![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 55. This is the beginning of the thread.
Posted by Trevpr on September 23, 2012, at 17:47:02
Hello everyone,
I am currently over 10 months into a major depressive episode triggered by chronic stress I experienced at UC Berkeley, which, needless to say, forced me to withdrawal from the university. The episode began with extreme stress due to a long term relationship breakup, academic demands, and difficulty adjusting to the new dynamics of college life and that campus. I began to have panic attacks, anhedonia, extreme anxiety, insomnia, and "dark moods," forcing me to withdrawal from my second year last January. The symtoms of insomnia, anxiety, and panic attacks quickly vanished upon returning home, and after my first hospital visit, however, I have been stuck in an anhedonic, apathetic, flat emotioned, zombielike state ever since. This has been very distressing, as I feel no empathy, cannot cry, cannot enjoy anything, and feel invariably unmoved by anything, which makes for a poor quality of living. There has been no variation in this symptom, and I do not have "good days" and "bad days," just "flat days."Due to my engineering mindset I researched everything in excruciating detail, and what I have come up with is that anhedonic symptoms are theorized to be a result of the breakdown of dopaminergic pathways, particularly the mesolimbic reward pathway, in the brain. Somehow the chronic stress caused a "meltdown" and disrupted my dopaminergic systems. The two neurotransmitters, dopamine and norepinepherine, are intimately involved in this (catecholamines). The fact that the book that we are using directly lists in a chart of neurotransmitters that dopamine, out of all the transmitters listed, has a role in "emotion," without mentioning that about any of the others only reinforces my point.
There seems to be two "camps" that psychiatrists fall under, and I have dealt with both. In one camp are the psychiatrists who tend to disregard anhedonia as "just a symptom of the underlying depression/other illness" and not mainly a dopaminergic phenomenon saying "treat the underlying depression/other illness, and the symptoms go away with it like a cascade." These psychiatrists believe that SSRIs are most effective for any type of depression, regardless of symptoms, (usually calling me "obsessive" for researching or disregard science backing it up as "just theories, and that nobody knows whats actually going on in the brain" etc.) and often deny that serotonergics make anhedonia worse (I've been with two of this type). Psychiatrists falling under the second camp listen to symptoms and recognize anhedonia as mainly dopaminergic or to do with norepinepherine, and recommend medications accordingly (I have been with several of this type).
Serotonergic drugs seem to be effective at lowering anxiety, helping with insomnia through metabolization to melatonin, and helps with "dark moods," but do not seem to be very effective at dealing with anhedonic symptoms such as blunted emotions, and in fact, seem to perpetuate them. It's been long known, for example, that serotonergics lower the hedonic response of libido. Now, there are two main mechanisms by which elevated serotonin levels blunt hedonic response. The first is by "tricking" dopaminergic neurons into sending serotonergic signals, and thus this competition or "outcrowding" effect attenuates dopaminergic transmission. The second mechanism is the activation of 5ht2a/c receptor sites which inhibit dopamine (some serotonergics appear to do the opposite, but this is not due to their serotonergic properties. Prozac, for example, is often cited as being "more activating" due to 5ht2a/c antagonism). Serotonin also raises prolactin levels which have been known to have an inhibitory effect on drive. Scientific studies have proven that prolonged use of serotonergics can lower levels of dopamine in the prefrontal cortex. It doesn't seem that serotonergics are the best choice for all types of depression. I have located 3 different studies published in reliable scientific journals to back up my point:
http://bjp.rcpsych.org/content/195/3/211.abstract
http://www.biologicalpsychiatryjournal.com/article/S0006-3223(09)01322-5/abstract
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989833/
Here is another interesting article. It has been found that in lab rats the SSRI Prozac blunted mesolimbic reward response:
http://www.biopsychiatry.com/fluoxrew.htmFor instance, SSRIs and antipsychotics reduce testosterone and increase prolactin activity, which in turn theoretically decreases the amount of free dopamine available for distribution to the pleasure centers. Furthermore, the reuptake inhibition of serotonin decreases the availability of dopamine through neural pathways, due to its use of the same substrate and also through inhibitory action after activation of receptors such as the 5HT-1A and 5HT2A/C receptors. SSRIs like Prozac have been proven to decrease serotonin transporters (leading to more free serotonin) and increase dopamine transporters (leading to less free dopamine). This may explain reports of persistent apathy after discontinuation of serotonergic medications. http://www.sciencedirect.com/science/article/pii/S0924977X05000349
Now, there is a sort of catch-22 situation with anhedonia because serotonergics blunt hedonic response, but the administration of dopaminergic agents also can worsen the problem. Downregulation, desensitization, or tolerance may develop. In addition, many dopaminergic/norepinepheric agents have many side effects such as elevated blood pressure or heart rate (such as Ritalin). So this is where I am stuck.
