77 replies to this topic

[Catwoman]

I am thinking, there is no guarantee clomi will work if fluvoxamine isn't working, they are both known to 'work' for a longer time than other SSRIs, perhaps when one poops-out on enough SRI-based drugs, then no SRI will keep working. If that's the case, then you need to focus on the cause of the poop-out (for which the models, we all can admit, are highly theoretical at this point).

 

 

https://www.ncbi.nlm...pubmed/21508860

 

Sarcosine therapy for obsessive compulsive disorder: a prospective, open-label study.

BACKGROUND:
Several lines of evidence implicate glutamatergic neurotransmission in the pathophysiology of obsessive compulsive disorder (OCD). Sarcosine is an endogenous antagonist of glycine transporter-1. By blocking glycine uptake, sarcosine may increase the availability of synaptic glycine and enhance N-methyl-d-aspartate (NMDA) subtype glutamatergic neurotransmission. In this 10-week open-label trial, we examined the potential benefit of sarcosine treatment in OCD patients.
METHOD:
Twenty-six outpatients with OCD and baseline Yale-Brown Obsessive Compulsive Scale (YBOCS) scores higher than 16 were enrolled. Drug-naive subjects (group 1, n = 8) and those who had discontinued serotonin reuptake inhibitors for at least 8 weeks at study entry (group 2, n = 6) received sarcosine monotherapy. The other subjects (group 3, n = 12) received sarcosine as adjunctive treatment. A flexible dosage schedule of sarcosine 500 to 2000 mg/d was applied. The primary outcome measures were Y-BOCS and Hamilton Anxiety Inventory, rated at weeks 0, 2, 4, 6, 8, and 10. Results were analyzed by repeated-measures analysis of variance.
RESULTS:
Data of 25 subjects were eligible for analysis. The mean ± SD Y-BOCS scores decreased from 27.6 ± 5.8 to 22.7 ± 8.7, indicating a mean decrease of 19.8% ± 21.7% (P = 0.0035). Eight (32%) subjects were regarded as responders with greater than 35% reduction of Y-BOCS scores. Five of the responders achieved the good response early by week 4. Although not statistically significant, drug-naive (group 1) subjects had more profound and sustained improvement and more responders than the subjects who had received treatment before (groups 2 and 3). Sarcosine was tolerated well; only one subject withdrew owing to transient headache.
CONCLUSION:
Sarcosine treatment can achieve a fast therapeutic effect in some OCD patients, particularly those who are treatment naive. The study supports the glycine transporter-1 as a novel target for developing new OCD treatment. Large-series placebo-controlled, double-blind studies are recommended.

 

 

Sarcosine and Agmatine are dirt cheap, and are very low risk when taken at clinically relevant dosages. I don't see why you shouldn't experiment with them before moving to clomipramine. According to animal models, 200-400 mg of Agmatine per day is all you need for anti-ocd/anti-depressant potentiation effects, and 500-1000 mg Sarcosine.

 

I'm beginning to think the same regarding SSRI's and clomipramine. The only difference is that clomi's Ki-value for SERT is much lower  (0.14–0.28) than fluvoxamine (2.2), but this doesn't say everything about efficacy I guess. 
After all, I was on sertraline for 8 months and it had no effect at all. 

So on one side there's a suspicion that long term use of SSRI's has something to do with the loss of response. 
It isn't such a weird idea to focus on getting them work again, since I was able to tolerate them and it was a successful treatment.

On the other hand I do want to consider taking an anti-psychotic.
I seem to be dealing with an overactive thought process. Not the same as racing thoughts and/or intrusive voices, but maybe long term use of SSRI's does have influence on dopamine release? 

I'll look into agmatine and sarcosine again and I'm dropping the idea of trying NAC for a second time.

[Mind_Paralysis]

Memantine.

Ziprasidone.

 

VORTIOXETINE.

[Catwoman]

Memantine.

Ziprasidone.

 

VORTIOXETINE.

Hahaha, I love you Stink  

You already know that Geodon (Ziprasidone) isn't available in my country.

Brintellix (Vortioxetine) is promising. I checked out another board and most people recommend it.

Memantine...well, I let you know ;-)

Edited by Catwoman, 10 November 2017 - 12:18 PM.

