![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 30 to 54 of 67. Go back in thread:
Posted by hello123 on January 26, 2015, at 16:34:40
In reply to Re: feeling like im out of options, posted by Hugh on January 26, 2015, at 11:17:21
i had slowly raised the dose of Naltrexone over a couple of weeks. i dont think ive felt any effect from it. depression hasnt gotten worse or anything.
and i'll have to read in to that treatment you mentioned. i like to very thorougbly read about any treatment thes days, as opposed to how i used to just look on WebMD for any info.
...and my appointment today was a waste of time and money. the Clinic is an hour from my home, so i drove all that way only to be told id be seeing a nurse today since my Pdoc wasnt there. this irritated me a bit since every time ive seen a nurse for psych treatment, they dont want to do much of anything. my situation is complicated and they tend to have a very structured way of thinking. Its like they got all their ideas from WebMD., but i hoped for the best anyway. long story short, she decided it was best to see the Psychatrist when he gets back. i mentionedat the end of talking to her i mentioned i was a bit irritated because i expected to be talking to a real doctor today, and about the gas money i have to spend for the hour drive there and back. of course all she could say is "aww im sorry" and i just said "im sure you are"
the more hopeless i feel, the less willing anyone has been willing to try helping me. i cant stand dealing with this dumb medical system filled with sorry doctors getting their bank account filled by sick people. it doesnt matter if anyone benefits from an appointment with them. they still get paid for simply having a sick person in their presence. Oh they ask if im suicidal or homicidal at the beginning of my appointment, but the main reason fir that is sko they dont get sued if i do anything bad after i keave there. otherwise it doesnt matter if i EVER feel any better. tbey still get paid just for having me sit in a chair in front of their desk.
Posted by hello123 on January 26, 2015, at 19:32:16
In reply to Re: feeling like im out of options, posted by hello123 on January 26, 2015, at 16:34:40
im done with this. im not going to continue playing games with these dumb doctors. the more hopeless my situation gets, the less willing they are to even try to help me. im so unable to function, and am suffering, i cant put up with this. i couldnt even get a doctor to file an appeal for me when Medicare denied coverage for VNS. the people at the hospital that did the surgery told me my psychiatrist would have to do it. and my psychiatrist told me the people at the hospital would have to do it. im way past done with this BS.
And no, i dont have any hope in trying any treatment anymore. i dont at all feel that anything i try is going to help me.
Posted by Tomatheus on January 26, 2015, at 21:33:21
In reply to Re: feeling like im out of options, posted by hello123 on January 26, 2015, at 19:32:16
Hello123,
I know that it's hard to see how improvement might come when you've tried so many treatments with so little success. The thing is, though, that no matter how unlikely improvement may seem, you never really know what might be around the corner. So, maybe seeing your condition improve isn't what you or I would necessarily expect, but unexpected things do happen, sometimes when we least expect them to happen.
It's also too bad that your appointment didn't go well and that the doctors you've tried contacting have given you the runaround on appealing Medicare's decision to deny VNS coverage. It must be frustrating to not get the opportunity to see an actual doctor when you don't seem to be in the best of shape. If your doctor is reachable via telephone, maybe you could try calling him to at least let him know the urgency of your situation. Perhaps he could call in a prescription for a different medication or at least let you come in to see him again soon.
I hope that your situation can somehow improve.
Tomatheus
Posted by ed_uk2010 on January 27, 2015, at 6:51:13
In reply to Re: feeling like im out of options, posted by hello123 on January 26, 2015, at 19:32:16
Well.... the good thing is you're not out of options. In addition, you also know what some of the options are. It's extremely hard to remain hopeful when you feel depressed, but you have to remember that you do in fact have options.
When can you see your actual doctor?
Posted by hello123 on January 28, 2015, at 0:18:01
In reply to Re: feeling like im out of options » hello123, posted by Tomatheus on January 26, 2015, at 21:33:21
well, thank you guys for the kind words. i'll just continue to keep trying to find something that works.
im not sure if im even supposed to mention this on babble, but i ended up having to order the Naltrexone and Selegiline that im currently taking from an overseas site. i used the site a few years ago and had good results, and read other people said they had good results, so i used this site again. it was a last resort after my pdoc wouldnt even prescribe Emsam in the lowest dose. and i didnt even bother asking for Naltrexone. i just had gotten to the point where i wasnt going to wait for a pdoc to come around to deciding to try something new.