I initially tried taking a "natural" route at treating my depression. I tried the monoamine precursors l-tyrosine, 5HTP, l-theanine, and DLPA without any effect on my mood. I have tried vitamin D, fish oil, vitamin b complex, SAM-E, rhodiola rosea, magnesium, zinc, and calcium supplements. The only effect I noticed was extreme agitation with l-theanine.
I was then put on the SNRI Effexor (velafaxine) which made me feel more "out of it."
I was then placed on the NRI Wellbutrin (bupropion) 450mg and AP Abilify (aripiprazole), on which I had remission of all symptoms but the anhedonia. I stayed on this for 8 weeks with no other effect. I was first administered benzodiazepines for the insomnia, but asked to be switched to trazodone 100mg. I no longer needed either in a matter of weeks. The Wellbutrin and Abilify, no matter how long I was on them, did not seem to touch the anhedonia.
I was then administered the stimulants Ritalin (methylphenidate) and Adderall (various amphetamine salts). Ritalin was the only drug so far that I noticed any marginal improvement, but it was short lasted, I crashed after it wore off, and I formed a tolerance quickly. Adderall only raised my heart rate.
I was then given the tricyclic NRI Desipramine 200mg for several weeks with no noticeable effect.
I was then given the dopamine agonist, Mirapex (pramipexole) 0.375-0.650mg daily. The rationale for this was it would hit the DRD3 and DRD2 receptors which are expressed heavily in the limbic system. This medication only made me tired, I am presuming from the alpha-2 agonism it also posesses, like Remeron.
I am currently on the tricyclic NRI Vivactil (Protriptyline) along with Abilify and am titrating up my dose over the course of 2 weeks. So far I have not noticed any effect on my emotions. I am currently taking 15mg daily and titrating up an extra 5mg every 3 days.So far, no antidepressant has touched my anhedonic symptoms, though Ritalin was the closest to helping. I'm starting to wonder why, and am beginning to wonder if the "antidepressant effect" is too subtle. I've narrowed down possible treatments:
STIMLANTS
Ritalin (Methylphenidate), Dextroamphetamine, Adderall (mixed amphetamine salts), Focalin (Dextromethylphenidate)DOPAMINE AGONISTS
Mirapex (Pramipexole), Requip (Ropinirole), Dostinex (Cabergoline), (Apomorphine), (Bromocriptine), (Rotigotine), (Amantadine)ANTIPSYCHOTICS
Abilify (Aripiprazole), Amisulpride, Sulpride, ZyprexaSEROTONIN RECEPTOR ANTAGONISTS
Buspar (Busiprone), Low dose Prozac (Fluoexitine), Remeron, Periactin (Cyproheptadine)DOPAMINE REUPTAKE INHIBITORS
(Amineptine), To a small extent Wellbutrin (Bupropion)SELECTIVE SEROTONIN REUPTAKE ENCHANCERS
(Tianeptine)NOREPINIPHERINE REUPTAKE INHIBITORS
(Desipramine), (Atomoxetine), Vivactil (Nortryptaline), Wellbutrin (Bupropion)MAOIs
Parnate, Nardil, Selegiline, MarplanMOOD STABILIZERS
Lithium, LamactilSUPPLEMENTS
L-Tyrosine, L-Theanine, L-Glutamine, Saint Johns Wort, Phenylethylamine, Levodopa, SAM-E, Saffron, Fish Oil, Magnesium, Zinc, Calcium, Vitamin B Complex, Multivitamins, Vitamin DSEROTONERGICS WHICH HAVE ACTIVATING FEATURES
Pristiq, Effexor, Various TCAsOTHER
Nicotine, Testosterone, Exercise, ETC, rTMSPreclinical neurobiological studies of anhedonia have primarily targeted neural substrates involved in motivation and reinforcement(want-ing). Across a variety of studies, liking and wanting have been linked to a variety of brain regions, neural circuits and neurotransmitters. These include primarily the neurotransmitter dopamine, norepinepherine, and opioid neuropeptides, sub-cortical structures such as the basal ganglia and striatum (particularly the nucleus accumbens(NAcc),ventral pallidum (VP),ventral tegmental area(VTA),substantia nigra(SN), amygdala and hippocampus), as well as cortical regions such as the ventro medial prefrontal cortex(vmPFC), encompassing aspects of orbital frontal cortex(OFC), anterior cingulated cortex(ACC)and medial prefrontal cortex(mPFC). (http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=8&cad=rja&sqi=2&ved=0CFIQFjAH&url=http%3A%2F%2Fzaldlab.psy.vanderbilt.edu%2Fresources%2FPublications%2Fmtt10nbr.pdf&ei=LppeUM67DOOPiALS0YHAAw&usg=AFQjCNFYaIO2t9JVX_sHcRjpzxUsWbpnVg&sig2=vBu2VN_DFfJTI9lVWS34Ig)
QUESTIONS
1.) Has anyone here had remission from anhedonic symptoms? If so, how? What was it like? How long did it take before remission?
2.) Anyone have any experience with the beforementioned treatments? Any of them help anhedonic symptoms?
