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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by Girlnterrupted78 on November 17, 2009, at 4:23:25
I've been taking Parnate 80mgs + Adderall 15mgs for about 3 months now.
When I was on Parnate 60mgs and adderall 15mgs, Parnate kicked in and I was on remission for about a month.
Then for whatever reason, Parnate stopped working to its fullest and I went from remission, to just "somewhat" feeling better than depressed. The effects of Parnate didn't completely vanish--
but they were greatly reduced.The emotional distress and chronic gut wrenching feeling that I had from depression are back, although not as severe as before; and my socializing, although not as good as when on remission, is still somewhat above what it was before Parnate, but I still experience some distress.
So I guess I could say the relief I first experienced with Parnate dropped from an 85% to a 55-60%.
Now I'm just wondering about Adderall. I took it years ago for attention deficit and I built tolerance to it within a month (or less) and then it did nothing at all for me, so I stopped it.
After about a year, I decided to give it a second try to see if the "tolerance" had diminished. But no, apparently I was permanently tolerant and immune to it, so I figured I'd never use it again.
But now my doctor decided to give it to me along with Parnate. I don't know if somehow, mixed with Parnate, adderall might have some "other" (synergic?) effects I'm not aware of, but from experience, it does nothing for me anymore, and since now Parnate, even at a high dose of 80mgs, is just giving me partial benefits, I was thinking that maybe I should just drop the adderall altogether?
I can add something else (nortryptiline) like others have suggested, but should I keep taking the adderall or drop it?
Any advice on this would be appreciated.
Posted by SLS on November 17, 2009, at 6:13:17
In reply to Should I discontinue Adderall as Parnate 'augment', posted by Girlnterrupted78 on November 17, 2009, at 4:23:25
I think your doctor is taking a reasonable course try to build a combination treatment around Parnate - at least for now. I have not tried Adderall, but I have tried Dexedrine (d-amphetamine) in combination with Parnate 120mg. I felt a little better for the first few days, but that was it. I am not much of an example, though. It seems that I am not very responsive to anything anymore. My doctor now shies away from the idea of adding a stimulant. I think I'll have another conversation with him about it.
There are people on Psycho-Babble who report having success when adding a stimulant to Parnate. I just don't know how long it takes start working once treatment is initiated. One would think that it would be within a matter of days rather than within a matter of weeks as long as the dosage of Parnate is adequate.
I hope people who have actually tried Adderall or Dexedrine chime in. My guess is that this treatment doesn't help the majority of people. There really are no statistics to support it one way or another. If it were me, and Adderall had not shown efficacy over the course of weeks, I would discontinue it. One of the disadvantages of taking amphetamine chronically is that it facilitates neurotoxicity via the loss of DA uptake sites in the striatum and nucleus accumbens. It can also form free radicals because it is very oxidative.
Parnate is a drug that traditionally has been considered a good candidate to combine with lithium, even for unipolar depression. There are a few other things you can use as augmenters. You just need to be careful not to use a drug with significant serotonin reuptake inhibition. Such a combination is very likely to precipitate serotonin syndrome, a potentially fatal reaction. I would advise using either nortriptyline of desipramine if you plan on adding a tricyclic. Even imipramine is too serotonergic. Certainly, clomipramine is. Desipramine is probably more activating than nortriptyline, although nortriptyline is not usually sedating except for early in treatment. With nortriptyline, I would advise having blood tests to assay drug levels. Most people respond within a range of 50-150 ng/ml. Obviously, if you don't take enough, you won't respond. However, nortriptylne is a weird one. If you take too much, you actually lose the response. This behavior is called having a therapeutic window. Most people respond at dosages between 75mg and 100mg.
Sorry for writing so much. I just don't like dissuading people from trying something that might be effective, as long as it is safe. People differ so much in their responsivity to different drugs. What works for me might not work for you. Even methylphenidate is a drug worth considering. I probably wouldn't make it my first choice, though.
- Scott
Posted by Girlnterrupted78 on November 17, 2009, at 7:50:16
In reply to Re: Should I discontinue Adderall as Parnate 'augment', posted by SLS on November 17, 2009, at 6:13:17
Thank you for your detailed response.
