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Catwoman

Worried that the next one won't work either....Immunity to SSRI's?

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3 hours ago, Catwoman said:

I was thinking the same, but my pdoc called me back and didn't want to prescribe an AP. She gave me a prescription for a benzodiazepine instead (I forgot which one), but I didn't pick it up yet.  I can take one as needed of course, but still....it wouldn't help with the intrusive thoughts.

Well it might...many use benzos to shut their mind off a little 

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7 minutes ago, Iceberg said:

Well it might...many use benzos to shut their mind off a little 

@Iceberg does have a valid point, @Catwoman. While medications that stabilize dopamine activity do seem to improve OCD symptoms. Medications that reduce glutamate also seem to be fairly effective. Specifically the combination of a therapeutic dose of an SSRI combined with lamotrigine. Glutamate and GABA are like ying and yang. There are enzymes in the body that convert glutamate to GABA and other enzymes that convert GABA back to glutamate. Glutamate is the excitatory neurotransmitter and GABA is the "depressing" neurotransmitter (I say depressing of course in that it depresses certain brain functions but not necessarily mood). Benzodiazepines will help to increase the brain's sensitivity to GABA activity. It may be theoretically possible that your obsessive thought is caused by your body's genetically decreased ability to convert glutamate into GABA so that the brain can "slow itself down". Purely hypothetical, keep in mind. Therefore, a benzodiazepine may be effective because it allows your brain to more efficiently use the GABA that it has available.

Curious as to what benzo she prescribed, dose and whether it's as needed or taken regularly.

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On 7/29/2018 at 2:44 AM, notloki said:

My pdoc thinks I will not be bothered by depression again. I'm in long term remission and will stay that way. We have found the right combo of Wellbutrin+Abilify+Dextroamphetamine+benzo. 

@notloki - That your pdoc would say with confidence that you will not be bothered by depression again is a remarkable statement. Given the duration of treatment that you cite, you must have endured multiple episodes of depression, and the conventional wisdom is that each successive episode increases the likelihood of relapse by a significant percentage until finally one is almost guaranteed to relapse. My depression began about a decade earlier than yours, and I've had so many successive bouts that I no longer think in terms of a life without the possibility of depression. Yet your pdoc is willing to take a position that you have achieved control-in-remission that is tantamount to cure after 30 years of progression? If so, that is an extraordinary claim. It becomes even more extraordinary coming from someone with your reputation for thoroughly vetted content. I am ecstatic for you if it proves accurate, but extraordinary claims do require extraordinary evidence. Can you elaborate further?

Edited by Cerberus

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I have always received excellent mental health care, I have not had a bad pdoc (nor one who denies benzos) ever. I started seeing my present doc 12-13 yrs ago. He is a private doctor and takes no insurance. When I first came to see him I was on Remeron for sleep and getting some bad feelings. Insomnia is a big problem and I have tried all the sedating meds, like antihistamines, antidepressants and had limited success with the hypnotic benzos. My doc said "I think it is time to look at the true hypnotics" so we tried all the Zdrugs. He saved the Lunesta for last and as I was leaving the room, he had given me some samples and said you my have to go up to 6 mg, its the same dose they take in the UK in there difficult insomnia cases. 6 mg and 13 years later I am still sleeping well, often through the night. No tolerance or dependance. No other doc had been able to do that. All throughout my treatment my doctor makes it possible for me the taylor doses to fit me.

Edited by notloki

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It's interesting- sometimes I find that type of confidence reassuring and sometimes it pisses me the fuck off...I'm glad that your doc seems to be finding the right individual approach for you. Unfortunately, I did get some bad pdoc-ing and they started off with promises they couldn't keep so now I'm very suspicious of any absolute. I'm sure if I had a doc with the relationship you have it might have been a whole different story. Regardless, I really hope he's right!  

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18 hours ago, browri said:

@Iceberg does have a valid point, @Catwoman. While medications that stabilize dopamine activity do seem to improve OCD symptoms. Medications that reduce glutamate also seem to be fairly effective. Specifically the combination of a therapeutic dose of an SSRI combined with lamotrigine. Glutamate and GABA are like ying and yang. There are enzymes in the body that convert glutamate to GABA and other enzymes that convert GABA back to glutamate. Glutamate is the excitatory neurotransmitter and GABA is the "depressing" neurotransmitter (I say depressing of course in that it depresses certain brain functions but not necessarily mood). Benzodiazepines will help to increase the brain's sensitivity to GABA activity. It may be theoretically possible that your obsessive thought is caused by your body's genetically decreased ability to convert glutamate into GABA so that the brain can "slow itself down". Purely hypothetical, keep in mind. Therefore, a benzodiazepine may be effective because it allows your brain to more efficiently use the GABA that it has available.