3.) Has anyone gotten their sex drive back after having it absent for months? Did it come back fully?
4.) Anyone have any advice on treating anhedonia?Let's have a discussion about this!
Posted by Trevpr on September 23, 2012, at 17:52:42
In reply to ANHEDONIA - Questions and Answers, posted by Trevpr on September 23, 2012, at 17:47:02
Also anyone find any good MAOI cocktails for anhedonia? My Psychiatrist is reluctant to prescribe Parnate because she's reading that it can't be combined with anything
Posted by jono_in_adelaide on September 23, 2012, at 18:25:59
In reply to ANHEDONIA - Questions and Answers, posted by Trevpr on September 23, 2012, at 17:47:02
Given all you've tried, I'd suggest trying either Parnate or Emasem (L-deprenyl, selegine)
I found Bupropion + an SSRI very helpful, but obviously this hasnt been the case for you
Posted by jono_in_adelaide on September 23, 2012, at 18:33:07
In reply to Re: ANHEDONIA - Questions and Answers, posted by Trevpr on September 23, 2012, at 17:52:42
Parnate or selegine can be combined with nortriptyline or desipramine, or bupropion, without any great difficulty - just dont combine them with any drug that has an effect on seretonin reuptake
Posted by Trevpr on September 23, 2012, at 18:39:53
In reply to Re: ANHEDONIA - Questions and Answers, posted by jono_in_adelaide on September 23, 2012, at 18:33:07
Are Parnate/selegiline really that significantly different in efficacy than other ADs? I know they WORK differently, but considering that I havent felt ANY difference on these drugs, why should parnate or selegiline be much different? Really what I'm missing are the "highs and lows" in life, and I'm beginning to think unless a drug makes me high, which isnt sustainable, ill be stuck in this flat state. Did you have success with your anhedonia after the ssri bupropion combo or just depression in general? Literally at times I feel like I'm so flat that I'm a zombie.
Posted by jono_in_adelaide on September 23, 2012, at 19:03:24
In reply to Re: ANHEDONIA - Questions and Answers, posted by Trevpr on September 23, 2012, at 18:39:53
I had releif from the general melancholic depression in general and the anhedonia
I dont know that Emasem and Parnate are that different, but given your situation, I think they are both worth trying, you have nothing to lose and everything to gain.
Posted by phillipa on September 23, 2012, at 19:07:23
In reply to Re: ANHEDONIA - Questions and Answers, posted by Trevpr on September 23, 2012, at 18:39:53
It almost sounds like you are looking for the highs like in mania and the lows of depression. You are so intelligent I've most likely misread your initial post. If so please forgive me. Phillipa
Posted by Trevpr on September 23, 2012, at 19:13:43
In reply to Re: ANHEDONIA - Questions and Answers » Trevpr, posted by phillipa on September 23, 2012, at 19:07:23
I've never been manic in my life, but by "highs" I mean getting excited, having some sort of passion, there being color in life, feeling satisfied, having a normal libido and orgasm, etc. By "lows" I mean feeling sad or empathy when appropriate, not being so apathetic about life, etc. Right now, I feel like if a loved one died I wouldnt be able to grieve properly because emotions are "numbed."
Posted by jono_in_adelaide on September 23, 2012, at 20:00:19
In reply to ANHEDONIA - Questions and Answers, posted by Trevpr on September 23, 2012, at 17:47:02
Given your situation, I would try (under your doctors supervision of course)
* Welbutrin + an SSRI, Welbutrin + Nortriptyline
*Parnate alone, Parnate with Nortriptyline, Parnate with Welbutrin
*Emasem alone, Emasem with Nortriptyline, Emasem with Welbutrin
* Some combination of the above + either an amphetamine or methylphenidate
Also, the pathways in the brain arnt totaly black and white, there are a lot of shades of grey, changes in one neurotransmitter can effect levels of the others
The main thing is, dont give up
Posted by Trevpr on September 23, 2012, at 20:22:27
In reply to Re: ANHEDONIA - Questions and Answers, posted by jono_in_adelaide on September 23, 2012, at 20:00:19
Do you guys know of any articles or literature pointing to it being okay to mix Parnate with Wellbutrin, protriptyline, or nortriptyline to show to my psychiatrist?
Intuitively it makes sense to me, since these drugs are not serotonergic and won't cause serotonin syndrome, but they are apparently contraindicated so my doc will probably not let me unless there is something to back it up. A stimulant+maoi might be good I'm thinking; so far the norepinepherine drugs (Wellbutrin, protriptyline, desipramine) haven't done a single thing, and basically to me feel like placebos with minor side effects. I've really wanted to try Parnate or selegiline.
Anyone build up a tolerance rapidly to stimulants? I noticed after the first week or two all they did was PHYSICALLY give me energy without any impact on my mood, anhedonia, or emotions. Basically after a week they just elevated my heart rate. At first there were minor improvements in mood, motivation, and emotional response, which wasn't much, but believe me, any improvement is a breath of fresh air. Elevating the dose is not an option. I stupidly raised it on my own without any change, but then my heart rate got too high and I had to go to the ER.
