On April 15th, 2025, Sage Therapeutics withdrew their postpartum depression breakthrough,

IV Brexenolone from the U.S. market. Today, we look at what was lost and what to do without it.

Welcome to the Carlyte Psychiatry Podcast, keeping psychiatry honest since 2003.

I'm Khrasekine, the editor-in-chief of the Carlat Psychiatry Report.

And I'm Kelly Newsom, a psychiatric MP and a dedicated reader of every issue.

We launched the first Carlatte podcast in May of 2019, just two months after the FDA approved

Brexanolone, Zorozo, as the first medication for postpartum depression.

Six years later, the manufacturer withdrew Brexanolone to focus on its oral version,

Xerenolone, Zorzo oral version, zorenolone, zerzuvie.

However, these two medications are different. Brexenolone is intravenous, and zarenolone is oral.

And that means different plasma levels and a potentially different effect size.

Today, I'm going to explore this drug and its oral cousin, starting with what's lost in the transition.

Potency.

In terms of potency, IV bruxenolone had a very large effect size, 1.2, while oral xeranolone's

effect size was only moderate, 0.5.

You know, an effect size of 1.2 is remarkable.

Very few treatments in psychiatry rise above 1.0, among them, ECT and IV ketamine.

Yes, I said IV ketamine.

The IV version of ketamine has an effect size that's actually similar to Brexenolone's, 1.2,

but its effect falls to 0.3 when we use the intranasial version, S-ketamine spravato.

IV medications are more common in Europe, where inpatient psychiatrists have long used IV valproate for mania in mixed states and IV catalopram for depression.

Anecdotally, these psychiatrists tell me they get better results with the IV drug.

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