Psycho-Babble Medication Thread 1118094

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Esmethadone helps treatment-resistant depression

Posted by Hugh on January 11, 2022, at 9:21:23

https://www.healio.com/news/psychiatry/20220104/esmethadone-effective-for-patients-with-major-depressive-disorder

Esmethadone produced fast and consistent positive outcomes in patients for whom previous treatments for depression were not effective, according to a randomized, double-blind study published in the American Journal of Psychiatry.

"In this study, we hypothesized that REL-1017 would confirm, in patients with major depressive disorder, the favorable tolerability, safety and pharmacokinetic profiles observed in phase 1 trials," Maurizio Fava, MD, of the department of psychiatry at Massachusetts General Hospital, and colleagues wrote.

"Additionally, based on available preclinical and clinical data, we hypothesized that REL-1017 would provide rapid-onset and effective treatment for patients with major depressive disorder."

Fava and colleagues sought to examine the impact of esmethadone, also known as REL-1017 (Relmada Therapeutics Inc.), a novel N-methyl-Daspartate receptor (NMDAR) channel blocker, in patients diagnosed with major depressive disorder who showed no positive effects when previously prescribed anywhere from one to three standard antidepressants during a major depressive episode.

The researchers conducted a weeklong phase 2 multicenter randomized, double-blind, placebo-controlled trial, comprising three segments, to assess the effects of two different dosages of esmethadone. Among the 62 patients, 34 were male and 28 female, all were aged 18 to 65 years and had experienced a major depressive episode lasting 8 weeks to 36 months.

Patients were randomly assigned on an equal basis to be given either a placebo, 25 mg per day or 50 mg per day of esmethadone. Fifty-seven patients finished the trial. The primary efficacy endpoint for the study was the Montgomery-Åsberg Depression Scale (MADRS) score.

Results showed that patients experienced mild or moderate adverse events that passed quickly and the treatment produced no evidence of dissociative or psychotic behaviors, nor any signs or symptoms of withdrawal. Improvement in MADRS score began on the fourth day of the trial within both esmethadone dosage groups, was sustained through the seventh day in which the last dose was given, then extended until 7 days after administration of the final dose. The researchers wrote that the results will require further confirmation through subsequent, longer trials that examine drug efficacy in larger sample sizes.

"In summary, in this phase 2a trial in patients with major depressive disorder and inadequate responses to antidepressant treatments, REL-1017 confirmed favorable safety, tolerability and pharmacokinetic profiles and showed a robust signal for rapid and sustained antidepressant effects that warrant confirmation in longer trials," Fava and colleagues wrote.

 

Re: Esmethadone helps treatment-resistant depression » Hugh

Posted by SLS on January 11, 2022, at 11:03:19

In reply to Esmethadone helps treatment-resistant depression, posted by Hugh on January 11, 2022, at 9:21:23

Hi, Hugh.

Thank you for continuing to provide such great information.


What do you think of this compound? It might be worth finding out in what ways it differs from memantine. Memantine pretty much sucks as an depression. It is equally dismal as an anti-Alzheimer's drug.


- Scott

 

Re: Esmethadone helps treatment-resistant depression » SLS

Posted by undopaminergic on January 11, 2022, at 12:23:52

In reply to Re: Esmethadone helps treatment-resistant depression » Hugh, posted by SLS on January 11, 2022, at 11:03:19

>
> What do you think of this compound?

It has an interesting name that makes me wonder if this stereoisomer is part of ordinary methadone. Apparently it has no opioid effects.

> It might be worth finding out in what ways it differs from memantine. Memantine pretty much sucks as an depression. It is equally dismal as an anti-Alzheimer's drug.
>

Memantine actually worked "too well" in my experience, inducing a manic condition. Finding the right dose was difficult. First it worked at less than 10 mg and later I needed about 60 mg. I wonder how high it would have gone if I had kept using it. The reason I didn't was my impulsive massive overdose of it, which was a more or less direct result of the mania. I left the container in plain sight and it was gone when I came back home after hospitalisation.