Curious as to what benzo she prescribed, dose and whether it's as needed or taken regularly.

I'll report back which one she prescribed. I'm sure it wasn't Xanax or Vallium, because I'v never taken benzo's before, other than for sleeping (if I recall correctly this was temazepam, more than 13 years ago and I only slept for a few hours). So it's probably short-acting. 

I do have to admit that I sometimes have a small glass of strong liquor in the evening when I feel anxious or tense. Of course it has a overall relaxing effect, but it also lessens the intrusive thought a bit. 
Alcohol works as a GABA agonist, but I assume a benzo is a safer alternative and might act for a longer time than a few sips of whiskey.
 

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On 7/29/2018 at 4:14 AM, Catwoman said:

I mean, SSRI's are selective for serotonin and not much else, so isn't it natural that inhibiting one neurotransmitter will have a negative effect on other neurotransmitters?
I have no idea if this theory about SSRI's depleting dopamine is plausible?




 

SSRI's do effect more than 1 neurotransmitter. Each SSRI is different from the others except they all affect serotonin. The theory of SSRI depleting came from the Internet, made up on some board, and not from science.

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SSRIs went all weird on me after 20 years. They suddenly started giving me paresthesia. Same with SNRIs. I tolerated it for about a year but eventually it got to much. Reboxetine has proven to be useless. Got an appt with Psych next week to see where we go from here.

Fortunately ive got Lyrica and Diazepam to keep me calm(sort of...barely) whilst intrusive thoughts are trying their hardest to tip me over the edge

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thank you for this discussion. while i admit that a lot of it is more than i can fully understand, the concepts of "immunity" or "tolerance" are very interesting to consider. i have never had an AD , mood stabilizer, or AP help. I've been on and off the med-go-round since 1987. I've tried just about everything there is out there over the years without effect. now either my issues are not treatable with medication (or these particular types of meds), or my brain could be immune to the action of the meds they've rx'd. 

i really need to look at this thread more deeply and try and understand better what the science is behind all of this. i wish i could remember all the drugs i've been on, but 30 years is a lot of drugs.

i'm really fascinated by this whole idea of immunity. it's either that, or my issues stem from other brain chemicals than those addressed by ADs , mood stabilizrs, or APs (like hormones or something)

thank you again for this thread. 

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22 minutes ago, WytchyWoman said:

thank you for this discussion. while i admit that a lot of it is more than i can fully understand, the concepts of "immunity" or "tolerance" are very interesting to consider. i have never had an AD , mood stabilizer, or AP help. I've been on and off the med-go-round since 1987. I've tried just about everything there is out there over the years without effect. now either my issues are not treatable with medication (or these particular types of meds), or my brain could be immune to the action of the meds they've rx'd. 

i really need to look at this thread more deeply and try and understand better what the science is behind all of this. i wish i could remember all the drugs i've been on, but 30 years is a lot of drugs.

i'm really fascinated by this whole idea of immunity. it's either that, or my issues stem from other brain chemicals than those addressed by ADs , mood stabilizrs, or APs (like hormones or something)

thank you again for this thread. 

Hello @WytchyWoman! Glad we could provide information!

Keep in mind, as I said, that "immunity" to antidepressants can be the result of desensitization of serotonin receptors after long periods of time. I know that for some people, they go on an antidepressant, take it for a few years, go off it, then go back to it for a subsequent depressive episode and it doesn't work at all where it did the first time. I have no explanation for that, and I don't think they have a really solid explanation for "antidepressant tachyphylaxis".

However, I've always wondered if some patients would benefit from an antidepressant "holiday" much the way they do for stimulants in kids during the summer when they aren't in school. In my mind, this would allow your serotonin receptors to resensitize or almost "reset" for lack of better words, then you pick the antidepressant back up in the Fall to get through the Winter when depression is more prominent for many people. This isn't for anyone though. I know @mikl_pls is more likely to experience summer depressions than Fall/Winter depressions like I do.

