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Dr. Bob is Robert Hsiung, MD,
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Posted by Economist on March 26, 2010, at 17:52:16
In reply to Re: Severe anhedonia...I can't live like this anym » Economist, posted by conundrum on March 26, 2010, at 15:10:18
conundrum,
I'll take a look at it. I am scheduled to increase my EMSAM to 9 mg, at which point it becomes an MAO-A inhibitor. Do you know anything about that drug or the MAOIs and their impact on norepinephrine?
What kind of anhedonia do you have? Is it depressed anhedonia or no-emotion, flat anhedonia?
Posted by conundrum on March 26, 2010, at 21:32:25
In reply to Re: Severe anhedonia...I can't live like this anym » conundrum, posted by Economist on March 26, 2010, at 17:52:16
I know that MAOIs can cause a drop in norepinephrine and often lower blood pressure. I have heard many here augment parnate with nortriptyline for norepinephrine support.
I would say my anhedonia is my only really bad mood symptom. I don't get down or sad. I feel like the world is in black and white. To me a day at the beach in florida feels no different than shoveling a foot of snow in the winter. I can't really enjoy music anymore. I wouldn't say i'm totally flat. I can still laugh and display normal emotions, but I don't feel them fully and never feel real satisfaction.
Posted by Economist on March 26, 2010, at 22:49:49
In reply to Re: Severe anhedonia...I can't live like this anym » Economist, posted by conundrum on March 26, 2010, at 21:32:25
When you think about how you can't feel fun, does it make you really frustrated and tortured? Or do you simply not care about the fact that you can't feel anything?
When did the anhedonia start?
I am starting up a blog about my experience with anhedonia, and eventually I'd like to compile a bunch of experiences from other people with anhedonia. Would you like to be a part if it?
Posted by conundrum on March 26, 2010, at 23:36:54
In reply to Re: Severe anhedonia...I can't live like this anym » conundrum, posted by Economist on March 26, 2010, at 22:49:49
I'd say it bothers me. I can't just except it. Its not on my mind all the time, but somethings wrong. It started when I came off prozac and was moderately bad for 2 years. During those two years I took ginko biloba religiously everyday. When i stopped that herb the anhedonia got worse.
Its funny you mention a blog because I was thinking of starting a blog or website for Post SSRI syndrome. Mainly for people who have had bad experiences after stopping SSRIs, not while still on them. Thats a different can of worms but related.
But yest I would participate. I didn't have this while on prozac the first time. I also didn't have it before i started the drug, I just had anxiety and sadness then. IMO this is worse. I'd probably have gotten over the anxiety on my own. Now I can't even feel real anxiety or sadness. I'm hoping that an NRI can help with that.
Posted by conundrum on March 26, 2010, at 23:38:15
In reply to Re: Severe anhedonia...I can't live like this anym » conundrum, posted by Economist on March 26, 2010, at 22:49:49
I should mention I've had this for about 7 years after stopping prozac. For 6 years I hadn't taken any meds. The brain does not seem to go back to baseline, like Bleauberry recently said.
Posted by bleauberry on March 27, 2010, at 19:21:18
In reply to Re: Severe anhedonia...I can't live like this anym » bleauberry, posted by Economist on March 25, 2010, at 20:53:15
> bleauberry,
>
> Did you have anhedonia too? How long did it last and what caused it (depression or negative symptoms)?Yes, it was (is) my primary symptom. Better in the last year, but still a heavy crutch. I can identify things that may have caused it, but who knows:
Longterm SSRI usage.
Amalgam fillings and mercury toxicity.