[Catwoman]

They are all prescription drugs though.

I think what Adam meant was that it could be easier to try an over-the-counter alternative before asking for the big guns

[Mind_Paralysis]

 

Memantine.

Ziprasidone.

 

VORTIOXETINE.

Hahaha, I love you Stink  

You already know that Geodon (Ziprasidone) isn't available in my country.

Brintellix (Vortioxetine) is promising. I checked out another board and most people recommend it.

Memantine...well, I let you know ;-)

 

 

Aww, cheers for the luv', mate! ^^ I think you're pretty cool too.

 

 

D'oh! I actually forgot about Ziprasidone not being available - but hey, there is always the black markets, yes...? ; )

 

Interesting and encouraging to hear that others may have trialled Vortioxetine for OCD and had promising results btw. I'm actually considering it myself, since I have some issues with both depressive and obsessive thoughts myself - seems to be an agent starting to become more commonly prescribed for people with attentive problems like me btw, here in my jurisdiction.

 

 

They are all prescription drugs though.

I think what Adam meant was that it could be easier to try an over-the-counter alternative before asking for the big guns

 

 

Ok, a fair point - I don't think anything but the big guns are going to work though, since you have such a treatment-resistant form of OCD.

Edited by Stinkorninjor, 10 November 2017 - 08:08 PM.

[Catwoman]

 

Interesting and encouraging to hear that others may have trialled Vortioxetine for OCD and had promising results btw. I'm actually considering it myself, since I have some issues with both depressive and obsessive thoughts myself - seems to be an agent starting to become more commonly prescribed for people with attentive problems like me btw, here in my jurisdiction.

 

 

Been reading up on Trintellix / vortioxetine.
According to its Wikipedia it inhibits SERT and NET, but it is considered a serotonin modulator and stimulator. I don't understand how it is different from an SSRI if it inhibits SERT?  

Or does this have to do with the antagonistic and agonist properties of vortioxetine?

If I understand correctly, SSRI's usually don't antagonize or agonize anything? 


 

Vortioxetine and Ziprasidone in particular are both 5ht1d-antagonists, which is a receptor connected to OCD-symptoms - some new hypothesis postulate that much like with the down-regulation of other 5ht-receptors for depression and anxiety respectively, the down-regulation of 5ht1d is what makes SSRI's work on OCD.

 

Both escitalopram and fluvoxamine helped me, but their binding profiles don't mention the 5-HT1D receptor.
Sertraline didn't work for me and according to Wikipedia it binds to 5-HT1A ,5-HT2A and 5-HT2C.

So maybe 5-HT1D is still 'untouched' territory in my body?

I'm not sure if Trintellix could help with anything other than depression though. It's trial and error probably.
 

[Catwoman]

Sarcosine and Agmatine are dirt cheap, and are very low risk when taken at clinically relevant dosages. I don't see why you shouldn't experiment with them before moving to clomipramine. According to animal models, 200-400 mg of Agmatine per day is all you need for anti-ocd/anti-depressant potentiation effects, and 500-1000 mg Sarcosine.

 

 

 

Well, since I found your post promising I looked for both agmatine and sarcosine, but couldn't find them at any store in my country. 
The problem with agmatine is that it's not approved by the food and drug administration in my country (or anywhere else in Europe). It is considered a 'novel food' and is under investigation for safety. I don't have good experience with buying supplements at stores like iherb.com, because I had to pay import taxes every time I ordered something. With agmatine I'm not even sure they would ship it to my country either.

I found this article https://nootropix.co...osine-d-serine/
but I guess sarcosine and d-serine aren't as popular as N-acetylcysteine and because I never tried NAC as an adjunct to an SSRI I decided to order it again. And it's really cheap as well. 
It might pairs nicely with magnesium and zinc, which I still have in my cupboard.

