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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 12 of 12. This is the beginning of the thread.
Posted by Ant-Rock on June 14, 2000, at 13:59:54
Does anyone know if these two meds can be combined?
My current ritalin/amisulpride augmentation isn't cutting it and I would like to try a different augmentor before once again increasing the parnate. I just recieved my adrafanil so I could start right away.
Also, my IAS(int.anti-aging system) price list has a new anti-depressant listed called Nivalin(Galantamine),says it's a "reversible acetylcholine transferase inhibitor". Anyone ever try this med. How does it work? what does it do?
Sincerely,
Anthony
Posted by JohnL on June 15, 2000, at 3:39:12
In reply to Parnate and Adrafanil?, posted by Ant-Rock on June 14, 2000, at 13:59:54
> Does anyone know if these two meds can be combined?
> My current ritalin/amisulpride augmentation isn't cutting it and I would like to try a different augmentor before once again increasing the parnate. I just recieved my adrafanil so I could start right away.
> Also, my IAS(int.anti-aging system) price list has a new anti-depressant listed called Nivalin(Galantamine),says it's a "reversible acetylcholine transferase inhibitor". Anyone ever try this med. How does it work? what does it do?
> Sincerely,
> AnthonyAnthony,
I don't know anything about Nivalin.But I am familiar with Adrafinil and I don't see any reason you couldn't combine it with Parnate. My primary concern would be the combined effect of hyperadrenergic effects, which would likely manifest itself in feelings of agitation or irritation or worsened depression.
Since neither Ritalin or Amisulpride are cutting it, that kind of hints that dopamine is not a chemistry you respond to. So that makes the case for Adrafinil more convincing, since it acts on the NE system rather than the dopamine system. Also worth considering is that neurotransmitter levels with you could likely be OK, and down-regulation by increasing those levels not necessary. If your levels were low, or down regulation needed, then I would think you would have had a more positive reaction to Parnate alone. It's just a guess, and you know better than me, but the whole Parnate thing might be off target.
Personally I found Adrafinil to be the kindest gentlest and yet most effective of all the stimulants. But that's just me.
In your shoes I would start by cutting a 300mg pill into halves and start with 150mg a day for a week just to feel it out and test the waters before jumping in. But again, that's just me. I tend to be cautious, and I believe in low and slow, especially when dealing with medications our personal physicians are not real familiar with. If after a week all is well, then higher doses could be tried.
In one source I noticed Adrafinil's usual dose is 600mg to 1200mg. In another it is 300mg to 600mg. Personally I found 300mg perfect, after trying all different doses.
JohnL
Posted by Ant-Rock on June 15, 2000, at 8:28:28
In reply to Re: Parnate and Adrafanil?, posted by JohnL on June 15, 2000, at 3:39:12
> Anthony,
> I don't know anything about Nivalin.
>
> But I am familiar with Adrafinil and I don't see any reason you couldn't combine it with Parnate. My primary concern would be the combined effect of hyperadrenergic effects, which would likely manifest itself in feelings of agitation or irritation or worsened depression.
>
> Since neither Ritalin or Amisulpride are cutting it, that kind of hints that dopamine is not a chemistry you respond to. So that makes the case for Adrafinil more convincing, since it acts on the NE system rather than the dopamine system. Also worth considering is that neurotransmitter levels with you could likely be OK, and down-regulation by increasing those levels not necessary. If your levels were low, or down regulation needed, then I would think you would have had a more positive reaction to Parnate alone. It's just a guess, and you know better than me, but the whole Parnate thing might be off target.
>
> Personally I found Adrafinil to be the kindest gentlest and yet most effective of all the stimulants. But that's just me.
>
> In your shoes I would start by cutting a 300mg pill into halves and start with 150mg a day for a week just to feel it out and test the waters before jumping in. But again, that's just me. I tend to be cautious, and I believe in low and slow, especially when dealing with medications our personal physicians are not real familiar with. If after a week all is well, then higher doses could be tried.
>
> In one source I noticed Adrafinil's usual dose is 600mg to 1200mg. In another it is 300mg to 600mg. Personally I found 300mg perfect, after trying all different doses.