What you suggested about hormones actually hits the nail on the head more than you thought, and it does play a major role in genetics as well. For example, I mentioned that I have under-expressed MAO-A (monoamine oxidase A) and COMT (catechol-O-methyltransferase) genes. Because those genes are responsible for the creation of enzymes that break down neurotransmitters and because mine are under-expressed, I have less of the enzyme needed to break down monoamines and catecholamines leading to higher levels of serotonin, norepinephrine, and dopamine. Therefore, I've always gotten along really well with serotonin and dopamine antagonists because they dampen the effects of the higher neurotransmitter levels in my brain.

But hormones play a major role in compensating for these dysfunctions. Testosterone is known to increase expression of COMT and thus break down catecholamines. As a man, I should be able to manipulate COMT myself by simply exercising and eating well to increase my testosterone levels and thus my COMT expression can make a huge difference in how I feel. MAO-A is carried on mitochondrial DNA, which you always get from your mother. My maternal half-sister also has an under-expressed MAO-A gene. She notices her mood swings and depression most around menstruation:

Hormone Cycle

Estrogen and progesterone both increase expression of MAO-A. So my sister has higher serotonin outside of her cycle, which can lead to lower dopamine. But then, the latter half of the follicular phase leading into ovulation, progesterone and estrogen both increase which increase MAO-A expression and higher levels of the enzyme, which then breaks down serotonin rapidly. With lower serotonin comes higher dopamine, and the combination of lower serotonin and higher dopamine can result in depression. You can see that the hormones do drop off, but even for the latter half of the cycle, there's still quite a bit of turmoil from a hormonal perspective.

So you see that hormones do have a profound effect on neurotransmitters in both men and women. One important thing to grasp that I pointed out in a previous post is that much of the metabolism of neurotransmitters occur while neurotransmitters are inside cells or "intracellular". Taking SSRIs reduces the expression of the gene that encodes the serotonin transporter which returns serotonin to the sending neuron once serotonin has passed on its message to the receiving neuron. If you can prevent serotonin from being reabsorbed by neurons and keep it in the synapse, it may less impacted by the changes in MAO-A expression during menstruation.

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Thank you for your comprehensive response.

So, if I  am reading this right,  menopause and a significant drop in estrogen could well trigger serotonin/  dopamine functionality based events.

How did you learn about your genes such as you mention? Is there a specific section of the forum that discusses genetic testing for deeper inquiry?

I would LOVE to know my genetic predispositions to help troubleshoot MI issues with my healthcare team.

Edited by WytchyWoman

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21 minutes ago, WytchyWoman said:

Thank you for your comprehensive response.

So, if I  am reading this right,  menopause and a significant drop in estrogen could well trigger serotonin/  dopamine functionality based events.

Yep. In fact, extensive study of PMDD is how there's enough data to correlate changes in hormones to changes in neurotransmitter levels, BUT.....

21 minutes ago, WytchyWoman said:

How did you learn about your genes such as you mention? Is there a specific section of the forum that discusses genetic testing for deeper inquiry?

I would LOVE to know my genetic predispositions to help troubleshoot MI issues with my healthcare team.

....there is likely less data that specifically correlates hormone changes to changes in actual gene expression which ultimately lead to those changes in neurotransmitter levels.

As for how I know so much about it......a lot of reading. An obsessive number of hours doing so. In fact, the research has been a bit therapeutic when combined with talk therapy. What I've found is that for few studies that correlate specific genes to certain neurological functions, there's a smaller few more that directly contradict those findings. It's difficult reading the papers sometimes, because over time, you clearly see the bias that comes from certain people's work, especially when the papers were of clinical trials that were funded by pharmaceutical companies. It's good to look at that data, but in psychiatry, pharmaceutical companies rarely want to compare their new product to "incumbent" therapies to which medical professionals have grown accustomed.

But a lot of my research has shown me just how "in-absolute" your genes are. For example, they've found a correlation between inflammation and many different mental disorders. A large genome analysis study found that of all the mental health disorders from autism to schizophrenia to bipolar disorder, they all share crossover on CD genes or rather, the genes that encode your white blood cells. An overactive immune system where your white blood cells are constantly releasing toxins that are intended to destroy foreign bodies like bacteria and viruses end up inadvertently impacting the brain and other bodily systems. This would effectively make some mental conditions auto-immune disorders....if by a bit of a stretch. But this is also why there are some studies that show omega-3 from fish oil can reduce inflammation and a few that say it also is a good supplement for depression. I think there might be a small handful that show it can modestly improve the efficacy of antidepressants.