SSRIs sound like a bad idea, for reasons I mentioned in my first post, unless they possess extra qualities like 5HT1a/2a/2c antagonism or something, such as low dose prozac, but even that seems to be pretty weak.
I just don't get why everyone else seems to notice SOMETHING from taking these antidepressants, while I don't? I am beginning to feel like they work by the placebo effect and I'm unfortunately the only one smart enough to not be affected by it because I'm so analytical or something, lol. I really hope that isn't the case.
And what about libido? I'm in my prime here and still single. I'd rather not miss these years and/or end up alone. I don't just mean sex, I mean romantic attraction or attraction of any kind. I just feel...."blah" towards it all. Does it come back? It's been gone for almost 11 months now with no signs of changing... Man this sucks big time.
Posted by jono_in_adelaide on September 23, 2012, at 20:38:20
In reply to Re: ANHEDONIA - Questions and Answers, posted by Trevpr on September 23, 2012, at 20:22:27
There is a fair bit of infomation out there about combining a TCA with an MAOI, do a pubmed search, and use google as well.
Nortriptyline + nardil/Parnate, while not exactly common, isnt unheard of, and there is evedence to support it.
Take a look at Dr Ken Gillmans site, Psychotropical.com.au, lots of material there..... he is experienced in using MAOI's alone and in combination, and could give you a lot of help (he does online consults via Skype is you ask him)
Posted by SLS on September 24, 2012, at 0:39:33
In reply to ANHEDONIA - Questions and Answers, posted by Trevpr on September 23, 2012, at 17:47:02
> Hello everyone,
Hi.
You are one smart and well-read dude/dudette.
Your treatment alternatives are extremely well chosen, in my opinion. It makes for a good review of what many of us on Psycho-Babble have already proposed as treatments.
I hope you find this forum interesting and helpful enough to stick around for a while. I'm sure your knowledge and perspectives would help a great many people.
- Scott> possible treatments:
>
> STIMLANTS
> Ritalin (Methylphenidate), Dextroamphetamine, Adderall (mixed amphetamine salts), Focalin (Dextromethylphenidate)
>
> DOPAMINE AGONISTS
> Mirapex (Pramipexole), Requip (Ropinirole), Dostinex (Cabergoline), (Apomorphine), (Bromocriptine), (Rotigotine), (Amantadine)
>
> ANTIPSYCHOTICS
> Abilify (Aripiprazole), Amisulpride, Sulpride, Zyprexa
>
> SEROTONIN RECEPTOR ANTAGONISTS
> Buspar (Busiprone), Low dose Prozac (Fluoexitine), Remeron, Periactin (Cyproheptadine)
>
> DOPAMINE REUPTAKE INHIBITORS
> (Amineptine), To a small extent Wellbutrin (Bupropion)
>
> SELECTIVE SEROTONIN REUPTAKE ENCHANCERS
> (Tianeptine)
>
> NOREPINIPHERINE REUPTAKE INHIBITORS
> (Desipramine), (Atomoxetine), Vivactil (Nortryptaline), Wellbutrin (Bupropion)
>
> MAOIs
> Parnate, Nardil, Selegiline, Marplan
>
> MOOD STABILIZERS
> Lithium, Lamactil
>
> SUPPLEMENTS
> L-Tyrosine, L-Theanine, L-Glutamine, Saint Johns Wort, Phenylethylamine, Levodopa, SAM-E, Saffron, Fish Oil, Magnesium, Zinc, Calcium, Vitamin B Complex, Multivitamins, Vitamin D
>
> SEROTONERGICS WHICH HAVE ACTIVATING FEATURES
> Pristiq, Effexor, Various TCAs
>
> OTHER
> Nicotine, Testosterone, Exercise, ETC, rTMS
>
> Preclinical neurobiological studies of anhedonia have primarily targeted neural substrates involved in motivation and reinforcement(want-ing). Across a variety of studies, liking and wanting have been linked to a variety of brain regions, neural circuits and neurotransmitters. These include primarily the neurotransmitter dopamine, norepinepherine, and opioid neuropeptides, sub-cortical structures such as the basal ganglia and striatum (particularly the nucleus accumbens(NAcc),ventral pallidum (VP),ventral tegmental area(VTA),substantia nigra(SN), amygdala and hippocampus), as well as cortical regions such as the ventro medial prefrontal cortex(vmPFC), encompassing aspects of orbital frontal cortex(OFC), anterior cingulated cortex(ACC)and medial prefrontal cortex(mPFC). (http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=8&cad=rja&sqi=2&ved=0CFIQFjAH&url=http%3A%2F%2Fzaldlab.psy.vanderbilt.edu%2Fresources%2FPublications%2Fmtt10nbr.pdf&ei=LppeUM67DOOPiALS0YHAAw&usg=AFQjCNFYaIO2t9JVX_sHcRjpzxUsWbpnVg&sig2=vBu2VN_DFfJTI9lVWS34Ig)
>
> QUESTIONS
> 1.) Has anyone here had remission from anhedonic symptoms? If so, how? What was it like? How long did it take before remission?
