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Dr. Bob is Robert Hsiung, MD,
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Posted by gilmourr on September 9, 2012, at 3:15:28
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ » gilmourr, posted by phidippus on September 8, 2012, at 16:14:01
I'm a bit hesitant to try Pristiq since it is the cleaner version of effexor. Effexor made me have severe chest pains and my BP raised to 165/125'ish.
I could try it, but I'd rather try a stimulant or a TCA. I am really not a fan of SSRI's or SNRI's. They seem to always cause 10x the trouble.
Posted by SLS on September 9, 2012, at 8:58:48
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ » gilmourr, posted by phidippus on September 8, 2012, at 16:14:01
> Nardil actually decreases norepinephrine and epinephrine levels through a complicated (I won't bother explaining it) interaction with octopamine,
For anyone who is interested:
MAO inhibitors yield an elevation in the levels of cytosolic octopamine along with norepinephrine (NE). Octopamine becomes a "false transmitter". It competes with NE for vesicular storage. When released along with the NE, it binds to NE receptors, but does not stimulate them. Thus, the increase in NE levels is offset by a simultaneous accumulation of octopamine. Perhaps Phiddipus has data on the net effect that MAOIs have on NE neurotransmission. Is it reduced rather than increased? I wouldn't know where to look for this information. Perhaps it is still increased, but to a lesser degree than serotonin. I just don't know.
> resulting in a lower though still significant therapeutic response, and side effects like orthostatic hypotension.
Clorgyline is the most powerful and selective inhibitor of MAO-A in existence. Clorgyline thus preferentially inhibits the deaminatation (break-down) of serotonin. It is considered by many to be the most effective antidepressant MAOI (although no longer available). It does not increase NE. Therefore, one could make the argument that the accumulation of octopamine has very little influence on the efficacy of Nardil and Parnate.
> If you think you need more norepenephrine, might I suggest Wellbutrin, a strong norepenephrine reuptake inhibitor, or Pristiq, another strong norepenephrine reuptake inhibitor
Interesting choices. I might not be current. I thought the NE reuptake inhibition values of Wellbutrin and Pristiq were rather low compared to tricyclics. Perhaps they are lower, but still sufficient? The Ki of Wellbutrin for NET is 1000.0 or greater. Pristiq is approximately 500.0. By comparison, that of desipramine is 5.0 or lower. (The lower the number, the more potent). Wellbutrin is still a bit of an enigma. Despite its observed effects on transporters, there might be more important mechanisms at work in its therapeutic effects in the treatment of depression. The nitrergic system is currently one area if focus. I know that nicotinic pathways are also being looked at. These mechanisms might have the net effect of increasing NE and/or DA activity. For me, amphetamine and methylphenidate were somewhat activating early in treatment and neutral thereafter. By contrast, Wellbutrin made me significantly more depressed. I am leaning in the direction that the weak NET and DAT inhibition are not a sufficient explanation for its antidepressant effect.
- Scott
Posted by SLS on September 9, 2012, at 9:30:21
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ » gilmourr, posted by phidippus on September 8, 2012, at 16:14:01
> Nardil actually decreases norepinephrine and epinephrine levels through a complicated (I won't bother explaining it) interaction with octopamine, resulting in a lower though still significant therapeutic response, and side effects like orthostatic hypotension.
I found this. Perhaps it is a demonstration of an anti-adrenergic property of phenelzine.
- Scott
Posted by phidippus on September 9, 2012, at 14:45:10
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ, posted by SLS on September 9, 2012, at 8:58:48
>The Ki of Wellbutrin for NET is 1000.0 or greater. >Pristiq is approximately 500.0. By comparison, >that of desipramine is 5.0 or lower.
Did you know that Atomoxetine inhibits NET with Ki value of 5?
Eric
Posted by phidippus on September 9, 2012, at 14:53:04
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ, posted by gilmourr on September 9, 2012, at 3:15:28
Like Scott said, TCAs have a more potent noradrenergic effect than Pristiq. My personal favorite TCA is Clomipramine.
If you were to go with a stimulant, I'd recommend Adderall, Vyvanse or Dextroamphetamine.
Atomoxetine inhibits NET with Ki values of 5, which makes it as powerful as desipramine. Atomoxetine also acts as an NMDA-receptor antagonist at clinically relevant doses-this can impart antidepressant qualities.
Eric
Posted by gilmourr on September 9, 2012, at 15:44:34
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ » gilmourr, posted by phidippus on September 9, 2012, at 14:53:04
I have yet to try Clomipramine, Amitriptyline, Nor, Des, any of the TCA's actually.
The thing is, Nardil and Zoloft (1st time worked, 2nd time it didn't) are the ONLY drugs that have ever worked for me. Out of all the SSRI's and MAOI's.
