SRI induced emotional blunting & broken reward system

[NNorim]

Hello,

I'm suffering from depressions and social anxiety. Unfortunately it looks like I have very unpleasant side effects from SRIs: I can't feel anymore, my emotions are numbed. My motivation is non-existent and I am indifferent to everything. When I watch some emotional video I used to cry before, now I can't feel that emotion any more. I'm also not sure if I can fall in love any more. I had 1.5 year "sort of a relationship" and I really liked that girl, now I feel nothing for her. I also have that feeling like I can't really enjoy good moments anymore. I just never feel truly happy or sad. I can't laugh, I can't cry, it looks like I can't experience intense feelings. I also have problems to reach orgasm and I don't enjoy sex, masturbation and erotic sensations like I used to.

And they have all caused me to lose my appetite almost completely + weight loss. My doctor said it's unlikely the SSRIs causing my weight & appetite loss. I am currently considered "underweight", I was a "healthy normal weight". I can go 24 hours without food and still won’t be hungry or have appetite…

Now I don't know what to do. I need some meds cause it seems like I'm not able to live without it but I also don't want to go back to emotional emptiness & Zombieland. I haven't tried any combination of medications yet. All of them separately.

I tried:
Venlafaxine - emotional blunting + severe weight loss.
Fluoxetine - this was actually quite good. Gave me some emotional blunting, but only modest. I had to discontinue it due to suicidal ideation.
Paroxetine - emotional blunting + horrible physical side effects.
Citalopram - emotional blunting + absence of motivation.
Sertraline - emotional blunting + absence of motivation.

I'm starting to be really desperate and my doctor told me she don't want to treat me any more due to I'm not good patient and I'm not trying. I found a new psychiatrist and I will have a first appointment in 2 weeks but I don't know what to suggest to her. I was thinking about Wellbutrin but what I read it doesn't help with anxiety and weight gain. Has anybody some experience with a similar situation? Which antidepressant would be suitable for me? I don't know which one and I have the feeling that I'm starting to go out of options.

If there is someone who had the same problem and found some solution: please write me

 

[Phenpsycho]

Hi, NNorim, welcome to bluelight!

I'm sorry to hear about your doctor giving up on you, that always hurts. I suffer from anxiety and depression and sought help for my afflictions from a psychiatrist with mixed results. I respond the same way as you do to SSRI's where I experience too many side effects to continue treatment. The SSRI's i've been RX'd include fluoxetine, sertraline, citalopram and escitalopram. If I remember correctly all of them caused anhedonia as a side effect and the lack of appetite as you stated, loss of libido too. Citalopram was trialed and I got severe mood swings on it so was switched over to escitalopram because it was supposed to be better tolerated but it was no better.

Now as I checked off the list of meds on the AD conveyor belt I was eventually tried on buspirone(Buspar) which had a positive effect on the depression but made my anxiety worse. I can say with the buspirone anhedonia and loss of libido was no longer an issue however the lack of appetite remained due to the nervousness. The last of my experiences with AD's and the one which had the best overall result for me was mirtazapine(a tetracyclic antidepressant).

The mirtazapine truly started out as a miracle medication for me as i've also suffered from insomnia and a small dose(7.5mg) would send me right off to slumber. The regimen I was put on was 15mg in the morning and 7.5mg at night and I noticed a delightful increase in appetite for a change! Also there was no anhedonia present and while there wasn't outrageous feelings of positivity or benzo-tier anxiety reduction there was enough of a reduction in both my depression and anxiety to foster a sense of well-being. Unfortunately after some time it lost efficacy and my psychiatrist at the time switched around the doses a bit to where I was on 30mg in the morning and 15mg at night which still didn't bring back the relief I had gotten used to. A funny thing about mirtazapine iirc is that it has more of a sedative/relaxant effect the lower the dose is and as the dose increases it feels more stimulating so i'm not sure why my psychiatrist would increase to 15mg at night but I guess it didn't hurt to try

I have had excellent relief from my anxiety when I was prescribed clonazepam daily by my GP but taking that every day I found out is a good way for them to lose any efficacy as well...