[hydrus]

 

 

 

It changes from person to person. I like to call ashwagandha a pseudo-adaptogen, because it is not perfectly adaptogenic, I'll explain. In a majority of people ashwagandha normalizes cortisol and thyroid markers, if they're high then it decreases them, if they're low then it increases them. However, for some people it will decrease cortisol and increase thyroid dose dependently, which can lead to hyperthyroidism. Ashwagandha doesn't directly increase sex hormones, but can indirectly effect them as it changes the cortisol and thyroid levels. Decreasing high levels of cortisol can increase sex hormones. Increasing low levels of cortisol can restore sex hormones too. Increasing hypothyroid to euthyroid can increase estrogen and testosterone, but if it increases further to hyperthyroidism then that can increase SHBG which decreases "free" sex hormones.

 

 

 

 

 

How long does one need to take it to achieve that effect?

[Mind_Paralysis]

 

 

Interesting and encouraging to hear that others may have trialled Vortioxetine for OCD and had promising results btw. I'm actually considering it myself, since I have some issues with both depressive and obsessive thoughts myself - seems to be an agent starting to become more commonly prescribed for people with attentive problems like me btw, here in my jurisdiction.

 

 

Been reading up on Trintellix / vortioxetine.

 

1. According to its Wikipedia it inhibits SERT and NET, but it is considered a serotonin modulator and stimulator. I don't understand how it is different from an SSRI if it inhibits SERT?  

2. Or does this have to do with the antagonistic and agonist properties of vortioxetine?

3. If I understand correctly, SSRI's usually don't antagonize or agonize anything? 


 

Vortioxetine and Ziprasidone in particular are both 5ht1d-antagonists, which is a receptor connected to OCD-symptoms - some new hypothesis postulate that much like with the down-regulation of other 5ht-receptors for depression and anxiety respectively, the down-regulation of 5ht1d is what makes SSRI's work on OCD.

 

4. Both escitalopram and fluvoxamine helped me, but their binding profiles don't mention the 5-HT1D receptor.
Sertraline didn't work for me and according to Wikipedia it binds to 5-HT1A ,5-HT2A and 5-HT2C.

So maybe 5-HT1D is still 'untouched' territory in my body?

I'm not sure if Trintellix could help with anything other than depression though. It's trial and error probably.
 

 

 

1. It's actually an SNRI when it comes to the indirect effects though, not an SSRI - a bit like Venlafaxine and Duloxetine - the added actions at different receptors alters those effects though, much like how many whom have tried TCA's (primarily snri's), the old Antidepressants, swear that they experience different effects, so does the added actions of Vortioxetine make it more than an SNRI.
 

2. It most definitively does - the other actions actually both compete with, and enhance the effects of the SRI-effects - ALL SRI's attach to ALL serotonin-receptors, but SECONDARILY - i.e, they increase Serotonin, which then, of course, attaches to every single receptor and increases signalling - the added serotonin-actions of Vortioxetine makes it so that the already boosted actions of Serotonin, are then even FURTHER enhanced, or actually diminished. This then leads to increased efficacy in some regards, and decreased side-effects to some extent. (at least that was the general idea when it was created - the 5ht1a -effects are supposed to make it a faster-acting antidepressant, by increasing activity at that receptor immediately)

 

3. Not directly, but all SSRI's act through Serotonin itself on every single serotonin-receptor - in practise this is mostly just agonism, but some SSRI's make serotonin punch certain receptors so damn hard, that after a certain dosage, the body corrects the heightened activity by over-compensating, essentially causing antagonism, but thrice removed from the original effect.

 

So it doesn't matter if Escitalopram and Fluvoxamine doesn't have direct actions on the 5ht1d-receptor, through this effect, which comes in stages, they would still effect the 5ht1d-receptor - Escitalopram in particular, since it is so unbelievably potent, will overload serotonin-activity much quicker, causing the body's own antagonisation to kick in faster.

 

You have me questioning the effects of Vortioxetine on OCD though... because the agonising effects on 5ht1a does increase the antidepressant effects of Vort'... so, would then the antagonisation of 5ht1d instead SLOW DOWN the beneficial effects on OCD...? Hard to tell... It might be the other way around though - which is why I suggested it at the start.

 

 

Btw, a quick look at sertralin shows me that the affinities for those receptors are more than 2000 each - this actually means that Sertraline is still an SSRI, since that means the affinity is so low, that unless you take an inhumanly dangerously high over-dose of it, it won't ever effect those receptors in any meaningful way - most of the sertraline will attach to the 5ht-transporter, and the small, small amount left, won't be able to actually effect those receptors, it's too little.

