# Clomipramine | The "Gold Standard" when it comes to depression and OCD?



## Hordak (May 5, 2017)

I've been reading the following articles: 
https://psychotropical.info/clomipramine-potent-snri-anti-depressant/
https://psychotropical.info/tca-intro/
https://psychotropical.info/snri-intro/

Seems to be a pretty potent drug: SNRI, antagonist of the α1-adrenergic receptor, the histamine H1 receptor, the serotonin 5-HT2A, 5-HT2C receptors, the dopamine D1, D2, and D3 receptors, and the muscarinic acetylcholine receptors. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system; so that speaks for itself.

The reviews on drugs.com and other sites also are quite positive.

Who here has been on Clomipramine and what were your experiences with it?


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## Hordak (May 5, 2017)

> It is available as a generic medication.[4] The wholesale price in the developing world is between 0.11 and 0.21 per day as of 2014.[7] *In the United States the wholesale costs as of 2018 is about 9 USD per day*
> 
> source: https://en.wikipedia.org/wiki/Clomipramine


WTF? What's going on in the United States? :afr:roll

German prices are normal... :click:


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## Gillman fan (Sep 24, 2016)

I will point to this ranking here: slatestarcodex.com/2015/04/30/prescriptions-paradoxes-and-perversities/

These numbers are based on aggregated patient ratings.
Top 4 drugs:
Nardil 1.25
Parnate 1.23
Chlomipramine 1.22
Emsam/selegeline 1.07

The top 3 drugs are pretty close to neck-and-neck, then there is a huge dropoff to the next tier of drugs (Emsam is also an MAOI, sorta, like an attempt to make a "diet" MAOI)


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## versikk (Nov 25, 2013)

Barely ever heard of it....


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## Hordak (May 5, 2017)

Gillman fan said:


> I will point to this ranking here: slatestarcodex.com/2015/04/30/prescriptions-paradoxes-and-perversities/
> 
> These numbers are based on aggregated patient ratings.
> Top 4 drugs:
> ...


Interesting! Clomipramine roughly on pair with MAOI, followed by Nefazodone (R.I.P) and Imipramine. Imipramine is also a potent SNRI, but lacks the strong 5HT-antagonism compared to Clomipramine. I suppose that's the pharmacological difference which makes Clomipramine superior... ?

Clomipramine also exhibits some antagonism of dopamine D1, D2 and D3 receptors... can one expect some clinical & therapeutic benefits from this?

EDIT: Clomipramine also acts as a functional (potent!) inhibitor of acid sphingomyelinase (FIASMA)
https://en.wikipedia.org/wiki/FIASMA

Some interesting graphs regarding antidepressant FIASMAs: https://d-nb.info/1011278227/34 (alternative link: http://docplayer.org/23019817-Konze...en-sphingomyelinase-durch-antidepressiva.html )


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## Hordak (May 5, 2017)

versikk said:


> Barely ever heard of it....


:O
Did you try any TCA?

here you go: https://en.wikipedia.org/wiki/Clomipramine


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## Pharmville (Feb 11, 2018)

My father took Clomipramine for approximately 30 years and I also take Clomipramine. I have been fairly treatment resistant to SSRIs and SNRIs. Clomipramine is a very good drug. I have GAD, PD, and Major Depression. I currently take 150 mg of Clomipramine but have taken it at the highest dose of 250 mg while hospitalized and shortly after. I take quite a lot of medication. What questions do you have?

Meds:
Risperidone 1.5 mg
Propranolol 30 mg
Klonopin 2 mg
Gabapentin 600 mg
Prozac 20 mg
Mirtazapine 15 mg
Clomipramine 150 mg

Those are just the psych meds I take.


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## Hordak (May 5, 2017)

Pharmville said:


> My father took Clomipramine for approximately 30 years and I also take Clomipramine. I have been fairly treatment resistant to SSRIs and SNRIs. Clomipramine is a very good drug. I have GAD, PD, and Major Depression. I currently take 150 mg of Clomipramine but have taken it at the highest dose of 250 mg while hospitalized and shortly after. I take quite a lot of medication.


