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Dopamine deficiency and depression/low motivation

alec_empire

alec_empire

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Joined
May 24, 2007
Messages
16
Recent literature suggests that the common neural basis of anergia and melancholic/retarded depression is a decrease in striatal dopamine function.

But why are there so few antidepressants on the market that effectively block dopamine reuptake to compensate for depression-induced hypodopaminergia?


And what are the best pharmaceuticals on the market to enhance dopamine brain function that are devoid of extremely harmful long-term side-effects?
 
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Buproprion isn't very effective for many MDD patients and it's either explicitly or tacitly contraindicated if the depression's symptomatology includes psychotic features, or if there's any hx of mania or hypomania.

Amineptine failed to acheive FDA approval because of its high abouse potential.

Amphetamine is problematic because of the common comorbidity of depression and addiction.

Modafinil is promising, but its cost in the US is prohibitive to many.

Just about every pharmaceutical company has one or several SNDRIs in their research
pipelines. Some have been abandoned in the midst of preliminary trials.

The neurotransmitter imbalance model of depression is perhaps a gross oversimplification, but the drugs that have been developed to treat depression have been largely guided by this model.

Psychiatry remains embryonic.

Tell Hanin Elias I said hey.

Edit: Modafinil's schedule IV!?
 
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Though Amineptine didn't show any physical harm as far as I know! Forbidding a serious depressive the stimulant option because someone else might abuse it is unethical behaviour if you ask me.Btw in certain european countries (I know it from Switzerland) Ritalin is available to treat depression,albeit off-label.An SSRI plus a dopaminergic is especially effective,also when dealing with the common sexual side-effects.

And check out this fine paper from Gabriele Stotz:
http://www.dialogues-cns.org/brochures/03/pdf/03.pdf

Or scroll down to my post and follow the link which leads you to the pdf file of the paper:
http://bluelight.ru/vb/showthread.php?t=421016
 
Hugo:

That whole issue is fantastic. Thanks for pointing it out.

Just so there's no misunderstanding, US doctors are relatively free to prescribe any medicine they wish to prescribe, so long as it's approved for some condition.

Whether or not a pharmacist will fill the prescription is another matter entirely.
 
^^^^^^^^
I dont think the obstacle is a pharmacist who wouldnt fill the script. First off, paper beats rock and doctor beats pharmacist. Second off, the pharmacist often does not know what condition a particular med is being prescribed for.

The problem with scripting off label meds that carry abuse potential lies in the doctor's fear of being investigated. Unfortunately, despite the hippocratic oath, a doctor's ACTUAL oath starts off more like:

First-do no harm to your medical license. - DG
 
daddysgone said:
^^^^^^^^
I dont think the obstacle is a pharmacist who wouldnt fill the script. First off, paper beats rock and doctor beats pharmacist. Second off, the pharmacist often does not know what condition a particular med is being prescribed for.

The problem with scripting off label meds that carry abuse potential lies in the doctor's fear of being investigated. Unfortunately, despite the hippocratic oath, a doctor's ACTUAL oath starts off more like:

First-do no harm to your medical license. - DG
Click to expand...

I love that Hippocratic oath change! So true. The Controlled Substances Act is stricter than all hell, but to me, that's a good thing. Too many people I've known trying to piece their lives back together due to drug abuse. But I digress.

I would think the main rationale of a strictly dopaminergic agonist or reuptake inhibitor would be fantastic for people with clinically diagnosed depression IF due to dopamine exclusively. But how would you know that without trial and error of drug classes? Also, many neurotransmitters, including serotonin can act on the dopamine release pathway and cause some dopamine release from the synapse. But since dopamine is the big chemical in psychosis and drug abuse/reward pathways, it would most likely be a scheduled drug, if not a C-II entirely. You'd be looking at a drug like the amphetamines, that inhibit NE and dopamine reuptake and stimulate more dopamine and NE release from the neurons. Makes you happy and focused, which equals Schedule-II in U.S.

Bupropion is the only antidepressant that I know has dopaminergic effects along with NE. However, it's small I would gather, since Wellbutrin is not controlled . I personally take Bupropion and it is fantastic for my depression. I am a bit more anxious and more easily agitated, but my mood in general is much better.
 
seep said:
Hugo:

That whole issue is fantastic. Thanks for pointing it out.

Just so there's no misunderstanding, US doctors are relatively free to prescribe any medicine they wish to prescribe, so long as it's approved for some condition.

Whether or not a pharmacist will fill the prescription is another matter entirely.
Click to expand...