but since ive been taking the Selegiline and Naltrexone, i havent noticed any effect on mood (which isnt abnormal, thats been my experience with many meds ive tried) but my main concern is that the meds i received might have been handled improperly, such as being store in a hot wearhouse or something, causing them to become innefective. but i have noticed one thing, ive had vivid dreams every night since i started taking them, a.d i read many experiences with Naltrexone where they described vivid dreams as a side effect. so maybe thats a sign that at least the Naltrexone is in good condition.
but... i think my next idea is to take a med that focuses on Norepinephrine and continue taking it for some time even if it makes me feel horrible like the ones i mentioned, in hopes the bad effects will eventually turn to good. thats basically how my experience with Dopamine meds like Adderall and Mirapex went. Except it was opposite, they started out GRRREAT! but then after about 6 weeks the effects suddenly reverse and they just left me much worse off.... i dont know if this idea i have sounds all that great, but i just dont know what else to do. hopefully when i see the actual psychiatrist on 2/10, he will have an idea. i used to see him in the past, and this is my first appointment with him in 5 years. and i remember him being much better than the pdoc ive been seeing lately.
Posted by ed_uk2010 on January 28, 2015, at 3:45:31
In reply to Re: feeling like im out of options, posted by hello123 on January 28, 2015, at 0:18:01
Hi.
>but... i think my next idea is to take a med that focuses on Norepinephrine
Which med would you like to try?
NRIs do not have the immediate 'feel good' effect that stimulants often produce. If they are going to work, they normally do so over a period of a few weeks. You might notice some improvement after a couple of weeks. Like all widely prescribed ADs, the AD effect appears to occur mainly in response to adaptations in the brain, and is therefore not immediate, but delayed and sustained. With tricyclic NRIs, the appearance of the AD effect is thought to be correlated with beta adrenergic receptor down-regulation in the brain.
Starting tricyclics at full doses may be poorly tolerated. It would be best to get a prescription for the lowest strength of tablet since you're not familiar with this type of med... and have concerns about tolerability.
Do you have any non-psych medical problems? And are you on any non-psychiatric meds?
Posted by Tomatheus on January 28, 2015, at 9:23:21
In reply to Re: feeling like im out of options, posted by hello123 on January 28, 2015, at 0:18:01
Hello123,
It can be hard to know for sure if the reason why your mood symptoms don't seem to be responding to naltrexone and selegiline has to do with the quality of your pills or if it just has to do with the fact that the medications aren't effectively treating your mood symptoms. I suppose that the only way to know for sure if the quality of the pills is a factor would be to see if you can get the medications prescribed so you can take what's available at your pharmacy. Of course, you may or may not want to attempt to do this, as it might make more sense to try moving on to different treatment options, but trying to get the naltrexone and selegiline that you're taking prescribed might be an option.
At any rate, I wish you luck with the psychiatrist that you'll be seeing. Hopefully your upcoming appointment will go quite a bit better than your most recent appointment went.
Tomatheus
Posted by hello123 on January 28, 2015, at 13:53:00
In reply to Re: feeling like im out of options » hello123, posted by ed_uk2010 on January 28, 2015, at 3:45:31
>
> Which med would you like to try?
>
> NRIs do not have the immediate 'feel good' effect that stimulants often produce. If they are going to work, they normally do so over a period of a few weeks. You might notice some improvement after a couple of weeks. Like all widely prescribed ADs, the AD effect appears to occur mainly in response to adaptations in the brain, and is therefore not immediate, but delayed and sustained. With tricyclic NRIs, the appearance of the AD effect is thought to be correlated with beta adrenergic receptor down-regulation in the brain.
>
> Starting tricyclics at full doses may be poorly tolerated. It would be best to get a prescription for the lowest strength of tablet since you're not familiar with this type of med... and have concerns about tolerability.
>
> Do you have any non-psych medical problems? And are you on any non-psychiatric meds?
>
>
>
>im really not sure which NRI id like to try. ive not read much into Tricyclics and the experiences people tend to have with them. though i plan to before my dr visit. So i basically had Strattera in mind in mind at the moment, even with it not being FDA Aproved for Depression, that doesnt mean a whole lot to me. i doubt if the med i tried that had the biggest benefit for me in the past, Cyproheptadine, would be approved for Depression.
and unless its different with Tricyclics, ive read Stratteras benefefits usually occur with the "Alpha" Adrenergic receptors, and not the Beta Receptors?
