What works for depression once SSRIs fall short — Semax, or something else?

bk0004

bk0004

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Curious whether anyone here has first-hand experience with Semax — or any other peptide — for depression, after both SSRIs and herbal approaches came up short?

My wife has been living with depression that comes and goes over many years (it started back in middle school), generally mild to moderate. SSRIs simply haven't done much for her, which is why we're exploring other routes.

For anyone who has used both antidepressants and peptides: how did the two compare in your case? Anything you'd recommend, or warn us away from?

I realize everyone responds differently — I'm just hoping to learn from people who have actually been through it.

Thanks so much in advance!
 
From what I understood, Semax leans more toward focus and mental clarity than it does toward mood. For lifting mood and easing anxiety, Selank is the one people point to. Happy to be corrected if that's off base.
 
Selank gave me some benefit, though I was on an SSRI alongside it rather than using it as a replacement. What ultimately moved the needle for me was changing SSRIs and pairing one with an antipsychotic — that combination has worked very well in my case. Worth trying, in my view; I can't see it doing harm. Just don't count on miracles. Some placebo effect usually shows up at the start, so watch whether the improvement holds. Best of luck!
 
bk0004 said:

toologic said:

It didn't do anything for me, yet PE 22-28 brought a mild lift
Click to expand...
What sort of change did the 22-28 peptide bring for you?
Click to expand...
My mood lifted and the depression eased. I began with the nasal route, then moved over to sub q. Plenty of people claim results arrive within 4 days, but in my case it took 2 weeks before anything registered. Has P21 been on your list?
 
arborealtrout said:

Antidepressants extend well past SSRIs — there are piles of them
Click to expand...
Plenty, agreed! The problem is that SNRIs and TCAs are ruled out entirely in her case — heart problems (which stem from an eating disorder she had as a teen) — and prescribing an atypical such as Wellbutrin won't happen either, again because of that history. So SSRIs are essentially the only class left open to her.

On the bright side, it stays mild most of the time and we cope. I'm simply after something that adds a bit of support.
 
bk0004 said:

arborealtrout said:

Antidepressants extend well past SSRIs — there are piles of them
Click to expand...
Plenty, agreed! The problem is that SNRIs and TCAs are ruled out entirely in her case — heart problems (which stem from an eating disorder she had as a teen) — and prescribing an atypical such as Wellbutrin won't happen either, again because of that history. So SSRIs are essentially the only class left open to her.

On the bright side, it stays mild most of the time and we cope. I'm simply after something that adds a bit of support.
Click to expand...
Other avenues do exist beyond the ones you listed. I'm guessing you're stateside. A fair number of FDA-approved drugs sit outside what you named. Research happens everywhere, not only in the US, and bringing in substances your country doesn't carry — whole drug classes among them, RIMAs for instance — is surprisingly simple and, typically, legal. A drug's actions aren't limited to its approved indication; often they reach considerably further. A compound that plainly functions as an antidepressant but never gets that label is sometimes simply a commercial choice (fluvoxamine, atomoxetine...). Relative is the right word for contraindications. Back when I began residency, TCAs and MAOIs were all we had. A post-MI patient in the CCU would have cardiology asking us which TCA to use. That's largely off the table now, but monitoring makes it possible.
 
Without knowing the specifics of her heart problem, I'd say the contraindication worry does sound a bit overcautious — I'm on tricyclics myself despite having heart disease. And unless she's genuinely underweight, ruling out bupropion over that past history strikes me as excessive; it does shave off a little weight on average, but only a little. Also worth noting: SNRIs exist, not just SSRIs.

Even supplements have some support for depression. None of them meets a gold standard, but plenty carry several human trials behind them plus low to moderate certainty evidence — fish oil, adding l-methylfolate to an SSRI, vitamin D, l-carnitine, and PEA among them. And there's a long tail of others with evidence of varying quality.
 
arborealtrout said:

bk0004 said:

arborealtrout said:

Antidepressants extend well past SSRIs — there are piles of them
Click to expand...
Plenty, agreed! The problem is that SNRIs and TCAs are ruled out entirely in her case — heart problems (which stem from an eating disorder she had as a teen) — and prescribing an atypical such as Wellbutrin won't happen either, again because of that history. So SSRIs are essentially the only class left open to her.

