77 replies to this topic

[CWF1986]

My personal experience is that the medications help give me enough of a push in the right direction so I can work on the skills and life changes to better manage the symptoms of my behavioral health diagnoses even further.  So instead of downward spiral I get a positive feedback loop!

[Nate-2004]

Honestly I'm glad it works for me but I think I can safely generalize when it comes to the theory/hypothesis that depression is a problem of post industrial times, or perhaps even post agricultural times, but most likely a modern disease that has become epidemic with the information age.  *If* it is true that depression is a disease of civilization and post industrial times then we are *all*, as homo sapiens, going to respond well to what I'm talking about to varying degrees of success. Our biology isn't THAT different and the term "chemical imbalance" is about as vague and unhelpful as an imbalance of the humours was pre-20th century. 

 

I love technology and I have a career in it, but we are *all* maladapted to it. We are all human. What works for me may actually work for you because of that. I don't doubt you've tried some of these things, that's not the point. The point is ALL of the things at the same time consistently for at least six months just to get it all going and then being continuously consistent about it forever, because that's what it takes to barely mimic what we were doing in the hunter gatherer times. You, as a human, have to work around our evolution. This isn't just me, it's not just you, it's all humans and probably most animals... I mean... dogs are getting depressed. This is our biology. It's not always such an individual case. Yes there are varying degrees of chemistry in us making us allergic to some things, making some drugs work but not others, etc, but when it comes to this, our basic common biology, we are ALL adapted mostly to the pre-agricultural revolution. Some of us might be able to drink milk, most people (65%) aren't. It will take thousands of years to catch up if CRISPR isn't a widely adopted approach to resolving these mal-adaptions. I'm telling you, it's not going to come down to a drug or supplement unless that drug modifies our base biology.

 

I'm just laying this out there, I know most people won't do it, but it's what you have to do to stay out of a chronic funk or to stop being so chronically anxious. This may even include some of the more tragic and difficult mental-illnesses like borderline and bi-polar disorder. 

[hydrus]

Bipolar disorder is even less of a lifestyle disease IMO. There have been studies with the amish tracing back ancestors with the illness over several generations. They felt it was something that was in their blood that was passed on and their lifestyle is a traditional as it gets.

 

There are structural brain abnormalities in borderline and bipolar disorder.

 

I don't understand why people accept that autism or schizophrenia or tourette's is an organic illness but deny that depression is.

 

I mean... dogs are getting depressed

 

 

Dogs get cancer too.

Edited by hydrus, 22 October 2017 - 08:34 AM.

[BlueCloud]

It's quite wrong to adopt a binary position on neurological and psychological views. The brain has a feedback loop where chemical issues rewire thought processes, which in turn can precipitate physiological changes in the brain, which in turn rewire the thought processes even more, etc... Thinking is basically rewiring synaptic pathways, and vice-versa.

 

I think It's been sufficiently demonstrated by now that some ( not all ) mental issues are a combination of BOTH chemical and psychological  issues. Depression and anxiety issues ( as well as some forms of OCD, which seems to be Catwoman's problem)  are up there in the list of problems that have a strong psychological aspect, while others like alzheimer or schizophrenia have little to no psychological influence.

 

That means that both aspects have to be tackled simultaneously in many cases of depression and anxiety to break the loop.

 

 

 

Edited by BlueCloud, 22 October 2017 - 01:24 PM.

[hydrus]

 

It's quite wrong to adopt a binary position on neurological and psychological views. The brain has a feedback loop where chemical issues rewire thought processes, which in turn can precipitate physiological changes in the brain, which in turn rewire the thought processes even more, etc... Thinking is basically rewiring synaptic pathways, and vice-versa.

 

 

I don't think mental illness has been shown being due to rewiring of synapses rewiring of synapses causing a chemical imbalance but maybe I am wrong. I think this idea has been promoted by pop psychology self-help book authors.

 

I think the neuroendocrine abnormalities found in depression show that the brain is unable to turn off a stress response/cortisol release. This can include happy stressors as well. 

 

People who go off an antipressant relapse fairly quickly even when they were stable and had normal thoughts for a long time. This is not consistent with a rewiring  model.

 

Also can one determine that schizophrenia is biological and depression is not?

Edited by hydrus, 22 October 2017 - 02:00 PM.

[BlueCloud]

 

 

It's quite wrong to adopt a binary position on neurological and psychological views. The brain has a feedback loop where chemical issues rewire thought processes, which in turn can precipitate physiological changes in the brain, which in turn rewire the thought processes even more, etc... Thinking is basically rewiring synaptic pathways, and vice-versa.

 

 

I don't think mental illness has been shown being due to rewiring of synapses rewiring of synapses causing a chemical imbalance but maybe I am wrong. I think this idea has been promoted by pop psychology self-help book authors.

 

I think the neuroendocrine abnormalities found in depression show that the brain is unable to turn off a stress response/cortisol release. This can include happy stressors as well. 

 

People who go off an antipressant relapse fairly quickly even when they were stable and had normal thoughts for a long time. This is not consistent with a rewiring  model.

 

Also can one determine that schizophrenia is biological and depression is not?

 

 

You misread what I wrote. The whole point of what I'm saying is that depression and anxiety have often BOTH ( emphasis is important ) biological AND psychological aspects. It's not a binary EITHER biological OR psychological. Saying that there may be psychological aspects in many cases, does not mean it automatically excludes biological bases.  That's precisely what I'm saying. I don't know where this binary concept came from in the first place.

 

Thoughts ARE biological processes, unless one believes in the soul and stuff like that. This is not pop-psychology. Thinking is a process of physically rewiring synaptic pathways.  But thoughts are a sort of "meta" biological processes, that involve many pathways through many parts of the brain. Anxious thoughts or perceptions ( whether justified or not ) will launch a spiral of physiological reactions throughout the body, heart increase, more sweating, cortisol changes, blood flow, etc..  There are studies that followed people doing heavy meditation, and shown through CAT scans that their amygdala physically shrinked after a few months. 