Maybe talk with your new psychiatrist about prescribing mirtazapine instead of an SSRI for a change? If it hadn't pooped out on me I would still be taking it today, it had no side effects accept the sedative nature of it at the lower 7.5mg dose and the increase in appetite which were both beneficial in my case. You might have better luck with it and it will maintain the desired result? could be worth a try

 

[Cotcha Yankinov]

Getting a new psychiatrist was definitely the right path for you.

Sometimes people have to venture outside of SSRIs. As mentioned above, Mirtazapine can work for some people that don't respond well to SSRIs. It tends to increase appetite indeed.

 

[NNorim]

Hi, NNorim, welcome to bluelight!

Thank you very much

I suffer from anxiety and depression and sought help for my afflictions from a psychiatrist with mixed results. I respond the same way as you do to SSRI's where I experience too many side effects to continue treatment. The SSRI's i've been RX'd include fluoxetine, sertraline, citalopram and escitalopram. If I remember correctly all of them caused anhedonia as a side effect and the lack of appetite as you stated, loss of libido too. Citalopram was trialed and I got severe mood swings on it so was switched over to escitalopram because it was supposed to be better tolerated but it was no better.

So I am not alone with this problem. I've been doing some reading & research and there is the hypothesis that SSRI-induced-agonism of 5HT2C & 5HT2A receptors dampens the dopaminergic transmission in the prefrontal cortex thus causing the specific SSRI side effects. Antagonism / Inverse Agonism of these receptors should theoretically resolve the problem. What medications do antagonize / inverse agonize these receptors? Well, according to my sources: Nortriptyline, Mirtazapine, Agomelatine, Trazodone, Nefazodone... so far.

Are there any other reliable theories on what is causing this? And what could help?

Now as I checked off the list of meds on the AD conveyor belt I was eventually tried on buspirone(Buspar) which had a positive effect on the depression but made my anxiety worse. I can say with the buspirone anhedonia and loss of libido was no longer an issue however the lack of appetite remained due to the nervousness.

Buspirone might be worth a try: I have it on my to-do-list.

The last of my experiences with AD's and the one which had the best overall result for me was mirtazapine(a tetracyclic antidepressant).

The mirtazapine truly started out as a miracle medication for me as i've also suffered from insomnia and a small dose(7.5mg) would send me right off to slumber. The regimen I was put on was 15mg in the morning and 7.5mg at night and I noticed a delightful increase in appetite for a change! Also there was no anhedonia present and while there wasn't outrageous feelings of positivity or benzo-tier anxiety reduction there was enough of a reduction in both my depression and anxiety to foster a sense of well-being. Unfortunately after some time it lost efficacy and my psychiatrist at the time switched around the doses a bit to where I was on 30mg in the morning and 15mg at night which still didn't bring back the relief I had gotten used to. A funny thing about mirtazapine iirc is that it has more of a sedative/relaxant effect the lower the dose is and as the dose increases it feels more stimulating so i'm not sure why my psychiatrist would increase to 15mg at night but I guess it didn't hurt to try

I definitely want to try Mirtazapine, but first have to find a doctor who will prescribe it to me

 

[jaiho]

Are there any other reliable theories on what is causing this? And what could help?

You've researched well. I've been trying to spread the word about this to alot of places.
Basically if you want to avoid, to the highest possibility, emotional blunting / apathy / sexual dysfunction, you want, SSRI , 5ht1a agonism, 5HT2A & C antagonism, NRI, and DRI.

Sertraline at doses of 200mg+ are a decent SDRI, Nortriptyline for the NRI portion + 5HT2A & C antagonism, and you can add Buspirone for 5HT1A agonism.

Other option is high dose Cymbalta, for SNDRI + Geodon, an anti psychotic with 5ht1a agonism + 5ht2a+c antagonism.

 

[WSH]

Sertraline at doses of 200mg+ are a decent SDRI, Nortriptyline for the NRI portion + 5HT2A & C antagonism, and you can add Buspirone for 5HT1A agonism.