 

 

Interesting note on Vortioxetine btw... the cognitive effects could actually be caused by the 5ht3-antagonism it carries! Because 5ht3-antagonism is being researched as a means of treating negative symptoms within schizophrenia. Maybe I ought to start suggesting Vortioxetine for the schiz' on this forum, whom have depression...? The 5ht3-antagonism is actually one of it's strongest affinities!

[Catwoman]

Right, so vortioxetine could be something....or not....  
I'm meeting with a new psychiatrist in a few weeks. Maybe she can tell me more about it.

I'm almost sure that Luvox, or any other SSRI, will not kick in. After 6 weeks I should have noticed something.

I'm not overly excited about the anti-psychotic route, but 

 

 

The dopamine system plays a modulatory role with regard to the 'stress response' system, often indirectly through serotonin pathways. There appears to be an inverse relationship between brain dopamine and serotonin, which is neurodevelopmentally based. In the prefrontal cortex, dopaminergic innervation in nonhuman primates changes dramatically during adolescence before stabilizing in the adult. In contract, serotonergic innervation of the prefrontal cortex is fully developed much earlier in the life-cycle (Goldman-Rakic & Brown, 1982, Roserberg & Lewis, 1994, Rosenberg & Keshavan 1998). Specifically the delicate balance between dopamine and serotonin is changing, producing a relative excess of dopamine transmission during the age of onset of certain anxiety disorders (e.g OCD)(Rosenberg & Keshavan, 1998). In as far as increased activity of the direct basal ganglia pathway (Baxter et.al, 1996)compared to the indirect pathway [lays a major role in pathophysiology of disorders such as OCD, dopaminergic modulation can represent a therapeutic strategy (McDougle et.al 1990). Dopamine receptor stimulation results in activation of the direct basal gangla pathway while D2 stimulation inhibits the indirect pathway (Gerfen, 1992). Both of these action would tend to exacerbate OCD symptoms resulting in increased intrusive thoughts and behaviours (D1 activation) and lessened ability to inhibit these intrusive thoughts (D2 activation). For this reason, dopamine blockade, particularly mixed D1/D2 antagonists favouring D1 are used as adjunctive agents in treatment-resistent OCD (McDougle et.al 1990).

 

From: Anxiety Disorders in Children and Adolescents: Research, Assessment and Intervention, by Wendy K. Silverman, Philip D. A. Treffers

this is an interesting read. Though the book (2001) and the research sources are a bit old, they are probably reasonably up-to-date concerning the typical anti-psychotics.

And my intrusive thoughts started when I was around 19 years old. As a child I had anxiety attacks. 
Plus there's the genetic disposition of anxiety disorders and addiction issues of different family members.
Add the long-term use of SSRI's to the mix and.....tadaaa?? (or am I thinking too simple?)

Edited by Catwoman, 14 November 2017 - 01:14 PM.

[Catwoman]

 

 

P.S. As a last thought, Bacopa also increases SERT expression, but it doesn't seem to be antidepressant, instead the SERT expression is linked to the memory enhancement. Antidepressants will tend to target specific parts of the brain, maybe SSRIs and Bacopa upregulate expression in different parts of the brain? Could be worth pairing with SSRIs, needs to be studied.

Ordered a bottle of Bacopa today.
Most of the brands which are mentioned / recommended on Longecity forums aren't available in my country (or I'll need to order from amazon or iherb, with the risk of paying import taxes) but I finally found one with 50% bacosides. It was somewhat expensive, but better to get a good brand than something with only a very low percentage or without a complete label with ingredients at all. 

[Leon93]

Hi Catwoman,

 

I stumbled upon this post and I really want to offer you some help. I have been struggling with OCD a bit for more than 10 years now, but the last 3 years it was pretty harsh. Here is what helped: rTMS!!!

 

It´s amazing! You wouldn´t believe all the things I´ve tried: multiple medicine, CBT 3x, some talks, 2 other therapies I don´t even know what it was called.. but rTMS really helped!

I thought I would never got rid of the OCD, thought it was something life-ridden... just like sthira said in the first reply. But it can get better! Please, give rTMS a try! An average person needs about 30 sessions, I needed more, but I noticed improvements around the 20nd time.