> 2.) Anyone have any experience with the beforementioned treatments? Any of them help anhedonic symptoms?
> 3.) Has anyone gotten their sex drive back after having it absent for months? Did it come back fully?
> 4.) Anyone have any advice on treating anhedonia?
>
> Let's have a discussion about this!
>
Posted by Trevpr on September 24, 2012, at 0:42:56
In reply to Re: ANHEDONIA - Questions and Answers » Trevpr, posted by SLS on September 24, 2012, at 0:39:33
Also added to that list should be adrafinil, modafinil, nortiptyline, and mazindol.
Amyone have good hedonic responses to these or ones previously listed? Including libido?
Posted by jono_in_adelaide on September 24, 2012, at 1:42:46
In reply to Re: ANHEDONIA - Questions and Answers, posted by Trevpr on September 24, 2012, at 0:42:56
Ijust checked Dr Ken Gillmans site, psychotropical.com, and he specificaly suggests bupropion + tranylcypromine as a treatment for severe, resistant melancholic depression...... it might be worth a shot in your case.
Posted by alchemy on September 24, 2012, at 11:30:09
In reply to Re: ANHEDONIA - Questions and Answers » Trevpr, posted by SLS on September 24, 2012, at 0:39:33
Your post comes right when i am struggling with ritalin. I have taken it off and on for a long time, mostly for work. Sometimes it would help. But it is also the only thing that has touched my anhedonia and at times my mood. Unfortunately I dont offer any good news from my situation. I have tried quite a few meds over 30ish years.
Because i have been so treatment resistant and stimulants are the only thing that have touched mood and/or motivation, my dr recently actually suggested trying to increase my ritalin, take it consistently, and throughout the day as it only seems to last about 3-4 hrs with the long-acting for me. I crashed a couple of times pretty hard over the weekend and it is losing its effectiveness. Today i have been trying to hold back tears as i really wonder if what i am afraid of will really shortly happen.
Anti-psychotics make me more depressed and agitated. I have tried amantadine and am currently on wellbutrin. Im not sure if the wellbutrin is actually helping though.
Posted by Trevpr on September 24, 2012, at 12:22:55
In reply to Re: ANHEDONIA - Questions and Answers, posted by alchemy on September 24, 2012, at 11:30:09
Anyone find anything other than Ritalin useful? While it was useful, I didnt find that it helped all the way. It made me enjoy things a bit more and increased libido slightly while making me a bit more motivated (and chatty) but didnt really make me feel empathetic or caring or "emotional." These are all traits that have seemed to dissapear with the apathy. Before, I used to find that crying, for example, was quite refreshing, as well as laughing, orgasming (tmi I know), etc. I just dont get that "refreshing" satisfied feeling anymore. Everything feels "blah."
I hope theres something besides ritalin that works! I dont think that there would be much use in augmenting parnate with wellbutrin, as I felt no different on wellbutrin alone, and with any other norepinepherine reuptake inhibitor (desipramine and now protryptaline for example).
Maybe parnate alone would be useful, but not if its as wussy (sorry I just cant think of any other word to describe how weak/useless these other drugs have been to me) or subtle as these other drugs I've tried.
That's why I've asked if parnate is more "noticeable" or "strong" than wellbutrin, TCAs, abilify, Mirapex, effexor, etc. If it's not, I'm SOL, you see. I've never even felt discontinuation symptoms.
Does parnate allow you to experience life's "highs?" Essentially that is what I am missing. There seems to be a ceiling on how good I feel, and it's rather low. I've found most antidepressants clip life's lows, but also highs, so they arent much use to me here.
And yes, libido is important too.
Posted by AlexCanada on September 24, 2012, at 13:38:06
In reply to ANHEDONIA - Questions and Answers, posted by Trevpr on September 23, 2012, at 17:47:02
I been also dealing with severe Anhedonia. Zoloft currently is blunting the hell out of me and I may be dropping it all together in a few weeks.
I been dealing w/ strong treatment resistant Melancholic Depression for a decade. Anhedonia has been one symptom which has been especially difficult to deal with. My best experiences would have been with Ritalin/Dexedrine (astonishing improvement, could feel a bit like my old normal self but tolerance onset of course), Vivalan/Vivarint (available only in France now), Stablon (it's very pro-sexual too), Parnate (quick onset and amphetamine-like initial boost, anti-dep effect would be better than most meds I've tried, some old hobbies would return), Paxil (some old hobbies would return), Risperidal (interest in things would suddenly emerge).
L-Tyrosine may be worth a try as well. I have had such horrible days on my current trial of Zoloft but L-Tyrosine has been making it easier and I feel with 500-1000mg I am a bit more able to enjoy things at least on some marginal level.