Posted by hello123 on January 28, 2015, at 13:53:17
In reply to Re: feeling like im out of options » hello123, posted by ed_uk2010 on January 28, 2015, at 3:45:31
>
> Which med would you like to try?
>
> NRIs do not have the immediate 'feel good' effect that stimulants often produce. If they are going to work, they normally do so over a period of a few weeks. You might notice some improvement after a couple of weeks. Like all widely prescribed ADs, the AD effect appears to occur mainly in response to adaptations in the brain, and is therefore not immediate, but delayed and sustained. With tricyclic NRIs, the appearance of the AD effect is thought to be correlated with beta adrenergic receptor down-regulation in the brain.
>
> Starting tricyclics at full doses may be poorly tolerated. It would be best to get a prescription for the lowest strength of tablet since you're not familiar with this type of med... and have concerns about tolerability.
>
> Do you have any non-psych medical problems? And are you on any non-psychiatric meds?
>
>
>
>im really not sure which NRI id like to try. ive not read much into Tricyclics and the experiences people tend to have with them. though i plan to before my dr visit. So i basically had Strattera in mind in mind at the moment, even with it not being FDA Aproved for Depression, that doesnt mean a whole lot to me. i doubt if the med i tried that had the biggest benefit for me in the past, Cyproheptadine, would be approved for Depression.
and unless its different with Tricyclics, ive read Stratteras benefefits usually occur with the "Alpha" Adrenergic receptors, and not the Beta Receptors?
Posted by hello123 on January 28, 2015, at 14:03:37
In reply to Re: feeling like im out of options, posted by hello123 on January 28, 2015, at 13:53:17
i understood that when starting on an NRI, the overstimulation of Alpha receptors slowed down NE release, likely leading to a worsening of symptoms, until they downregulate after chronic stimulation. with the benefits beginning with this downregulation.
ive been thinking this is possibly what caused me to feel so terrible when i tried SNRI's.
Posted by europerep on January 28, 2015, at 16:50:02
In reply to Re: feeling like im out of options, posted by hello123 on January 28, 2015, at 13:53:00
> ive not read much into Tricyclics and the experiences people tend to have with them.
Then don't. You're not going to read yourself to a treatment that will work. As much as it sucks, trial-and-error is the state of the art for treatment-resistant depression. And really the one thing that could be an indicator of where to look for solutions -- namely decades of successful use by experienced clinicians -- you dismiss anyway.
It almost looks like you want to prove to yourself that you are a hopeless case by using the weirdest treatments -- I have never come across any kind of scientific documentation of selegiline plus naltrexone* -- rather than going for what's (statistically) most likely to help you.
Don't get me wrong, I'm not trying to attack you or anything, and thinking in a reasonable and analytical way is really tough when depressed, but I really don't think you're doing yourself a favor by proceeding the way you do.
*That doesn't mean it shouldn't be ever be tried, but it is not rational to start there before having tried well-established and safe treatments that have a much higher chance of helping you.
Posted by hello123 on January 28, 2015, at 17:40:25
In reply to Re: feeling like im out of options » hello123, posted by europerep on January 28, 2015, at 16:50:02
youre way off the mark, europrep. i thought id take the time to explain how, but i doubt it would be any use.
Posted by hello123 on January 28, 2015, at 18:15:00
In reply to Re: feeling like im out of options » hello123, posted by europerep on January 28, 2015, at 16:50:02
> Then don't. You're not going to read yourself to a treatment that will work. As much as it sucks, trial-and-error is the state of the art for treatment-resistant depression. And really the one thing that could be an indicator of where to look for solutions -- namely decades of successful use by experienced clinicians -- you dismiss anyway.
>
> It almost looks like you want to prove to yourself that you are a hopeless case by using the weirdest treatments -- I have never come across any kind of scientific documentation of selegiline plus naltrexone* -- rather than going for what's (statistically) most likely to help you.
>
> Don't get me wrong, I'm not trying to attack you or anything, and thinking in a reasonable and analytical way is really tough when depressed, but I really don't think you're doing yourself a favor by proceeding the way you do.
>
> *That doesn't mean it shouldn't be ever be tried, but it is not rational to start there before having tried well-established and safe treatments that have a much higher chance of helping you.oh what the hey...