I recently did a study with 23andMe. They signed up 10,000 people I believe with either bipolar disorder or major depressive disorder. They allowed us to do the full 23andMe test for free and then had us take questionnaires about our mood and cognitive tests once a month for 9 months. I don't believe that the results of the study have been published yet. They partnered with another foundation and the pharmaceutical company. Lundbeck. for the study. I don't believe this was for Lundbeck's research. I believe they actually supplied the cognitive test. Because the same test I took for 9 months was ultimately used to add labeling to the Trintellix label showing that it improves cognitive function in those with depression. Bit of a coincidence? I think not.

Once your sample has been analyzed you can export the raw data and then use other online tools to analyze it SNP by SNP (single nucleotide polymorphism). There are some decent free tools, but I personally use SelfDecode. It is a recurring annual cost, but I use it enough that it's worth it to me. The nice thing about SelfDecode is that for each gene, it explains its general function, provides a list of SNPs for that gene in your DNA sample (if they were analyzed), and then also show you which substances alter the expression or reaction of those different genes. Then for each of your own SNPs on that gene, it will provide studies that analyzed the function of that specific SNP. I have A LOT of SNPs that say I'm at a higher risk for schizophrenia, but I'm bipolar, again lending to that lack of absolute effect that your genes have on who you are as a person.

I actually just finished reading an interesting study that correlated a specific variant of a SNP on the COMT gene matching mine that showed when taken with valproate, dextromethorphan significantly reduced the symptoms of bipolar depression in individuals that were otherwise stabilized. Dextromethorphan of course is the cough suppressant in all kinds of over-the-counter cold medicine, but of course you've heard of people going on "Robo-trips" and dextromethorphan is what causes the high. In moderate doses though it has shown a pretty robust antidepressant effect all its own. Only problem is that it doesn't last all day. So there's actually a company that's working on a combo of Wellbutrin+dextromethorphan for depression because Wellbutrin will increase dextromethorphan's blood levels.

Point of bringing up dextromethorphan though is that one of its most potent effects is its ability to block glutamate receptors in the brain. Glutamate is important for cognition and neuronal activation, but in high levels can be quite toxic. With low COMT and increased dopamine activity, this may have a downstream effect of increased release of glutamate to "excite" the brain and reinforce the "feel goods" that dopamine gives you. dextromethorphan blocks a specific type of glutamate receptors called NMDA receptors to cancel out some of the depressive effects that glutamate can have in excitotoxic levels.

The brain is a proxy war. Enemy A and Enemy B fight on Enemy C's turf. Like a game of whack-a-mole or trying to plug a leaky boat. Great, that antidepressant increased your serotonin, but now your dopamine activity is low, which may explain why you can't feel any pleasure and you can't have an orgasm. Add Wellbutrin to deal with the anhedonia and sexual dysfunction, now that increased norepinephrine and dopamine ramps up cortisol and glutamate which for bipolar disorder probably would lead to bipolar depression. Ketamine is being heavily researched right now for its antidepressant effects and it is a glutamate blocker at NMDA receptors like dextromethorphan. Another more natural over-the-counter example is your basic magnesium :)

Lots going on in this post, I know. But the point is, you can take the time to do all this research and find that all the things your doctor has been telling you to do to make you feel better are actually legitimate. Aspartame is an artificial sweetener quite frequently used. In the body, it can be converted to a compound that can bind to and activate NMDA receptors like glutamate. NMDA does stand for N-methyl-D-aspartate after all. Glutamate and gluten also sound similar for a reason. What do you think your body does with all that gluten? I'm not saying eliminate it, but a super high carb diet might just give you a sugar rush and ultimately make you more depressed. As I indicated in a previous post, if I eat healthy, quit smoking, and start exercising, it'll increase my testosterone, subsequently my COMT, and I'll probably feel a lot better.

