9 replies to this topic

[Mental_Divergence]

Hi all, I have a slightly long story to tell, so please bear with me.

 

Anyway, I unknowingly suffered from depression for a few years and finally decided enough was enough last year. I decided to take Zoloft again (took it 6 years prior for horrible social anxiety and it worked wonders). When I was first on it I stupidly stopped taking it because I was drinking alcohol every night, and it was then that I first experienced what I later learned were sensations called brain zaps. Anyway, I weaned off it, deciding I was cured (dumb af), and after a few months IIRC I started taking it again. It didn't have an appreciable effect this time so I weaned off yet again. At the time I wasn't a medical professional and I was clueless about everything, including side effects (otherwise I would've obsessed over them as I suffer from OCD, and hypochondria is also often part of clinical depression). But in retrospection, I'm pretty sure I wasn't suffering from depression at the time. Anyway, over the next following years I succumbed to the insidious disease. I also had major problems with social anxiety.

 

These years were characterized by horrible errors in reasoning and judgment and a complete lack of insight on my part (which is, notably, another major component of major depression). So last year I decided I'm going to do something about it. I had read so many horror stories about the so-called PSSD online and started obsessing, as usual. However, I dismissed the claims. So I start taking Zoloft because it worked so well for me in the past. 3 weeks go by, nothing much happens. 6 weeks go by, nothing extraordinary happens. 8 weeks go by and I notice my melancholic thoughts are gone. I also notice the infamous SSRI-induced indifference creeping up on me as well. I notice my once strong sex drive is now literally non-existent. I notice what I surmise can't possibly be nocebo - near anorgasmia. Deciding after three months the drug has failed to produce a favorable benefit-to-harm ratio (by a wide margin), I halve the dose (from 50 to 25 mgs). After a few days the withdrawals hit me like a truck (flu-like symptoms - horrible malaise, sweating, fever etc.). I go back to 50 and they disappear after a few days. So I did a slower taper and successfully weaned off. The zaps lasted for full 2.5 months this time. I was going crazy. At the time I still had poor insight and my maladaptive reasoning was getting the better of me. The drug seemed to have lost its potency because of prior discontinuation? I haven't found anything on this and it's still a mystery to me.

 

I would also like to point out that I was zombie-like for months after coming off it. I remember how I was impervious to depressive thinking and feeling, but also to all the highs in life. My libido was still gone but at least I wasn't suicidal. So I decided to do labs thinking my hormones might be out of whack. Btw, by this time I had dismissed the PSSD claims as nonsense and concluded the sufferers simply relapsed into major depression, which I still believe strongly to this day, and have found evidence to support my assertion. Anyway, the labs came back and they did show abnormalities but nothing an endocrinologist would deem worthy of intervention. My SHBG was pretty high, my estradiol was low, LH and FSH high normal, total T high normal, free T quite low. I considered starting TRT but didn't in the end. At this time my unprofessional, gut feeling was that this last stint with sertraline changed me somehow. I lost interest in music, gym, sex. I was a different person than I had been before. Depression came back, lack of sex drive and anhedonia remained.

 

 

So I start taking Remeron over 2 months ago. The drug banished suicidal ideation, lifted psychomotor retardation, awakened my appetite (I had been anorexic for years) and brought back pleasure of eating. But I still have zero interest in music and absolutely no sex drive. I am suffering from appetitive anhedonia, whereas before I only had a degree of consummatory anhedonia. This new state was probably brought on by a hard relapse and worsening of depression after Zoloft, which did squat. My question is - how do I treat this?! I know this is unremitted depression with residual symptoms. Anhedonia is a core component of depression, but I have no idea how to battle it. More antidepressants? What do I add to Remeron that doesn't worsen it? I'm at 30 mgs now, 15 was inadequate (though 30 is as well obviously). I'm looking into behavioral therapy now.