Lyme.>
> I think I have been excessively targeting dopamine for the past three months to no avail. I have tried Wellbutrin, low-dose amisulpride, Adderall, and now low dose EMSAM/seligiline. The supplements I have tried are glycine, pregnenolone, panax ginseng, NAC, and now DLPA.Glycine is more in the family of GABA, so I can see why that didn't help. Wellbutrin, yuck. Adderall, mmm, with an ssri sometimes good not always, by itself usually not. The only reliable gingseng I am aware of is actually not a true ginseng...Siberian Ginseng (eleuthero)...but it takes several months to do its thing. NAC is primarily involved in the toxicity cleanup department. DLPA will go to both dopamine and NE, as well as preserving the length of time the endorphins circulate. But, it all depends on whether our bodies metabolize it properly and manufacture the stuff the way a textbook says it should. That's a huge assumption. A lot of things can go wrong in that process. Precursors only work when all the downstream factories are working like they are supposed to.
Amisulpride should have helped, but maybe the dose was too high. I know the doses are usually talked about as being 50mg-100mg. Me, I find anything over 25mg is not helpful, under is.
All that said, the one biggest success I had against anhedonia was Savella. Huge difference. So forget the theory stuff and the textbook stuff. NE is a big player, and since savella also hits serotonin a little, that also plays into the picture. Since it also blocks NE in a part of the brain where no dopamine reuptake receptors exist and dopamine is taken up by the NE receptors, savella increases dopamine also. I think the important point is...it isn't this neuro or that neuro, it's all of them in concert...at the right balance. Things are too complicated to analyze. We as humans know only a fraction of what there is to know.
>
> I can't see how norepinephrine would be factor in this anhedonia. I don't feel sluggish or lack energy. I just can't feel emotions and have no interest in any thing, any person, any activity, or any thoughts.Not feeling sluggish doesn't mean you don't have a NE problem. There is epinephrine, norepinephrine, and adrenaline, just for starters, all similar but different, different roles. You could have one or two working just fine for physical stuff and one or two working bad for psychological stuff. Add to that the interplay with the serotonin, dopamine, and opioid systems, and well, you just gotta throw the theory book out the window.
Posted by bleauberry on March 28, 2010, at 8:14:48
In reply to Severe anhedonia...I can't live like this anymore., posted by Economist on March 23, 2010, at 13:07:29
When it comes to anhedonia, I think it deserves mention that another component besides just meds is very important for potential recovery.
Let's assume someone has had a severe knife wound that damaged a nerve in the wrist. Now the hand is partially paralyzed with a lot of numbness and lack of feeling.
To heal that damaged nerve, no pill alone is going to do that. Certainly an anti inflammatory might help. Probably some other meds I'm not aware of. But it is not going to heal without physical therapy. That is, movement, exercise, routine, massage... To just let that injured hand sit in a sling indefinitely month after month, year after year, it aint gonna recover its feelings. That nerve however can recover in time if it is encouraged to do so.
I do not see the nerves in the brain as being much different. That hand may never recover completely, or it might, but it will certainly recover more thoroughly with encouragement and therapy than it will with merely a prescription.
That's why physical therapy plays such a large role in medicine. It's heals injured stuff and returns it to optimal function.I see the same thing with anhedonia. A part of the brain has gone numb. Don't know why, it just did. Maybe a pill can wake it up, maybe not. But for sure, exercising that part of the brain will encourage it to start working again.
That means going out and forcing oneself to do things that are almost universally fun to normal healthy people, regardless that you feel no emotion and no fun in it yourself. A roller coaster, a horse ride, a walk on the beach, some kind of game, movies of some kind, anything...force input into that part of the brain that is asleep.
It is forced behavior. It is exercise. It is actually not much different than going to the gym when you don't feel like it. The muscles still need work whether you feel like it or not. And they are not going to do anything except deteriorate if you don't.
Results I believe are slow, come in waves, and happen in tiny steps. But for sure, the brain can learn how to have pleasure again, and to feel again, but it has to be exposed to the kinds of environments surrounded by pleasures and emotions. It has to be challenged. It has to be exercised, no different than a muscle or a nerve. It has to be worked.
Just my thoughts on that.