Genes have also helped me target medications. Ultimately I have an under-expressed serotonin transporter, which MIGHT mean I can't tolerate antidepressants but historically I've never known them to be an issue. Nevertheless, my pdoc and I try to operate without them. I have an under-expressed MAO-A and COMT gene, which is likely why Depakote is my dream drug. It increases MAO-A and while it doesn't increase COMT, it does seem to prevent dopamine synthesis. If you can't help get rid of it, just keep the brain from making it in the first place. Lol. Also, it increases the conversion of glutamate to GABA and prevents it from being converted back or broken down into unusable compounds. 

Anyway, back to work. Enjoy! :)

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On 6-8-2018 at 12:56 PM, notloki said:

SSRI's do effect more than 1 neurotransmitter. Each SSRI is different from the others except they all affect serotonin. The theory of SSRI depleting came from the Internet, made up on some board, and not from science.

Yeah...when you google 'ssri dopamine depletion' you'll find a lot of discussion on the matter. Maybe some one came up with this theory and it was taken over by others, spreading all over forums.
I'm not sure if I ever read a scientific piece about this theory but surely it's all over the forums saying this is what's happening after prolonged use of SSRI's. 

In my case -with just my basic understanding of how the brain works- I think my brain must have adapted its self. I've been taking Luvox of and off for a few years, it pooped out, switched to Lexapro and after being in remission for 5 years it pooped out on me as well.
I took a drug holiday of 4 months, went on Zoloft but I wasn't responding to it like I was to the previous two meds. 
After 9 months I got back on Luvox. With my first Luvox trial it kicked in after 6, 7 weeks, but with the 2017 trial it took 3 months and it only partially worked for me.

So I figured that something has changed.
Depletion of dopamine doesn't actually make sense, because low dopamine isn't a typical symptom of intrusive thoughts. There just wasn't a reaction to the inhibition of serotonin anymore but that doesn't mean that dopamine is low. I don't have sexual dysfunction or anhedonia either. Just this unwanted annoying thought that keeps coming back.

Edited by Catwoman

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A Journal of Psychosomatics. Great.

psy·cho·so·mat·ic
ˌsīkōsəˈmadik/
adjective
 
  1. (of a physical illness or other condition) caused or aggravated by a mental factor such as internal conflict or stress.
    "her doctor was convinced that most of Edith's problems were psychosomatic"
    synonyms: (all) in the mind, psychological, irrational, stress-related, stress-induced, subjective, subconscious, unconscious
    "psychosomatic illnesses can produce very real physical symptoms"
    • relating to the interaction of mind and body.
  • Haha 1

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4 hours ago, notloki said:

A Journal of Psychosomatics. Great.

psy·cho·so·mat·ic
ˌsīkōsəˈmadik/
adjective
 
  1. (of a physical illness or other condition) caused or aggravated by a mental factor such as internal conflict or stress.
    "her doctor was convinced that most of Edith's problems were psychosomatic"
    synonyms: (all) in the mind, psychological, irrational, stress-related, stress-induced, subjective, subconscious, unconscious
    "psychosomatic illnesses can produce very real physical symptoms"
    • relating to the interaction of mind and body.

Well restless legs syndrome is a good example of a physical condition which is clearly caused by chemical changes happening in the brain. There's nothing wrong with the muscles, bones, the skin or the blood circulation. I don't think RLS has anything to do with internal conflicts or stress, but it's due the process with neurotransmitters that the restlessness is occuring. I'm not sure if RLS could be called a psychosomatic condition....

Edited by Catwoman

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4 hours ago, browri said:

 

@Catwoman has regularly reported restless leg syndrome with many SSRIs she has taken. This isn't necessarily because of dopamine depletion, but is quite possibly the result of reduced dopamine signaling due to higher serotonergic activity:

https://www.psychosomaticsjournal.com/article/S0033-3182(98)71370-2/abstract

Interesting article! I knew that my RLS is caused by increased serotonin, directly coming from using SSRI meds.  The RLS went away when I quit SSRI's.
But what I didn't realize is that dopamine signaling changes due to the inhibition of serotonin.

What I would like to figure out is what relation there is in the change in dopamine signaling is and my intrusive thought.
I know it disappeared after being on Luvox for 9 weeks. Same thing with Lexapro. 

We've always concentrated on serotonin, we know that OCD and related disorders are helped by inhibiting serotonin. But somehow things have changed 'inside' and some people stop responding to this method of action. Resulting in a relapse and less or even no response to other SSRI's.
What happened with dopamine when we're relapsing?