 

Anyway, PubMed has failed me, there are countless studies elucidating the obscure pathophysiology of this state but none offering solutions. If I read another study I will implode in frustration and anger. Does anyone have an answer? Or a similar experience to share? Thank you, and thanks for reading.

 

 

Some info on these anhedonic aspects: https://www.ncbi.nlm...525714/#S4title

 

I can't believe there's still saps coming out with studies like "Is there role for dopamine in depression" or "Anhedonia revisited" and yet all we've got are fucking SSRIs. I look forward to new drugs on the horizon, for the sake of myself and millions of people suffering from this repugnant disease.

 

Edited by Mental_Divergence, 08 May 2017 - 04:28 PM.

[Otto F.]

I also have high testosterone in conjunction with high SHBG...and severe anhedonia. I've never even considered, until reading your post, the possibility that there might be some sort of association between high SHBG and anhedonia. If the testosterone is "bound", is it physiologically equivalent to having low-T? Also, if that were the case, would T-therapy be effective or would it simply cause more SHBG to be produced? I wonder if there is any way to cause the release of bound T??? I don't know, probably not. Maybe the right question is "why is my T-level so high in the first place?" I've asked a variety of MD's including a psychiatrist, neurologist and endocrinologist and none had any answer or suggestion. Personally I think it is caused by repetitive stress and the consequent inflammation which makes sense to me, but I have found no science to support the idea directly. There is however plenty of science suggesting that inflammation is associated with depression and anhedonia, and that is what I'm focused on recently. In particular, abnormalities in kynurenine metabolism ...activation of the PGC-1 pathway which increases kynurenine aminotransferase which converts kynurenine(able to cross the BBB and cause depressive behaviors) into kynurenic acid (which cannot enter the brain)..."reducing plasma kynurenine protects the brain from stress induced changes associated with depression"..."anhedonia neuropathology involves dopamine as opposed to serotonin and NE involved in depression"..."activation of KP neurotoxic branch can alter dopamine neural reward circuitry...QUIN(quinolinic acid which is an NMDA agonist) induces dopaminergic and Gabergic neuronal death"..."decreased endogenous KA results in decreased dopamine release. .."peripheral activation of IDO lead to parallel activation of the KP in the brain...peripheral INHIBITION of IDO blocked the central transcription of IDO in the brain and the development of depressive behaviors"...sorry no links but you have plenty of keywords to find all this easily......it's all very complicated but ultimately comes down to a strategy to activate the PGC-1 pathway which can be accomplished by actually BEING the physical, evolutionarily "designed" human-animals that we are...PGC-1 is strongly activated by cold exposure, ROS-cellular stress, endurance exercise, sexual activity, socializing...also with supplements such as 20mg PQQ, EGCG, R-lipoic acid etc....

 

 

[PeaceAndProsperity]

I also have high testosterone in conjunction with high SHBG...and severe anhedonia. I've never even considered, until reading your post, the possibility that there might be some sort of association between high SHBG and anhedonia. If the testosterone is "bound", is it physiologically equivalent to having low-T? Also, if that were the case, would T-therapy be effective or would it simply cause more SHBG to be produced? I wonder if there is any way to cause the release of bound T??? I don't know, probably not. Maybe the right question is "why is my T-level so high in the first place?" I've asked a variety of MD's including a psychiatrist, neurologist and endocrinologist and none had any answer or suggestion. Personally I think it is caused by repetitive stress and the consequent inflammation which makes sense to me, but I have found no science to support the idea directly. There is however plenty of science suggesting that inflammation is associated with depression and anhedonia, and that is what I'm focused on recently. In particular, abnormalities in kynurenine metabolism ...activation of the PGC-1 pathway which increases kynurenine aminotransferase which converts kynurenine(able to cross the BBB and cause depressive behaviors) into kynurenic acid (which cannot enter the brain)..."reducing plasma kynurenine protects the brain from stress induced changes associated with depression"..."anhedonia neuropathology involves dopamine as opposed to serotonin and NE involved in depression"..."activation of KP neurotoxic branch can alter dopamine neural reward circuitry...QUIN(quinolinic acid which is an NMDA agonist) induces dopaminergic and Gabergic neuronal death"..."decreased endogenous KA results in decreased dopamine release. .."peripheral activation of IDO lead to parallel activation of the KP in the brain...peripheral INHIBITION of IDO blocked the central transcription of IDO in the brain and the development of depressive behaviors"...sorry no links but you have plenty of keywords to find all this easily......it's all very complicated but ultimately comes down to a strategy to activate the PGC-1 pathway which can be accomplished by actually BEING the physical, evolutionarily "designed" human-animals that we are...PGC-1 is strongly activated by cold exposure, ROS-cellular stress, endurance exercise, sexual activity, socializing...also with supplements such as 20mg PQQ, EGCG, R-lipoic acid etc....

