> But the network meta analysis did not show zuranolone beating placebo due to wide effect size.
It did not, using 1 of the studies, but my optimism is that the drug it was based on (brexanolone) was significant and is unfortunately only available IV (so difficult to access and expensive), so the hope is that this will play out similarly and why I feel is sufficient reason to give Big Pharma the benefit of the doubt that this isn't purely a money making play.
> Alprazolam beats SSRI for depression with significant anxiety and insomnia with faster onset but treatment must be time limited.
Sure, for anxiety-predominant scenarios but as you're alluding to there are significant dependence and abuse risks and hence why they're used as adjuncts.
If this turns out to work in the same pathway but safer that would be a huge win. If it turns out to work in the same pathway but not safer than non-benzo sedatives then you're right it's a scam. With that said:
> That's uncanny to me esp as both are PAM for GabaA
My clinical pharmaceutical resource lists mechanism not fully known. This is getting outside of my comfort zone to comment on validity or fully understand but this editorial (citing for my own accessibility) suggests a different mechanism from benzodiazepines:
Antonoudiou et al. (6) offer key insights into the potential mechanisms of rapid affective switching following brexanolone treatment of postpartum depression, despite the use of male subjects for all the studies. The remarkable discoveries include the parallels in human and rodent brain network dynamics associated with depression that are responsive to GABAergic analogs of allopregnanolone, the role of δ-subunit–containing receptors in some of these effects in mice, and the lack of effect of benzodiazepines on the electroencephalographic network dynamics, consistent with the lack of antidepressant efficacy of these compounds.
It did not, using 1 of the studies, but my optimism is that the drug it was based on (brexanolone) was significant and is unfortunately only available IV (so difficult to access and expensive), so the hope is that this will play out similarly and why I feel is sufficient reason to give Big Pharma the benefit of the doubt that this isn't purely a money making play.
> Alprazolam beats SSRI for depression with significant anxiety and insomnia with faster onset but treatment must be time limited.
Sure, for anxiety-predominant scenarios but as you're alluding to there are significant dependence and abuse risks and hence why they're used as adjuncts.
If this turns out to work in the same pathway but safer that would be a huge win. If it turns out to work in the same pathway but not safer than non-benzo sedatives then you're right it's a scam. With that said:
> That's uncanny to me esp as both are PAM for GabaA
My clinical pharmaceutical resource lists mechanism not fully known. This is getting outside of my comfort zone to comment on validity or fully understand but this editorial (citing for my own accessibility) suggests a different mechanism from benzodiazepines:
Antonoudiou et al. (6) offer key insights into the potential mechanisms of rapid affective switching following brexanolone treatment of postpartum depression, despite the use of male subjects for all the studies. The remarkable discoveries include the parallels in human and rodent brain network dynamics associated with depression that are responsive to GABAergic analogs of allopregnanolone, the role of δ-subunit–containing receptors in some of these effects in mice, and the lack of effect of benzodiazepines on the electroencephalographic network dynamics, consistent with the lack of antidepressant efficacy of these compounds.
https://www.sciencedirect.com/science/article/pii/S000632232...
Antonoudiou et al: https://www.sciencedirect.com/science/article/pii/S000632232...