> JohnLThanks for the response John,
Parnate is helping in some ways, just not completely. Anhedonia and apathy still strongly pervail. This is what led me to believe Dopamine must be responsible. The funny thing about Ritalin is that at first I began getting a positive response at a low dose, but it was short lived and never returned with either gradual increases, or augmenting with parnate.
I find what you said about neurotransmitter levels being ok very interesting, i just don't know enough about this stuff to really grasp this theory.
Anyway, I actually started with 1/2 adrafanil pill yesterday, and just took my second dose today and will stay at this 1/2 dose for a week like you suggested.
Again John, thank you so much for your response, I was afraid I wasn't gonna get a reply.
Sincerely,
Anthony
Posted by SLS on June 15, 2000, at 15:37:28
In reply to Re: Parnate and Adrafanil? » JohnL , posted by Ant-Rock on June 15, 2000, at 8:28:28
> Thanks for the response John,
> Parnate is helping in some ways, just not completely. Anhedonia and apathy still strongly pervail. This is what led me to believe Dopamine must be responsible. The funny thing about Ritalin is that at first I began getting a positive response at a low dose, but it was short lived and never returned with either gradual increases, or augmenting with parnate.
> I find what you said about neurotransmitter levels being ok very interesting, i just don't know enough about this stuff to really grasp this theory.
> Anyway, I actually started with 1/2 adrafanil pill yesterday, and just took my second dose today and will stay at this 1/2 dose for a week like you suggested.
> Again John, thank you so much for your response, I was afraid I wasn't gonna get a reply.
> Sincerely,
> Anthony
Good luck Anthony. I'll be praying for you. One question - I'm confused. Did you take both Parnate and amisulpride together? How would you describe your experience with amisulpride? I am considering combining Parnate and Provigil, so I'll be keeping an eye on you. Again, good luck.Hey John - Have you gone back to adrafinil?
- Scott
Posted by Ant-Rock on June 15, 2000, at 19:01:03
In reply to Re: Parnate and Adrafanil?, posted by SLS on June 15, 2000, at 15:37:28
> > Thanks for the response John,
> > Parnate is helping in some ways, just not completely. Anhedonia and apathy still strongly pervail. This is what led me to believe Dopamine must be responsible. The funny thing about Ritalin is that at first I began getting a positive response at a low dose, but it was short lived and never returned with either gradual increases, or augmenting with parnate.
> > I find what you said about neurotransmitter levels being ok very interesting, i just don't know enough about this stuff to really grasp this theory.
> > Anyway, I actually started with 1/2 adrafanil pill yesterday, and just took my second dose today and will stay at this 1/2 dose for a week like you suggested.
> > Again John, thank you so much for your response, I was afraid I wasn't gonna get a reply.
> > Sincerely,
> > Anthony
>
>
> Good luck Anthony. I'll be praying for you. One question - I'm confused. Did you take both Parnate and amisulpride together? How would you describe your experience with amisulpride? I am considering combining Parnate and Provigil, so I'll be keeping an eye on you. Again, good luck.
>
> >
> - ScottThank you Scott, I'll do the same for you.
Yes, I was taking 1/2 pill daily of Amisulpride along with Parnate & ritalin. Then lowered to 1/4 pill amisulpride and still no results. So now It's just the 50mg Parnate and 150mg Adrafanil, possibly increasing parnate and/or adding small doses of ritalin if nothing happens, but I am going to give the Adrafanil 1week at 150 then up to 300 before I give up on this combo. I think it was John who mentioned Adrafanil takes a few weeks to really take effect, so I will use this as a guide.
By the way, this was my 2nd amisulpride trial, I did try it alone at 50 then 100mg a while back with no improvement. I feel like I've thrown everything but the kitchen sink at this illness.
If this current regimen doesn't hit, I still have all those other combo's you gave me to try with the parnate. Thank you again for that Scott,
Sincerely,Anthony
Posted by JohnL on June 16, 2000, at 3:26:25
In reply to Parnate and Adrafanil?, posted by Ant-Rock on June 14, 2000, at 13:59:54
Anthony,
Just a quick followup. I think you already know this, so forgive me if I'm being repetitive.