Not entirely true. MD's can prescribe medications freely, sure, but as long as it is relevant to their practice. For example, especially with the Controlled Substances Act, it is illegal for an MD to prescribe controlled drugs outside his/her scope of practice. A general practitioner cannot prescribe oxycodone for a patient unless they are a specified pain specialist or have some kind of indication to do so (and I can think of ZERO). Also, suboxone for opioid dependence, can only be written by practitioners licensed with the board and has a pain-management specialty, etc, etc, in order to prescribe suboxone.. They even have a new DEA character to do so.

A physician here where I live recently was arrested by the DEA after a year-long investigation. His charge was prescribing controlled substances for patients outside the realm and scope of his practice. He was a general medical practitioner, no specialty, just a little clinic, who was prescribing Oxycontin 160 mg (2 80 mg twice daily), Soma 350 every 6 hours (which is insane), and Xanax 2mg four times daily (also insane). He's facing at least 20 years in prison for EACH count of just C-II prescriptions alone.

You bet your ass, as a pharmacy intern, soon to be pharmacist, if I see a prescription come on by for craziness from a general PCP, I'm getting on that phone and asking why, why, why. And then reporting if no good reason. All the pharmacies in our metro area and surrounding cities stopped taking that doctor's prescriptions, because they were not willing to be dragged into a conspiracy issue with this guy and lose their license. Neither would I.

Sorry, I tend to ramble...lol :)
 
taylorbb said:
Not entirely true. MD's can prescribe medications freely, sure, but as long as it is relevant to their practice. For example, especially with the Controlled Substances Act, it is illegal for an MD to prescribe controlled drugs outside his/her scope of practice. A general practitioner cannot prescribe oxycodone for a patient unless they are a specified pain specialist or have some kind of indication to do so (and I can think of ZERO). Also, suboxone for opioid dependence, can only be written by practitioners licensed with the board and has a pain-management specialty, etc, etc, in order to prescribe suboxone.. They even have a new DEA character to do so.
Click to expand...

PCPs prescribe painkillers all the time. You can't tell me that if I'm a PCP and a patient walks in with a legitimate pain-related issue I can't prescribe him a couple of weeks worth of percocet and refer him to a specialist. In the same way, plenty of pcps prescribe buprenorphine to opiate addicts. I've only been denied these by (a handful of) pharmacists. What about the psychiatrists who recognize the antidepressant value of buprenorphine and prescribe it 8 mg bid every month?

There's always the croakers that prescribe oxys to any junkie who crosses their threshold and ever since there's been a DEA there's been a cat and mouse thing there. I'll bet you $10 that in 2020 there still will be plenty of them around.
 
Definitely. Sure I would send a patient home with 5 days of percocet or lortab. Definitely not 30 day supply of oxy ER. If their pain is that bad, they should see a specialist ASAP. And MDs and psychiatrists can prescribe suboxone if they are registered with the DEA to do so and I believe it can only be in the treatment of opioid addiction, but don't quote me on that. I don't see the therapeutic benefit in using buprenorphine as an antidepressant anyway. It's a weak partial agonistat the mu opioid receptors with no NE or DA effects that I know of. There's a relatively crappy high unless consumed in larger doses I would imagine. My sibling is on suboxone currently for opioid addiction and she says it's basically worthless in terms of being euphoric. Just helps with withdrawal and sometimes it's not even great for that. If you have any experiences or know anything different let me know. She asks me a lot about it so it would be good to know some new things to try and keep her sticking with it and not relapsing.
 
taylorbb said:
Definitely. Sure I would send a patient home with 5 days of percocet or lortab. Definitely not 30 day supply of oxy ER. If their pain is that bad, they should see a specialist ASAP. And MDs and psychiatrists can prescribe suboxone if they are registered with the DEA to do so and I believe it can only be in the treatment of opioid addiction, but don't quote me on that. I don't see the therapeutic benefit in using buprenorphine as an antidepressant anyway. It's a weak partial agonistat the mu opioid receptors with no NE or DA effects that I know of. There's a relatively crappy high unless consumed in larger doses I would imagine. My sibling is on suboxone currently for opioid addiction and she says it's basically worthless in terms of being euphoric. Just helps with withdrawal and sometimes it's not even great for that. If you have any experiences or know anything different let me know. She asks me a lot about it so it would be good to know some new things to try and keep her sticking with it and not relapsing.
Click to expand...

Well, just because you wouldn't send a patient home with a month's supply of oxy ER doesn't mean PCP's aren't allowed to do it. Some people can't afford the specialist visit every month in addition to the cost of their medicine. I know of a family practice office that has patients on long term high dose painkillers (75ug fent patches, 120mg oxy/day, etc).

In reference to bupe being antidepressant, you're confusing recreational potential with antidepressant potential. Who cares if its worthless in terms of euphoria? Do you expect to get a buzz off your wellbutrin/prozac/effexor?
 
