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Dr. Bob is Robert Hsiung, MD,
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Posted by PeterMartin on April 23, 2018, at 21:44:31
Maybe of interest to some. Seems like a novel method of action so perhaps the analogs (if developed for oral consumption) might be helpful in time.
NDA Submitted for Postpartum Depression Treatment Brexanolone
Brexanolone is a proprietary allosteric modulator of both synaptic and extrasynaptic GABAA receptors. The NDA is supported by 3 multicenter, randomized, double-blind, placebo-controlled trials (Study 202A, Study 202B, and Study 202C) in women with moderate to severe PPD who were screened ≤6 months after giving birth.
Posted by Hugh on April 24, 2018, at 12:19:56
In reply to NDA Submitted for Postpartum Depression Drug, posted by PeterMartin on April 23, 2018, at 21:44:31
Sounds very promising. And maybe this will be an effective off-label treatment for other forms of depression.
Posted by sigismund on April 24, 2018, at 23:58:36
In reply to NDA Submitted for Postpartum Depression Drug, posted by PeterMartin on April 23, 2018, at 21:44:31
>Brexanolone is a proprietary allosteric modulator of both synaptic and extra synaptic GABAA receptors.
Can anyone put this in more simple terms?
Like what the effects might be?
It sounds interesting.
Posted by SLS on April 25, 2018, at 5:38:57
In reply to Re: NDA Submitted for Postpartum Depression Drug, posted by sigismund on April 24, 2018, at 23:58:36
> >Brexanolone is a proprietary allosteric modulator of both synaptic and extra synaptic GABAA receptors.
>
> Can anyone put this in more simple terms?No.
:-)
Summary:
Brexanolone is a synthetic form of the naturally-occurring hormone, allogregnanolone, the levels of which become very high during pregnancy. It is given intravenously (IV). It is likely to improve post-partum depression and anxiety in women only when levels drop after childbirth.
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Allosteric = Changes the shape of (a protein).
Modulator = Adjust the activity of
Synapse (synaptic) = Where one neuron transfers a message to another at the terminal-dendrite junction
Extra synaptic = Where one neuron adjusts the activity of another at a site other than the synapse.
GABA = Gaba amino butyric acid; the most numerous inhibitory neurotransmitter. It puts the "brakes" on the excitatory neurons throughout the brain.
GABA-A = GABA receptor responsible for reducing anxiety and promoting sleep. It adjusts the actiivity of other types of neurons.Brexanolone is an intravenous form of the naturally occurring hormone, allopregnanolone. Allopregnanolone, a neurosteroid, is a product of progesterone - one of the two primary hormones involved in female reproductive function. Normally, it regulates and supports GABA-A receptors. Immediately upon childbirth, levels of progesterone and allopregnanolone drop precipitously, which prevents GABA neurons from functioning nominally. As a result, depression and anxiety emerges in many women. I'm guessing that during pregnancy, there is tolerance to higher levels of allopregnanolone - maybe through reduced GABA receptor numbers. So, dropping allopregnalol too fast may look like a sort of withdrawal, perhaps similar to benzodiazepine or SSRI withdrawal.
- Scott
Posted by Hugh on April 25, 2018, at 9:57:49
In reply to Re: NDA Submitted for Postpartum Depression Drug, posted by SLS on April 25, 2018, at 5:38:57
Sage Therapeutics is testing an oral drug similar to brexanolone to treat major depressive disorder, postpartum depression, essential tremor, Parkinson's, and insomnia. Here's a description of it from Sage's website:
"SAGE-217 is a novel, selective, next generation GABAA positive allosteric modulator that shares similar pharmacology properties to brexanolone. We are initially developing SAGE-217 as a once-daily, oral therapy for treatment of various CNS disorders."
The phase 2 clinical trial results for SAGE-217 for major depressive disorder were released late last year.
"At day 15, 64% of patients in the treatment group achieved remission compared to 23% for placebo (p=0.0005). Other secondary endpoints were also met."
Posted by SLS on April 25, 2018, at 12:28:58
In reply to Re: NDA Submitted for Postpartum Depression Drug, posted by Hugh on April 25, 2018, at 9:57:49
> Sage Therapeutics is testing an oral drug similar to brexanolone to treat major depressive disorder, postpartum depression, essential tremor, Parkinson's, and insomnia. Here's a description of it from Sage's website:
>
> "SAGE-217 is a novel, selective, next generation GABAA positive allosteric modulator that shares similar pharmacology properties to brexanolone. We are initially developing SAGE-217 as a once-daily, oral therapy for treatment of various CNS disorders."
>
> The phase 2 clinical trial results for SAGE-217 for major depressive disorder were released late last year.
>
> "At day 15, 64% of patients in the treatment group achieved remission compared to 23% for placebo (p=0.0005). Other secondary endpoints were also met."That sounds great. I'll be curious to see how they choose subjects for phase three trials. My guess is that when diagnostic inclusion criteria for depression are followed strictly, better numbers emerge for treatment response. From the 1960s through the early 1980s, the response rates to antidepressants were reported to be about 65%. That is much better than placebo response.
- Scott
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