Anhedonia is my primary symptom. Over 3 years I have gained back some of those emotions. The only pill that ever had any impact was Savella. Other than that, all my gains have come from forcing myself to do something that was supposedly fun even though it wasn't to me. Over time the brain learns and reconfigures itself. The brain has amazing recovery and adaptability powers, but it needs to be pushed in the desired direction to put the chain reactions into play.
Again, just my thoughts on the topic. Nobody ever said life was easy. Nobody ever said healing sickness was easy. They aren't. They take purposeful goal oriented forced work. Which is especially hard for us who are ill, but even more critical because of that. The harder it is for us to do something, the more we need to do it.
As for specific meds, I would focus on the noradrenergic and/or dopaminergic, especially the ones that do not have overwhelming sedating or anticholinergic side effects. Somewhere in there serotonin probably plays a role too, but will likely worsen things if it is manipulated more than the others.
Use it or lose it.
Posted by conundrum on March 28, 2010, at 10:05:28
In reply to Re: Severe anhedonia...I can't live like this anymore., posted by bleauberry on March 28, 2010, at 8:14:48
Didn't you say that adrafinil with prozac helped with anhedonia as well as savella?
Posted by bleauberry on March 29, 2010, at 19:17:24
In reply to Re: Severe anhedonia...I can't live like this anymore. » bleauberry, posted by conundrum on March 28, 2010, at 10:05:28
> Didn't you say that adrafinil with prozac helped with anhedonia as well as savella?
Yes definitely. Sorry I temporarily misplaced that one. ECT still gets me sometimes.
Posted by Laney on March 30, 2010, at 18:49:34
In reply to Re: Severe anhedonia...I can't live like this anymore., posted by bleauberry on March 28, 2010, at 8:14:48
Bleauberry,
That was very enlightening to read. It does make sense. Thanks for you input!
Laney
Posted by Economist on April 3, 2010, at 15:52:58
In reply to Re: Severe anhedonia...I can't live like this anym » Economist, posted by conundrum on March 24, 2010, at 21:36:46
Amphetamines work on norepinephrine too, right? Well whenever I take Adderall it does not cause a change in my motivation or interest in things. All it does is increase my heart rate.
Posted by conundrum on April 3, 2010, at 17:19:02
In reply to Re: Severe anhedonia...I can't live like this anym » conundrum, posted by Economist on April 3, 2010, at 15:52:58
Ritalin does the same thing to me and it also increases NE. I think I respond better to drugs that work over a 24 hr period rather than shorter acting stims. Maybe a 24 hr DRI would help too if one existed. Maybe brand wellbutrin xl? It's weak but does increase dopamine. I guess you don't want to try a tricyclic?
Posted by Economist on April 3, 2010, at 18:43:06
In reply to Re: Severe anhedonia...I can't live like this anym, posted by conundrum on April 3, 2010, at 17:19:02
Brand name Wellbutrin also had no effect on me. I wouldn't rule out taking a tricyclic.
Have you tried Nardil or Parnate?
Posted by conundrum on April 3, 2010, at 19:05:33
In reply to Re: Severe anhedonia...I can't live like this anym » conundrum, posted by Economist on April 3, 2010, at 18:43:06
Nope, I would consider parnate, I think nardil would be too serotonergic. I actually haven't tried too many drugs. Like I said low dose Prozac and the initial boost From pristiq were the best experiences for motivation and anhedonia I've had.
Posted by Economist on April 3, 2010, at 19:10:35
In reply to Re: Severe anhedonia...I can't live like this anym, posted by conundrum on April 3, 2010, at 19:05:33
But aren't Prozac and Pristiq also serotonergic ?