Even if you have high shbg it's still not a good explanation because... look at women with low testosterone. But shbg binds a lot of different hormones than just testosterone, including estrogen. You could always try injections and see.

T injections lower shbg as opposed to raising it.

 

I find that DHEA did wonders for anhedonia (but not 100%) probably because it is a sigma receptor agonist or something.

Glucosamine sulfate also had a small but positive effect on my emotions.

 

[vader]

Anhedonia won't even budge without some sort of behavioral activation. Force yourself to socialize.

[ThreeKings12341]

 

I also have high testosterone in conjunction with high SHBG...and severe anhedonia. I've never even considered, until reading your post, the possibility that there might be some sort of association between high SHBG and anhedonia. If the testosterone is "bound", is it physiologically equivalent to having low-T? Also, if that were the case, would T-therapy be effective or would it simply cause more SHBG to be produced? I wonder if there is any way to cause the release of bound T??? I don't know, probably not. Maybe the right question is "why is my T-level so high in the first place?" I've asked a variety of MD's including a psychiatrist, neurologist and endocrinologist and none had any answer or suggestion. Personally I think it is caused by repetitive stress and the consequent inflammation which makes sense to me, but I have found no science to support the idea directly. There is however plenty of science suggesting that inflammation is associated with depression and anhedonia, and that is what I'm focused on recently. In particular, abnormalities in kynurenine metabolism ...activation of the PGC-1 pathway which increases kynurenine aminotransferase which converts kynurenine(able to cross the BBB and cause depressive behaviors) into kynurenic acid (which cannot enter the brain)..."reducing plasma kynurenine protects the brain from stress induced changes associated with depression"..."anhedonia neuropathology involves dopamine as opposed to serotonin and NE involved in depression"..."activation of KP neurotoxic branch can alter dopamine neural reward circuitry...QUIN(quinolinic acid which is an NMDA agonist) induces dopaminergic and Gabergic neuronal death"..."decreased endogenous KA results in decreased dopamine release. .."peripheral activation of IDO lead to parallel activation of the KP in the brain...peripheral INHIBITION of IDO blocked the central transcription of IDO in the brain and the development of depressive behaviors"...sorry no links but you have plenty of keywords to find all this easily......it's all very complicated but ultimately comes down to a strategy to activate the PGC-1 pathway which can be accomplished by actually BEING the physical, evolutionarily "designed" human-animals that we are...PGC-1 is strongly activated by cold exposure, ROS-cellular stress, endurance exercise, sexual activity, socializing...also with supplements such as 20mg PQQ, EGCG, R-lipoic acid etc....

Even if you have high shbg it's still not a good explanation because... look at women with low testosterone. But shbg binds a lot of different hormones than just testosterone, including estrogen. You could always try injections and see.

T injections lower shbg as opposed to raising it.

 

I find that DHEA did wonders for anhedonia (but not 100%) probably because it is a sigma receptor agonist or something.

Glucosamine sulfate also had a small but positive effect on my emotions.

