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Dopamine Uptake Reinhibitors for Depression

stratofortress

Bluelighter
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EDIT - I know i messed up on the thread title. Dopamine ReUptake Inhibitors........


In the UK, DRIs are not approved for treatment of depressive illnesses. The British National Formulary states that Methylphenidate, when being considered as a medication for use in patients with ADD/ADHD, is contraindicated in those with a history of, or suffering from depression. I'm making an assumption here, but I imagine this is the case in most countries. I've certainly never read about DRI's being prescribed for depression or any other mental illness.

So any ideas why this is the case? Antidepressants inhibiting the uptake of the other two main neurotransmitters are prescribed to patients presenting as depressed without a second thought. Why do pharmaceutical companies only focus on serotonin and norepinephrine activity in developing new antidepressant drugs? Why can't doctors and psychiatrists prescribe MPH as part of a patient's medication regimen?

You might argue that doctors are wary of prescribing more drugs with a high potential for abuse. Yet in the UK DRI's are the first choice of medication for the treatment of patients with Attention Deficit disorders. Chances are if you have ADD you'll be prescribed MPH; heck, my brother was on the stuff as a kid. And prescription rates are even higher in the US. Patients suffering depression often take a number of drugs before they find the one that is effective. If a patient has tried a number of drugs with no improvement in condition, psychiatrists may turn to less commonly prescribed drugs to give them a shot. DRI's would almost certainly be amongst these 'last resort' drugs, and so would rarely be prescribed in the treatment of mental illness. Such a change in prescribing rules would hardly lead to an epidemic of stimulant abuse.

Stimulant drugs taken by themselves can cause significant symptoms of anxiety and depression during the comedown. Speaking for myself, before I was forcibly made to stay in a psychiatric hospital, my use of Ethylphenidate caused some of the worst feelings of anxiety and dread that I'd ever felt. Every day I was a teary sobbing mucus faced mess. Surely evidence that those prone to depression should steer well clear of dopaminergic drugs? Perhaps if prescribed as the sole medicine a patient had to take. When I came out of hospital 6 months later I was being treated with an SNRI and Pregabalin. Unable to resist another go with the EPH i bought more, this time experiencing only a very mild and managable comedown. In combination with other psychiatric medications I believe those suffering mental illness would tolerate DRI's much better.

So using the example above, why not just say that the lack of comedown proved the efficacy of my SNRI and Pregabalin in the treatment of depression. Well depression comes with many symptoms, some of which are not always improved by currently licensed medicine. For example, I still found my motivation and enthusiasm for life were very low. Starting and finishing simple tasks was far more gruelling than it should have been. If you had to add another drug to this chemical cocktail, would you see a DRI as an obvious candidate? Improved motivation and concentration; the very same desired results from MPH prescribing in ADD/ADHD patients.

I don't know. Perhaps the governing bodies deciding prescribing rules are doing us a favour. Many more people suffer depression than ADD/ADHD. Maybe these dopaminergic drugs simply aren't as safe as the serotonin alternatives. It could be that the medical profession wishes to prevent more DRI prescriptions because the long term health effects of such drugs are more likely to be neurotoxic. But that sounds a bit tin foil hat to me.

Shit I've rambled on. Well you can't fault these drugs on their ability to increase productivity.

So any thoughts?
 
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First off, hi to the ADD community. 3-year member here, on a new account for security reasons. Neuroscience junkie, in the middle of a minor :)

Any DRI will cause receptor downregulation, which is the same thing as tolerance and dependance. SSRIs do successfully make one generally feel better about one's life for a prolonged period of time, in my experience. I'm not sure that a DRI could do the same. I know that amphetamine seemed like an awesome "antidepressant" for a while. Until I needed it to not feel like a miserable wreck.

Bupropion (Wellbutrin) is a norepinepherine-heavy NDRI used for depression. It bugs me that they'll let me take this because its an "antidepressant", but another NDRI that lasts a sane amount of time (methylphenidate) my current shrink won't give me. sigh.
 