 

 

 

Abstract Mindfulness, a psychological process reflecting attention and awareness to what is happening in the present moment, has been associated with increased well-being and decreased depression and anxiety in both healthy and patient populations. However, little research has explored underlying neural pathways. Recent work suggests that mindfulness (and mindfulness training interventions) may foster neuroplastic changes in cortico-limbic circuits responsible for stress and emotion regulation. Building on this work, we hypothesized that higher levels of dispositional mindfulness would be associated with decreased grey matter volume in the amgydala.

http://journals.plos...al.pone.0064574

 

So, thought processes absolutely do create physical changes in the brain, since thoughts ARE physical changes. If you read my post again, I never said that depression ( and anxiety) is purely psychological, I said that they are among issues that are very likely to have a strong psychological component on top of the chemical aspect. The choice of words is very important here . "Very Likely" is not synonymous with "Always".There are certainly a lot of depression and anxious problems that can be precisely related to an identifiable single ( or not ) chemical imbalance. Vey likely  means there is a" high chance" of a psychological component, as opposed to "very low chance" of a psychological component in the case of problems like Alzheimers. 

We do know of many depression and anxiety cases that were successfully solved purely trough psychological therapy. As far as I know, we never heard of a single case of Alzheimers or Parkinson that got better purely through psychological therapy. 

It is very likely that we will find the definitive cure to Alzheimer or Parkinson before we find one for anxiety or depression, because the former can be very much reduced to a single ( or a number of ) physiological components, while the latter are in many cases a complex and inter-related combination of psy and phy components.

 

So, in cases where both components are present, tackling the psychological issues ( ON TOP of the chemical issues) prevents these from adding additional negative physiological changes , which in turn will be the source of more harmful thought processes, etc... A feedback loop. 

Edited by BlueCloud, 22 October 2017 - 03:25 PM.

[hydrus]

We do know of many depression and anxiety cases that were successfully solved purely trough psychological therapy. As far as I know, we never heard of a single case of Alzheimers or Parkinson that got better purely through psychological therapy. 

 

 

 

Just to be clear I think that "Depression" can be many things with different causes. I am not referring to situational depression (e.g living in a abusive relationship or divorce, financial problems etc.)

 

I was talking about serious clinical depression (recurring or chronic type)

 

I don't doubt that people can resolve personal issues and move on or that people with not so serious depression can learn to manage it with psychotherapy but I have known a fair share of people with depression and my impression is that resolving it with psychotherapy is the exception not the rule. I can only generalize and I am sure there will be cases that contradict this but it is generally true, at least my impression.

 

How many people get better with medication? A lot.

 

A lot of people say they were 'depressed' and they had a relationship breakup that makes them sad and for some reason they think they suffer from depression and treat it and get better but these people never had depression. They were depressed. I have known people who said they had depression and overcame it. Turns out they never had any mood problems in their life and developed it in middle age after losing a relative. After a few months they are out of it. They never had a depressive illness.

 

 

Edited by hydrus, 22 October 2017 - 04:32 PM.

[Adam Karlovsky]

 

It's just my opinion, but I think SSRIs are terrible drugs. Talk to your doctor about trying a prescription of tranylcypromine. It has a tapering up and adjustment period, but that's something to deal with because tranylcypromine is a powerful drug. It is a third line therapy, but you have tried two different antidepressants already, so you can now take it. If your doctor doesn't want to give you a MAOI because he's paranoid about the risks of MAOIs then find a new doctor.

For supplements, I'd suggest trying the sarcosine and n-acetyl-cysteine combo.

If 8 weeks of tranyl, sarc and NAC do not work, you could look into lamotrigine and memantine.

Important to note, assuming you haven't been medically diagnosed with OCD, you might just have depressive ruminations, which are quite different to OCD.

Most of the doctors I've spoken to say I have OCD. I like calling it "OCD-spectrum' because it's not the typical Pure O, but it's clearly obsessive in nature. Ruminations are part of it, the depressive symptoms are directly caused by the intrusive thought coming back again and again.

I would have no issues with staying on an SSRI for the rest of my life. If they only kept on working against the stupid intrusive thought....

I think my doctor would rather try me on a TCA first, like Anafranil (clomipramine), before starting any MAOi. There's not much research done on MAOis and OCD, and since I don't have the typical OCD (like obsessive cleaning or fears to hurt other people)....no idea if my new gdoc is open to it.
On the other hand, if I don't react to SSRI's anymore (thanks to tolerance????) then I need to look at other methods of action, instead of medications that inhibit the serotonin reuptake.

I might give NAC another try to go along with Luvox / fluvoxamine. I want to work my way up to 300 mg before switching to another psych med.
Adding sarcosine -don't know much about it- might be something. What does it do when combined with NAC?

Is adding a low dose of lamotrigine to an SSRI an idea? I've think I've read about this combo somewhere.

 

 

I should correct my previous statement by clarifying think it is a terrible choice to prescribe SSRIs as a first-line treatment for plain old depression. SSRIs and SRI TCAs like Clomi are entirely appropriate for OCD.  Certainly, if you are sure your symptoms are on the OCD-spectrum, then you should try Clomipramine next, as Clomipramine has the most evident efficacy for OCD, and OCD is likely most responsive to serotonin reuptake. 

 

You can safely combine Clomi with adjunct Sarcosine and NAC as far as I know. Remember sarcosine and NAC take 2-4 weeks to work, much like SSRIs.

 

I'll add that Agmatine can be a helpful adjunct for some people too.

If your symptoms are treatment-resistant enough to warrant starting Lamotrigine, remember to start low, 12.5-25 mg per day, and work your way up to your effective dose, so as to minimize your risk of rashes and other side effects.

