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!
poster:Trevpr
thread:1026437
URL: http://www.dr-bob.org/babble/20120922/msgs/1026437.html