Clomipramine is very interesting but I'm not sure I can take going back into severe depression again..I literally sit around all day thinking about depression and wanting to die and staying inside seeing no friends.
On Nardil my severe depression is now mild moderate (from a 10 to a 5 or 6). Anxiety is very similar too. I go out every weekend and am content enough to hang with all my friends/party but not go to school or work yet (stress worsens the depression).
I'd prefer augmenting the Nardil. If this was you, wouldn't you do the same? And also, what do you suggest I add. Stimulant/TCA/NRI/NDRI?
And if Nardil and Zoloft have worked, do you think maybe dopamine is a big factor for me?
BTW, great link reference, been looking for something like that. Bookmarked!
Posted by gilmourr on September 9, 2012, at 15:47:14
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ, posted by gilmourr on September 9, 2012, at 15:44:34
Scott I appreciate the response.
Isn't there a direct relation with NE and blood pressure? If it slightly raises NE but to a lesser degree that of serotonin, wouldn't my BP go up?
My bp is almost 120/80 instead of 140/90 normally.
Posted by phidippus on September 9, 2012, at 16:16:21
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ, posted by gilmourr on September 9, 2012, at 15:44:34
>Clomipramine is very interesting but I'm not sure >I can take going back into severe depression again
Are you saying Clomipramine would worsen your depression? I have used it as an augmenter with great success.
I think augmenting the Nardil is the smart choice.
Stimulants aren't the most reliable way of enhancing mood, plus I think they don't go well with MAOIs-though I know they are used. Stimulants work primarily through increasing norepenephrine and dopamine, both of which modulate reward seeking in our brain, indirectly affecting mood.
TCAs act like SNRIs and have robust effects on mood. I would probably have to go with a TCA to augment Nardil therapy.
Atomoxetine and Viloxazine are the only NRIs I know of. Studies don't support Atomoxetine as an antidepressant.
Wellbutrin is the NDRI of choice, but is contraindicated with MAOIs.
You may respond to dopamine well.
Don't forget Mirtazapine. It hits everything!
Eric
Posted by SLS on September 9, 2012, at 21:57:43
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ » SLS, posted by phidippus on September 9, 2012, at 14:45:10
> >The Ki of Wellbutrin for NET is 1000.0 or greater. >Pristiq is approximately 500.0. By comparison, >that of desipramine is 5.0 or lower.
>
> Did you know that Atomoxetine inhibits NET with Ki value of 5?
>
> Eric
It just goes to show you that NET inhibition as we currently measure it doesn't tell the whole story. Desipramine is a much better antidepressant than is atomoxetine.
- Scott
Posted by gilmourr on September 9, 2012, at 22:05:08
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ, posted by phidippus on September 9, 2012, at 16:16:21
I'm saying if I came off Nardil and switched to Clomipramine i would be severely depressed again because there is a 1 week period (about). Don't ever do 2 weeks.
And the clomipramine might not even work so it's possible that I could be severely depressed for 1 week (switch) 6 week wait then go back to nardil if it doesn't work (3 weeks) . Total of 9 weeks very depressed.
I think augmenting nardil makes more sense first
Posted by phidippus on September 9, 2012, at 22:05:24
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ » phidippus, posted by SLS on September 9, 2012, at 21:57:43
I'm trying to find the Ki values for Vyvanse. Where would you suggest I look?
Eric
Posted by SLS on September 9, 2012, at 22:08:17
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ, posted by phidippus on September 9, 2012, at 16:16:21
> Wellbutrin is the NDRI of choice, but is contraindicated with MAOIs.
This is true. However, it can be done safely despite the contraindication. Personally, I have combined Wellbutrin with Parnate without sequelae. Unfortunately, it just made me more depressed.
I would not combine an MAOI with imipramine or clomipramine.
- Scott
Posted by SLS on September 9, 2012, at 22:18:10
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ » SLS, posted by phidippus on September 9, 2012, at 22:05:24
> I'm trying to find the Ki values for Vyvanse. Where would you suggest I look?
>
> Erichttp://pdsp.med.unc.edu/indexR.html
This site has been available for quite a few years.
You will need to look up "amphetamine,(+)" in the test ligand search box. Vyvanse (lisdexamfetamine) is the inactive prodrug of amphetamine, and is not listed.
- Scott
Posted by gilmourr on September 10, 2012, at 0:07:17
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ » phidippus, posted by SLS on September 9, 2012, at 22:18:10
What do you think about augmenting with an anti psychotic?
I have mild/moderate anxiety leftover, mild/moderate depression,
and moderate/severe nausea randomly like every week for certain days which can go on for like 7 hours.I was thinking maybe a second generation, or maybe a low dose of a first generation like thorazine or stelazine (I'd only go on 2 mg/day of stelazine max, don't want EPS or TD at all).
I have just heard anti psychotics are sometimes good augmenters and especially good for nausea.
