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Dr. Bob is Robert Hsiung, MD,
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Posted by SLS on September 13, 2012, at 7:50:18
In reply to Re: is a GABA antagonist what i need?, posted by poser938 on September 12, 2012, at 21:44:21
> oh and she mentioned me getting which ever GABA antagonist we decide on at a compounding pharmacy
A GABA antagonist might be mimicked by using a pro-glutamatergic agent like modafinil (Provigil). This drug modulates the GLU/GABA ratio in favor of glutamate, a generally excitatory neurotransmitter.
Whether or not you need a GABA antagonist is unclear.
- Scott
Posted by phidippus on September 13, 2012, at 16:41:41
In reply to Re: is a GABA antagonist what i need?, posted by poser938 on September 12, 2012, at 19:58:21
What makes you think you're emotions are gone?
Eric
Posted by AlexCanada on September 13, 2012, at 17:10:40
In reply to Re: is a GABA antagonist what i need? » AlexCanada, posted by phidippus on September 12, 2012, at 17:13:11
ty for the suggestions. they are much appreciated.
I been trying to convince my doctor regarding memantine. i only been able to find one other study which states 30-40mg doses can help with MDD. Do you have any other possible sources?
I may just end up ordering it. And will definitely look into the others.
Dexedrine and ritalin I have tried. They worked exceptionally well but not in the long term. Much tolerance build up.
Modafinil I have tried. Short term works well for cognition drive motivation energy productivity but very mildly for actual ability to ''enjoy'' anything. It sometimes makes me feel empty, especially several hours after taking a dose and even can make me feel a bit sad and very procrastinated, non reactive. This may be a modafinil crash. It's a very perplexing medication.
Abilify I tried as an add-on for Parnate a few years ago and rapidly I felt worse.
The dopamine based medications you mentioned are they generally fine to take if I stay on ritalin?
> Researchers theorize that anhedonia may result from the breakdown in the brain's reward system, involving the neurotransmitter dopamine.
>
> Keeping that in mind, the drugs I'm going to recommend to you are mostly dopiminergic in nature or affect dopamine in the CNS.
>
> Mirapex and Requip are both dopamine enhancing drugs. Pramipexole(Mirapex) acts as a partial/full agonist at the following receptors: D2S receptor (Ki = 3.9 nM; IA = 130%)
> D2L receptor (Ki = 2.2 nM; IA = 70%)
> D3 receptor (Ki = 0.5 nM; IA = 70%)
> D4 receptor (Ki = 5.1 nM; IA = 42%)
> Ropinirole (Requip) acts as a D2, D3, and D4 dopamine receptor agonist with highest affinity for D2
>
> Nuvigil - Orexin neurons are activated by Nuvigil. Orexinergic neurons are found exclusively in the lateral hypothalamic area. Their activation is associated with enhanced pleasure-seeking and motivation as well as arousal. Orexinergic fibers project to the entire central nervous system. Its dopamine-releasing action in the nucleus accumbens is weak and dose-dependent.
>
> Rotigotine (Neupro) - has been shown effective in the treatment of anhedonia and depression. It is a dopamine agonist.
>
> Abilify is a partial dopamine agonist of the third generation class of atypical antipsychotics with additional antidepressant properties that is used in the treatment of schizophrenia, bipolar disorder, and clinical depression. Abilify is also a 5ht1a partial agonist.
>
> Memantine treatment reverses anhedonia, normalizes corticosterone levels and increases BDNF levels in the prefrontal cortex induced by chronic mild stress in rats.
>
> http://www.ncbi.nlm.nih.gov/pubmed/22327556
>
> Dextroamphetamine increases dopamine in the brain and can reverse anhedonia
>
> Ritalin (methylphenidate hcl) presumably activates the brain stem arousal system
>
> Buprenorphine can help with anhedonia
>
> Eric
Posted by AlexCanada on September 13, 2012, at 21:31:53
In reply to Re: is a GABA antagonist what i need?, posted by linkadge on September 12, 2012, at 18:42:27
> Dopamine can actually cause anhedonia too.
>
> Dopamine release in the NAA can cause feelings of pleasure (acutely, in the short term). However when the NAA recieves prolonged exposure to dopamine, it can result in behavioral depression.