[BlueCloud]

 

Just to be clear I think that "Depression" can be many things with different causes. I am not referring to situational depression (e.g living in a abusive relationship or divorce, financial problems etc.)

 

I was talking about serious clinical depression (recurring or chronic type)

 

I don't doubt that people can resolve personal issues and move on or that people with not so serious depression can learn to manage it with psychotherapy but I have known a fair share of people with depression and my impression is that resolving it with psychotherapy is the exception not the rule. I can only generalize and I am sure there will be cases that contradict this but it is generally true, at least my impression.

 

How many people get better with medication? A lot.

 

A lot of people say they were 'depressed' and they had a relationship breakup that makes them sad and for some reason they think they suffer from depression and treat it and get better but these people never had depression. They were depressed. I have known people who said they had depression and overcame it. Turns out they never had any mood problems in their life and developed it in middle age after losing a relative. After a few months they are out of it. They never had a depressive illness.

 

 

People do commit suicide while in situational depression. Situational depression or anxiety can become permanent and chronic if it's not resolved. Being exposed to significant and long stress situations will wreak havoc in your body and leave you with a permanent change in your sympathic/parasympathic system. 

What starts as situational can easily become a permanent biological and chemical change.

Edited by BlueCloud, 23 October 2017 - 10:36 AM.

[Catwoman]

 

 

I should correct my previous statement by clarifying think it is a terrible choice to prescribe SSRIs as a first-line treatment for plain old depression. SSRIs and SRI TCAs like Clomi are entirely appropriate for OCD.  Certainly, if you are sure your symptoms are on the OCD-spectrum, then you should try Clomipramine next, as Clomipramine has the most evident efficacy for OCD, and OCD is likely most responsive to serotonin reuptake. 

 

You can safely combine Clomi with adjunct Sarcosine and NAC as far as I know. Remember sarcosine and NAC take 2-4 weeks to work, much like SSRIs.

 

I'll add that Agmatine can be a helpful adjunct for some people too.

If your symptoms are treatment-resistant enough to warrant starting Lamotrigine, remember to start low, 12.5-25 mg per day, and work your way up to your effective dose, so as to minimize your risk of rashes and other side effects.

 

Clomipramine is a logical choice for OCD because of it's high affinity for serotonin, right? Since a drug like escitalopram worked for me, I could imagine clomi could as well.
Looking at Ki values for SERT I get the impression that it's a more effective drug to treat refractory OCD. On the other hand, if tolerance is the case (my case) -caused by long-term treatment with SSRI's- will clomipramine still work? 

I'll wait a little while with adding NAC, sarcosine, memantine, etc. This afternoon I have an appointment with my gdoc. I'm at 100 mg's of fluvoxamine right now, but I'm 3 weeks left from the 6-weeks mark. I think I'll need to go up in dose in order to get it working. 

 

 

It's quite wrong to adopt a binary position on neurological and psychological views. The brain has a feedback loop where chemical issues rewire thought processes, which in turn can precipitate physiological changes in the brain, which in turn rewire the thought processes even more, etc... Thinking is basically rewiring synaptic pathways, and vice-versa.

 

I think It's been sufficiently demonstrated by now that some ( not all ) mental issues are a combination of BOTH chemical and psychological  issues. Depression and anxiety issues ( as well as some forms of OCD, which seems to be Catwoman's problem)  are up there in the list of problems that have a strong psychological aspect, while others like alzheimer or schizophrenia have little to no psychological influence.

 

That means that both aspects have to be tackled simultaneously in many cases of depression and anxiety to break the loop.

I think I'll have to agree with BlueCloud on this one. 
I can't reallt explain, but my feeling is that my brain is thinking that thinking / having the 'death thought' is normal. I feel 'adjusted' to this thought. I don't like it, but I don't get anxious anymore. It has become a habit to have the thought in my head regularly. When I'm waking up in the middle of the night, the first thought that comes up is that thought. I just can't help it. And I'm still not able to unlearn to not react to this thought with aversion. 

Why am I'm not able to unlearn? Or take up a neutral standpoint? I'm suspecting this has psychological, chemical and biological reasons.
Maybe it even got harder to unlearn because of the tolerance effect.

[Finn]

 

I'll wait a little while with adding NAC, sarcosine, memantine, etc. This afternoon I have an appointment with my gdoc. I'm at 100 mg's of fluvoxamine right now, but I'm 3 weeks left from the 6-weeks mark. I think I'll need to go up in dose in order to get it working. 
 

 

 

 

 

When adding NAC, consider going pharmacy-sold effervescent tablets, preferably single-packed, but I suppose maybe tube doesn't degrade in 3-4 days too much for it to matters, if going for 3 x 600 mg a day. Getting them from Germany is probably cheaper, at cheapest around 15 cents a tablet for tube ones and slightly more for foil/blisterpack ones .

 

https://www.medizinf...rams[view]=list

 

 

 

Fox example, hospitals don't use concentrated oxygen when nebuliser dosing for liquid acetylcholine, because of oxygen causing degradation.

 

http://www.pharmpres...rugs sample.pdf

As a mucolytic via nebuliser (unlicensed): the adult dose is 3--5 mL acetylcysteine 20% injection, nebulised 3--4 times daily using air (use of concentrated oxygen causes degradation).

 

https://en.wikipedia.../wiki/Nebulizer

Nebulizers use oxygen, compressed air or ultrasonic power to break up solutions and suspensions into small aerosol droplets that can be directly inhaled from the mouthpiece of the device

 

 

Also there were couple interesting autism studies with different results, in the one with foiled tablets, there was great reduction in ABC irritability, in the other with non-foiled tablets didn't have similar effect.

 

 

http://www.sciencedi...006322312000534

 

https://molecularaut...3229-016-0088-6

Edited by Finn, 24 October 2017 - 10:21 AM.

