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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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PostPosted: Mon Sep 04, 2017 11:55 pm 
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I held onto that ketamine for a fair while, a few months, holding onto it for when my bipolar blues returned. And return they did in the last couple of weeks. I often claim I get sick around April, but the reality is it can come at any time of the year. It started with little things, like getting really messed up emotionally over little things at work / uni, and needing to crash in bed the moment I got home. I hated waking up because the moment I became conscious, that feeling of emptiness returned. So I upped the exercise, and pretended to myself it wasn't actually happening in the hope things would pick up on their own. This slowed the onset a bit, but in the end the depression won. I've spent most of the time since Thursday last week either in bed or on the couch. I've postponed appointments and absconded from uni. It's really not good. I have commitments that I'm avoiding, and I can't help being angry at myself for being "lazy". The thing is a month ago I loved my commitments! I loved studying and learning. Now my brain feels like a marshland and it can't retain information for sh*t. I delay my appointments with clients as long as possible in the hope that it'll give me more time to recover before I see them, and when I eventually have to force myself to go, putting on that smile and front for a couple of hours is really draining.

Anyway the point of this post was to talk about the ketamine. I tried it a couple of times once I could no longer be in denial about my state of mind. The first time I took it, I got a mild antidepressant boost the next day that had pretty much worn off completely by 48 hours. A week later I tried again, a slightly higher dose, only this time I didn't really get much of a residual antidepressant effect at all. If anything the second time was potentially dangerous, as I went into the experience with self-harm on my mind a bit, and the whole experience revolved around the idea of death and self-harm in a way that was quite negative. I woke up the morning after feeling not much better.

So I think I'm going to give up on the K-train. If there were benefits to be derived from it, it wasn't enough to make up for the unsettling trippy experience you get when you take it, and the mild nausea I felt for the rest of the evening.

I'll keep my ears to the floor for any new treatments that are on the horizon that I can pin some hope onto.

To end on a positive note, something that's interesting is that I actually have no desire to relapse into abusing drugs even though my mood is dark. Being depressed is usually a huge trigger for me, and more often than not in the past I have run back into addiction as a result. This year I did a lot of work with a counsellor that taught me to practice acceptance when I get sick, rather than to beat myself up for not functioning well. Nowadays I see spending a week without leaving my flat as a success, and something to be proud of, as long as I don't end up using drugs. It's better to be a hermit than a junkie. Small victories, huh. But it is harder to stay clean when all the things that help keep me clean, like work, social life, dating, exercise etc. Hopefully the boredom won't get to me. Taking my Suboxone each morning is one of the big things that's keeping me safe, I will admit.


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PostPosted: Tue Sep 05, 2017 1:36 pm 
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Tee Jay,
Sorry to hear that Ketamine did not help much. I've never used it, so I have no idea what it or any other hallucinogenic drugs are like. Sounds like you've gotten some good counseling- are you still working with the counselor? I would think that it would be a good idea now since you are feeling a bit depressed.

I really just wanted to say that I know exactly what you mean about those signs of getting depressed. For me, I will be living my life, pursuing goals, enjoying things like reading, watching TV shows, or Football, feeling productive at work. Then almost overnight I find myself tired and kind of bored. The next thing I know I realize I don't care about football Or tv shows, I have no interest in reading, my goals seem meaningless, and I can stare for long periods of time at my computer at work with no idea what to do or how to do it. As it progresses I find that I have trouble focusing long enough to read, forget how to do simple things, and have trouble problem solving, even simple problems. Eventually getting out of bed and getting dressed takes so much mental energy, that if able to do that I just can't accomplish anything else all day. It's so awful. So I understand what you are saying.

My worst time of year is the fall- so right now. This will be my first year on Buprenorphine, so I'll be interested to see if it makes a difference. If I have problems this year I'm going to try one of those lights that is supposed to help with seasonal stuff. Anyways, take care of yourself, and congrats for not going back to drugs even though you aren't feeling so hot right now. Best
Tragicom


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PostPosted: Wed Sep 06, 2017 3:39 pm 
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Tragicom u explained that so perfectly, it's like u took me right there with u. I went through something pretty similar to that for about 5 months after rehab.... didn't care about anything and couldn't focus on anything. I couldn't motivate myself or care enough to shower or get up in the morning. I think that was all to do with stopping opiates, paws and cravings, but that's the closest I've really ever come to depression. I've always said that I couldn't imagine just how tough that would be to deal with. It has to be very tough on all of u that suffer with depression. U guys are very strong too.

On another note, I've always loved loved Fall. I do sometimes get down whenever Summer is starting, not depression but just a down mood for awhile. The reason is where I live it's becoming so incredibly hot in the summertime. The humidity is unbearable and it's a wet like heat that keeps ppl from being able to even get outside without the risk of heatstroke. So that's why I hate summers. But Fall..... I'm so excited! Halloween and cool weather, I'm very excited. I know not many ppl feel like I do about Fall though lol.

Anyway I just wanted to tell ya that u did a great job explaining some of the things ppl suffering from depression go through. I have so much respect for the ppl who go through this.

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PostPosted: Thu Sep 07, 2017 8:08 pm 
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Thanks as always for the support, Jenn!

I do enjoy the fall weather and the changing colors of the leaves. I'm doing okay right now, so maybe I really will enjoy it this year.

Just want to give everyone a little hope when they are feeling that depression. Hopefully people can come here, or go to other forms of support rather than back to active addiction.

Jenn, you are so strong, and keep so many people going. Thanks for all you do!

Tragicom


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