> I have not tried Adderall, but I have tried Dexedrine (d-amphetamine) in combination with Parnate 120mg. I felt a little better for the first few days, but that was it.
That is what worries me. Since I already know that I am completely tolerant to Adderall (I tried it while in college twice, and the most it ever worked was like 2 weeks, then it barely worked, then it stopped competely--and never worked again,) I am concerned that it is in fact doing nothing for me, other than making me even more tolerant to treatment in general, and that would be just fatal in my case, since my resistance to treatment is so high already.
I personally would like to drop it altogether. I'm almost sure it won't make a difference. I remember telling me doctor "What are we going to do if Parnate stops working?" And his answer was "That doesn't worry me in the least, right now I'm more worried about your low bood pressure." And within 2 weeks, Parnate stopped working. I guess from experience I already know how easily I become tolerant to just about any drug, and my guess from day 1 was that Adderall was not going to do anything for me, and I continue to believe that.
"One of the disadvantages of taking amphetamine chronically is that it facilitates neurotoxicity via the loss of DA uptake sites in the striatum and nucleus accumbens. It can also form free radicals because it is very oxidative."
And what would be the consequences of something like that? Is it worth taking the risk, knowing beforehand that I am already immune to Adderall?
How easy is to become tolerant to the other augmenters? Nortriptyline, and the rest that are being used?
Once you become tolerant to everything, is there anything left to try? Or that is simply the end of the journey?
Thanks again for your informed contribution.
Posted by Phillipa on November 17, 2009, at 10:31:41
In reply to Re: Should I discontinue Adderall as Parnate 'augment' » SLS, posted by Girlnterrupted78 on November 17, 2009, at 7:50:16
That is what I also wonder as I read the maoi posts. What comes next? Love Phillipa
Posted by maxime on November 17, 2009, at 11:31:10
In reply to Should I discontinue Adderall as Parnate 'augment', posted by Girlnterrupted78 on November 17, 2009, at 4:23:25
When I was on Parnate the first time, I was on 30 mg of Adderall XR. It helped for a while (about a year) but then both meds pooped out on me. I was so surprised because I thought Parnate was one med that doesn't poop out. This time I am taking Nortriptyline with the Parnate.
Posted by desolationrower on November 20, 2009, at 17:13:22
In reply to Re: Should I discontinue Adderall as Parnate 'augment' » SLS, posted by Girlnterrupted78 on November 17, 2009, at 7:50:16
>it facilitates neurotoxicity via the loss of DA uptake sites in the striatum and nucleus accumbens.
what makes you think loss of DATs is 'neurotoxic' and not the therapeutic normalization? thats what drug warrior say, but people with adhd have higher DAT levels.
Literature Review: Update on Amphetamine Neurotoxicity and Its Relevance to the Treatment of ADHD
Claire AdvokatLouisiana State University, cadvoka{at}lsu.edu
Objective: A review of amphetamine treatment for attention-deficit/hyperactivity disorder (ADHD) was conducted, to obtain information on the long-term neurological consequences of this therapy. Method: Several databases were accessed for research articles on the effects of amphetamine in the brain of laboratory animals and ADHD diagnosed individuals. Results: In early studies, high doses of amphetamine, comparable to amounts used by addicts, were shown to damage dopaminergic pathways. More recent studies, using therapeutic regimens, appear contradictory. One paradigm shows significant decreases in striatal dopamine and transporter density after oral administration of "therapeutic" doses in primates. Another shows morphological evidence of "trophic" dendritic growth in the brains of adult and juvenile rats given systemic injections mimicking "therapeutic" treatment. Imaging studies of ADHD-diagnosed individuals show an increase in striatal dopamine transporter availability that may be reduced by methylphenidate treatment. Conclusion: Clarification of the neurological consequences of chronic AMPH treatment for ADHD is needed. (J. of Att. Dis. 2007; 11(1) 8-16)
i think the oxidative stress just comes from metabolizing DA, so if anything its likely to just be bringing it up to normal levls. if you're worried, take an maoi.