It may have applications in Parkinson's disease and tolerance to amphetamines and opioids.

-undopaminergic

 

Re: Esmethadone helps treatment-resistant depression » SLS

Posted by Hugh on January 11, 2022, at 20:41:21

In reply to Re: Esmethadone helps treatment-resistant depression » Hugh, posted by SLS on January 11, 2022, at 11:03:19

Ketamine, memantine (NAMENDA XR®), and REL-1017 [esmethadone] share the same core mechanism of action, inhibiting the NMDA receptor directly as channel blockers. Ketamine and its metabolites are also thought to have other activities in the brain that may be responsible for some of its effects.

Ketamine enters the NMDA receptor channel when it is activated, blocking its unwanted function and showing significant activity in reducing symptoms of depression within a few hours after administration. However, it remains "trapped" in the channel to a high degree after closure. This prolonged blocking activity is believed to be a causative factor in ketamine's unfavorable side effects including hallucinations, delusion and delirium, which are found even at therapeutic doses

REL-1017 acts very similarly by blocking the NMDA receptor at a channel level when the receptor is activated and potentially showing similar rapid therapeutic effect. However, several studies have demonstrated that differences in the degree of trapping exist among use-dependent NMDA receptor antagonists and that these differences are correlated with efficacy and safety. For example, the NMDA receptor antagonist memantine is currently FDA approved to treat Alzheimer's disease, but it hasn't shown efficacy in treating depression or neuropathic pain in studies to-date.

Complete article:

http://bionapcfa.com/2016/10/an-interview-with-relmada-therapeutics.html

 

Re: Esmethadone helps treatment-resistant depression

Posted by Hugh on January 11, 2022, at 20:47:00

In reply to Re: Esmethadone helps treatment-resistant depression » SLS, posted by Hugh on January 11, 2022, at 20:41:21

The therapeutic potential of esmethadone was first identified and explored at New York Presbyterian/Weill Cornell Medicine. Researchers observed that when esmethadone was tried in late-stage cancer patients, their pain did not improve but there were positive effects on mood. In parallel, we were learning more about the NMDAR's role in depression. Since then, phase 1 and 2 studies have supported esmethadone's continued development as a potentially safe, effective antidepressant with quite rapid onset. However, these very encouraging results need to be further confirmed in larger and longer phase 3 studies. Relmada Therapeutics, Inc is currently conducting these studies as part of our RELIANCE Clinical Research Program.

Complete article:

https://www.psychiatrictimes.com/view/exploring-the-potential-of-an-investigational-nmdar-channel-blocker-for-major-depressive-disorder

 

Re: Esmethadone helps treatment-resistant depression

Posted by SLS on January 11, 2022, at 21:25:59

In reply to Re: Esmethadone helps treatment-resistant depression » SLS, posted by undopaminergic on January 11, 2022, at 12:23:52

> >
> > What do you think of this compound?
>
> It has an interesting name that makes me wonder if this stereoisomer is part of ordinary methadone. Apparently it has no opioid effects.
>
> > It might be worth finding out in what ways it differs from memantine. Memantine pretty much sucks as an depression. It is equally dismal as an anti-Alzheimer's drug.

> Memantine actually worked "too well" in my experience, inducing a manic condition.

My doctor once said that if a given drug never triggers mania in at least some people, it would be relatively ineffective as an antidepressant in general. Sometimes, triggering a hypomania using an antidepressant is the first step in bringing someone out of a refractory depression. The second step is to use an antimanic agent to cap the hypomania while continuing the antidepressant. For some people, their hypomania, if not impacting their life negatively, are left feeling euphoric, having enormous energy, and accelerated thinking. They are often hyperfunctional. Why rock the boat?


> Finding the right dose was difficult. First it worked at less than 10 mg and later I needed about 60 mg. I wonder how high it would have gone if I had kept using it. The reason I didn't was my impulsive massive overdose of it, which was a more or less direct result of the mania. I left the container in plain sight and it was gone when I came back home after hospitalization.