I been on few dozen meds and a dozen+ supplements/herbals. Grasping at straws here too.
> Hello everyone,
> I am currently over 10 months into a major depressive episode triggered by chronic stress I experienced at UC Berkeley, which, needless to say, forced me to withdrawal from the university. The episode began with extreme stress due to a long term relationship breakup, academic demands, and difficulty adjusting to the new dynamics of college life and that campus. I began to have panic attacks, anhedonia, extreme anxiety, insomnia, and "dark moods," forcing me to withdrawal from my second year last January. The symtoms of insomnia, anxiety, and panic attacks quickly vanished upon returning home, and after my first hospital visit, however, I have been stuck in an anhedonic, apathetic, flat emotioned, zombielike state ever since. This has been very distressing, as I feel no empathy, cannot cry, cannot enjoy anything, and feel invariably unmoved by anything, which makes for a poor quality of living. There has been no variation in this symptom, and I do not have "good days" and "bad days," just "flat days."
>
> Due to my engineering mindset I researched everything in excruciating detail, and what I have come up with is that anhedonic symptoms are theorized to be a result of the breakdown of dopaminergic pathways, particularly the mesolimbic reward pathway, in the brain. Somehow the chronic stress caused a "meltdown" and disrupted my dopaminergic systems. The two neurotransmitters, dopamine and norepinepherine, are intimately involved in this (catecholamines). The fact that the book that we are using directly lists in a chart of neurotransmitters that dopamine, out of all the transmitters listed, has a role in "emotion," without mentioning that about any of the others only reinforces my point.
>
> There seems to be two "camps" that psychiatrists fall under, and I have dealt with both. In one camp are the psychiatrists who tend to disregard anhedonia as "just a symptom of the underlying depression/other illness" and not mainly a dopaminergic phenomenon saying "treat the underlying depression/other illness, and the symptoms go away with it like a cascade." These psychiatrists believe that SSRIs are most effective for any type of depression, regardless of symptoms, (usually calling me "obsessive" for researching or disregard science backing it up as "just theories, and that nobody knows whats actually going on in the brain" etc.) and often deny that serotonergics make anhedonia worse (I've been with two of this type). Psychiatrists falling under the second camp listen to symptoms and recognize anhedonia as mainly dopaminergic or to do with norepinepherine, and recommend medications accordingly (I have been with several of this type).
>
> Serotonergic drugs seem to be effective at lowering anxiety, helping with insomnia through metabolization to melatonin, and helps with "dark moods," but do not seem to be very effective at dealing with anhedonic symptoms such as blunted emotions, and in fact, seem to perpetuate them. It's been long known, for example, that serotonergics lower the hedonic response of libido. Now, there are two main mechanisms by which elevated serotonin levels blunt hedonic response. The first is by "tricking" dopaminergic neurons into sending serotonergic signals, and thus this competition or "outcrowding" effect attenuates dopaminergic transmission. The second mechanism is the activation of 5ht2a/c receptor sites which inhibit dopamine (some serotonergics appear to do the opposite, but this is not due to their serotonergic properties. Prozac, for example, is often cited as being "more activating" due to 5ht2a/c antagonism). Serotonin also raises prolactin levels which have been known to have an inhibitory effect on drive. Scientific studies have proven that prolonged use of serotonergics can lower levels of dopamine in the prefrontal cortex. It doesn't seem that serotonergics are the best choice for all types of depression. I have located 3 different studies published in reliable scientific journals to back up my point:
>
> http://bjp.rcpsych.org/content/195/3/211.abstract
>
> http://www.biologicalpsychiatryjournal.com/article/S0006-3223(09)01322-5/abstract
>
> http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989833/
>
> Here is another interesting article. It has been found that in lab rats the SSRI Prozac blunted mesolimbic reward response:
> http://www.biopsychiatry.com/fluoxrew.htm
>
> For instance, SSRIs and antipsychotics reduce testosterone and increase prolactin activity, which in turn theoretically decreases the amount of free dopamine available for distribution to the pleasure centers. Furthermore, the reuptake inhibition of serotonin decreases the availability of dopamine through neural pathways, due to its use of the same substrate and also through inhibitory action after activation of receptors such as the 5HT-1A and 5HT2A/C receptors. SSRIs like Prozac have been proven to decrease serotonin transporters (leading to more free serotonin) and increase dopamine transporters (leading to less free dopamine). This may explain reports of persistent apathy after discontinuation of serotonergic medications. http://www.sciencedirect.com/science/article/pii/S0924977X05000349
>
> Now, there is a sort of catch-22 situation with anhedonia because serotonergics blunt hedonic response, but the administration of dopaminergic agents also can worsen the problem. Downregulation, desensitization, or tolerance may develop. In addition, many dopaminergic/norepinepheric agents have many side effects such as elevated blood pressure or heart rate (such as Ritalin). So this is where I am stuck.