Adrafinil will likely take some time to do its work. So as long as it is mixing OK with your other meds, try not to discontinue it too early due to lack of effectiveness. For me I wasn't really aware that it was doing anything until the end of week 2 at 900mg. I don't know exactly or for sure, but I think the way Adrafinil binds to receptors and accumulates in certain parts of the brain is a slow process, building up over time.
Hope all is going well so far. Just wanted to reassure you that if you don't feel any benefit, hang in there. Give it at least 2 weeks, preferably 4, at the highest dose you can tolerate.
While I usually advocate quick trials and quick responses, Adrafinil is an exception to my general belief system. Whereas SSRIs for example immediately block the reuptake of serotonin, setting into motion a cascade of other events, I think Adrafinil slowly binds and slowly accumulates to certain receptors. It doesn't just bind all at once. I think a lot of it is wasted in metabolism. Kind of like throwing little handfuls of spaghetti at the wall until finally the whole wall is covered. With each throw, a lot drops to the floor, but a little bit sticks to the wall. Keep throwing. Something like that. :-) Only not so messy.
Things to look for that indicate it's starting to work: You'll realize you're getting interested in activities; you will notice you're talking more and being more comfortable doing it; you'll actually look forward to stuff. Kind of like a kid in a candy store. Or kind of like a prisoner sentenced to life who is suddenly pardoned and let free.
JohnL
Posted by AndrewB on June 16, 2000, at 3:47:04
In reply to Parnate and Adrafanil?, posted by Ant-Rock on June 14, 2000, at 13:59:54
Anthony,A question: Do you still have fatigue or is all that remains anhedonia and apathy?
Nivalin is like Tacrine. It is used to modestly improve the memory (or limit deterioration) of those with Alzheimers and (possibly) dementia. It is an acetylcholine breakdown inhibitor. Acetylcholine is a neurotransmitter that is essential for memory. Nivalin would neither improve the memory in the healthy or improve one’s mood. This is not the first time IAS has mislabeled a product of theirs.
You have closed the books on amisulpride after a fair trial. I am sorry it was not effective for you. I hope your results with adrafinil will be something worth talking about.
To set the record straight. Stimulants like ritalin act both on norepinephrine (NE) and dopamine (D) receptors. When someone finds a stimulant ineffective, it does not preclude subsequent success with a dopaminergic drug or a norandrenergic (NE) drug. As evidence, in the Tips section one can kind find an account of a psych. who used dopaminergics with success for fatigue where stimulants had failed. Similarly, CFS patients rarely respond to stimulants but often have success with norandrenergic drugs.
Let me explain why this may happen (and someone please tell me if I am wrong here). A stimulant like ritalin works by emptying the NE neurotransmitter out of its storage vesicle so the NE can flood the receptor site and create the increase in the stimulation of the receptor that makes us feel better. Sometimes the NE in the storage vesicle is not replaced fast enough, so as time passes, the stimulant is unable to empty NE out of the storage vesicle, the well is dry so to speak, and therefore the effect one enjoyed at first with the stimulant has quickly disappeared. A stimulant also acts with this mode of action on the dopamine (D2) receptor.
All this means is what you already know, if a stimulant doesn’t work, another class of NE or dopamine acting drugs might. I’m rooting for the adrafinil to work for you. John said it worked for his anhedonia I think.
But if Adrafinil doesn’t work I have another suggestion; try a dopamine D2/D3 agonist like Requip, Mirapex, or bromocriptine. I think Scott mentioned this. Just because amisulpride, a D2/D3 presynaptic receptor antagonist, did not work doesn’t mean an agonist won’t. Mirapex did NOT work for me, but amisulpride of course has. The reverse may be true in your case if you will accept a bit of counter reasoning. I mention all three of those agonists because which you would decide to use would depend on your circumstances: will you have a prescription, do you have insurance that covers the cost of the medicine, and how much are you willing to spend. But if you do decide to go the dopamine agonist route, let me know and I will help steer you through the decision.
One other option that I’ve read of is precursor loading the stimulant. I don’t know just how effective it is as a norm. You use Sinemet or tyrosine (Sinemet would have more efficacy I would think). It may take 6 weeks to see a difference.
Andrew B
Posted by Ant-Rock on June 16, 2000, at 8:09:21
In reply to Re: Parnate and Adrafanil?, posted by AndrewB on June 16, 2000, at 3:47:04
>
> Anthony,
>
> A question: Do you still have fatigue or is all that remains anhedonia and apathy?