> This is associated with an elevation of BDNF in the neucleus accumbens (bad) - and decrease of BDNF in the hippocampus.
>
> Pleasure is meant to come only here and there (usually after the sucessful completion of a positive task). You don't want dopamine coming out of nowhere, for no reason, else you develop an addiction to the pleasure producing short cut, not the natural events in life that produce it.
>
> People who use stimulants or opioids usually become antisocial. This is because the drug produces reward and the individual begins to focus more on the reward produced by the drug rather than natural social interaction (which can do the same thing).
>
> The effect of dopamine on pleasure is inverse 'U' shaped. Why do you think that antipsychotics can reverse the severe behavioral withdrawl, apathy and other negative symptoms associated with schizophrenia?
>
> Depression can be a side effects of ADD drugs like ritalin or dexedrine. According to my psychiatrist (who deals in ADD), its a fairly common side effect.
>I've been on ritalin for years. It used to help greatly a long time ago but has since developed much tolerance. A few times I've given it a break and then had positive results when starting up again. These days it sometimes makes me feel slightly better while other times slightly worse. It is very possible that long term ritalin use has compounded my melancholic depression.
How would you suggest reversing any possible damage that may have been done? I have been cutting back on my doses little by little but may take some time. Ritalin was the first med to make me feel as if I had part of my life back many years ago (dexedrine was similar in this regard).
Posted by poser938 on September 13, 2012, at 21:39:01
In reply to Re: is a GABA antagonist what i need? » poser938, posted by SLS on September 13, 2012, at 7:50:18
> A GABA antagonist might be mimicked by using a pro-glutamatergic agent like modafinil (Provigil). This drug modulates the GLU/GABA ratio in favor of glutamate, a generally excitatory neurotransmitter.
>
> Whether or not you need a GABA antagonist is unclear.
>
>
> - Scottwell, i did try Nuvigil recently. i feel nothing from it. i had that idea in my head too try and mimic a GABA antagonist with it.
Posted by phidippus on September 13, 2012, at 22:26:40
In reply to Re: is a GABA antagonist what i need?, posted by poser938 on September 13, 2012, at 21:39:01
Have you tried dextroamphetamine?
How about Memantine?
Eric
Posted by phidippus on September 13, 2012, at 22:34:55
In reply to Long term Ritalin use... » linkadge, posted by AlexCanada on September 13, 2012, at 21:31:53
Studies show that certain receptors in the brain respond to dopamine in a previously unknown way that occurs over a period of hours rather than minutes or seconds. In this manner, researchers say the chemical may affect the brain indefinitely.
Receptors are proteins found on the surface of nerve cells that recognize and translate the signals from a chemical messenger to trigger a response by the cell.
In laboratory tests with mice, researchers found prolonged exposure to dopamine through this pathway inactivated a regulatory protein in the brain known as Akt and caused the mice to behave like they were depressed in response to stress.
In addition, inactivation of this protein caused a molecular chain of events that caused the mice to become desensitized to certain drugs.
What damage do you think has been done?
Eric
Posted by poser938 on September 13, 2012, at 23:25:49
In reply to Re: Long term Ritalin use... » AlexCanada, posted by phidippus on September 13, 2012, at 22:34:55
heh.. basically what you described seems to be my problem. i dont respond to many medicines now sinnce after mirapex had its effect on me. adderall doesnt do anything for me now. i cant feel any effects from an antipsychotic other than a side effect from serotonin antagonism increasing my hunger.
before taking mirapex i could feel effects from provigil. and i responded to stimulants.
it is as if a big part of my dopamine system is shut down. i can close my eyes while driving and be just as comfortable as i am sitting on the couch. i am not able to enjoy music, it sounds so shallow and empty. my emotions may not be completely blank, but it is as if i dont have a dopamine reaction to things. i am a very timid person.and i did try ketamine back in april, so im not so sure memantine would be worth a try.
i honestly think i'm about out of medications to try which is why i believe it is time to give a GABA antagonist a shot.
Posted by phidippus on September 13, 2012, at 23:27:33
In reply to Re: is a GABA antagonist what i need? » phidippus, posted by AlexCanada on September 13, 2012, at 17:10:40
>Do you have any other possible sources?
http://www.ncbi.nlm.nih.gov/pubmed/17545748
>The dopamine based medications you mentioned are >they generally fine to take if I stay on ritalin?