-d/r
Posted by SLS on November 20, 2009, at 19:18:34
In reply to Re: Should I discontinue Adderall as Parnate ')SLS, posted by desolationrower on November 20, 2009, at 17:13:22
> >it facilitates neurotoxicity via the loss of DA uptake sites in the striatum and nucleus accumbens.
> what makes you think loss of DATs is 'neurotoxic' and not the therapeutic normalization?Just some stuff I read. I just wish I could find it again. I guess they were all animal studies. I don't think there was any attempt to simulate the levels used in humans. I hope the authors were wrong.
> i think the oxidative stress just comes from metabolizing DA, so if anything its likely to just be bringing it up to normal levls.
I understand where you are coming from. However, one of the major signs of amphetamine-induced neurotoxicity is the loss of DA uptake sites, at least in the striatum and accumbens. Of course, this is an association and not a demonstration of cause and effect. I don't know which comes first, the reduction in DAT or the neurotoxic process.
No one wants to believe that amphetamine is neurotoxic. I don't. Hopefully, any neurotoxicity that is associated with amphetamine use is small and clinically negligible. On the plus side, it seems that there is a recover process capable of reversing the neurotoxic effects of amphetamines. It is very slow, though.
- Scott
Posted by floatingbridge on November 21, 2009, at 23:40:28
In reply to Re: Should I discontinue Adderall as Parnate ')SLS, posted by SLS on November 20, 2009, at 19:18:34
> No one wants to believe that amphetamine is neurotoxic. I don't. Hopefully, any neurotoxicity that is associated with amphetamine use is small and clinically negligible.>On the plus side, it seems that there is a recover process capable of reversing the neurotoxic effects of amphetamines. It is very slow, though.
>What is a recover process? Scott, I know you're busy and in demand...anyone know?
BTW, GI, I'd love to chime in, but can't. I want to try Emsam w/ a little dex, but have a no-go at present. I'll follow your thread.
best to you,
fb
Posted by SLS on November 22, 2009, at 6:11:41
In reply to Re: Should I discontinue Adderall as Parnate ')SLS » SLS, posted by floatingbridge on November 21, 2009, at 23:40:28
Hi FB.
This is one I came across recently. Note that it is a study of mice and that the concentrations of amphetamine used are probably far higher than those used therapeutically in humans. Neurotoxicity is dosage deprendent.
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Selective (+)-amphetamine neurotoxicity on striatal dopamine nerve terminals in the mouse.G. Jonsson and E. Nwanze
Abstract:
1 Infusion of large doses of (+)-amphetamine continuously for 7 days by means of osmotic minipumps caused a long-lasting reduction of endogenous dopamine levels, dopamine nerve terminals demonstrated histochemically and [3H]-noradrenaline uptake in vitro in the striatum of mice. 2 The effect was dose-dependent, fully developed after 4 days and selective for striatal dopamine up to a dose of (+)-amphetamine of 25 microgram/h. Higher doses, which produced increased mortality, also affected dopamine levels in the olfactory tubercle as well as noradrenaline in several regions. 3 Fluorescence histochemical studies using the Falck-Hillarp technique disclosed catecholamine accumulations in the striatum after (+)-amphetamine; a sign of neurotoxic damage. No effects on the dopamine cell bodies were noted. There were also no indications of neurotoxic damage to noradrenaline or 5-hydroxytryptamine neurones induced by (+)-amphetamine. 4 Large doses of (-)-amphetamine were without effect, demonstrating that the long-lasting impairment of transmitter uptake-storage mechanism in striatal dopamine nerve terminals is selective for (+)-amphetamine. 5 There was a slow gradual recovery of endogenous dopamine and [3H]-noradrenaline uptake in the striatum with time, which was almost complete 6 months after the (+)-amphetamine administration. 6 The results give further evidence for the view that (+)-amphetamine in large doses can have a selective neurotoxic action on a vulnerable population of a dopamine nerve terminals in the striatum. The results suggest in addition that there is a slow regrowth and regeneration with time of damaged dopamine nerve terminals.
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Posted by floatingbridge on November 22, 2009, at 14:57:15
In reply to Re: Should I discontinue Adderall as Parnate ')SLS, posted by SLS on November 22, 2009, at 6:11:41
This is the end of the thread.
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