Naltrexone is very similar to Buprenorphine, a med you said youve taken in a response to what i posted a week or 2 ago on an interesting new med in clinical trials. that med is a mix of Buprenorphine, and a new med that blocks the addictive properties of Buprenorphine, while letting its Kappa antagonism go to work. Reading about this med in trials is what gave me the idea to try Naltrexone, since i cant get a hold of any Buprenorohine. im not sure why youd call this weird, considering youve tried Buprenorphine in the past.Ive been diagnosed with Depersonalization as well as Depression, and there has been some success in using Naltrexone to treat Depersonalization.
and im not really taking these meds as a combination, in the sense you made it sound like. i just made sure there were no serious interactions and decided to start taking them at the same time in hopes at least one would bebefit me.
and no, i dont read other experiences with meds thinking i will likely react them in about the same way. i just made that statement because, other than some minor details, i just dont know much of anything about Tricyclic AD's
i think next time you need to ask so,e more questions before making a judgement.
Posted by hello123 on January 28, 2015, at 18:45:12
In reply to Re: feeling like im out of options » hello123, posted by europerep on January 28, 2015, at 16:50:02
"namely decades of successful use by experienced clinicians -- you dismiss anyway."
and the last clinician i talked to, with her decades of experience, insists Emsam at its lowest dose, has all the same interactions with foods as oral Selegiline. and when i mentioned to her a doc prescribed Ketamine for my Depression in the past, she said she had never heard of it being used for Depression.
and a couple of years ago when i mentioned to the same psychiatrist that i will be seeing on 2/10, that Wellbutrin actually caused a decrease in my libido, he said something along the lines of "but Wellbutrin doesnt cause a decrease in libido." i corrected him, saying Wellbutrin doesnt cause a decreased libido in most cases.
Posted by baseball55 on January 28, 2015, at 19:57:27
In reply to Re: feeling like im out of options, posted by hello123 on January 28, 2015, at 18:15:00
The active ingredient in buprenorphine that can relieve depression is buproprion - an opiate. Naloxone (which is the active ingredient in naltrexone) is mixed with buproprion in order to prevent overdose or abuse of the drug by opiate addicts. The naloxone itself has no anti-depressant properties.
Posted by hello123 on January 28, 2015, at 21:08:16
In reply to Re: feeling like im out of options » hello123, posted by baseball55 on January 28, 2015, at 19:57:27
> The active ingredient in buprenorphine that can relieve depression is buproprion - an opiate. Naloxone (which is the active ingredient in naltrexone) is mixed with buproprion in order to prevent overdose or abuse of the drug by opiate addicts. The naloxone itself has no anti-depressant properties.
im referring to this med currently in Clinical Trials:ALKS-5461 is a combination of buprenorphine, a moderate partial agonist of the μ-opioid receptor (MOR) and antagonist/very weak partial agonist of the κ-opioid receptor (KOR),[9][10][11] and samidorphan, a selective antagonist of the MOR.[12][13] The combination of these two drugs results in what is functionally a selective blockade of KORs with minimal or negligible effects on the MOR.[13][11]
Through activation of the KOR, dynorphins, opioid peptides that are the endogenous ligands of the KOR and that can, in many regards, be figuratively thought of as functional inverses of the morphine-like, euphoric and stress-inhibiting endorphins,[14] induce dysphoria and stress-like responses in both animals and humans,[15] as well as psychotomimetic effects in humans,[16][17] and are thought to be essential for the mediation of the dysphoric aspects of stress.[18] In addition, dynorphins are believed to be critically involved in producing the changes in neuroplasticity evoked by chronic stress that lead to the development of depressive and anxiety disorders, increased drug-seeking behavior, and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis.[14][18][19] In support of this, in knockout mice lacking the genes encoding the KOR and/or prodynorphin (the endogenous precursor of the dynorphins), many of the usual effects of exposure to chronic stress are completely absent, such as increased immobility in the forced swimming test (a widely-employed assay of depressive-like behavior) and increased conditioned place preference for cocaine (a measure of the rewarding properties and addictive susceptibility to cocaine).[20] Accordingly, KOR antagonists show robust efficacy in animal models of depression, anxiety, anhedonia, drug addiction, and other stress-related behavioral and physiological abnormalities.[14][15][21][22] As such, there has been great interest in developing KOR antagonists for the treatment of these and other psychiatric conditions in humans.[14][21] Progress has been limited until recently however, due to difficulty in finding selective KOR antagonists with suitable drug profiles (e.g., good pharmacokinetic parameters, short-acting KOR inactivation, lack of toxicity, etc.) for clinical development and use in humans.[15][21]
It has been known for decades that buprenorphine binds to at high affinity and antagonizes the KOR.[23][24] In addition, there have been many reports over the years supporting the idea of it being effective in the management of depressive and anxious symptomatology, and two small clinical trials have shown it to produce remission even in depressive patients refractory to conventional antidepressants and electroconvulsive therapy.[14][25][26][27][28][29][30][31][32][33][34][35] However, buprenorphine has never previously been seriously pursued for mental health indications, presumably due to concerns about its liability for abuse and dependence (and the additional difficulty in gaining regulatory approval that would certainly come with that).[36] In conjunction with samidorphan, as in ALKS-5461, however, its potential for abuse and dependence appears to be effectively negated.[37] As a result, it seems that ALKS-5461 may allow for buprenorphine to be employed safely and unrestrictedly in the treatment of depression and other conditions that it has shown efficaciousness in but that it would otherwise be used to treat likely only very rarely.