Posted by phidippus on September 10, 2012, at 13:21:49
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ, posted by gilmourr on September 10, 2012, at 0:07:17
Depends on the anti-psychotic you want to augment with. From personal experience, Latuda and Abilify were the most helpful for me in the mood department and the anxiety department, but I have OCD which responds to different medications than regular anxiety. Both Abilify and Latuda are 5ht1a partial agonists-5ht1a agonism results in decreased anxiety and helps with mood.
Geodon is another possibility. Its actually an SNRI and 5ht1a partial agonist. I was on Geodon for several months and experienced a lot of mood enhacement. This can be one energizing pill.
Thorazine and Stelazine will do wonders for your anxiety, but I doubt they will improve your mood
As for the nausea and vomiting, I would recommend Ondensetron. Its an antiemetic that antagonizes 5ht3 receptors which are implicated in anxiety. You'll treat the ills as well as your anxiety.
Eric
Posted by phidippus on September 10, 2012, at 13:29:25
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ » phidippus, posted by SLS on September 9, 2012, at 22:18:10
Thank you very much. After your post comparing Ki I got on a Ki kick.
Eric
Posted by phidippus on September 10, 2012, at 13:32:55
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ, posted by gilmourr on September 9, 2012, at 22:05:08
I agree with you.
Let me know what you pick to augment with.
Eric
Posted by phidippus on September 10, 2012, at 13:34:57
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ » phidippus, posted by SLS on September 9, 2012, at 21:57:43
atomoxetine isn't even an antidepressant. Curiously though, it is an NMDA antagonist.
Eric
Posted by SLS on September 10, 2012, at 14:33:47
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ » gilmourr, posted by phidippus on September 10, 2012, at 13:21:49
> As for the nausea and vomiting, I would recommend Ondensetron. Its an antiemetic that antagonizes 5ht3 receptors which are implicated in anxiety.
I saw a recent study reporting that granisetron, another 5-HT3 antagonist, was effective for OCD. I wonder if the same is true of ondensetron.
- Scott
Posted by SLS on September 10, 2012, at 14:38:48
In reply to Re: atomoxetine » SLS, posted by phidippus on September 10, 2012, at 13:34:57
> atomoxetine isn't even an antidepressant. Curiously though, it is an NMDA antagonist.
Funny...
When this drug was being developed as an antidepressant, it was called tomoxetine. Later, when it was shown to be a rather poor antidepressant, the "A" was added as a prefix and the drug was marketed for ADHD.
- Scott
Posted by phidippus on September 11, 2012, at 4:32:06
In reply to Re: atomoxetine » phidippus, posted by SLS on September 10, 2012, at 14:38:48
My son is on Straterra. It works very well for him, which surprises the hell out of me.
Eric
Posted by phidippus on September 11, 2012, at 4:37:49
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ » phidippus, posted by SLS on September 10, 2012, at 14:33:47
Ondansetron has been studied as a treatment for OCD and has had some positive results.
I have taken Ondensetron for my OCD and it had little impact.
Memantine is another 5ht3 antagonist.
Eric
Posted by SLS on September 11, 2012, at 6:56:32
In reply to Re: atomoxetine » SLS, posted by phidippus on September 11, 2012, at 4:32:06
> My son is on Straterra. It works very well for him, which surprises the hell out of me.
>
> EricI know one guy who was misdiagnosed for years as having MDD. He complained about depression all of the time, even though he displayed no vegetative symptoms. He never told his doctor about his inability to keep things organized in his life. At some point, his doctor decided to play a hunch that he had adult ADD. He was placed on Straterra and never complained of depression again. He was also able to clean and organize his apartment.
Perhaps Strattera is selective as to which regions of the brain it acts on. NE alpha-2 activation in PFC via NRI rather than limbic activation?
In what ways is atomoxetine different from desipramine?
- Scott
Posted by SLS on September 11, 2012, at 6:57:34
In reply to Ondansetron » SLS, posted by phidippus on September 11, 2012, at 4:37:49
> Memantine is another 5ht3 antagonist.
Thanks. Good to know.
- Scott
Posted by phidippus on September 11, 2012, at 17:23:01
In reply to Re: atomoxetine » phidippus, posted by SLS on September 11, 2012, at 6:56:32
Atomoxetine increased extracellular levels of NE in the prefrontal cortex 3-fold. Atomoxetine also increased DA concentrations in the PFC 3-fold but did not alter DA in nucleus accumbens or striatum.
Optimal doses of ATM improved PFC cognitive function in monkeys. These enhancing effects appeared to involve indirect stimulation of α(2) adrenoceptors and D(1) dopamine receptors in the PFC.
Desipramine still has an effect on serotonin, whereas Atomoxetine has no effect on serotonin. Also, what I can find in the literature suggests Atomoxetine is a stronger re-uptake inhibitor of Norepenephrine.
Eric
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