Hi TCMVegas,

That's just the sort of information I was after, thanks. I hadn't considered receptor downregulation; is this what causes tolerance to all habit forming drugs? I'll have to look it up; I've no idea how it works.

So why don't SSRIs cause receptor downregulation? Also, what's the deal with norepinephrine reuptake inhibitors? I'm sure I'm being really naive here, but being flooded with adrenaline makes me feel awful. Why increase brain norepinephrine levels to treat depression?

Sorry lots of questions......
 
norepinepherine is energizing, that's pretty much it's purpose as an antidepressant.

SSRIs do lead to receptor downregulation. their mechanism appears to be from structural changes. One of these is neurogenesis in the hippocampus.

Receptor downregularion does not necessarily mean that neurotransmission is a zero-sum game if increased concentrations are present.
 
Receptor downregularion does not necessarily mean that neurotransmission is a zero-sum game if increased concentrations are present.

Hence the need for ever increasing amounts of the substance?

Huh thanks again, you're making my blog look very erudite.
 
Hence the need for ever increasing amounts of the substance?

Well yes, but I'm saying that even though your transmitters downregulate and become dependent, you can still probably sustain higher than normal levels of receptor activity. I'm not sure on this one though, I'm not totally comfortable with mechanisms of downregulation.
 
sorry to keep bugging you, but you seem to know your stuff well enough. what fields exactly do you study? my ignorance of science is shameful. again, sorry to pester you.
 
They will only work long term in combination with something for tolerance like memantine or tolerance to the antidepressive effects develop.

UK healthcare is a total disaster between, beyond horrible when you come from belguim or another country with actual decent healthcare.
For ADHD tolerance usually doesnt develop as the D4 receptor doesnt downregulate, this receptor plays the major role in the pfc and explains most therapeutic effects for ADHD.
 
Any DRI will cause receptor downregulation, which is the same thing as tolerance and dependance. SSRIs do successfully make one generally feel better about one's life for a prolonged period of time, in my experience. I'm not sure that a DRI could do the same. I know that amphetamine seemed like an awesome "antidepressant" for a while. Until I needed it to not feel like a miserable wreck.

Bupropion (Wellbutrin) is a norepinepherine-heavy NDRI used for depression. It bugs me that they'll let me take this because its an "antidepressant", but another NDRI that lasts a sane amount of time (methylphenidate) my current shrink won't give me. sigh.

Could you explain what makes SSRIs work long term in comparison to DRIs and give a source?

People who've taken both methylphenidate and bupropion will attest that they produce wildly different effects for having such a similar pharmacological profile

SSRIs do lead to receptor downregulation. their mechanism appears to be from structural changes. One of these is neurogenesis in the hippocampus.

Receptor downregularion does not necessarily mean that neurotransmission is a zero-sum game if increased concentrations are present.

Do you know how much?

They will only work long term in combination with something for tolerance like memantine or tolerance to the antidepressive effects develop.

UK healthcare is a total disaster between, beyond horrible when you come from belguim or another country with actual decent healthcare.
For ADHD tolerance usually doesnt develop as the D4 receptor doesnt downregulate, this receptor plays the major role in the pfc and explains most therapeutic effects for ADHD.

Yet bupropion is prescribed A LOT long-term
 
Bupropion is not really a DRI, for 20% or so perhaps wich is probably to low to cause therapeutic effects, they most likely just come from its ne releasing property's (its not a nri)
 
....stratofortress ive often asked myself the same question/s but was not sure how to ask the questions, so I just want to quickly say this post has been excellent, informative reading :-) Thanks :-)
 
Amphetamines of a few flavors (as well as methylphenidate) are occasionally prescribed in relatively low doses to augment preexisting treatment regimens for depressive disorders. DRI/DRA monotherapy isn't completely unheard either, at least here in the States. Here's a recent review of the available literature on the subject of psychostimulant monotherapy in MDD.
 
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