Yes, in fact they tend to have a synergistic effect when taken with stimulants. I took Requip with Vyvanse for almost a year and it was a couple weeks into taking the Requip that I noticed my mood and motivation had significantly increased moreso than when taking Vyvanse alone prior.
Between the two, Requip and Mirapex, I would recommend Mirapex. It has a lot more data backing its efficacy at treating depression.
I too suffer from anhedonia during periods of depression, so I can relate. Of all the drugs I've tried to treat it, Buprenorphine was the most succesful, but had the most side effects, unfortunately.
What is your diagnosis and what drugs doo yoou take?
Eric
Posted by phidippus on September 14, 2012, at 17:40:29
In reply to Re: Long term Ritalin use..., posted by poser938 on September 13, 2012, at 23:25:49
Have you tried Wellbutrin?
Eric
Posted by poser938 on September 14, 2012, at 18:49:46
In reply to Re: Long term Ritalin use... » poser938, posted by phidippus on September 14, 2012, at 17:40:29
yes, i dont get anything good from it either.
Posted by AlexCanada on September 14, 2012, at 22:46:05
In reply to Re: Long term Ritalin use... » poser938, posted by phidippus on September 14, 2012, at 17:40:29
> Have you tried Wellbutrin?
>
> EricYes I have. Didn't work well for me. I don't recall the specific effects though.
Posted by AlexCanada on September 14, 2012, at 23:02:03
In reply to Re: is a GABA antagonist what i need? » AlexCanada, posted by phidippus on September 13, 2012, at 23:27:33
> >Do you have any other possible sources?
>
> http://www.ncbi.nlm.nih.gov/pubmed/17545748
>
> >The dopamine based medications you mentioned are >they generally fine to take if I stay on ritalin?
>
> Yes, in fact they tend to have a synergistic effect when taken with stimulants. I took Requip with Vyvanse for almost a year and it was a couple weeks into taking the Requip that I noticed my mood and motivation had significantly increased moreso than when taking Vyvanse alone prior.
>
> Between the two, Requip and Mirapex, I would recommend Mirapex. It has a lot more data backing its efficacy at treating depression.
>
> I too suffer from anhedonia during periods of depression, so I can relate. Of all the drugs I've tried to treat it, Buprenorphine was the most succesful, but had the most side effects, unfortunately.
>
> What is your diagnosis and what drugs doo yoou take?
>
> EricMy diagnosis is erroneous. My doctor thinks I may have bi-polar even though I've never been manic or exhibited any of the symptoms. He happened to once see me during a time when I was taking a lot of gingko biloba and protein powder and was able to be interested in one thing in my miserable life... sex, so he felt it must have somehow been possible. Whatever. He also feels it might just be unipolar but me and him have been able to basically agree upon Melancholic Depression from my own research. I shouldn't have to do this. Doctors should know the symptoms but he is one of the very few doctors who will bother to listen to me.
At the bottom of this post I'll paste my symptoms in greater detail along with what I have tried. Basically almost all melancholic symptoms can be applied to me. Also I deal with some anxiety issues. Anxiety which manifests itself out of nowhere. it is less prominent these days than years ago. Zoloft is compounding my poor cognition and making me feel emotionally numb and very dull.
Right now i'm on valium 2.5mg 4x a day (around), ritalin 2.5 mg 4x a day (around), Zoloft 25mg a day (day 8 on it), 250mg Rhodiola Rosea, stopped Magnesium Glycinate recently (caused anxiety at times), stopped Vit D3 recently, Sometimes I take Gapapentin for short term relief of many symptoms, Once in a while I take modafinil if I really need energy and productivity but it usuaully causes me to feel lousy after 5 hours, sometimes even dysphoric.
Below are my symptoms and meds I have tried...