Buspirone is pretty much the worst choice for 5-ht1a, because of its weak partial agonism. Vilazodone and especially Vortioxetine have higher intrinsic activities and intrinsic activities are very important when it comes to antidepressant effects:

we studied the relationship between the maximal receptor activation produced by various 5-HT1A receptor ligands and their antidepressant-like effects Ži.e., decreased immobility in the forced swimming test in rats. [...] This relationship constitutes evidence that the magnitude of the psychotropic activity of 5-HT1A receptor ligands is a positive function of their intrinsic activity at the receptor, and suggests that F 13714, which had maximal effects in the forced swimming test significantly larger than any of the other compounds examined here, did so because of its higher intrinsic activity at 5-HT1A receptors

5-HT1A receptor activation and antidepressant-like effects: F 13714 has high efficacy and marked antidepressant potential

 

[psy997]

Perhaps GABApentoids such as Gabapentin or Pregabalin may help?

 

[Cotcha Yankinov]

I would like to see Pimavanserin trailed alongside SSRIs to see if it can reduce side effects, but I do wonder if 5-HT2A/5-HT2C activation can play some role in antidepressant response.. but as WSH points out I think it's the post synaptic 5-HT1A agonism that's doing most of the heavy lifting.

 

[NNorim]

Getting a new psychiatrist was definitely the right path for you.

Sometimes people have to venture outside of SSRIs. As mentioned above, Mirtazapine can work for some people that don't respond well to SSRIs. It tends to increase appetite indeed.

Yeahh, it shouldn't be a problem to get it prescribed. I would have liked to try Nortriptylin, but: https://www.lundbeck.com/de/service/nortrilen-truxal

You've researched well. I've been trying to spread the word about this to alot of places.
Basically if you want to avoid, to the highest possibility, emotional blunting / apathy / sexual dysfunction, you want, SSRI , 5ht1a agonism, 5HT2A & C antagonism, NRI, and DRI.

Sertraline at doses of 200mg+ are a decent SDRI, Nortriptyline for the NRI portion + 5HT2A & C antagonism, and you can add Buspirone for 5HT1A agonism.

Other option is high dose Cymbalta, for SNDRI + Geodon, an anti psychotic with 5ht1a agonism + 5ht2a+c antagonism.

Thanks for your answer
Is there like an overview on the different receptors and how they feel when agonized, antagonized, inverse agonized?
Aren't SSRIs 5HT1a agonists?

 

[NNorim]

Buspirone is pretty much the worst choice for 5-ht1a, because of its weak partial agonism. Vilazodone and especially Vortioxetine have higher intrinsic activities and intrinsic activities are very important when it comes to antidepressant effects:

5-HT1A receptor activation and antidepressant-like effects: F 13714 has high efficacy and marked antidepressant potential

So Buspirone wouldn't help?

 

[xbandit07x]

Do not bother taking SSRIS unless you have a clear reason to scientifically suspect a real serotonin deficiency.

 

[NNorim]

Do not bother taking SSRIS unless you have a clear reason to scientifically suspect a real serotonin deficiency.

So what's the alternative?

 

[Neithman]

well try other meds,if that doesnt work aswell you have to change your ways,try to wean off the meds do alot of exercise,try different sports,for some people doing group sports also helps them to combat their social anxiety because people doing a kind of sport together have something that unite them,so they are nice to each others,which helps you regain trust into people,along this try to combat the issues that leads to this symptoms you have with a psyschologist

 

[jaiho]

Do not bother taking SSRIS unless you have a clear reason to scientifically suspect a real serotonin deficiency.

Except that increased serotonergic transmission alleviates the symptoms he lists.

The problem here is that sometimes SSRIs induce a flat affect / apathy. They don't inherently cause this, this is why doctors change drugs, add drugs, or change doses to resolve it.

The entire purpose of these drugs is to make your reward circuitry more responsive so that you're better able to lift yourself out of the depression.

OP, you should look at the SSRI + Nortriptyline combination.

http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.534.5853&rep=rep1&type=pdf

 

[cr33py]

Perhaps try another route.. lamotrigine and bupropion? or bupropion along side an SSRI? HAving tried all of those SSRIs Id guess your next step would be augmenting with some receptor antagonists. TCAs, nefazodone, atypical antipsychotics. Some folks claim that aripiprazole helps with SSRI apathy. Personally Id exhaust all the other options before I took an AP.