[Catwoman]

 

 

I'll wait a little while with adding NAC, sarcosine, memantine, etc. This afternoon I have an appointment with my gdoc. I'm at 100 mg's of fluvoxamine right now, but I'm 3 weeks left from the 6-weeks mark. I think I'll need to go up in dose in order to get it working. 
 

 

 

 

 

When adding NAC, consider going pharmacy-sold effervescent tablets, preferably single-packed, but I suppose maybe tube doesn't degrade in 3-4 days too much for it to matters, if going for 3 x 600 mg a day. Getting them from Germany is probably cheaper, at cheapest around 15 cents a tablet for tube ones and slightly more for foil/blisterpack ones .

 

https://www.medizinf...rams[view]=list

 

 

So if I understand correctly then the tablets / capsules in bottles of NAC which are sold by supplement stores are less effective than the tablets which are individually packed in blisters or foils?

I also found a shop online in my own country which sells a powder form of NAC (and quite cheap as well). But that's not such a good idea as a thought looking at effectiveness of the product?

 

[Adam Karlovsky]

Yup, OCD responds particularly well to serotonin reuptake inhibition, likely also to some serotonin antagonists. Now I think about it, might be worth augmenting your Clomipramine with Agmatine and Nelumbo Nucifera extract. Agmatine has been shown to enhance antidepressants in rat studies, and Nelumbo has serotonin 2A/2C/7 antagonism and serotonin 1A agonism.

 

Just a note on the cognitive/experiential stuff... The main therapy for OCD is Exposure and Response Prevention Therapy, and in general Cognitive Behavioural Therapy is better than placebo for both OCD and OCPD. Medication with therapy has better efficacy than either alone.

[Catwoman]

Yup, OCD responds particularly well to serotonin reuptake inhibition, likely also to some serotonin antagonists. Now I think about it, might be worth augmenting your Clomipramine with Agmatine and Nelumbo Nucifera extract. Agmatine has been shown to enhance antidepressants in rat studies, and Nelumbo has serotonin 2A/2C/7 antagonism and serotonin 1A agonism.

 

Just a note on the cognitive/experiential stuff... The main therapy for OCD is Exposure and Response Prevention Therapy, and in general Cognitive Behavioural Therapy is better than placebo for both OCD and OCPD. Medication with therapy has better efficacy than either alone.

 I did 4 years of different therapies  I started out with hypnotherapy (this didn't have much effect), moved on to acupuncture and chinese herbs and a few years later I started with CGT. 
The psychotherapist I advised me to add medication (paroxetine was the one he mentioned) and once the medication started working (in my case, fluvoxamine) I was free of intrusive thoughts. 

I'm sure it was the serotonin reuptake inhibition effect and once it pooped out I moved on to escitalopram, which is very selective for serotonin. 

The problem is now...it seems like the things I learned with CGT didn't stick and escitalopram pooped out as well. Sertraline, the third SSRI, didn't work at all. 

If fluvoxamine (I'm at the 4 week mark today) doesn't work, I think I will try clomipramine. 

On the other hand, this is also a reuptake inhibitor. If tolerance to SSRI's is the case, I wonder if I'll respond to serotonin reuptake inhibition at all.

I know how these therapies and medications work....But I don't know how to keep these working.

[Adam Karlovsky]

Ashwagandha can help 5-ht1 to 2a signalling ratios and treat the HPA axis. This might help with your SSRI tolerance, but it's highly theoretical. I suspect Poop-out Effect is a combination of genetic predisposition for SERT gene dysregulation, and the ratio'd balance of serotonin receptor signalling, for you in particular the 2aR gene dysregulation (OCD), which can have downstream effects on the HPA axis.

 

I mean, pretty much all antidepressants upregulate SERT expression, change the 1a to 2a receptor ratios, and treat HPA axis under/over- activity. The neglected research question is why doesn't it last?

 

One hypothesis is that SERT upregulates, this leads to 5-HT accumulation, and over time the accumulation leads to receptor ratio changes, and there is an initial improvement in the HPA axis. Then those ratio changes predispose the system to a compensatory dysregulation of the HPA axis, which then works back around to suppressed SERT expression, receptor dysfunction, and unfavourable receptor ratios. Bleargh.

 

An excerpt from "The mechanisms of tolerance in antidepressant action"

 

5HT2post-synaptic down-regulation,a putative final common path way of different antidepressant actions (Leonard, 1996), by facilitating 5HT1receptor mediated neurotransmission, may induce an activation of the HPA axis. This latter, in turn, may unfavorably affect serotonin receptor functioning(Van Praag, 1996). An example of this interaction is provided by the use of specific 5HT2 receptor antagonists (ritanserin and ketanserin) in Cushing's disease, which often yield only a temporary decrease in ACTH and cortisol secretion, followed by an escape phenomenon (Soninoet al., 2000). An impressive body of evidence (Holsboer and Barden,1996; Pariante and Miller, 2001) supports the concept of an antidepressant mechanism of action that exerts its effects beyond the cell membrane receptors of biogenic amines and lead to enhanced glucocorticoid receptor function and expression. The phenomena observed with long-term use of serotonin receptor antagonists inCushing's disease have thus considerable relevance, particularly if compared to the fact that long-term treatment with inhibitors of steroid production is unlikely to yield the same phenomenon (Sonino and Fava,2002). It has thus been postulated (Sonino and Fava, 2002)thatlong-term treatment with antidepressant drugs in non-endocrine depression, after an initial phase of normalization of the HPA axis, may recruit its ACTH dependent activation, which results in loss of clinical effect. The poor prognosis of remitted patients still displaying abnormalities of the HPA axis is in line with this hypothesis (Sonino and Fava, 2002). Activation of hormonal markers of stress response following discontinuation of SSRI has been described (Michelson et al., 2000b) and thus may lead to increased vulnerability to relapse in susceptible individuals.

 

OCD has been linked to the SERT gene mutations and 2a receptor gene mutations.