this is info from its Wikipedia article
Posted by ed_uk2010 on January 29, 2015, at 9:49:25
In reply to ALKS-5461, posted by hello123 on January 28, 2015, at 21:08:16
Hello :)
Buprenorphine is an opioid with high binding affinity for mu opioid receptors, but it only partially stimulates them; this is responsible for its typical opioid-like pain relieving properties. Buprenorphine also acts on other opioid receptors (kappa and delta), but as an antagonist ie. it blocks them, with no stimulation. Partial agonist activity at mu receptors combined with antagonist activity at kappa receptors may elevate mood in some types of depression, but mu agonist drugs can cause dependence, and bupe is not an exception. Buprenorphine also has an active metabolite called norbuprenorphine, with somewhat different opioid properties.
Buprenorphine is used both for pain relief (for moderately severe pain), and as part of the treatment for opioid dependence. Like methadone, it relieves opioid withdrawal symptoms and reduces the risk of relapse into IV drug misuse. Bupe is generally safer than methadone - which is very dangerous in overdose. Withdrawal symptoms from bupe and methadone can be rather prolonged, especially if high doses have been taken. Bupe withdrawal symptoms are less intense, however.
Bupropion is the generic name for Wellbutrin, an antidepressant. Bupropion has a similar name to buprenorphine but is not related to it in any way.
Buprenorphine is not similar to naltrexone. The fact that bupe stimulates mu receptors whereas naltrexone potently blocks them makes the drugs very different clinically.
Naltrexone and naloxone are different drugs too. They have similar effects but are used differently in practice. Naloxone is a short acting opioid antagonist - it blocks all opioid receptors, but is most potent at blocking the mu receptors, followed by the kappa receptors. It's used a lot by injection to treat opioid overdose, and in combination with buprenorphine to discourage the IV misuse of Suboxone tablets. Naltrexone is a long acting opioid antagonist - it blocks opioid receptors but for a much longer duration than naloxone. Naltrexone is used by mouth for a variety of reasons. It is sometimes used to decrease relapse after opioid detox, and to reduce drinking after alcohol detox. If naltrexone is taken by someone who is physically dependent on opioids, it will rapidly induce severe withdrawal symptoms. As a result, it can only be started once withdrawal is complete - with the aim of preventing relapse by blocking drug effects if opioids are taken. Low dose naltrexone (usually 4.5mg/day), has been recommended by alternative practitioners for a huge range of illnesses.
ALKS-5461 is a combination product containing buprenorphine and samidorphan. It is being studied for TR-depression. The idea is that samidorphan blocks the activity of buprenorphine at the mu receptor, and therefore presumably prevents dependence. In this combination, buprenorphine is still able to block the kappa receptors, which is thought to improve depression. Presumably, this combination will have more antagonist activity at the kappa receptors than naltrexone, while having minimal effect at the mu receptors. Naltrexone is a very strong mu antagonist, which may cause some unpleasant effects except at very low doses....
Posted by ed_uk2010 on January 29, 2015, at 9:52:09
In reply to Re: feeling like im out of options, posted by hello123 on January 28, 2015, at 17:40:25
>youre way off the mark, europrep. i thought id take the time to explain how, but i doubt it would be any use.
