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PostPosted: Fri Aug 11, 2017 12:27 pm 
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I have taken and discontinued taking several SSRIs including Paxil and don't remember too many problems other than the brain zaps, weird feelings, and fatigue. However, I was taking Effexor XR, high dose and ran out of medication due to having to miss an appointment. My doctor was a jerk then and wouldn't give me a refill, or even a few to hold me over until our appointment like a week later.

The withdrawal from that drug was god-awful, very similar for me to opiate withdrawal (maybe a little less intense). I remember rolling around on the floor in pain, cursing the drug and my doctor. She also never told me about withdrawal, it was very new, and people didn't think withdrawal was real. (Still, they call it "discontinuation syndrome", its withdrawal).

Never would I ever consider taking that drug again. It was helpful for depression, but not worth that withdrawal. At least with opiate withdrawal you got something good out of it before the crappy feelings.

I've suffered with treatment resistant for a long time. Things will work for a few weeks or months and then just stop. And it's hell when you can't find anything to help. I'm excited that new drug class is finally being worked on. Once it's in the mainstream and covered by insurance I would love to try Ketamine, if I need it. Since starting Suboxone my depression is gone completely. But it's only been a few months, so who knows . . .


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PostPosted: Fri Aug 11, 2017 3:56 pm 
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Tragicom wrote:
Since starting Suboxone my depression is gone completely. But it's only been a few months, so who knows...
Reminds me of a recent excellent teejay thread article-the-new-york-times-opioids-for-depression-t13463.html where he asks about opiates for depression. He was talking about bup only for depression and I goofed and thought he was talking about Alkermes' new ALKS 5461 drug in development that focuses on the KAPPA receptor and silences the MU.

ALKS 5461, combines samidorphan and buprenorphine and phase 2 showed significantly reduced depression symptoms as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) compared to placebo.

The problem came in Phase 3 when the results were only effective at the higher dose as the lower dose results were matched by the placebo group which apparently happens in treatment resistant depression trials bc the placebo effect can be so strong w those who are suffering.

Phase 3b just announced http://www.businesswire.com/news/home/2 ... -ALKS-5461 Would be nice if it works - folks need help...

Here is a VERY complex detailed review. I'll let you read - perhaps thought to be contraindicated in bi polar and separately in those needing opiate pain relief bc the mu pain relief receptor is blocked by samidorphan which also avoids drug dependence.
https://en.wikipedia.org/wiki/Buprenorphine/samidorphan

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PostPosted: Fri Aug 11, 2017 4:51 pm 
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So wait, if approved, would this new ALKS 5461 Kappa receptor anti depression med even be appropriate for folks w Opiate Use Disorder (OUD) needing buprenorphine or methadone at the MU receptor? Samidorphan w similar molecular structure to naltrexone, blocks the MU receptor to avoid drug dependence. Or what if on Vivitrol (aka naltrexone) a strong MU blocker?

Would ALKS-5461 cause WDs if taken too close to prior opiate use?

Geez I've confused myself. Ha.

I need help w this! Help !!! Dr J, docm2, Teejay, Tragicom... others...

If it gets approved, we'll need to know...

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PostPosted: Sat Aug 12, 2017 7:01 pm 
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Yeah I would definitely not be taking a strong mu-antagonist while on Suboxone. Samidorphan kicks all bupe off mu-receptors very quickly. It would be like compressing 12 days of buprenorphine withdrawal into 24-36 hours. NOT fun at all. That being said it probably wouldn't kill you, but it would feel like it.

It'd be likely that the new anti-depressant would be excluded from use in people on pain-management, methadone & Suboxone. It also adds a layer of impracticality given people on it won't be able to receive pain-management in case of emergency, similar as for those on naltrexone. They may be given a card or a bracelet to inform emergency services of the fact.

Apparently emergency services give patients ketamine for intense pain instead of narcotics when they're being treated with mu-antagonists. Interesting side-fact.

Wikipedia article says it here:

Quote:
Opioid analgesics

Due to occupation and antagonism of the MOR by ALKS-5461, an anticipatable drug interaction between ALKS-5461 and opioid analgesics may exist in that the effects of the latter may be significantly reduced or possibly abolished, and hence ALKS-5461 may prove contraindicated in patients who require opioid analgesics for pain management.


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PostPosted: Sat Aug 12, 2017 10:59 pm 
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This is all very interesting and a bit confusing to me. I have to read up on this myself. So, prior to going on Suboxone I was excited about ALKS 5461 for depression because of the buprenorphine. I've definitely experienced antidepressant effects from a variety of opiates and so far buprenorphine has had the most "stabilizing" antidepressant effect of all. It sounds like due to the other drug, Samidorphan, that while on Suboxone I could never take this drug (but I take buprenorphine anyway), and could never take other opiates on that medication. I don't plan on stopping Suboxone any time soon, so it's all a moot point.

On the surface it seems easy to confuse "antidepressant" with "euphoria" or "being high" and make the argument that"of course opioids make you feel less depressed," "you are high". I have experienced being high, euphoric, sedatedetc. So I get that part. But that is not what I am referring to when I speak of an antidepressant effect.

Even at low doses I have experienced an increase in motivation, goal directed activity, more social, less irritable, basically the type of effects you would want to get if you were prescribed an antidepressant. It almost feels like a separate feeling though, than the high. The problem is that the antidepressant effect, when dose increased, or just continued, turns into the experience of being high, the addiction, all the problems. And the antidepressant effect itself wears off and evolves into a different experience.

I have found Bup to have only the antidepressant effect and with the ceiling there isn't any raising doses or highs. The main reason I take Buprenorphine is for the relief I get from horrible opioid cravings. It has been great to see the antidepressant effects working for me.

I am not as familiar with all the opioid receptors as I would like to be so I am going to read up on it.
Pelican, Teejay, anyone else who knows, is it the Kappa receptors that are responsible for antidepressant effects of ALKS 5461? Are Kappa receptors involved in other opioids? Is there some other aspect of opioids involved in my experience of antidepressant effect other than the traditional mu opioid effects inducing euphoria? Or am I way off in all of this?

Also, I want to know, would the buprenorphine in ALKS 5461 effect one differently due to the Samidorphan, and if so how? I guess ALKS would not help with addiction at all?
I'm very interested in psychopharmacology, but I don't know so much.


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PostPosted: Mon Aug 14, 2017 6:54 pm 
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Yeah the Samidorphan would make a big difference. The reason we take Suboxone is because of its mu-agonist activity. Samidorphan not only blocks that mu-agonist activity, but it would also displace all the buprenorphine off the mu-agonist receptors. Would mean a nasty experience.

Personally re ALKS, the drug seems a bit "messy" to me. It's one of those things that will look good in theory, but I fear the practicality of mixing a potent antagonist with a potent agonist will be fraught. Just my 2c.

I did write a post about the difference between agonist and antagonist etc but I seem to have lost it. Damn.


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PostPosted: Mon Aug 14, 2017 11:41 pm 
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Thanks Teejay. It sounds like I didn't fully understand how ALKS 5461 worked and I am glad that I am on Suboxone and the Buprenorphine seems to be helping with depression, at least for now. The new medication does sound kind of messy. I will be really interested though to see if/ when it is approved and how people respond to it. I do understand the basics of agonists and antagonist, but not much past that. So, with ALKS the Samidorphan rips off the mu receptors to help with prevention of addiction?
I will try to find out more about this. Thanks


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