 

I reckon we could test this hypothesis in ashwaganhda-responsive patients. If the hypothesis is true, and the ashwa prevents the compensatory HPA-axis dysregulation, ashwa could also prevent Poop-out Effects?

 

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.

[Eryximachus]

Ashwa?

 

 

1) Psychology is a social science.  It is not a medical science.  Marxists who did not believe in genetics and religiously believed in the tablua rasa myth used psychology as a propaganda tool, one of which was psychotherapy.  This conflict is mostly not discussed in the West as psychology was originally primarily about eugenics.  While never really implemented in the Third Reich due to war, it is taboo for this reason.   

 

2) The taboo is less relevant today as eugenics doesn't really matter anymore.  Every dog breeder even in some remote Alaskan village knows you breed the smart, obedient ones with the smart, obedient ones and you get even smarter, obedient ones.  The basics of genetics are common knowledge, but make social organization in modern times difficult.  The reality is most people do not have the requisite intelligence to serve any meaningful function in society.  In the US, we pretend these problems don't exist. I won't get into my personal theories on the reasons, but as another poster mentioned - CRISPR technology is already being used to edit the genomes of fertilized eggs to maximize high intelligence and minimize psychological problems.  Evolutionary psychology, since 2003, has always been about correlating human behavior with genetics.  To clarify, while we will be able to design humans for various tasks rather quickly and are already doing so, it will be a long time before we can alter adult humans.  Using CRISPR on a single egg is entirely different from anything else.

 

3) For the above poster, antipsychotics are the way to go.  SSRIs are mostly crap and you've been at this game for 10 years.  It's time to bring out the big guns, and Zoloft is not it.   

[Catwoman]

Hi Adam, thanks for replying. 
I don't think herbs like ashwagandha and bacopa should be combined with SSRI's. I'm also wondering if ashwaganda isn't more effective against direct anxiety. I don't feel anxious at all.

 

[Catwoman]

 

 

3) For the above poster, antipsychotics are the way to go.  SSRIs are mostly crap and you've been at this game for 10 years.  It's time to bring out the big guns, and Zoloft is not it.   

Can you clarify why you think anti-psychotics are the way to go, for me? And which one comes to mind?

 

[hydrus]

Ashwa?

 

 

1) Psychology is a social science.  It is not a medical science.  Marxists who did not believe in genetics and religiously believed in the tablua rasa myth used psychology as a propaganda tool, one of which was psychotherapy.  This conflict is mostly not discussed in the West as psychology was originally primarily about eugenics.  While never really implemented in the Third Reich due to war, it is taboo for this reason.   

 

2) The taboo is less relevant today as eugenics doesn't really matter anymore.  Every dog breeder even in some remote Alaskan village knows you breed the smart, obedient ones with the smart, obedient ones and you get even smarter, obedient ones.  The basics of genetics are common knowledge, but make social organization in modern times difficult.  The reality is most people do not have the requisite intelligence to serve any meaningful function in society.  In the US, we pretend these problems don't exist. I won't get into my personal theories on the reasons, but as another poster mentioned - CRISPR technology is already being used to edit the genomes of fertilized eggs to maximize high intelligence and minimize psychological problems.  Evolutionary psychology, since 2003, has always been about correlating human behavior with genetics.  To clarify, while we will be able to design humans for various tasks rather quickly and are already doing so, it will be a long time before we can alter adult humans.  Using CRISPR on a single egg is entirely different from anything else.

 

3) For the above poster, antipsychotics are the way to go.  SSRIs are mostly crap and you've been at this game for 10 years.  It's time to bring out the big guns, and Zoloft is not it.   

 

 

 

The reality is most people do not have the requisite intelligence to serve any meaningful function in society.

 

 

Depends on how you define meaningful. If you need a haircut, will you do it yourself? A large part of society depends on supposedly unimportant workers with meaningless jobs. We could easily live without astrophysicists but would not survive without farmers.

 

wouldn't it  be better to try SNRI's or other non-SSRI antidepressants before moving on to antipsychotics?

 

At least some antipsychotics can cause permanent neurological damage that can be very distressing. While the symptom described is very distressing it is nothing like Psychosis where the benefits of APs can outweigh the risks and side effects.

Edited by hydrus, 02 November 2017 - 05:17 PM.

[Eryximachus]

 

 

It's quite wrong to adopt a binary position on neurological and psychological views. The brain has a feedback loop where chemical issues rewire thought processes, which in turn can precipitate physiological changes in the brain, which in turn rewire the thought processes even more, etc... Thinking is basically rewiring synaptic pathways, and vice-versa.

 

 

I don't think mental illness has been shown being due to rewiring of synapses rewiring of synapses causing a chemical imbalance but maybe I am wrong. I think this idea has been promoted by pop psychology self-help book authors.

 

I think the neuroendocrine abnormalities found in depression show that the brain is unable to turn off a stress response/cortisol release. This can include happy stressors as well. 

 

People who go off an antipressant relapse fairly quickly even when they were stable and had normal thoughts for a long time. This is not consistent with a rewiring  model.

 

Also can one determine that schizophrenia is biological and depression is not?

 

 

 

For any human behavior that can be reliably measured, there is a genetic component.  So, in this sense, all human behavior is biological in origin.  

[Eryximachus]

 

Ashwa?

 

 

1) Psychology is a social science.  It is not a medical science.  Marxists who did not believe in genetics and religiously believed in the tablua rasa myth used psychology as a propaganda tool, one of which was psychotherapy.  This conflict is mostly not discussed in the West as psychology was originally primarily about eugenics.  While never really implemented in the Third Reich due to war, it is taboo for this reason.   