>
>
> To set the record straight. Stimulants like ritalin act both on norepinephrine (NE) and dopamine (D) receptors. When someone finds a stimulant ineffective, it does not preclude subsequent success with a dopaminergic drug or a norandrenergic (NE) drug. As evidence, in the Tips section one can kind find an account of a psych. who used dopaminergics with success for fatigue where stimulants had failed. Similarly, CFS patients rarely respond to stimulants but often have success with norandrenergic drugs.
>
> Let me explain why this may happen (and someone please tell me if I am wrong here). A stimulant like ritalin works by emptying the NE neurotransmitter out of its storage vesicle so the NE can flood the receptor site and create the increase in the stimulation of the receptor that makes us feel better. Sometimes the NE in the storage vesicle is not replaced fast enough, so as time passes, the stimulant is unable to empty NE out of the storage vesicle, the well is dry so to speak, and therefore the effect one enjoyed at first with the stimulant has quickly disappeared. A stimulant also acts with this mode of action on the dopamine (D2) receptor.
>
> All this means is what you already know, if a stimulant doesn’t work, another class of NE or dopamine acting drugs might. I’m rooting for the adrafinil to work for you. John said it worked for his anhedonia I think.
>
> But if Adrafinil doesn’t work I have another suggestion; try a dopamine D2/D3 agonist like Requip, Mirapex, or bromocriptine. I think Scott mentioned this. Just because amisulpride, a D2/D3 presynaptic receptor antagonist, did not work doesn’t mean an agonist won’t. Mirapex did NOT work for me, but amisulpride of course has. The reverse may be true in your case if you will accept a bit of counter reasoning. I mention all three of those agonists because which you would decide to use would depend on your circumstances: will you have a prescription, do you have insurance that covers the cost of the medicine, and how much are you willing to spend. But if you do decide to go the dopamine agonist route, let me know and I will help steer you through the decision.
>
> One other option that I’ve read of is precursor loading the stimulant. I don’t know just how effective it is as a norm. You use Sinemet or tyrosine (Sinemet would have more efficacy I would think). It may take 6 weeks to see a difference.
>
> Andrew BFirst of all, I am very grateful for all of the support and knowledge that has been given to me here. The impact of this help has improved my state of mind more than I can express
in words. I hope I have helped others even a fraction as much.
Andrew,
the parnate has helped with the fatigue a lot. In the past, this has also been the case. I still don't recover from exercise as well as I should, but I force my self to run or jog(20-30min.) three to four x a week. Certainly not 100%, but I will continue to try. I really notice a problem with my calf muscles, like they aren't getting enough oxygen or something. I hope to get some answers to this when i have my follow up visit with my new endo doc Monday, and address my low cortisol/ low testosterone outcome from my last bloodwork.
My ability to concentrate is a little better, but i think if i can get this anhedonia/apathy thing beat my concentration will also come back to normal.
I will certainly take you up on your offer if need be Andrew. I know very little about dopamine agonist.
I hope all is well with you, and I will let everyone know how things develop.
Sincerely,Anthony
Posted by JohnL on June 16, 2000, at 18:43:10
In reply to Re: Parnate and Adrafanil?, posted by AndrewB on June 16, 2000, at 3:47:04
Andrew mentioned that he thought Adrafinil had worked on my anhedonia. Definitely. Absolutely. Completely. No ifs, and, or buts about it. The list of previous meds is staggering.
We often think of dopamine as the pleasure center, and focus on dopamine for anhedonic type symptoms and such. But I am living proof that the norepinephrine system is just as powerful a pleasure center as dopamine is, if not more so.
But yes, Adrafinil completely wiped out a loonnnggg stubborn depression marked by prominent anhedonia.
JohnL
Posted by SLS on June 17, 2000, at 9:46:25
In reply to Re: Parnate and Adrafanil?, posted by JohnL on June 16, 2000, at 18:43:10
> Andrew mentioned that he thought Adrafinil had worked on my anhedonia. Definitely. Absolutely. Completely. No ifs, and, or buts about it. The list of previous meds is staggering.