Posted by conundrum on April 4, 2010, at 11:06:19
In reply to Re: Severe anhedonia...I can't live like this anym » conundrum, posted by Economist on April 3, 2010, at 19:10:35
Well prozac is a 5 HT2A/C antagonist. So it antagonizes, meaning blocks, those receptors. Normally when those receptors are activated its normal ligand, serotonin, it decreases NE and DA release. By blocking them prozac increases NE and DA release. Thats why some ppl feel more motivated on prozac than other SSRIs and why its sometimes bad for people with anxiety. Prozac does however increase serotonin which actually works in opposite effect. At lower doses not enough of the serotonin (5 HT) transporters are blocked to significantly increase serotonin, but the drug is still able to block the 5 HT2A/C receptors enough to have an effect. So at lower doses more NE and DA are released.
Brainbeard made some good posts on this in the neurotransmitter section.
http://www.dr-bob.org/babble/neuro/20091104/msgs/931609.html
However prozac does increase serotonin at this dose. I can feel it, since most serotonergics give me a headache and diarrhea and prozac still does this even at 2.5 mgs per day. So something that can block those receptors without increasing serotonin would be good. APs and TCAs do this as well as Remeron.
Pristiq only felt good in the beginning when it didn't feel like an SSRI. After the first day I felt more "color" which is something that had been gone for a long time. After a couple weeks that faded and I started to get those serotonergic headaches.
I found a study from wWeth that shows that NE increase with pristiq after the first dose then serotonin begins to increase. So right now its not helping at all really, although the headaches aren't as bad as with a straight SSRI.
This is from a study showing how Pristiq(desvenlafaxine) increases NE right away compared to serotonin. They actually had to add another drug to get it to increase serotonin.
"Effect of DVS(Pristiq) on Hypothalamic Levels of Monoamines (5-HT, NE, and DA). Acute oral administration of DVS (30 mg/kg) did not significantly [F(2,19) = 0.74, P = 0.4898] alter concentrations of 5-HT in the hypothalamus (Fig. 4A). However, pretreatment with WAY-100635 (5-HT1A antagonist, 0.3 mg/kg s.c.), which did not alter 5-HT levels on its own, resulted in a significant 78% increase in extracellular 5-HT levels [F(1,9) = 36.09, P = 0.0001] in the rat hypothalamus.
In contrast to the observations with 5-HT levels, acute administration of DVS, when given alone, produced a significant [F(2,16) = 6.11, P = 0.0107] increase in NE concentrations (Fig. 4B)."
Here is a link. The part I copied is about 2/3s down the page.
http://jpet.aspetjournals.org/content/318/2/657.full
Its interesting that it kind of reflects how I felt. So I think there might be some value in understanding the science behind the drugs.
Just curious, I guess your pdoc believes you have anhedonia, since they are willing to prescribe so many dopaminergics. Is this right?
Posted by Economist on April 4, 2010, at 13:34:18
In reply to Re: Severe anhedonia...I can't live like this anym » Economist, posted by conundrum on April 4, 2010, at 11:06:19
My doc understands I have anhedonia, but at first I think he was going to prescribe me a regular ol' SNRI until I convinced him my problem might be dopamine. He said he wasn't sure more dopamine would help, since the Adderall did not raise my interest levels or desire to do things. But he prescribed me the EMSAM anyway and now I am on my third week. As predicted, EMSAM's actions on dopamine haven't done a thing.
After this EMSAM trial fails I'll try to convince him to prescribe me a tricyclic. Or perhaps another MAOI like Nardil or Parnate. Or maybe Prozac? I really don't know at this point.
Posted by conundrum on April 4, 2010, at 14:05:34
In reply to Re: Severe anhedonia...I can't live like this anym » conundrum, posted by Economist on April 4, 2010, at 13:34:18
Well its good you have someone who will treat it as a stand alone illness. I think anything different would atleast give you some direction. It could be easy to get discouraged if you keep trying things to increase dopamine and nothing works. Its also interesting since you are taking DLPA, Adderall, and EMSAM and nothing is helping. BTW is EMSAM dosed twice a day?