>
> I initially tried taking a "natural" route at treating my depression. I tried the monoamine precursors l-tyrosine, 5HTP, l-theanine, and DLPA without any effect on my mood. I have tried vitamin D, fish oil, vitamin b complex, SAM-E, rhodiola rosea, magnesium, zinc, and calcium supplements. The only effect I noticed was extreme agitation with l-theanine.
> I was then put on the SNRI Effexor (velafaxine) which made me feel more "out of it."
> I was then placed on the NRI Wellbutrin (bupropion) 450mg and AP Abilify (aripiprazole), on which I had remission of all symptoms but the anhedonia. I stayed on this for 8 weeks with no other effect. I was first administered benzodiazepines for the insomnia, but asked to be switched to trazodone 100mg. I no longer needed either in a matter of weeks. The Wellbutrin and Abilify, no matter how long I was on them, did not seem to touch the anhedonia.
> I was then administered the stimulants Ritalin (methylphenidate) and Adderall (various amphetamine salts). Ritalin was the only drug so far that I noticed any marginal improvement, but it was short lasted, I crashed after it wore off, and I formed a tolerance quickly. Adderall only raised my heart rate.
> I was then given the tricyclic NRI Desipramine 200mg for several weeks with no noticeable effect.
> I was then given the dopamine agonist, Mirapex (pramipexole) 0.375-0.650mg daily. The rationale for this was it would hit the DRD3 and DRD2 receptors which are expressed heavily in the limbic system. This medication only made me tired, I am presuming from the alpha-2 agonism it also posesses, like Remeron.
> I am currently on the tricyclic NRI Vivactil (Protriptyline) along with Abilify and am titrating up my dose over the course of 2 weeks. So far I have not noticed any effect on my emotions. I am currently taking 15mg daily and titrating up an extra 5mg every 3 days.
>
> So far, no antidepressant has touched my anhedonic symptoms, though Ritalin was the closest to helping. I'm starting to wonder why, and am beginning to wonder if the "antidepressant effect" is too subtle. I've narrowed down possible treatments:
>
> STIMLANTS
> Ritalin (Methylphenidate), Dextroamphetamine, Adderall (mixed amphetamine salts), Focalin (Dextromethylphenidate)
>
> DOPAMINE AGONISTS
> Mirapex (Pramipexole), Requip (Ropinirole), Dostinex (Cabergoline), (Apomorphine), (Bromocriptine), (Rotigotine), (Amantadine)
>
> ANTIPSYCHOTICS
> Abilify (Aripiprazole), Amisulpride, Sulpride, Zyprexa
>
> SEROTONIN RECEPTOR ANTAGONISTS
> Buspar (Busiprone), Low dose Prozac (Fluoexitine), Remeron, Periactin (Cyproheptadine)
>
> DOPAMINE REUPTAKE INHIBITORS
> (Amineptine), To a small extent Wellbutrin (Bupropion)
>
> SELECTIVE SEROTONIN REUPTAKE ENCHANCERS
> (Tianeptine)
>
> NOREPINIPHERINE REUPTAKE INHIBITORS
> (Desipramine), (Atomoxetine), Vivactil (Nortryptaline), Wellbutrin (Bupropion)
>
> MAOIs
> Parnate, Nardil, Selegiline, Marplan
>
> MOOD STABILIZERS
> Lithium, Lamactil
>
> SUPPLEMENTS
> L-Tyrosine, L-Theanine, L-Glutamine, Saint Johns Wort, Phenylethylamine, Levodopa, SAM-E, Saffron, Fish Oil, Magnesium, Zinc, Calcium, Vitamin B Complex, Multivitamins, Vitamin D
>
> SEROTONERGICS WHICH HAVE ACTIVATING FEATURES
> Pristiq, Effexor, Various TCAs
>
> OTHER
> Nicotine, Testosterone, Exercise, ETC, rTMS
>
> Preclinical neurobiological studies of anhedonia have primarily targeted neural substrates involved in motivation and reinforcement(want-ing). Across a variety of studies, liking and wanting have been linked to a variety of brain regions, neural circuits and neurotransmitters. These include primarily the neurotransmitter dopamine, norepinepherine, and opioid neuropeptides, sub-cortical structures such as the basal ganglia and striatum (particularly the nucleus accumbens(NAcc),ventral pallidum (VP),ventral tegmental area(VTA),substantia nigra(SN), amygdala and hippocampus), as well as cortical regions such as the ventro medial prefrontal cortex(vmPFC), encompassing aspects of orbital frontal cortex(OFC), anterior cingulated cortex(ACC)and medial prefrontal cortex(mPFC). (http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=8&cad=rja&sqi=2&ved=0CFIQFjAH&url=http%3A%2F%2Fzaldlab.psy.vanderbilt.edu%2Fresources%2FPublications%2Fmtt10nbr.pdf&ei=LppeUM67DOOPiALS0YHAAw&usg=AFQjCNFYaIO2t9JVX_sHcRjpzxUsWbpnVg&sig2=vBu2VN_DFfJTI9lVWS34Ig)
>
> QUESTIONS
> 1.) Has anyone here had remission from anhedonic symptoms? If so, how? What was it like? How long did it take before remission?