 

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5 hours ago, notloki said:

A Journal of Psychosomatics. Great.

psy·cho·so·mat·ic
ˌsīkōsəˈmadik/
adjective
 
  1. (of a physical illness or other condition) caused or aggravated by a mental factor such as internal conflict or stress.
    "her doctor was convinced that most of Edith's problems were psychosomatic"
    synonyms: (all) in the mind, psychological, irrational, stress-related, stress-induced, subjective, subconscious, unconscious
    "psychosomatic illnesses can produce very real physical symptoms"
    • relating to the interaction of mind and body.

Well they're called that because they follow the crossover/comorbidity of physical and mental illness. But I suppose this is a more suitable paper:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674976/

I'm sure you already know that some receptors cause dopamine release when activated like 5HT1A. However, the article linked above postulates that a good portion of the suppression of dopamine signaling can be overcome by a 5HT2C antagonist. It only focused on that one receptor of course because escitalopram is known to interact with that receptor and introducing a 5HT2C antagonist reduced escitalopram's negative impact on dopamine signaling.

Another good example would be this one:

https://academic.oup.com/ijnp/article/20/12/1036/3901225

Quote

"As previously mentioned, there is now a consensus that the majority of depressed patients treated with SSRIs do not obtain remission. The effect of these antidepressants on DA neurons may contribute to their low efficacy. Indeed, it has been shown that the administration of SSRIs such as fluoxetine or escitalopram induced a decrease in DA neuron firing rate in the VTA, whereas citalopram decreased the firing rate and the number of spikes per burst (Prisco and Esposito, 1995; Di Mascio et al., 1998; Dremencov et al., 2009). It is suggested that this class of antidepressant acts through 5-HT2C receptors (Prisco and Esposito, 1995; Dremencov et al., 2009). This is consistent with studies using lesions of the raphe nucleus showing an increase in the firing and bursting of DA neurons in the VTA (Guiard et al., 2008). Considering the critical role of DA in hedonic processes, the decrease in firing as well as the bursting activity by SSRIs might contribute to the resistance to antidepressants in some patients. Therefore, augmentation strategies, involving the addition of a second drug to an existing antidepressant therapy, are often used to optimize treatment, such as the addition of an atypical antipsychotic to an SSRI treatment (Ostroff and Nelson, 1999; Shelton et al., 2001; Thase et al., 2007). The United States Food and Drug Administration has approved several atypical antipsychotics as supplement to ongoing antidepressant treatment for treatment-resistant patients (Thase et al., 2007; Berman et al., 2009; Kato and Chang, 2013). The role of antipsychotics in increasing antidepressant activity has been confirmed by animal models. Thus, aripiprazole, an atypical antipsychotic, has been shown to potentiate the effect of citalopram in the forced swimming test (Bourin et al., 2009) and the effect of fluoxetine in the tail suspension test (Kamei et al., 2008). Interestingly, the combination of aripiprazole with the SSRI escitalopram reversed the inhibitory action of the antidepressant on serotoninergic, dopaminergic, and noradrenergic neuron firing (Chernoloz et al., 2009). The combination of fluoxetine with olanzapine, another atypical antipsychotic, also induces an increase in DA, 5-HT, and norepinephrine extracellular levels in the prefrontal cortex (Zhang et al., 2000). One question would be how would a D2 antagonist improve DA system function in a depressed state? We have found recently that repeated treatment with the second-generation antipsychotic quetiapine to the CMS rat model of depression effectively reversed the decrease in DA neuron population activity (Moreines et al., 2017). We believe this is due to the low-dose quetiapine activating the “silent” DA neurons to restore population activity, whereas the low level D2 blockade can be overcome via homeostatic compensation (e.g., increased D2 receptors, increased tyrosine hydroxylase activity, etc.)."

In a nutshell, antidepressants most likely cause anhedonia through suppression of dopamine signaling after chronic administration. If you consider that movement-related disorders from antipsychotic treatment such as restlessness could be related to a syndrome like restless legs, then perhaps the pathologies of akathisia vs RLS are not that dissimilar.

Another potential problem to consider is how these neurotransmitters are metabolized. If a patient has an over-expressed COMT gene, this could prove problematic with SSRI use. If dopamine signaling is reduced then that would mean most of the dopamine is intracellular which is where a good portion of monoamine and catecholamine metabolism occurs. If they're a fast metabolizer of catecholamines and their catecholamines are predominantly intracellular due to suppression of dopamine release, then you might have a problem. In that case, encouraging dopamine release with 5HT1A agonists or 5HT2A antagonists could be a good thing.

