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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 13 to 37 of 37. Go back in thread:
Posted by Lamdage22 on June 19, 2020, at 4:43:57
In reply to Re: Atomoxetine helping - fingers crossed, posted by Lamdage22 on June 18, 2020, at 20:50:07
Dopamine really needs to be right. Too little or too much, you will definitely feel it. Dopaminergic or dopamine-blocking drugs are not a joke.
Posted by porkpiehat on June 19, 2020, at 4:56:05
In reply to Re: Atomoxetine helping - fingers crossed, posted by Lamdage22 on June 18, 2020, at 20:50:07
It's funny NE drugs tend to help me focus but also put me in an uncomfortable zone of some kind where I feel very detached.
My estimatation is that it's my brain's PTSD response to NE/adrenaline, which can cause serious withdrawl/deatchment from what I've read.
Anyone have similar effets?
Posted by undopaminergic on June 19, 2020, at 6:52:39
In reply to Re: Atomoxetine helping - fingers crossed » Lamdage22, posted by porkpiehat on June 19, 2020, at 4:56:05
> It's funny NE drugs tend to help me focus but also put me in an uncomfortable zone of some kind where I feel very detached.
>
> My estimatation is that it's my brain's PTSD response to NE/adrenaline, which can cause serious withdrawl/deatchment from what I've read.
>
> Anyone have similar effets?
>Yes, I got depersonalisation-derealisation from reboxetine (Edronax). This effect lasted (many years!) even though I quit the drug. It did not get worse with atomoxetine or ephedrine, but maybe if I had tried them first?
-undopaminergic
Posted by SLS on June 19, 2020, at 8:04:46
In reply to Re: Atomoxetine helping - fingers crossed » Lamdage22, posted by porkpiehat on June 18, 2020, at 14:28:05
> > Cool. It is funny how Stimulants (Dopamine) make some people more organized, other people become more organized when they take Dopamine blockers. I belong to the latter. Were you able to get help for your skin issue? That doesn't look like fun.
>
> Which Dopamine blockers do you mean? I do really well on Buspar before the anger kicks in. Some atypicals also help but i'm not sure if it's the dopamine action or another property.Buspar (buspirone) is metabolized in the body to become 1-PP. 1-PP is a NE alpha-2 antagonist. It increases the activity of noradrenergic neurons. The anger makes sense.
- Scott
Posted by SLS on June 19, 2020, at 8:14:26
In reply to Re: Atomoxetine helping - fingers crossed » Lamdage22, posted by porkpiehat on June 19, 2020, at 4:56:05
> It's funny NE drugs tend to help me focus but also put me in an uncomfortable zone of some kind where I feel very detached.
>
> My estimatation is that it's my brain's PTSD response to NE/adrenaline, which can cause serious withdrawl/deatchment from what I've read.
>
> Anyone have similar effets?
>
Prazosin, when taken throught the day, might be capable of reducing not only nightmares, but also the daytime symptoms - especially depression and anxiety. I received a significant antidepressant effect at 30 mg/day t.i.d. It is a remarkably clean drug. My only complaint is that it killed my sex-drive - which seems to have peristed for over a year since I stopped taking it. I don't know if there is a cause-and-effect that produces a residual loss of libido after the drug is discontinued. Still, if you can't find anything that works for you, prazosin should be near the top of your list.Prazosin blocks several types of NE alpha-1 receptors in the brain. My favored explanation is that its positive effects are due to NE alpha-1b antagonism.
- Scott
Posted by undopaminergic on June 19, 2020, at 11:31:31
In reply to Re: Atomoxetine helping - fingers crossed, posted by SLS on June 19, 2020, at 8:14:26
>
> Prazosin blocks several types of NE alpha-1 receptors in the brain. My favored explanation is that its positive effects are due to NE alpha-1b antagonism.
>Modafinil is supposedly a central alpha1B-adrenoceptor *agonist*, hence purportedly its "eugeroic" effects, as separate from its stimulant action. In my understanding, alpha1B is more sensitive to adrenaline than noradrenaline. Although adrenaline from the adrenal medulla does not cross the BBB, there are PNMT-positive neurons in the CNS.
(PNMT is the final enzyme in the chain of L-dopa -> ... -> adrenaline synthesis.)
-undopaminergic
Posted by linkadge on June 19, 2020, at 14:31:21
In reply to Re: Atomoxetine helping - fingers crossed » linkadge, posted by porkpiehat on June 18, 2020, at 14:30:23
>Can you explain this "hypercholinergic" cluster >of symptoms and how you relate it to cholinergic >activity?
