Independent Actions on Fear Circuits May Lead to Therapeutic Synergy for Anxiety When Combining Serotonergic and GABAergic Agents

In last month’s BRAINSTORMS, we discussed the fact that benzodiazepines are still the leading treatments for anxiety disorders, despite their limitations and being relegated to second-line use in modern treatment guidelines. Benzodiazepines act upon GABAergic neurotransmission to enhance neuronal inhibition and are frequently used along with antidepressants that enhance serotonergic neurotransmission for the treatment of anxiety disorders today. Here we illustrate the neuroanatomical substrate of fear, showing that both GABA and serotonin have inhibitory actions on the output of the fear response from the amygdala.