I don't think europerep was intending to be critical. I think s/he was mainly suggesting that you look to more established treatment options when choosing what you want to try next.
So, look at the post in a positive light if you can!
Posted by europerep on January 29, 2015, at 16:39:00
In reply to Re: feeling like im out of options, posted by hello123 on January 28, 2015, at 18:15:00
Hmm, there is a bit of confusion in the thread now. Ed has already pointed out everything about the different mechanisms of action, so I'll just reply directly to what you said.
I don't think it is rational to try naltrexone as a substitute for buprenorphine, for various reasons. Primarily, it lacks the properties of buprenorphine and norbuprenorphine on mu- and delta-receptors, which I would personally suspect to play at least some role in the antidepressant effects of buprenorphine. And naltrexone is actually fairly extensive used for various illnesses (compared to buprenorphine in treatment-resistant depression), so if naltrexone had antidepressant properties, we would have some solid knowledge about it. Not necessarily from the Journal of Clinical Psychiatry, but certainly from patients. I just have difficulty understanding why you seem to have some faith in science and pharmacological treatments, but you stubbornly refuse to try tranylcypromine or phenelzine. Some people call them the gold standard for treatment-resistant depression.
As for what I said about clinicians, I of course meant clinicians who can back their statements up with science, as those who recommend MAOIs for treatment-resistant depression can.
I don't want this here to become some kind of proving-each-other-wrong thing, because that is not my intention. I would personally like it if you reflected a bit about where you're most likely to find a working treatment, and then go in that direction. But you're obviously free to decide, so I'll leave it at that.
Posted by europerep on January 29, 2015, at 16:40:02
In reply to Re: feeling like im out of options, posted by ed_uk2010 on January 29, 2015, at 9:52:09
> s/he was
Haha, I can clear this up, I'm a he :)...
Posted by ed_uk2010 on January 29, 2015, at 17:01:36
In reply to Re: feeling like im out of options » ed_uk2010, posted by europerep on January 29, 2015, at 16:40:02
> > s/he was
>
> Haha, I can clear this up, I'm a he :)...I thought you were a man.... but I realised I didn't know what I was basing my assumption on.
Posted by ed_uk2010 on January 29, 2015, at 17:11:14
In reply to Re: feeling like im out of options » hello123, posted by europerep on January 29, 2015, at 16:39:00
>you stubbornly refuse to try tranylcypromine or phenelzine.....
I don't get the impression that Hello is being stubborn :) I suspect that s/he (I have an impression of a man somehow) has possibly had two problems:
1. Unwillingness to prescribe certain medications on the part of the psychiatrist. Many psychiatrists are unfamiliar with MAOIs and may never prescribe them.
2. Anxiety about the effects that certain medications might have, partly based on past experience with other meds. This may have created a reluctance to try MAOIs. Understandably, some people also feel anxious about the dietary restrictions associated with MAOIs and the possible consequences of eating the wrong foods.
Naturally, the tendency to feel negative and/or anxious about the available treatment options is increased by the depression itself.
Am I right Hello?
I hope so! I seem to be writing on people's behalf!
Posted by hello123 on January 29, 2015, at 17:47:03
In reply to Re: feeling like im out of options » hello123, posted by europerep on January 29, 2015, at 16:39:00
> Hmm, there is a bit of confusion in the thread now. Ed has already pointed out everything about the different mechanisms of action, so I'll just reply directly to what you said.
>
> I don't think it is rational to try naltrexone as a substitute for buprenorphine, for various reasons. Primarily, it lacks the properties of buprenorphine and norbuprenorphine on mu- and delta-receptors, which I would personally suspect to play at least some role in the antidepressant effects of buprenorphine. And naltrexone is actually fairly extensive used for various illnesses (compared to buprenorphine in treatment-resistant depression), so if naltrexone had antidepressant properties, we would have some solid knowledge about it. Not necessarily from the Journal of Clinical Psychiatry, but certainly from patients. I just have difficulty understanding why you seem to have some faith in science and pharmacological treatments, but you stubbornly refuse to try tranylcypromine or phenelzine. Some people call them the gold standard for treatment-resistant depression.
>
> As for what I said about clinicians, I of course meant clinicians who can back their statements up with science, as those who recommend MAOIs for treatment-resistant depression can.
>
> I don't want this here to become some kind of proving-each-other-wrong thing, because that is not my intention. I would personally like it if you reflected a bit about where you're most likely to find a working treatment, and then go in that direction. But you're obviously free to decide, so I'll leave it at that.