 

 

also good to mention  is that many people have adrenal fatique syndrom (like me) so dhea plays a role.. many people i think do not even know that they have low dhea  or adrenal fatique syndrome.. so i would try that out . it doesnt hurt. im on it now and i must say i much less grumpy, and more energy. (taking it now  4 weeks already)
 

[sant2060]

Anhedonia won't even budge without some sort of behavioral activation. Force yourself to socialize.

I socialize as much as I can. And it only makes matters worse. Not all are created equal, I'm anhedonic and introverted.

Socialising exausts me so much that I feel even more dull, and just want to sleep.

[vader]

 

Anhedonia won't even budge without some sort of behavioral activation. Force yourself to socialize.

I socialize as much as I can. And it only makes matters worse. Not all are created equal, I'm anhedonic and introverted.

Socialising exausts me so much that I feel even more dull, and just want to sleep.

 

 

Get some quality one on one socialization then. Get to know someone.

[sant2060]

Anhedonia won't even budge without some sort of behavioral activation. Force yourself to socialize.

I socialize as much as I can. And it only makes matters worse. Not all are created equal, I'm anhedonic and introverted.

Socialising exausts me so much that I feel even more dull, and just want to sleep.

Get some quality one on one socialization then. Get to know someone.

As I said, not all are created equal.
I have 'quality socialization', and I know quite a few 'someone'. Probably more than regular people. There are people loving me, liking me, telling me their deepest fears, asking me to be their best man on weddings...

But I'm still anhedonic. There arent silver bullets in mental illnesses.

[vader]

 

 

 

Anhedonia won't even budge without some sort of behavioral activation. Force yourself to socialize.

I socialize as much as I can. And it only makes matters worse. Not all are created equal, I'm anhedonic and introverted.

Socialising exausts me so much that I feel even more dull, and just want to sleep.

Get some quality one on one socialization then. Get to know someone.

As I said, not all are created equal.
I have 'quality socialization', and I know quite a few 'someone'. Probably more than regular people. There are people loving me, liking me, telling me their deepest fears, asking me to be their best man on weddings...

But I'm still anhedonic. There arent silver bullets in mental illnesses.

 

 

How are those relationships "quality", if you are still anhedonic? I've had "friends" that told me the same, but honestly I couldn't feel the same for them. I think anhedonia is self-protective mechanism, basically not part of the pack order type of deal. Any drugs / dietary modifications are mostly patch-work imho, I've never had any consistent effect from any substance.

[sant2060]

Anhedonia won't even budge without some sort of behavioral activation. Force yourself to socialize.

I socialize as much as I can. And it only makes matters worse. Not all are created equal, I'm anhedonic and introverted.

Socialising exausts me so much that I feel even more dull, and just want to sleep.

Get some quality one on one socialization then. Get to know someone.

As I said, not all are created equal.
I have 'quality socialization', and I know quite a few 'someone'. Probably more than regular people. There are people loving me, liking me, telling me their deepest fears, asking me to be their best man on weddings...

But I'm still anhedonic. There arent silver bullets in mental illnesses.

How are those relationships "quality", if you are still anhedonic? I've had "friends" that told me the same, but honestly I couldn't feel the same for them. I think anhedonia is self-protective mechanism, basically not part of the pack order type of deal. Any drugs / dietary modifications are mostly patch-work imho, I've never had any consistent effect from any substance.

The same as some people have musical anhedonia.

And it is not a 'protective mechanism', it is the way their brain is wired.

When I say 'quality', I mean I'm not sitting at home not knowing anybody, I socialise. A lot for an introvert. Deep enough so that people like me, sometimes too much for my taste. Per your advice (it is not only your advice, it is advice most psyhologists or life coaches/self help books give)

But it doesnt work for everyone. I still have anticipatory and consummatory anhedonia. For decades.

For me the only time I had brief glimpse in how other people experience life was through drugs... unfortunatelly with shitload od side effects.

So, what I'm trying to say, everyone is different. I'm glad that you found your solution, but it doesnt mean that this solution will work for everyone.