On the bright side, it stays mild most of the time and we cope. I'm simply after something that adds a bit of support.
Click to expand...
Other avenues do exist beyond the ones you listed. I'm guessing you're stateside. A fair number of FDA-approved drugs sit outside what you named. Research happens everywhere, not only in the US, and bringing in substances your country doesn't carry — whole drug classes among them, RIMAs for instance — is surprisingly simple and, typically, legal. A drug's actions aren't limited to its approved indication; often they reach considerably further. A compound that plainly functions as an antidepressant but never gets that label is sometimes simply a commercial choice (fluvoxamine, atomoxetine...). Relative is the right word for contraindications. Back when I began residency, TCAs and MAOIs were all we had. A post-MI patient in the CCU would have cardiology asking us which TCA to use. That's largely off the table now, but monitoring makes it possible.
Click to expand...
Alright — my peptide thread seems to have drifted into a list of prescription antidepressant ideas.

I do appreciate the input, but this is a road we've been down for years. There's been a lot of reading on our side, and we work with good physicians plus a psychiatrist I trust completely.

What I wasn't asking for was more antidepressants to try; those have already been explored and eliminated.

My wife and her psychiatrist see peptides as the next avenue. That's why I posted on a peptide forum — to hear from people who have used them themselves. Peptides being the point.

Thanks to everyone who has shared what they tried. If you have personal experience with Semax, Selank, or any other peptide for depression — particularly when standard antidepressants were a poor fit — I'd genuinely like to hear it.
 
Pocket said:

From what I understood, Semax leans more toward focus and mental clarity than it does toward mood. For lifting mood and easing anxiety, Selank is the one people point to. Happy to be corrected if that's off base.
Click to expand...
Selank is on my list as well — appreciate it!
 
toologic said:

bk0004 said:

toologic said:

It didn't do anything for me, yet PE 22-28 brought a mild lift
Click to expand...
What sort of change did the 22-28 peptide bring for you?
Click to expand...
My mood lifted and the depression eased. I began with the nasal route, then moved over to sub q. Plenty of people claim results arrive within 4 days, but in my case it took 2 weeks before anything registered. Has P21 been on your list?
Click to expand...
I'll give that a read — thank you.

P21 hasn't come up for us yet either, no.
 
lessthanhalf said:

Without knowing the specifics of her heart problem, I'd say the contraindication worry does sound a bit overcautious — I'm on tricyclics myself despite having heart disease. And unless she's genuinely underweight, ruling out bupropion over that past history strikes me as excessive; it does shave off a little weight on average, but only a little. Also worth noting: SNRIs exist, not just SSRIs.

Even supplements have some support for depression. None of them meets a gold standard, but plenty carry several human trials behind them plus low to moderate certainty evidence — fish oil, adding l-methylfolate to an SSRI, vitamin D, l-carnitine, and PEA among them. And there's a long tail of others with evidence of varying quality.
Click to expand...
She's already on vitamin D, plus l-carnitine. PEA is a new one for me — never came across it as something for depression, so I'll look into it. Thanks!
 
Hello, and a big thank you to everyone who offered suggestions and shared what worked for them.

After considerably more digging on our end, the decision is to try a stack of Selank, Semax, and possibly P21. I figured I'd log the process here in case it proves useful to someone later on.

The approach is to bring them in one at a time, so any reaction or unwanted side effect can be pinned down before the next addition.

Current plan:

Selank

  • Begin at 250 mcg SC
  • Step up to 500 mcg gradually, provided it's tolerated well
Semax

  • Begin at 250 mcg SC
  • Step up to 500 mcg gradually, provided it's tolerated well
P21

  • Once two full cycles of Selank and Semax are behind us, take stock of mood and anxiety.
  • Then, depending on where she stands, either fine-tune the existing protocol or bring in P21 (intanasal) at that stage.
I'll keep posting updates as we go, for anyone who wants to follow how it turns out. Hopefully what we learn will be of use to others weighing a similar path.
 
Another P21 cycle is about to begin for me. It works nicely alongside Semax and the related compounds. My own experience with it was positive. Keen to hear how you see things.
 
My wife's been living with depression and anxiety for years now. Neither Semax nor selank moved the needle much for her, though we're going to give them another go. The thing that actually helped was oxytocin. It left her more connected to herself and clearer on what matters to her.
 
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