>I was simply hoping to benefit from from Naltrexones Kappa antagonism, since it has been shown to benefit Depression. The medication in Clinical Trials that i posted on works to treat Depressin with its blockade of the Kappa receptors. The FDA thinks this med has so much potential to benefit people that it has fast-tracked its approval:
http://mentalhealthdaily.com/2014/08/05/new-antidepressant-alks-5461-trials-2016-expected-availability/some info of Kappa antagonism from this article: "So why block the kappa receptor? When the kappa-opioid receptor becomes activated, naturally occurring peptides called dynorphins are released. Some research suggests that dynorphin levels are elevated among people with depression. Therefore blocking the kappa receptor will result in dynorphin reductions and may yield an antidepressant-like response.
Although dynorphins are important in a persons stress response, at high levels they block the release of glutamate. Blocking glutamate in the brain can prevent neuroplasticity, lead to poorer learning abilities, and can induce learned helplessness. Since ALKS-5461 would be blocking dynorphin, it is thought that glutamate would get released to increase hippocampal plasticity and thereby reversing learned helplessness.
Additionally, blocking dynorphin can improve signaling of dopamine, which could lead to further reductions in depressive symptoms as a result of stress. Many researchers believe that kappa-opioid receptor antagonists may be a valid treatment option for both depression and anxiety in the future. In animal studies with kappa-opioid receptor antagonists, significant improvements in depression, anxiety, anhedonia, drug addiction, and stress-related behaviors has been shown."
and i dont know why youd say i seem stubborn about trying either of those MAOI's after i posted this in one of my posts above:
"thats good to hear the effects from MAOI's feel much different than Reuptake Inhibitors for you. Thanks and it makes me feel more hopeful about trying them."though i am nervous about trying something with strong MAO-A inhibition because of the food restrictions.
also, as i said, i have Depersonalization, and Naltrexone has been shown to benefit this. http://www.ncbi.nlm.nih.gov/pubmed/15876908
and if you Google "naltrexone Depersonalization", you will see much talk about it on Forums about it being used to treat Depersonalization.
Posted by hello123 on January 29, 2015, at 18:03:21
In reply to Re: feeling like im out of options, posted by hello123 on January 29, 2015, at 17:47:03
and im guessing at least part of the reason Buprenorphine was chose to be combined with the new med that blocks the addictive properties of it, while leaving its Kappa antagonism alone, is because as the article i posted on the med thats being fast-tracked says, the Kappa receptor is essential to the Stress Response of the body, so im guessing a med that completely blocks the Kappa receptor, like Naltrexone, was seen as too strong. but a decrease in endogenous in stimulation of the Kappa receptor has indeed been shown to help Depression. and i likely would have tried Buprnorphine if it were available.
but look, as i have said, i have Depersonalization. as a result, my world is much smaller than it used to be. so little things bother me. if i werent in this situation, i probably wouldnt bother correcting you on things. i likely wouldnt even be on this site.
Posted by ed_uk2010 on January 29, 2015, at 18:17:24
In reply to Re: feeling like im out of options, posted by hello123 on January 29, 2015, at 17:47:03
>I was simply hoping to benefit from from naltrexone's kappa antagonism, since it has been shown to benefit depression....
It's an interesting option.
My opinion of naltrexone as a potential treatment for depression is that its very potent mu opioid antagonism may be an issue. It is a kappa antagonist as well, albeit less potent. A selective kappa antagonist would be more interesting as an antidepressant.
Mu agonists, such as morphine and hydrocodone frequently produce short-lived (but often marked) mood elevation followed by tolerance and dependence. The potential for problems is high, including the risk of worsening depression in the long run. Chronic use of mu agonists also disrupts the endocrine system, causing sexual dysfunction. Dependence on opioids may result in a state where the ability to experience pleasure naturally is reduced. I wouldn't be surprised if the long-term use of methadone is associated with more depression than buprenorphine (Suboxone etc) maintenance. In fact, I believe I've read that it is.
Mu antagonists such as naltrexone can sometimes feel subjectively unpleasant. I would be concerned about the potential for any potent mu antagonist to block the effects of natural endorphins in the body. This could, theoretically at least, aggravate anhedonia.
Really, it would probably be best to avoid hitting the mu receptor when treating depression.
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