 

2) The taboo is less relevant today as eugenics doesn't really matter anymore.  Every dog breeder even in some remote Alaskan village knows you breed the smart, obedient ones with the smart, obedient ones and you get even smarter, obedient ones.  The basics of genetics are common knowledge, but make social organization in modern times difficult.  The reality is most people do not have the requisite intelligence to serve any meaningful function in society.  In the US, we pretend these problems don't exist. I won't get into my personal theories on the reasons, but as another poster mentioned - CRISPR technology is already being used to edit the genomes of fertilized eggs to maximize high intelligence and minimize psychological problems.  Evolutionary psychology, since 2003, has always been about correlating human behavior with genetics.  To clarify, while we will be able to design humans for various tasks rather quickly and are already doing so, it will be a long time before we can alter adult humans.  Using CRISPR on a single egg is entirely different from anything else.

 

3) For the above poster, antipsychotics are the way to go.  SSRIs are mostly crap and you've been at this game for 10 years.  It's time to bring out the big guns, and Zoloft is not it.   

 

 

 

The reality is most people do not have the requisite intelligence to serve any meaningful function in society.

 

 

Depends on how you define meaningful. If you need a haircut, will you do it yourself? A large part of society depends on supposedly unimportant workers with meaningless jobs. We could easily live without astrophysicists but would not survive without farmers.

 

wouldn't it  be better to try SNRI's or other non-SSRI antidepressants before moving on to antipsychotics?

 

At least some antipsychotics can cause permanent neurological damage that can be very distressing. While the symptom described is very distressing it is nothing like Psychosis where the benefits of APs can outweigh the risks and side effects.

 

 

Psychology is a social science.  Psychiatry is medicine.   The purpose of medicine is not simply to cure disease, but to change people so they better function in society.  Meaning and function are social in origin, and mostly derive from the diverse evolutionary origins of man since civilization began.  Ultimately, until you or I become King, or opinions are irrelevant.  

 

To the OP, antipsychotics carry risks.  All psychiatric drugs carry risks.  This is someone who has had trouble functioning for 10 years.  Unlike SSRIs, AAPs work fast and results should manifest quickly.  

 

AAPs can cause irreversible tardive dyskinesia, but there is no risk they can cause permanent neurological damage.  

 

I've seen Seroquel work wonders on people who are in extreme distress.  I gave the OP a recommendation that should manifest results in a month.  After that, a decision can be made about the risks.  

[hydrus]

AAPs can cause irreversible tardive dyskinesia, but there is no risk they can cause permanent neurological damage.  

 

 I thought that  tardive dyskinesia would qualify as permanent neuro damage.

 

I've seen Seroquel work wonders on people who are in extreme distress. 

 

 

I think Seroquel is one of the better ones and is not associated with  tardive dyskinesia I believe. I am not saying that all AP are bad or will cause damage but many can do.

[Adam Karlovsky]

Ashwagandha can be taken safely with SSRIs. In fact here's a study where everyone was on SSRIs and got improvements specifically in OCD-symptoms from ashwagandha.

http://www.sciencedi...300504?via=ihub

 

 

All patients were under treatment with Selective Serotonin Re-uptake Inhibitors (SSRIs), and were instructed to take 4 capsules of the extract or placebo per day, preferably after meals, for a period of six weeks. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used in order to assess the severity of OCD symptoms at baseline and at the end of the trial.

Results

Comparison of the change in Y-BOCS score during the course of the trial revealed a significantly greater effect of W. somnifera (26 (14–40) [pre-treatment] versus 14 (4–40) [post-treatment]; change: −8 (−23 to 0)) versus placebo (18 (11–33) [pre-treatment] versus 16 (10–31) [post-treatment]; change: −2 (−4 to 0)) (P < 0.001). The extract was safe and no adverse event was reported during the trial.
Conclusion

W. somnifera extract may be beneficial as a safe and effective adjunct to SSRIs in the treatment of OCD.

 

Also, not all SSRIs are created equal. For example, poop-out effect is much less likely to occur for tricyclics, in fact tricyclics have 25% of the chance to poop-out compared to non-trycyclic SSRIs. Clomipramine is a trycyclic and has lower rates of poop-out, and has been shown to have a higher response rate for OCD than fluoxetine, so it's worth trying this before jumping on antipsychotics. Psychiatry algorithms will tend to Try fluoxetine first, clomipramine second, then clomipramine + antipsychotic third. I don't know why old algorithms have more than about 3 or 4 steps, jumping from SSRI to SSRI just makes people miserable and in the case of comorbidity with depression it literally kills people because people commit suicide before they're put on something that has a high chance of actually working.

 

 

wouldn't it  be better to try SNRI's or other non-SSRI antidepressants before moving on to antipsychotics?

 

Yes. I mentioned before the lotus extract, it's 2a/2c antagonism creates atypical antipsychotic effects, the advantage is it doesn't block dopamine so you don't have the risk of tardive.

 

There is no inherent mechanistic safety issue with combining bacopa with SSRIs, bacopa does not have any serotonin release effect, and has no MAO inhibition. You'd only want to know you're not taking drugs that are metabolized by CYP3A4. Neither fluoxetine nor clomipramine are metabolized by this enzyme, they are metabolized by CYP2D6. Lotus extract has some CYP2D6 inhibition so you shouldn't take that unless you're going to monitor your antidepressant blood levels, which you can do if you can be bothered, but maybe it's not worth it for you.

 

There are some mouse studies suggesting agmatine might be helpful for OCD as well, and it is a general potentiator of antidepressants and analgesics, without any enzyme interactions.

 

Anyway, clomipramine + ashwagandha + agmatine is a reasonable next step. This talk of taking antipsychotics is silly.

[Eryximachus]

Ashwagandha can be taken safely with SSRIs. In fact here's a study where everyone was on SSRIs and got improvements specifically in OCD-symptoms from ashwagandha.

http://www.sciencedi...300504?via=ihub

 

 

All patients were under treatment with Selective Serotonin Re-uptake Inhibitors (SSRIs), and were instructed to take 4 capsules of the extract or placebo per day, preferably after meals, for a period of six weeks. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used in order to assess the severity of OCD symptoms at baseline and at the end of the trial.