Biggest Issues: Severely poor long term memory and ability to retain new knowledge, Antero Grade Memory Loss, Poor Cognition, Lack of emotions, Anhedonia, Dysphoria, Mind feeling blocked/cloudy, Severe lack of enjoyment, Lack of drive/motivation/desire/sense of reward, Difficulty relating to others and feel bit like a zombie, Severe difficulty being social (also partially due to inability to relate), Anxiety (usually handled if I keep taking valium), Low energy
Effects of Memory and Cognitive Issues: Loss of current thought process and forgetfulness of what I was about to do, Forget what happened a day ago, people's names, difficulty imagining what people's faces look like, unable to recall events from tv shows/movies/media, slow speech usually, takes time to process thoughts and information,
Best Medications tried: Ritalin/Dex (especially first time), Parnate (first few months especially), Paxil (some resemblence of normalicy and integration into society). Valium/Ativan (some mood improvement + anti-anxiety), Gabapentin (Improvement of most symptoms including emotions and cognition, but tolerance builds quickly). Vivalan/Vivarint (only available in france now),Treatments Tried:
Benzo- Valium, Ativan, Klonopin, Xanax
SSRI- Celexa, Paxil, Zoloft,
SNRI/Other/Alternative- Wellbutrin, Effexor, Stablon, Remeron, Lithium, Adrafinil, Gabapentin, Narproxen, Vivarint, Buspar, Trivistal LA, ECT, rTMS, Reboxetine, Mirapex,
NRI- Reboxetine,
MAOI- Parnate, Nardil
Stimulant- Ritalin, Dexedrine, Provigil
Anti-Psychotics- Zyprexa, Risperidal, Abilify (as a low dose add-on), Seroquel,
Natural/Herbal- Rhodiola Rosea, Omega 3, Omega Complex, Korean Ginseng, Magnesium Glycinate, Royal Jelly, Niacin, Gingko Biloba, Bee Pollen, L-Arginine, Resveratrol, D3, Maca Root,Sensitivities: Vitamin A, Sunlight,
----Treatment Results:
Worse: Celexa (gradual worsening of depression and burning pain), Effexor (rapid worsening of depression and burning pain), Abilify (rapid worsening of depression when taken w Parnate), Cymbalta (gradual worsening of depression), Seroquel, ECT (Severely damaged my long term memory and overall cognition perminently), Nortriptyline, Lithium,
Better: Risperidal (some ability to enjoy things but overall would still be largely lacking), Parnate, Ritalin (first time this or Dexedrine was taken I was able to feel a bit like my old self, ability to experience pleasure, positive outlook, return of old hobbies, Was able to appreciate being alive), Dexedrine (similar to ritalin), Valium (some mood improvement, some anxiety improvement, most benzos have had similar effect), Ativan (was more social on this than other benzos while also on Paxil), Rhodiola Rosea (herbal similar to an MAOI) (A small miracle for mood, energy, cognition, general well being, would still be lacking pleasure. Has lost much effect over time), Gabapentin (tremendous cognitive improvement, imagination, more emotions, less cloudy thought process, feeling of greater intellectual capacity. Some improvement to mood, ability to be social. Although rapid tolerance onset, inconsistent, ironically sometimes cognitive impairment.), Vivarint (some mood improvement, massive improvement to sex drive),
Mixed Results: Remeron (sluggish on low doses, more active on higher doses, very mild mood improvement, impulsive spending), Zyprexa (some mood improvement, lot of lethargy, cognitive slowness, food tasted wonderful), Stablon, Modafinil (increased Cognition, Energy, Motivation but may compound dysphoria)
Negligible or Unsure: Zoloft, Nardil, Adrafinil, Narproxen, Buspar, rTMS (could not access any tangible improvement), Reboxetine, Mirapex, Piribedil, Klonopin, Wellbutrin,
Needs confirmation (not sure if taken): Prozac,
Posted by SLS on September 14, 2012, at 23:26:32
In reply to My diagnosis and what I take » phidippus, posted by AlexCanada on September 14, 2012, at 23:02:03
If there is a chance that you have ADHD, Strattera might be worth a try.
I can't say for sure what's doing what in my treatment regime. However, the addition of minocycline is helping me a great deal. The key might be to combine a NRI, Lamictal, and minocycline. If there is a bipolar thing going on, Lamictal + minocyline might be all that you need. I have yet to see if I need Abilify in the mix. I am currently taking 10 mg/day. However, I intend to attempt to discontinue it. As I gather more information as to how I respond to treatment adjustments, I'll post the results.
