5-HT1A agonist Exxua (gepirone) is FDA approved for MDD
Gepirone is a new antidepressant that agonises 5-HT1A without significant affinity for other serotonin receptors, and unlike SSRIs it also doesn’t block serotonin reuptake via SERT. 5-HT1A is generally considered an inhibitory serotonin receptor and can act as a counterbalance to 5-HT2A signalling, which is one of the receptors that has been implicated in VSS/HPPD.
Gepirone’s antidepressant action appears to be mediated almost entirely by this 5-HT1A agonism. One of its metabolites has some affinity for α2-adrenergic receptors as an antagonist, but it’s unclear how clinically meaningful that effect is and it probably isn’t relevant to VSS.
This makes gepirone an interesting candidate for treating comorbid depression, and perhaps anxiety, in people with VSS without necessarily worsening visual symptoms. I’d also be interested to see whether gepirone could have any positive effect on the visual symptoms themselves, since 5-HT1A has been highlighted by some as a potentially relevant mechanistic target.