Basically, its constant overthinking and always exploring (exhaustively) every single possible outcome to every single possible event to the point that have zero energy (mental or physical) to do anything. It also feels like hyper-awareness.
Now this could just be 'anxiety', but it's not always accompanied by feelings of fear. Also, anticholinergics (like scopolamine) seem to be the only antidotes to this state. That being said, the atomoxetine (perhaps by counteracting high acetylcholine) helps filter the thinking a bit more so that I can better chose what to think about.
Linkadge
Posted by linkadge on June 19, 2020, at 14:33:09
In reply to Re: Atomoxetine helping - fingers crossed » Lamdage22, posted by porkpiehat on June 19, 2020, at 4:56:05
I felt very detached on venlafaxine. I feel a bit detached on straterra but nothing like venlafaxine. Also, I feel less detached on atomoxetine than I did on ritalin.
Linkadge
Posted by linkadge on June 19, 2020, at 14:34:23
In reply to Re: Atomoxetine helping - fingers crossed » porkpiehat, posted by SLS on June 19, 2020, at 8:04:46
Anger on buspirone may **also be related to the reduction in serotonin function coming from the presynaptic 5-ht1a agonism.
Linkadge
Posted by porkpiehat on June 19, 2020, at 17:24:26
In reply to Re: Atomoxetine helping - fingers crossed » porkpiehat, posted by linkadge on June 19, 2020, at 14:31:21
> >Can you explain this "hypercholinergic" cluster >of symptoms and how you relate it to cholinergic >activity?
>
> Basically, its constant overthinking and always exploring (exhaustively) every single possible outcome to every single possible event to the point that have zero energy (mental or physical) to do anything. It also feels like hyper-awareness.
>
> Now this could just be 'anxiety', but it's not always accompanied by feelings of fear. Also, anticholinergics (like scopolamine) seem to be the only antidotes to this state. That being said, the atomoxetine (perhaps by counteracting high acetylcholine) helps filter the thinking a bit more so that I can better chose what to think about.
>
> LinkadgeAha. I asked because this just seems like me all the time lol
>
>
>
>
>
>
Posted by SLS on June 19, 2020, at 19:55:41
In reply to Re: Atomoxetine helping - fingers crossed » SLS, posted by undopaminergic on June 19, 2020, at 11:31:31
> Modafinil is supposedly a central alpha1B-adrenoceptor *agonist*, hence purportedly its "eugeroic" effects, as separate from its stimulant action.
Modafinil has always been a bit of an enigma. First, it was dopamine reuptake inhibition. Then, it was orexin activation. It turns out that orexin is more important for alertness / cognition than it is for wakefullness."Modafinil-induced wakefulness can be attenuated by the alpha-1 adrenergic antagonist, prazosin, which led to the initial conclusion that modafinil stimulates the central alpha-1 adrenergic system. However, in vitro assay systems responsive to alpha-adrenergic stimulation have not shown that modafinil is a direct or indirect alpha-1 adrenergic agonist."
https://www.wellrx.com/modafinil/monographs/
- Scott
Posted by undopaminergic on June 20, 2020, at 5:06:18
In reply to Re: Atomoxetine helping - fingers crossed » undopaminergic, posted by SLS on June 19, 2020, at 19:55:41
> > Modafinil is supposedly a central alpha1B-adrenoceptor *agonist*, hence purportedly its "eugeroic" effects, as separate from its stimulant action.
>
>
> Modafinil has always been a bit of an enigma. First, it was dopamine reuptake inhibition. Then, it was orexin activation. It turns out that orexin is more important for alertness / cognition than it is for wakefullness.
>
> "Modafinil-induced wakefulness can be attenuated by the alpha-1 adrenergic antagonist, prazosin, which led to the initial conclusion that modafinil stimulates the central alpha-1 adrenergic system. However, in vitro assay systems responsive to alpha-adrenergic stimulation have not shown that modafinil is a direct or indirect alpha-1 adrenergic agonist."
>
>
> https://www.wellrx.com/modafinil/monographs/
>
>
> - ScottThe dopamine transporter binding of modafinil has been ascertained, including proven essential for its effects. I don't know about other actions. It would be ironic if the atypical stimulant profile of modafinil were due to the *lack* of noradrenergic actions, ie. selectivity for dopamine.
-undopaminergic
Posted by linkadge on June 21, 2020, at 8:06:18
In reply to Re: Atomoxetine helping - fingers crossed » SLS, posted by undopaminergic on June 20, 2020, at 5:06:18
>ie. selectivity for dopamine.
I think modafinil also doesn't bind to the typical dopamine transporter sites (i.e. in the manner of cocaine) but to other sites (akin to wellbutrin and / or benztropine). I've read about this but am not really up on the differences.
