransmitter gamma-aminobutyric acid, known as GABA, for more 30 years. With one psychiatric drug that works within the GABA system approved and another on the horizon, he believes GABA modulators could one day be used in a broad range of therapeutic areas.

Dr. Zorumski, of the Departments of Psychiatry & Neuroscience, Taylor Family Institute for Innovative Psychiatric Research, Center for Brain Research in Mood Disorders, Washington University School of Medicine, St. Louis, Missouri, presented an update on GABA at the Psych Congress 2019 Practical Psychopharmacology Pre-Conference.

“There’s real potential in the GABA sphere for new treatments in psychiatry,” he said.

The field of psychiatry is in need of new treatments, Dr. Zorumski said, with psychiatric illnesses causing too much disability and death and current medications producing only fair response and remission rates and high relapse rates.

“We as a field have to do something different. We can’t keep doing the same thing,” he added.

GABA is the major inhibitory neurotransmitter in the brain and is used in about 20% of the synapses in the nervous system, the speaker explained.

“It is one of the main things that’s available for fine-tuning neural circuits, particularly in key regions of the brain like the hippocampus,” he said.

There are 2 types of GABA receptors: GABA_A receptors and GABA_B receptors. While Dr. Zorumski believes GABA_B receptors could play a part in drug development in the future, current work is focused on GABA_A receptors, he said.

GABA_A receptors try to create homeostasis in the brain and when cells are stressed, GABA_A receptors change their configuration and composition. Researchers are exploring these receptors as targets for novel psychiatric treatments and looking at the connection between depression and deficits in the GABA system, Dr. Zorumski explained.

The US Food and Drug Administration in March approved the intravenous drug brexanolone (Zulresso), an allosteric modulator of synaptic and extrasynaptic GABA_A receptors, for the treatment of postpartum depression. SAGE-217 (zuranolone), an oral drug with similar pharmacology, is in phase 3 studies for the treatment of major depressive disorder and postpartum depression.

Further and larger studies are needed to explore GABA’s potential role in the treatment of depression and other psychiatric disorders, as well as other therapeutic areas, Dr. Zorumski said.

—Terri Airov

Reference

“An update on GABA for clinicians.” Presented at the Psych Congress 2019 Practical Psychopharmacology Pre-Conference: San Diego, CA; October 2, 2019.