I found myself compulsively changing the dosage of Nardil up and down. It was a bad habit I picked up from one of my doctors in the 1980s.

Ouch.


> It may have applications in Parkinson's disease and tolerance to amphetamines and opioids.
>
> -undopaminergic
>

 

Re: Esmethadone helps treatment-resistant depression

Posted by Lamdage22 on January 11, 2022, at 21:55:22

In reply to Re: Esmethadone helps treatment-resistant depression, posted by SLS on January 11, 2022, at 21:25:59

That would be great. Slippery slope though.

>Sometimes, triggering a hypomania using an antidepressant is the first step in bringing someone out of a refractory depression. The second step is to use an antimanic agent to cap the hypomania while continuing the antidepressant. For some people, their hypomania, if not impacting their life negatively, are left feeling euphoric, having enormous energy, and accelerated thinking. They are often hyperfunctional. Why rock the boat?
´

 

Re: Esmethadone helps treatment-resistant depression

Posted by PeterMartin on January 12, 2022, at 14:36:18

In reply to Re: Esmethadone helps treatment-resistant depression » SLS, posted by Hugh on January 11, 2022, at 20:41:21

Where does Dextromethorphan fit in w/ these drugs that act on NMDA? I used to use it "recreationally" via cough syrup in the mid '00s and it was really good at helping my mood. In tandem w/ Lamotrigine I didn't "trip", but instead felt much more social and comfortable (removed depression/anxiety).

I've mentioned it a few times lately but AXS-05 (which is Dextromethorphan/Bupropion comb) seemed to do really well in phase 3 trials and should be approved by the end of the year.

 

Re: Esmethadone helps treatment-resistant depression » PeterMartin

Posted by Hugh on January 14, 2022, at 11:28:42

In reply to Re: Esmethadone helps treatment-resistant depression, posted by PeterMartin on January 12, 2022, at 14:36:18

Dextromethorphan can induce a dissociative state. Esmethadone "results showed that patients experienced mild or moderate adverse events that passed quickly and the treatment produced no evidence of dissociative or psychotic behaviors, nor any signs or symptoms of withdrawal."

 

You're welcome and thanks (nm) » SLS

Posted by Hugh on January 14, 2022, at 11:30:19

In reply to Re: Esmethadone helps treatment-resistant depression » Hugh, posted by SLS on January 11, 2022, at 11:03:19

 

Re: Esmethadone helps..Hugh, UD, SLS

Posted by Jay2112 on January 16, 2022, at 17:34:34

In reply to Re: Esmethadone helps treatment-resistant depression, posted by SLS on January 11, 2022, at 21:25:59

> > >
> > > What do you think of this compound?
> >
> > It has an interesting name that makes me wonder if this stereoisomer is part of ordinary methadone. Apparently it has no opioid effects.
> >
> > > It might be worth finding out in what ways it differs from memantine. Memantine pretty much sucks as an depression. It is equally dismal as an anti-Alzheimer's drug.
>
> > Memantine actually worked "too well" in my experience, inducing a manic condition.
>
> My doctor once said that if a given drug never triggers mania in at least some people, it would be relatively ineffective as an antidepressant in general. Sometimes, triggering a hypomania using an antidepressant is the first step in bringing someone out of a refractory depression. The second step is to use an antimanic agent to cap the hypomania while continuing the antidepressant. For some people, their hypomania, if not impacting their life negatively, are left feeling euphoric, having enormous energy, and accelerated thinking. They are often hyperfunctional. Why rock the boat?
>
>
> > Finding the right dose was difficult. First it worked at less than 10 mg and later I needed about 60 mg. I wonder how high it would have gone if I had kept using it. The reason I didn't was my impulsive massive overdose of it, which was a more or less direct result of the mania. I left the container in plain sight and it was gone when I came back home after hospitalization.
>
> I found myself compulsively changing the dosage of Nardil up and down. It was a bad habit I picked up from one of my doctors in the 1980s.
>
> Ouch.
>
>
> > It may have applications in Parkinson's disease and tolerance to amphetamines and opioids.
> >
> > -undopaminergic


Hugh, Scott and UD:

Methadone, it's isomer being esmethadone, is a very good choice of an antidepressant, in particular at low doses. So, I think esmethadone should have SOME opioid receptor agonism. It makes its therapeutic effects better, I would naturally think. I have been on trials of methadone, but for a few reasons, were discontinued because I didn't like having to go to the methadone clinic every day to get the stuff. (In a juice drink formulation.) My buddy has been on it for a year, and has lost tons of weight, and relieved his depression and anxiety.