>
> We often think of dopamine as the pleasure center, and focus on dopamine for anhedonic type symptoms and such. But I am living proof that the norepinephrine system is just as powerful a pleasure center as dopamine is, if not more so.
>
> But yes, Adrafinil completely wiped out a loonnnggg stubborn depression marked by prominent anhedonia.
> JohnL
John - I am still curious if you have decided to return to adrafinil. Did Provigil act upon anhedonia at all? Besides the headaches, what was it about Provigil that you found inferior to adrafinil? Was there a tendency for the positive effects of Provigil to dissipate? You did report a remarkably positive effect from it initially. What dosage did you work up to? Did you find that Provigil exhibited the same biphasic response curve as does adrafinil?I would be grateful for any input. If sulpiride does not prove helpful to me, I would probably want to try adding Provigil or adrafinil to Parnate at some point.
Thanks.
- Scott
Posted by JohnL on June 17, 2000, at 18:08:21
In reply to Re: Parnate and Adrafanil? » JohnL , posted by SLS on June 17, 2000, at 9:46:25
>
> John - I am still curious if you have decided to return to adrafinil. Did Provigil act upon anhedonia at all? Besides the headaches, what was it about Provigil that you found inferior to adrafinil? Was there a tendency for the positive effects of Provigil to dissipate? You did report a remarkably positive effect from it initially. What dosage did you work up to? Did you find that Provigil exhibited the same biphasic response curve as does adrafinil?
>
> I would be grateful for any input. If sulpiride does not prove helpful to me, I would probably want to try adding Provigil or adrafinil to Parnate at some point.
>
> Thanks.
>
>
> - ScottScott,
I dumped the Provigil. I couldn't even get past 50mg without feeling like I got hit by a freight train. At first it did seem pretty good. But that was short lived and soon overwhelmed by monsterous totally unexpected side effects. I think Provigil is a wonderful medication, but for some weird reason I was just super sensitive to it. My body just flat out rejected it.Returning to Adrafinil was the obvious move. But I did have some troubling impotence with Adrafinil. So that caused some hesitation. Then I began wondering, what else can I do to both enhance NE function and have a good sex life simultaneously? Surely there must be something. And there is. I found it. But I'll save that discussion for another post.
Anyway, in my lone n=1 trial, Adrafinil and Provigil are completely totally different drugs. I can't even imagine them being in the same class. But that's just me. Oh well. We try, we learn, right? As far as someone else deciding between one or the other, I think it would be wrong to base anything on my n=1 experience. I think a flip of the coin would be about as accurate a guess as we can make. Whatever works. I've never been able to predict in advance how any med would work out. Just have to try it and see. I wish I knew a better way.
JohnL
Posted by SLS on June 18, 2000, at 20:44:13
In reply to Re: Parnate and Adrafanil?, posted by JohnL on June 17, 2000, at 18:08:21
> Scott,
> I dumped the Provigil. I couldn't even get past 50mg without feeling like I got hit by a freight train. At first it did seem pretty good. But that was short lived and soon overwhelmed by monsterous totally unexpected side effects. I think Provigil is a wonderful medication, but for some weird reason I was just super sensitive to it. My body just flat out rejected it.
>
> Returning to Adrafinil was the obvious move. But I did have some troubling impotence with Adrafinil. So that caused some hesitation. Then I began wondering, what else can I do to both enhance NE function and have a good sex life simultaneously? Surely there must be something. And there is. I found it. But I'll save that discussion for another post.
I AM NOT GOING TO SLEEP UNTIL YOU TELL ME !> Anyway, in my lone n=1 trial, Adrafinil and Provigil are completely totally different drugs. I can't even imagine them being in the same class. But that's just me. Oh well. We try, we learn, right? As far as someone else deciding between one or the other, I think it would be wrong to base anything on my n=1 experience. I think a flip of the coin would be about as accurate a guess as we can make. Whatever works. I've never been able to predict in advance how any med would work out. Just have to try it and see. I wish I knew a better way.
> JohnLI can't tell you how much I appreciate your input. Both you and AndrewB make excellent reporters, and are invaluable to the pursuit of new treatment approaches here. I hope your response to your new treatment is as robust as is your enthusiasm. I am looking forward to hearing about it.
THANKS.
Good Luck.
- Scott
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