Currently:
Parnate 80 mg/day
nortriptyline 150 mg/day
Lamictal 200 mg/day
lithium 300 mg/day
Abilify 10 mg/day
minocycline 200 mg/day
- Scott
Posted by linkadge on September 15, 2012, at 5:53:01
In reply to Re: flumazenil is probably acutely neurotoxic » SLS, posted by phidippus on September 11, 2012, at 17:28:06
>"administration of the benzodiazepine receptor >antagonist flumazenil (4 mg/kg, IP) elicited a >marked increase (95 or 60%) in dopamine release in >the nucleus accumbens"
>That's a huge increase in dopamine.
Crack cocaine probably increases dopamine 5000% in the nucleus accumbens. That doesn't mean that crack cocaine is indicated.
Posted by linkadge on September 15, 2012, at 5:59:12
In reply to Re: is a GABA antagonist what i need?, posted by phidippus on September 11, 2012, at 17:49:44
The beta carbolines were recognized to be benzodiazapine antagonists quite some time ago. They were used to test gaba's mechanisms in anxiety and panic. It was recognized that they could produce extreme anxiety in test subjects and that this could be reversed by benzodiazapines.
If you want low doses of a gaba antagonist why not just drink coffee or eat chocolate (a natural source of beta carbolines)?
Posted by linkadge on September 15, 2012, at 6:01:48
In reply to Re: is a GABA antagonist what i need?, posted by poser938 on September 11, 2012, at 18:33:56
>my doc prescribed Gabapentin today and she said to >only get a 3 day fill of this. if it doesnt work >we will be trying a GABA antagonist. she said it >makes a lot of sense to try this next.
Yeah, sure it makes a lot of sense.
If driving north on road A doesn't get you to your destination, **surely** driving south on the same road will.
Linkadge
Posted by linkadge on September 15, 2012, at 6:02:22
In reply to Re: is a GABA antagonist what i need?, posted by poser938 on September 11, 2012, at 18:51:21
I think you're making this up. No doctor would be that foolish.
Linkadge
Posted by linkadge on September 15, 2012, at 6:15:04
In reply to Re: is a GABA antagonist what i need? » AlexCanada, posted by phidippus on September 12, 2012, at 17:13:11
Flooding the brain's pleasure centres with dopamine does about as much to fix depression as Ben Bernanke printing money (Quantitative Easing - QE3) fixes the economy.
Linkadge
Posted by linkadge on September 15, 2012, at 6:19:29
In reply to Re: is a GABA antagonist what i need?, posted by poser938 on September 12, 2012, at 19:58:21
So....let me see if I have this right. You were perfectly fine before using drugs. Then, for no apparent reason (in your perfectly mentally healthy state) you decide to take an antidepressant. Then, after permanently warping your brain you decide that taking *another* drug is the solution to the fact that you were perfectly fine without drugs to begin with.
Linkadge
Posted by linkadge on September 15, 2012, at 6:22:52
In reply to Re: is a GABA antagonist what i need?, posted by poser938 on September 12, 2012, at 19:58:21
You said that mirapex had the negative effect of making it difficult for you to experience pleasure.
So.........huh..........you're making no sense. If direct dopaminergic stimulation makes your anhedonia worse... why do you want to take a flumazenil based on the premise that it will work because it increases dopamine??
Linkadge
Posted by phidippus on September 15, 2012, at 15:21:04
In reply to Re: is a GABA antagonist what i need?, posted by linkadge on September 15, 2012, at 6:01:48
Hilarious.
You should leave the poor boy alone.
Eric
Posted by phidippus on September 15, 2012, at 15:23:05
In reply to Re: is a GABA antagonist what i need?, posted by linkadge on September 15, 2012, at 5:59:12
Thanks for the info. More coffee it is, then. Wait, I'm not the one that wants a GABA antagonist.
Eric
Posted by phidippus on September 15, 2012, at 15:24:27
In reply to Re: flumazenil is probably acutely neurotoxic, posted by linkadge on September 15, 2012, at 5:53:01
I love cocaine!
Eric
Posted by phidippus on September 15, 2012, at 16:16:01
In reply to Re: My diagnosis and what I take » AlexCanada, posted by SLS on September 14, 2012, at 23:26:32
>I intend to attempt to discontinue it.
I hope you don't become manic.
Eric
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Dr. Bob is Robert Hsiung, MD,
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