Linkadge
Posted by undopaminergic on June 21, 2020, at 8:48:08
In reply to Re: Atomoxetine helping - fingers crossed » undopaminergic, posted by linkadge on June 21, 2020, at 8:06:18
> >ie. selectivity for dopamine.
>
> I think modafinil also doesn't bind to the typical dopamine transporter sites (i.e. in the manner of cocaine) but to other sites (akin to wellbutrin and / or benztropine). I've read about this but am not really up on the differences.
>
> LinkadgeBut does binding to these "alternative" site(s) prevent the DAT from binding dopamine? Maybe to a certain degree that is less than classic DATIs? Could eg. cocaine + benztropine have additive effects?
-undopaminergic
Posted by SLS on June 21, 2020, at 10:37:52
In reply to Re: Atomoxetine helping - fingers crossed, posted by undopaminergic on June 21, 2020, at 8:48:08
> > >ie. selectivity for dopamine.
> >
> > I think modafinil also doesn't bind to the typical dopamine transporter sites (i.e. in the manner of cocaine) but to other sites (akin to wellbutrin and / or benztropine). I've read about this but am not really up on the differences.
> >> But does binding to these "alternative" site(s) prevent the DAT from binding dopamine? Maybe to a certain degree that is less than classic DATIs? Could eg. cocaine + benztropine have additive effects?
Interesting idea.
- Scott
Posted by linkadge on June 21, 2020, at 17:29:26
In reply to Re: Atomoxetine helping - fingers crossed, posted by undopaminergic on June 21, 2020, at 8:48:08
>But does binding to these "alternative" site(s) >prevent the DAT from binding dopamine?
Probably, put perhaps with greater selectivity for certain brain regions over other brain regions. There may too be differences in the binding kinetics (i.e. how quickly DAT is inhibited or the maximum inhibition). I have no idea.
>Maybe to a certain degree that is less than >classic DATIs? Could eg. cocaine + benztropine >have additive effects?
I remember reading that analogues of benztropine were being investigated for treatment of cocaine addiction. I.e. for their ability to reduce certain withdrawal symptoms but not producing much euphoria by themselves. Benztropine can be abused, but I don't know if it is more due to it's anticholinergic properties.
Posted by PeterMartin on July 1, 2020, at 23:43:14
In reply to Re: Atomoxetine helping - fingers crossed » undopaminergic, posted by linkadge on June 21, 2020, at 17:29:26
And I'm joining the atomoxetine club starting today. Only 18mg but I'm also on Marplan so just to be cautious.
Nausea ~1.5hr after taking the first pill. Then mood was real good but "different".
Now 5hrs later have acid reflux/heartburn which sucks. Gaviscon always works well for me when meds induce it, but I haven't had to take that since I stopped taking Nuvigil. Really hope this is just a start up side effect.
Posted by linkadge on July 2, 2020, at 17:23:53
In reply to Re: Atomoxetine helping - fingers crossed, posted by PeterMartin on July 1, 2020, at 23:43:14
Yeah, do watch this combination.
Although atomoxetine is (on paper) an NRI, I remember reading that in vivo (in higher doses) it can begin to occupy the serotonin transporter (as the norepinephrine transporter becomes saturated).
There was a study in primates suggesting that in the 1-2 mg/kg range there was a notable inhibition of serotonin transporters.
https://pubmed.ncbi.nlm.nih.gov/23933039/
At 18mg, I don't think there would be an issue, but I would raise the dose more slowly / cautiously beyond that.
Linkadge
Posted by PeterMartin on July 3, 2020, at 3:20:25
In reply to Re: Atomoxetine helping - fingers crossed » PeterMartin, posted by linkadge on July 2, 2020, at 17:23:53
> Yeah, do watch this combination.
>
> Although atomoxetine is (on paper) an NRI, I remember reading that in vivo (in higher doses) it can begin to occupy the serotonin transporter (as the norepinephrine transporter becomes saturated).
>
> There was a study in primates suggesting that in the 1-2 mg/kg range there was a notable inhibition of serotonin transporters.
>
> https://pubmed.ncbi.nlm.nih.gov/23933039/
>
> At 18mg, I don't think there would be an issue, but I would raise the dose more slowly / cautiously beyond that.
>
> LinkadgeHmm....this is a little scary actually. Is there ever a situations where serotonin is increased in some parts of the brain w.o. potentially causing SS?
Maybe I should quit while I'm ahead. Meh.
I wish I did better w desipramine. It gave me massive sweating....and I was also somewhat concerned about the possibility of mania w. It being a TCA and me having bp1 (although only been manic when pot was involved).