> 2.) Anyone have any experience with the beforementioned treatments? Any of them help anhedonic symptoms?
> 3.) Has anyone gotten their sex drive back after having it absent for months? Did it come back fully?
> 4.) Anyone have any advice on treating anhedonia?
>
> Let's have a discussion about this!
>
Posted by alchemy on September 24, 2012, at 13:39:35
In reply to Re: ANHEDONIA - Questions and Answers, posted by Trevpr on September 24, 2012, at 12:22:55
I wonder what it is like to have a libido. Always too much sadness and sympathy for others though.
Posted by AlexCanada on September 24, 2012, at 13:46:20
In reply to Re: ANHEDONIA - Questions and Answers, posted by Trevpr on September 24, 2012, at 0:42:56
> Also added to that list should be adrafinil, modafinil, nortiptyline, and mazindol.
>
> Amyone have good hedonic responses to these or ones previously listed? Including libido?Stablon I found exceptionally pro-sexual.
Korean Ginseng at moderate to high doses when taken with Parnate caused me to be extremely sexual. Normally my sex drive is quite low.
Gingko Biloba 300mg at a time can increase my libido moderately.
Posted by AlexCanada on September 24, 2012, at 13:48:46
In reply to Re: ANHEDONIA - Questions and Answers, posted by alchemy on September 24, 2012, at 11:30:09
I've read that Magnesium can suppossedly help prevent ritalin tolerance. Magnesium Glycinate or Chilate possibly.
> Your post comes right when i am struggling with ritalin. I have taken it off and on for a long time, mostly for work. Sometimes it would help. But it is also the only thing that has touched my anhedonia and at times my mood. Unfortunately I dont offer any good news from my situation. I have tried quite a few meds over 30ish years.
> Because i have been so treatment resistant and stimulants are the only thing that have touched mood and/or motivation, my dr recently actually suggested trying to increase my ritalin, take it consistently, and throughout the day as it only seems to last about 3-4 hrs with the long-acting for me. I crashed a couple of times pretty hard over the weekend and it is losing its effectiveness. Today i have been trying to hold back tears as i really wonder if what i am afraid of will really shortly happen.
> Anti-psychotics make me more depressed and agitated. I have tried amantadine and am currently on wellbutrin. Im not sure if the wellbutrin is actually helping though.
Posted by jono_in_adelaide on September 24, 2012, at 17:41:19
In reply to Re: ANHEDONIA - Questions and Answers » alchemy, posted by AlexCanada on September 24, 2012, at 13:48:46
You might well find that parnate plus welbutrin was usefull because of the threashold effect - each drug might only raise your neurotransmitter levels so far, but not enough to get remission, but the combo might get you over the line.
You have nothing to lose by trying, and everything to gain.
Given everything you've tried, you are running low on options, so I would encourage you to try Parnate both alone in combination.
If I can explain it like this - Excedrin is quite a potent analgesic, made up of aspirin, acetaminophen ans caffeine. The individual constituents, in the doses present, are onlyweak analgesics individualy, but in concert they provide a very usefull analgesic effect.You might find the same effect with Welbutrin + parnate (or any other logical combo) - two drugs that were mediocre along might turn out to be quite potent in combination.
Posted by jono_in_adelaide on September 24, 2012, at 17:58:02
In reply to Re: ANHEDONIA - Questions and Answers, posted by jono_in_adelaide on September 24, 2012, at 17:41:19
You might prefer the combo of emasem + welbutrin, and it might be that parnate/emasem + welbutrin + methylphenidate gets you over the line.
There are also the options of vagal stimulation, deep magnetic stimulation etc which might be worth exploring if you feel you have run out of med options
Posted by jono_in_adelaide on September 24, 2012, at 18:47:21
In reply to Re: ANHEDONIA - Questions and Answers, posted by jono_in_adelaide on September 24, 2012, at 17:58:02
Also, if you can get your hands on Stabelon through the grey market, that plus welbutrin or parnate or emasem would be well worth a try
Posted by Trevpr on September 24, 2012, at 19:29:41
In reply to Re: ANHEDONIA - Questions and Answers, posted by jono_in_adelaide on September 24, 2012, at 18:47:21
Well I cant get Stablon, but ill ask about emsam or parnate. I was going to go on parnate but for some reason the doc chose vivactil and abilify
Posted by jono_in_adelaide on September 24, 2012, at 19:44:31
In reply to Re: ANHEDONIA - Questions and Answers, posted by Trevpr on September 24, 2012, at 19:29:41
I'd seriously try Parnate, and if that doesnt get you over the line, try Parnate plus Welbutrin (for the reasons outlined above)
Dont be afraid to push the doseages either, 80mg per day of Parnate isnt unusual.
Best of luck!
Go forward in thread:
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.