Results

Comparison of the change in Y-BOCS score during the course of the trial revealed a significantly greater effect of W. somnifera (26 (14–40) [pre-treatment] versus 14 (4–40) [post-treatment]; change: −8 (−23 to 0)) versus placebo (18 (11–33) [pre-treatment] versus 16 (10–31) [post-treatment]; change: −2 (−4 to 0)) (P < 0.001). The extract was safe and no adverse event was reported during the trial.
Conclusion

W. somnifera extract may be beneficial as a safe and effective adjunct to SSRIs in the treatment of OCD.

 

Also, not all SSRIs are created equal. For example, poop-out effect is much less likely to occur for tricyclics, in fact tricyclics have 25% of the chance to poop-out compared to non-trycyclic SSRIs. Clomipramine is a trycyclic and has lower rates of poop-out, and has been shown to have a higher response rate for OCD than fluoxetine, so it's worth trying this before jumping on antipsychotics. Psychiatry algorithms will tend to Try fluoxetine first, clomipramine second, then clomipramine + antipsychotic third. I don't know why old algorithms have more than about 3 or 4 steps, jumping from SSRI to SSRI just makes people miserable and in the case of comorbidity with depression it literally kills people because people commit suicide before they're put on something that has a high chance of actually working.

 

 

wouldn't it  be better to try SNRI's or other non-SSRI antidepressants before moving on to antipsychotics?

 

Yes. I mentioned before the lotus extract, it's 2a/2c antagonism creates atypical antipsychotic effects, the advantage is it doesn't block dopamine so you don't have the risk of tardive.

 

There is no inherent mechanistic safety issue with combining bacopa with SSRIs, bacopa does not have any serotonin release effect, and has no MAO inhibition. You'd only want to know you're not taking drugs that are metabolized by CYP3A4. Neither fluoxetine nor clomipramine are metabolized by this enzyme, they are metabolized by CYP2D6. Lotus extract has some CYP2D6 inhibition so you shouldn't take that unless you're going to monitor your antidepressant blood levels, which you can do if you can be bothered, but maybe it's not worth it for you.

 

There are some mouse studies suggesting agmatine might be helpful for OCD as well, and it is a general potentiator of antidepressants and analgesics, without any enzyme interactions.

 

Anyway, clomipramine + ashwagandha + agmatine is a reasonable next step. This talk of taking antipsychotics is silly.

 

I really don't mean any offense.  You're young, idealistic, and as is often too common, naive. 

 

This is someone with a serious problem who really shouldn't be on this forum.  You are suggesting what amounts to quackery.  The Journal of Complementary Therapies in Medicine is not a medical journal. It carries no weight in the medical world. It is really of no significance whatsoever other than the supplement industry.  

 

I highly doubt clomipramine will be as effective as seroquel, but I'm all for giving it a go.  While it is true other drugs have less dopamine antagonism, seroquel does in fact have very little dopamine antagonism at doses of less than 200 mg. 

 

But this ashwagandha nonsense is just that, nonsense.  

 

If this particular botanical has medicinal value, someone would identify what it is.  

[Adam Karlovsky]

You say you don't mean offense and then follow up with a judgement of character, and say my suggestions are quackery. Cool story bro, either you lied or you should work on your social skills. Just you people understand, I am not a fan of naturopathy and I recognize many natural products are shit, and neither am I a medical industry brown-nose like many "cultural skeptics" I am surrounded by. I do recognize there is value in both of some mainstream medicine and some traditional medicine. I try to take the best of both worlds and rationally synthesize them without regard for popular opinion. Arguing on the internet with strangers is a waste of time so I won't engage with your comments further.

 

I doubt clomipramine by itself is as effective as clomi + seroquel, too. I appreciate the powerful positive effects that antipsychotics can confer, they've pulled me out of depression by making me sleep better, I later experimented with nuciferine and found it gave me the same benefits but without the dry mouth, somnolence and light tremor. But as I said, there's an enzyme interaction between lotus extract and fluox/clomi, so it's not a safe adjunct.

 

Clinically measured, I've seen plenty of IRL evidence that high doses of ashwaganda change people's physiological measures such as cortisol, thyroid and androgen hormones, there's no reason for me to doubt the psychological effects. Same with agmatine, I have seen people transform, either going from partial response to antidepressants to full response, or from brain zaps from SSRI-withdrawal to calm and sober, and from opiate tolerance to using a lower dose, or from opiate withdrawal to partial withdrawal, and it can definitely be used to potentiate THC. Neither are transformative on their own, usually, but as adjuncts they can be incredibly valuable.

[Catwoman]

 

This is someone with a serious problem who really shouldn't be on this forum.  You are suggesting what amounts to quackery.  The Journal of Complementary Therapies in Medicine is not a medical journal. It carries no weight in the medical world. It is really of no significance whatsoever other than the supplement industry.  

 

I highly doubt clomipramine will be as effective as seroquel, but I'm all for giving it a go.  While it is true other drugs have less dopamine antagonism, seroquel does in fact have very little dopamine antagonism at doses of less than 200 mg. 

 

 

As far as I know quetiapine is mostly sedative at low dosages. 
A very interesting read and opinion is the website of Ken Gillman. His conclusion about seroquel:

 

 

 

1. No reliable pharmacological data exists that would even suggest quetiapine is likely to be any use for depression except as an anti-histamine and therefore sedative and anxiolytic. But doxepin would be better and 100 x less expensive.
2. No reliable clinical data exists indicating useful superiority for schizophrenia.
3. No reliable clinical data exists indicating usefulness for any form of depression.