Posted by linkadge on July 3, 2020, at 16:41:06
In reply to Re: Atomoxetine helping - fingers crossed, posted by PeterMartin on July 3, 2020, at 3:20:25
I'm not trying to scare you. This was a study done in monkeys which doesn't necessarily directly translate to humans. Most research I have read suggests that atomoxetine is mostly norepinephrine selective in humans. Interestingly desipramine has a metabolite which acts as a relatively selective serotonin reuptake inhibitor. So, really nothing is perfectly selective.
If you're taking 18mg without experiencing problems then you're likely fine. From what I understand, serotonin syndrome rarely happens after long term administration of the same dose of a drug. It is usually something that happens fairly suddenly upon initiation of a new drug, or dose increase. Again, this is a theoretical interaction which may occur at higher doses.
I would just be aware of the symptoms of serotonin syndrome upon increasing the dose.
Interestingly NRIs can reduce the risk of hypertensive crisis from an MAOI, so in one sense it may make MAOI therapy 'safer'.
Linkadge
Posted by PeterMartin on July 3, 2020, at 18:53:53
In reply to Re: Atomoxetine helping - fingers crossed » PeterMartin, posted by linkadge on July 3, 2020, at 16:41:06
Thanks for the followup Linkage.
My doctor mentioned he though it did inhibit serotonin when he prescribed it. I questioned that as I thought it was completely an NRI. Either he trusts me and just told me to be mindful of the potential.
Today is day 3 and I was super tired after taking my dose this morning. The other issue I've had a little bit of is heartburn. Gaviscon helps but I don't want to have to take that daily. Hopefully these sides pass.
I'm on the "authorized generic" which is a new concept for me. It's the same exact pill as brand (Eli Lilly) just packaged by a different company and sold for the same price as other Strattera generics. The maker is Prasco and my local CVS had it.https://prasco.com/what-we-do/authorized-generics.html
I wish Lamictal had an authorized generic from Glaxo......ever since Teva discontinued their version in 2018 I feel as though it hasn't helped quite as much as it used to regardless of generic maker :/
Posted by undopaminergic on July 4, 2020, at 3:14:45
In reply to Re: Atomoxetine helping - fingers crossed » PeterMartin, posted by linkadge on July 3, 2020, at 16:41:06
>
> I would just be aware of the symptoms of serotonin syndrome upon increasing the dose.
>
> Interestingly NRIs can reduce the risk of hypertensive crisis from an MAOI, so in one sense it may make MAOI therapy 'safer'.
>Maybe keep some cyproheptadine (Periactin) available (as an antidote to serotonin syndrome).
-undopaminergic
Posted by PeterMartin on July 4, 2020, at 23:07:21
In reply to Re: Atomoxetine helping - fingers crossed, posted by undopaminergic on July 4, 2020, at 3:14:45
Welp bp is spiking a bit tonight (160/100 when it's usually 110/70 or less when I'm on Marplan - including last week). Had bad heartburn so checked the bp.
Prob done w strattera....blah.
I felt like it may have been helping a bit w desire to do things w/ less anxiety....sucks...
Posted by PeterMartin on July 4, 2020, at 23:15:17
In reply to Re: Atomoxetine helping - fingers crossed, posted by PeterMartin on July 4, 2020, at 23:07:21
And so just checked it again and now it's 111/74 (20min after the high reading / ~2hrs after my 18mg dose).
Maybe I'll give it another try tomorrow but just be monitoring my bp to see if it spikes again. I took a small piece of nuvigil this morning to try to stage off fatigue so there's a slight chance that factored in.....don't recall having bp issues w that when I used it daily though....
Sorry for rambling...
Posted by linkadge on July 5, 2020, at 8:34:55
In reply to Re: Atomoxetine helping - fingers crossed, posted by PeterMartin on July 4, 2020, at 23:15:17
No you're not rambling...
I have a similar concern with atomoxetine. It is helping drive / motivation and focus quite a bit, but it also leaves my emotions a bit raw, and it has made me a bit more angry. It seems to have mixed effects on my mood. On the one hand I am VERY happy to be less trapped in my head, and definitely more active during the day, but there is some increased emotionality / sadness (hopefully this will subside). Also, it can make my heart beat a bit faster / harder at times.
I guess I can explain it like this it's not improving my mood directly, but I seem to be giving up much less often - i.e. I have the energy to continue with tasks despite my mood being sour. I wonder if this (over time) will lead to a more 'bottom up' improvement in my mood.
It's annoying because the NRIs seem to have a really strong PUNCH, but I am always skittish about the effects on cardiac function.
I haven't monitored my BP recently. I should do this, but am always scared to do so.
Linkadge
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