I hope this is widely available soon without the god damn restricted/listed drug. I am SO SICK, and I say this as a mental health/addictions worker, of the stereotype mentality of ANY drug. We need like Portugal...delist/unrestrict EVERY drug out there...get pharmaceutical quality of EVERY drug, and just prescribe the damn stuff..NO bounds..

Jay

 

Re: Esmethadone helps treatment-resistant depression » Hugh

Posted by beckett2 on January 17, 2022, at 21:34:02

In reply to Esmethadone helps treatment-resistant depression, posted by Hugh on January 11, 2022, at 9:21:23

Any sense of when this might become available to the market? Thanks again for the information, Hugh.

 

Re: Esmethadone helps..Hugh, UD, SLS » Jay2112

Posted by Hugh on January 18, 2022, at 10:17:40

In reply to Re: Esmethadone helps..Hugh, UD, SLS, posted by Jay2112 on January 16, 2022, at 17:34:34

https://vimeo.com/180104373

> I hope this is widely available soon without the god damn restricted/listed drug. I am SO SICK, and I say this as a mental health/addictions worker, of the stereotype mentality of ANY drug. We need like Portugal...delist/unrestrict EVERY drug out there...get pharmaceutical quality of EVERY drug, and just prescribe the damn stuff..NO bounds..
>
> Jay

 

Re: Esmethadone helps treatment-resistant depression » beckett2

Posted by Hugh on January 18, 2022, at 10:36:07

In reply to Re: Esmethadone helps treatment-resistant depression » Hugh, posted by beckett2 on January 17, 2022, at 21:34:02

> Any sense of when this might become available to the market? Thanks again for the information, Hugh.

You're welcome. Relmada Therapeutics, Inc. is currently recruiting for phase 3 clinical trials using REL-1017 (esmethadone) for major depressive disorder. If these trials are successful, REL-1017 should receive FDA approval a few years from now.

https://clinicaltrials.gov/ct2/results?cond=&term=REL-1017&cntry=&state=&city=&dist=

 

Re: Esmethadone helps treatment-resistant depression » Hugh

Posted by beckett2 on January 18, 2022, at 16:40:16

In reply to Re: Esmethadone helps treatment-resistant depression » beckett2, posted by Hugh on January 18, 2022, at 10:36:07

> > Any sense of when this might become available to the market? Thanks again for the information, Hugh.
>
> You're welcome. Relmada Therapeutics, Inc. is currently recruiting for phase 3 clinical trials using REL-1017 (esmethadone) for major depressive disorder. If these trials are successful, REL-1017 should receive FDA approval a few years from now.
>
> https://clinicaltrials.gov/ct2/results?cond=&term=REL-1017&cntry=&state=&city=&dist=
>
>

In terms of medicine, I was born too early. In terms of the enviornment, I was lucky to catch the last of a relatively car scare and bird diverse earth. Sigh.

 

Re: Esmethadone helps treatment-resistant depression » beckett2

Posted by Hugh on January 20, 2022, at 13:04:05

In reply to Re: Esmethadone helps treatment-resistant depression » Hugh, posted by beckett2 on January 18, 2022, at 16:40:16

I wish I had a time travel machine. I'd travel to the future and take advantage of its marvelous depression treatments, and then I'd travel back in time to an era that's far less crazy than the one we're in now.

> In terms of medicine, I was born too early. In terms of the enviornment, I was lucky to catch the last of a relatively car scare and bird diverse earth. Sigh.


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