Quetiapine is an very expensive drug of minimal usefulness. The world would probably be better off without it. I suggest clinicians who ‘believe’ this works might read the story of Sir Arthur Conan Doyle and the ‘Cottingley Fairies’.

from https://psychotropic...le-of-seroquel 

Aside from this, he believes that clomipramine is probably still be the best and cheapest serotonin and noradrenalin reuptake inhibitor.
If this is med is effective for me....I know it once I try it, right? But I do have more faith in the opinion of a website which refers to various research article than just one opinion on a forum with people who have never written one research article in their lives!
Not that I mean you, but I have no idea who you are and if I can trust your insights about anti-psychotics.

Now, I also admit that I do have a problem. With intrusive thoughts.
That doesn't mean I can't think clearly and decide about complementary medicine. 
Aside from this annoying thought floating around all day, I am still a highly functioning human being. I'm not bipolar, I'm not schizofrenic and I don't clean or count all day, nor do I have panic attacks or social anxieties. I'm just some one who's trying to find a solution to a problem and I'm willing to look at it from all angles. I appreciate people who want to think outside the box (like Adam, for instance). Suggesting seroquel is kind of the easy way out. With lots of side effects. I don't need the sedation, as I already have trouble getting out of bed (and have some motivation issues) and I don't have racing thoughts and/or anxiety. No problems with insomnia, generally I'm sleeping fine. 

 

[hydrus]

Clinically measured, I've seen plenty of IRL evidence that high doses of ashwaganda change people's physiological measures such as cortisol, thyroid and androgen hormones, there's no reason for me to doubt the psychological effects. 

 

 

How do androgen, cortisol and thyroid levels change?

[Mind_Paralysis]

 

 

This is someone with a serious problem who really shouldn't be on this forum.  You are suggesting what amounts to quackery.  The Journal of Complementary Therapies in Medicine is not a medical journal. It carries no weight in the medical world. It is really of no significance whatsoever other than the supplement industry.  

 

I highly doubt clomipramine will be as effective as seroquel, but I'm all for giving it a go.  While it is true other drugs have less dopamine antagonism, seroquel does in fact have very little dopamine antagonism at doses of less than 200 mg. 

 

 

As far as I know quetiapine is mostly sedative at low dosages. 
A very interesting read and opinion is the website of Ken Gillman. His conclusion about seroquel:

 

 

 

1. No reliable pharmacological data exists that would even suggest quetiapine is likely to be any use for depression except as an anti-histamine and therefore sedative and anxiolytic. But doxepin would be better and 100 x less expensive.
2. No reliable clinical data exists indicating useful superiority for schizophrenia.
3. No reliable clinical data exists indicating usefulness for any form of depression.

Quetiapine is an very expensive drug of minimal usefulness. The world would probably be better off without it. I suggest clinicians who ‘believe’ this works might read the story of Sir Arthur Conan Doyle and the ‘Cottingley Fairies’.

from https://psychotropic...le-of-seroquel 

Aside from this, he believes that clomipramine is probably still be the best and cheapest serotonin and noradrenalin reuptake inhibitor.
If this is med is effective for me....I know it once I try it, right? But I do have more faith in the opinion of a website which refers to various research article than just one opinion on a forum with people who have never written one research article in their lives!
Not that I mean you, but I have no idea who you are and if I can trust your insights about anti-psychotics.

Now, I also admit that I do have a problem. With intrusive thoughts.
That doesn't mean I can't think clearly and decide about complementary medicine. 
Aside from this annoying thought floating around all day, I am still a highly functioning human being. I'm not bipolar, I'm not schizofrenic and I don't clean or count all day, nor do I have panic attacks or social anxieties. I'm just some one who's trying to find a solution to a problem and I'm willing to look at it from all angles. I appreciate people who want to think outside the box (like Adam, for instance). Suggesting seroquel is kind of the easy way out. With lots of side effects. I don't need the sedation, as I already have trouble getting out of bed (and have some motivation issues) and I don't have racing thoughts and/or anxiety. No problems with insomnia, generally I'm sleeping fine. 

 

 

 

I agree with your assessment - I've been meaning to reply, with some choice disagreements in this thread, but my SCT and bad self-asteem and medical side-effects have been blocking such.

 

Well, you know what I recommend, from my previous posts - but, I do think there seems to be merit to Clomipramine, from a statistical standpoint, so it might be worth a shot.

 

Edited by Stinkorninjor, 04 November 2017 - 10:09 AM.

[Catwoman]

I don't know when to start with clomipramine. I'm at 5 weeks of fluvoxamine now, 150 mg. 
My gdoc wants me to stay at 150 for about 4 weeks, but it hasn't kicked in really....

I could work my way up to 300 mg if my docter allows it, on the other hand, the RLS (restless legs) and the teeth grinding in the evening are getting more annoying. 
I wonder why side effects are noticable, but no big noticable effects on the intrusive thought.





 

Edited by Catwoman, 06 November 2017 - 10:23 AM.

[Adam Karlovsky]

 

Clinically measured, I've seen plenty of IRL evidence that high doses of ashwaganda change people's physiological measures such as cortisol, thyroid and androgen hormones, there's no reason for me to doubt the psychological effects. 

 

 

How do androgen, cortisol and thyroid levels change?

 

 

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.

 

 

 

I don't know when to start with clomipramine. I'm at 5 weeks of fluvoxamine now, 150 mg.
My gdoc wants me to stay at 150 for about 4 weeks, but it hasn't kicked in really....

I could work my way up to 300 mg if my docter allows it, on the other hand, the RLS (restless legs) and the teeth grinding in the evening are getting more annoying.
I wonder why side effects are noticable, but no big noticable effects on the intrusive thought.

 

I looked into some meta-analyses and there is some contention about whether clomipramine is meaningfully better than fluvoxamine. Some say clomi's effect sizes are bigger, but side effects can be greater, too. Others say the effect sizes are not comparable because of methodological differences across studies, and that the response rates are about the same. They tend to agree drop-outs (probably from side effects) are more frequent for clomi.

 

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.

Edited by Adam Karlovsky, 10 November 2017 - 05:36 AM.