The antidepressant effects of bupe are due to its antagonism at the kappa receptors, not its action at mu. Its been well documented that antagonism at kappa provides a very effective mechanism for an anti-depressant.=DG
 
daddysgone said:
The antidepressant effects of bupe are due to its antagonism at the kappa receptors, not its action at mu. Its been well documented that antagonism at kappa provides a very effective mechanism for an anti-depressant.=DG
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Thanks for that! Makes a bit more sense now and I have been trying to research it and coming up empty handed because I can't find FREE journal articles about it - freaking frustrating. Anyway...

If MDs are prescribing it for refractory depression, I don't think that would be allowed by law (at least with the Controlled Substances Act and the opioid dependent treatment act). As far as I know, you can only use Subutex/Suboxone for opioid dependence treatment. Period. Off-label for refractory depression I can see, but getting a authorized Suboxone DEA based on "treatment of refractory depression" is not gonna cut it with the DEA. The paperwork required to dispense it for opioid dependence alone is a pain in the ass and a lot of crap to complete. If the DEA wants to add on a rider for using it in refractory depression, that would work, but my guess is that they would require the manufacturer to do testing through the FDA to get FDA-approval for that. I can guarantee you Reckitt Benckiser is not gonna go through a IND application to do that. Especially when clozapine is first-line for refractory depression. Maybe if you developed agranulocytosis from the clozapine (which is rare) you could use bupe next...
 
Taylor-
First off, are you a MD? I ask because you mentioned how you would write a script for percocet for someone in pain. Perhaps you were speaking hypothetically.

As far as suboxone/subutex, I know that in the US doctors must obtain training and a license in order to prescribe suboxone/subutex for opioid maintenance. doctor who do not have this license cannot legally script these drugs for opioid maintenance/replacement therapy.
However, they MIGHT be able to script suboxone/subutex for other reasons. For instance, its entirely possible (in fact I think this is the case) that any doc can prescribe suboxone as an analgesic. Taking it a step further, I dont think there is any law which would prevent them for prescribing it for depression if they deemed it appropriate-they might get investigated by the DEA and be forced to answer some tough questions, but I dont think any law precludes this practice.
But again let me restate, there IS a law pertaining to suboxone/subutex when it comes to opioid maintenance/replacement. A doc must obtain a special license to prescribe this for maintenance purposes.

Can anyone here confirm my suspicions that though docs need a special license to script bupe for maintenance, any doc is technically free to prescribe bupe for non-maintenance reasons.-DG
 
DRI antidepressants that inhibit dopamine over 60% aren't really out there, because over 60% and it's basically a stimulant. The closest an antidepressant gets to being a decent DRI (used very loosely in this case) is bupropion. I think that has something like 50% DAT inhibition. But it also has shitty NE inhibiting properties, to offset any fun. It's harder, better, faster, stronger , cousin is methcathinone, and thats a big chemical of abuse...

DRI antidepressants tend to make you feel really great for a little while, then much worse after they wear off. 'tis the nature of the beast, my friend. Low doses are interesting, but still , lead to subtle depression.

The best non-novel (ie. SSRI) antidepressant drug out there IMO is suboxone. K-opiod receptor antagonism at low doses does seem to help with depression somewhat.

-lenses
 
DG, it's sort of a difficult question to answer because the 1st line of enforcement, pharmacists, will sometimes fill a bupe script without hesitation. In Fort Lauderdale there's like 40 pain clinics/outpatient detox centers that'll tell you the same thing Taylor is saying and then charge you $300 for a script. On a hunch one day I just went to a family doctor and told him the truth and he made a phone call I couldn't understand (he's Haitian) to check on something and then immediately wrote me a script for a month's supply. A big chain pharmacist filled it in 10 minutes. Later I found out he had called a psychiatrist colleague to ask if he had ever run into trouble for prescribing bupe. 6 months later I went to that psychiatrist and again told him the truth and he wrote me a script after lecturing me for a half hour. I could go on, but it looks to me that while there are Fed laws about who can prescribe the stuff, they're not really enforced (at least down there). Null enforcement = null legitimacy. Also what throws a cricket into the blender is that the trend varies from state to state I think. In (upsate) NY I've been denied bupe on 3 separate occasions and what I was told is there was a really strict STATE law that regulated these prescriptions.

The real litmus test is how many doctors have been disciplined for prescribing bupe for certain situations (not pill-mill docs but responsible practitioners).

On a side note, for a dually diagnosed person (depression + opiate addiction) I think bupe is ideal; it's dispensed that way in NY jails and after you get out you're referred to a (DEA certified) psychiatrist for monthly consults and what seems like indefinite bupe maintenance.
 
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