If you are interested in parnate I believe it gives much more of a kick than EMSAM. Tricyclics would be interesting. Even a low dose of prozac would be intersting. Higher doses like 20 mg might make you feel flatter, however some people do well, like Deneb who posted here that it restored her motivation. I just hate to tell anyone to take Prozac because coming off it messed me up so bad. If you do take it and it works, don't stop it and try to take the lowest effective dose. I don't want to freak you out. My mom took it for 9 years and came off it without suffering from anhedonia and cognitive problems. Everyone is different. I hope something works for you soon.
Posted by Economist on April 4, 2010, at 14:45:18
In reply to Re: Severe anhedonia...I can't live like this anym » Economist, posted by conundrum on April 4, 2010, at 14:05:34
EMSAM is a patch I put on and replace every day at the same time. Yeah, I don't know what it could mean when I take Adderall and it doesn't give me any psychotropic effect. I know that there IS supposed to be a psychotropic effect, and I know what it is supposed to feel like. Before the anhedonia set in, a 20 mg dose of Adderall used to make me extremely focused on whatever I was doing and it was also very interesting. There was a desire to want to continue and keep working on whatever task you were on. Now, if it weren't for the increased heart rate I wouldn't know I was on Adderall. From what I understand, Adderall also increases norepinephrine. So if it isn't dopamine, and it isn't norepinephrine, and it isn't serotonin, then what else left is there? Has there been some structural damage done to my brain? MRIs show everything intact.
Posted by conundrum on April 4, 2010, at 20:43:23
In reply to Re: Severe anhedonia...I can't live like this anym » conundrum, posted by Economist on April 4, 2010, at 14:45:18
I dunno, like I said before I was prescribed ritalin IR which boosts dopamine and norepinephrine and it did nothing for my motivation, anhedonia, or concentration, but it did increase my heart rate. When I tried pristiq it started to add what I describe as color back into my life.
I noticed this after the first dose. Not immediately, it was the next morning after not really sleeping the entire night. Perhaps the NRI needs to work over a 24 hour period instead of being short acting? Maybe its the added boost to serotonin?
Perhaps Milnacipran which is a more balanced SNRI would be good.
I wonder if your doctor could prescribe a small number of vicodin pills or something to see if those would atleast help.
Posted by Economist on April 4, 2010, at 22:03:31
In reply to Re: Severe anhedonia...I can't live like this anym » Economist, posted by conundrum on April 4, 2010, at 20:43:23
Before Pristiq, had you tried any other SNRI?
Posted by Economist on April 4, 2010, at 22:05:25
In reply to Re: Severe anhedonia...I can't live like this anym » Economist, posted by conundrum on April 4, 2010, at 20:43:23
For a moment I had some hope that if I tried Pristiq, maybe it would give me back some color, too. But then I remembered I was on another SNRI, Cymbalta, last year for two months, and it didn't do squat.
Posted by conundrum on April 4, 2010, at 23:03:57
In reply to Re: Severe anhedonia...I can't live like this anym » conundrum, posted by Economist on April 4, 2010, at 22:03:31
Nope
Posted by conundrum on April 4, 2010, at 23:05:04
In reply to Re: Severe anhedonia...I can't live like this anym » conundrum, posted by Economist on April 4, 2010, at 22:05:25
Are your sure that your problem isn't psychological? Did anything happen to you before the anhedonia began?
Posted by Economist on April 4, 2010, at 23:46:34
In reply to Re: Severe anhedonia...I can't live like this anym » Economist, posted by conundrum on April 4, 2010, at 23:05:04
I can't think of any reason that would cause me to not be able to enjoy or be interested in things. I did not experience any trauma like a bad break up, being fired from a job, failing grades, an argument with someone in my family, or a death of someone close.
I'm getting good grades in school, get weekly invitations to go out and party, and have a lot of friends and family who look up to me and care about me. Before anhedonia, these were things that made me feel good and happy. But now, pleasant feelings simply do not accompany these events. I simply do not experience anything. Only blankness and disinterest. I still go out and meet my friends, watch movies and engage in various recreational activities with them, but it always feels really boring and unpleasant. It feels extremely forced.
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