The Lancet Psychiatry

Within the spectrum of depression, the more treatment resistant you get, the more you have essentially lower dopamine signaling, the more the suggestion would be you would benefit from stimulating dopamine receptors.

What these studies have shown, one published in Lancet Psychiatry a year ago and one published earlier this year in Nature Medicine from a group at Lund, is that Pramipexole as a direct dopamine agonist has really outsized clinical benefit for these patients, treatment resistant or adjunctive treatment in depression.

And that's something that we haven't really seen amongst all available therapies, something that gets at anhedonia, that has a very strong clinical effect size.

But of course, the reason that it's not in clinical practice right now, it's a drug approved for Parkinson's and restless leg syndrome, is it also comes with a major limitation, which is nausea and vomiting.

Ondansetron is an anti-emetic and so it mitigates the main factor holding back.

Primapexole, and that combination they showed had a large effect.

This is an eight-point delta on the moderate between drug and placebo in Chase's study, and that complements the equivalent effect size in the Lancet Psychiatry PAX-D study, which translated from their outcome measure to Madras is a bit over seven point delta and that also complements the Lund study which looked at anhedonia as the outcome as opposed to traditional depressive symptoms that also showed a large effect.

We're talking 0.6, 0.8, 0.9, even as much as 1.1 Cohen's D effect sizes, which would be the equivalent of like three or four times the typical antidepressant effect in TRD patients.