 

About supplements, the people from the ´company´ I go to for rTMS know a lot about OCD and they told me all current supplements haven´t yet been shown to work. I don´t think they haven´t, there are RCTs, just very few. That´s why they say it. The three supplements (non-pharmaceutical) for OCD are inositol, valerian and NAC. I read you already tried NAC, not sure about the other two.

I haven´t tried them yet, but I think I´m only going to give valerian a try. Inositol has to be taken in 18g/day (which worries me for potential side-effects) and NAC messes with glucosamine (I suppose). My OCD is pretty good at the moment, but it can still do a little bit better. I am convinced OCD is a disease, just like any other physical disease.

 

I wonder how it goes! Keep me updated! Good luck,

 

Leon

[Catwoman]

Hi Catwoman,

 

I stumbled upon this post and I really want to offer you some help. I have been struggling with OCD a bit for more than 10 years now, but the last 3 years it was pretty harsh. Here is what helped: rTMS!!!

 

I wonder how it goes! Keep me updated! Good luck,

 

Leon

 
Hey Leon, thanks for posting on my topic!

I've read a lot about rTMS already and I've got the idea that results for OCD are still mixed. It also seems to depend on the severity and nature of the OCD.
dTMS  is supposed to treat OCD better than regular rTMS because it can reach areas deep within the brain. And that is neccessary with OCD, though not with all forms. 
I'm not sure what I would need, but to start with, my insurance only covers rTMS for depression. For other indications I need to pay for it myself. 
My gdoc could write me a referall to a rTMS clinic stating that I have depression (which is partly true, but most of my depression is caused by the Pure O) and the clinic could take my in for depression but treat me for OCD. Or so I'm guessing. 
It's a bit complicated, so I'm keeping it in mind if new medication doesn't work out.

Currently I'm taking 200 mg's of Luvox. 
I've also tried Bacopa for about a month. I liked it though I didn't notice any big results and I'm still pondering if I should buy a new bottle since I've run out. I also want to try ashwaghanda, so maybe I'll order both of them to see what the combination does.

I didn't feel anything special from NAC (Puritans Pride brand), but I still take magnesium citrate, which does help a little with restless legs.

On the 30th of Jan I have my first meeting with a psychiatrist.
My guess is that we'll consider an anti-psychotic, mood stabilizers and Anafranil. 

 

[rian]

I'm beginning to think the same regarding SSRI's and clomipramine. The only difference is that clomi's Ki-value for SERT is much lower  (0.14–0.28) than fluvoxamine (2.2), but this doesn't say everything about efficacy I guess. 
After all, I was on sertraline for 8 months and it had no effect at all. 

So on one side there's a suspicion that long term use of SSRI's has something to do with the loss of response. 
It isn't such a weird idea to focus on getting them work again, since I was able to tolerate them and it was a successful treatment.

On the other hand I do want to consider taking an anti-psychotic.
I seem to be dealing with an overactive thought process. Not the same as racing thoughts and/or intrusive voices, but maybe long term use of SSRI's does have influence on dopamine release? 

I'll look into agmatine and sarcosine again and I'm dropping the idea of trying NAC for a second time.

Sorry to chime in here, but I have a question: did you ever take sertraline on an empty stomach?

 

thanks much!

[Catwoman]

Sorry to chime in here, but I have a question: did you ever take sertraline on an empty stomach?

 

thanks much!

Sorry late reply...you might not read it unless you get reminders ;-)

I always took sertraline with some food or after breakfast. On an empty stomach made me nauseous. 

[Breakthrough]

Mind_paralysis have you ruled out drugs used to treat negative symptoms of schizophrenia (simple) for SCT?

[Mind_Paralysis]

Mind_paralysis have you ruled out drugs used to treat negative symptoms of schizophrenia (simple) for SCT?

 

Hmm, well a few of them - Reboxetine and Modafinil both didn't have much of an effect - I suppose third-gen antipsychotics like Brexpiprazole and the like, would be next then?

 

Do you have any suggestions?

[Breakthrough]

What sarcosine has managed to treat in some people seems like a similar set of symptoms to the cognitive troubles that I deal with.  I'm starting to consider treating this like simple schiz