But then again, who am I. I just like to read too much. :D

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On 13-8-2018 at 10:39 PM, browri said:

 

But then again, who am I. I just like to read too much. :D

Yes, you probably read too much :D But in contrast to me you understand all this stuff better than I do ;-)

As people might notice I've been breaking my head over this issue.
Why did SSRI's stop working for me?
I think no one really knows....which is annoying because insecurity is almost unbearable.

Have to wait for the clomipramine to kick in....stuck on 50 mg for a while untill pdoc is back from vacation.

Edited by Catwoman

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      I'm tapering off clomipramine, right now I'm down to 75 mg.
       
      I've been on it for almost a year, but I'm not impressed with the results. I was hoping it would work better than my last two SSRI's (which seemed to do the best job when I took them for the first time) but I can't go higher than 100 mg because of side effects.

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    • By Distorted Me
      I know that a lot of bipolar folks take an SSRI as part of their daily regimen of meds and apparently it seems to help.  But there's some growing concern in the pdoc world now that SSRI's may be causing manic symptoms and even directly causing manic episodes.  I was on SSRI's for 10 years before quitting last October.  In chronological order:  Celexa, Zoloft, Celexa again, Lexapro, Zoloft again, Prozac, Zoloft again briefly, back to Prozac to close it out. 
      For me, personally, after stopping them altogether, I was able to see what they were doing to my system.  I truly believe they made me much more unstable and greatly increased compulsiveness and just made a bad situation worse.  Switching from Lexapro to Zoloft sent me immediately full-on hypomanic for over a month in early 2015.  I was high as a kite and on top of the fucking world.  It was unreal and so obvious at the time. From the beginning of it, I was certain something unusual was going on. Now I wasn't diagnosed bipolar yet, just depressed, so I didn't even know what hypomania was then.  It fizzled out eventually (sigh) but I had at least two more, shorter, and less intense episodes late spring 2015.  I've not had anything quite as euphoric as those since.
      My last pdoc expressed some concern about the prozac but wasn't very insistent on me stopping it, just that I would want to eventually.  I've since read that there is increasing concern in the pdoc community.  Yet a lot of bipolar people still take SSRI's and don't seem to have problems. 
      Do SSRI's seem to help your causes?  Do you notice any unusual side effects?  Have any of you stopped taking SSRI's and noticed a change?  Other comments?   This could be interesting.
    • By Alexir
      Hi, I'm a new member. Former English professor, had to shift to train for another career after long-term unemployment and still looking. I'm also an author of horror and fantasy books. I joined up here because I'm looking for some help after withdrawing from the SSRI Lexapro. The only thing worse than the side effects that caused me to quit are the withdrawal symptoms. I'm three months in and seriously wondering if I have cognitive impairment. It's as if somebody took my emotions and put them on a dimmer switch. Everything is numbed out. Lexapro causes such radical changes to the brain that withdrawal seems to be especially fraught with complications, and I'm afraid I may have tapered down too quickly--over five days, after taking it about three months. The immediate result was horrific, as though my brain were on fire. That burning sensation lessened, but was replaced by a sort of emotional numbness. I know that Lexapro controls blood flow to the limbic system, which is the site of emotions, and wonder if it's possible I sustained damage from pulling the plug too quickly. Thanks. 
    • By ztarrsbright
      Im not saying that doing coke is good, i have done Ketamine on the past whit no bad reaction whit my meds.
      Im taking Sertraline and Fluoxetine and also on 300mg Seroquel XR.
      I have acces to cocaine, i can take cocaine whit my meds, or it will blunt the effect of cocaine?.
      can i have a serotoninergic syndrome?
      I know drugs are bad ok, dont need to tell me that.
    • By cosima
      has anyone experienced this? its been linked to paxil and zoloft. 
      i'm not sure whether zoloft caused this issue for me or just worsened it to the point that it became noticeable to myself and others (didn't seem to have this prior to taking zoloft for the first time and the condition persisted off zoloft for years.. on zoloft again and i think the problem might be enhanced but i can't say that for any certainty). i've looked into it and its never specified whether the problem persisted after stopping the meds or whether it can be a permanent thing. 
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