Thank you for the information.
Are you stable on Clomipramine?



Pharmville said:


> What questions do you have?


Well, an interesting question might be: How does Clomipramine feel compared to SSRIs & SSNRIs... in your experience? Does it cause a lot of sedation, somnolence? Or is it activating? What about insomnia? Does it cause a lot of headaches and GI-problems _(diarrhea, nausea, constipation)_? What about weight gain / weight loss? Tremor?

Do you have typical anticholinergic side effects, for example: blurred vision, dry mouth, accommodation problems (eye), micturition disorder?

And most important for me, because I had those side effects on SSRIs: What about motor restlessness, agitation & zombie stuff a la: indifference, amotivation, apathy, lethargy....



Pharmville said:


> Meds:
> Risperidone 1.5 mg
> Propranolol 30 mg
> Klonopin 2 mg
> ...


currently? All of them? That's a lot... :um

Do you take Propanolol and Gabapentin for GAD?
Ho do they compare to SSRIs for that matter?

Thanks again for your answer and contribution :thanks

EDIT: And welcome to the Forum! :smile2:


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## Pharmville (Feb 11, 2018)

Great questions!

*Are you stable on Clomipramine?*
I would definitely say yes. My anxiety is in control and I have a part time job. I graduated from college/university two summers ago. My depression could use some improvement. I have a big problem with motivation and energy and feeling overwhelmed. My doctor is considering adding Wellbutrin (bupropion). We'll see about that...

Well, an interesting question might be: *How does Clomipramine feel compared to SSRIs & SSNRIs... in your experience?*

Clomipramine is much more sedating than the SSRIs and SNRIs I've tried. This is felt immediately after dosing. When I first started on it I would be ready for bed at 10 pm (taken at 9pm) compared to my normal 1 am. Definitely not activating. This medicine would be very useful for someone with insomnia IMO. I also didn't experience any SSRI startup anxiety that I had from Zoloft one time.

The main GI problems I have is severe constipation. I take a stool softener (docusate sodium) as well as MiraLax (Polyethylene glycol). 
Clomipramine helps with nausea due to its antihistaminergic action as well as a modest 5-HT3 antagonist effect. I also have a slight hand tremor that doesn't bother me much.

*Do you have typical anticholinergic side effects?*

Yes to all! blurred vision, dry mouth, accommodation problems (eye), micturition disorder (trouble peeing), constipation, muscle twitches (also related to its dopaminergic activity).

No motor restlessness. 
Yes to the zombie stuff a la: indifference, amotivation, apathy, lethargy.... common with all SRIs in my experience. this is why my doc is considering adding Bupropion.

*All of them? That's a lot...*
Yeah I used to only take a few meds but then I went inpatient at Hopkins for a month after my anxiety skyrocketed due to too much marijuana usage. The doctors there added the risperidone first for acute severe anxiety, Hydroxyzine for moderate anxiety and then they added the gabapentin because they were running out of options.

*Do you take Propanolol and Gabapentin for GAD?
Ho do they compare to SSRIs for that matter?*

I LOVE propranolol. It eliminates most of the physical symptoms of anxiety and panic for me. It's really great for what I like to call "physical anxiety" and not so great at dealing with "mental anxiety."

The gabapentin was added at the last minute when I was still in the hospital. I honestly can't tell I'm on it. But I can tell when I don't take it.


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## Gillman fan (Sep 24, 2016)

versikk said:


> Barely ever heard of it....


It is really a shame. It is difficult to find quality information on different antidepressants, furthermore I believe that depressed patients are worse at advocating for themselves compared to people suffering from other ailments.

Clomipramine (I keep on wanting to type "chlom" ipramine since it is imipramine + chlorine) actually has a great wikipedia page.

Its potency as a serotonin reuptake inhibitor is drastically higher than... any other medication in existence.
It has low potency as a NE reuptake inhibitor, however its major metabolite is an extremely potent NE reuptake inhibitor, making it a balanced SNRI.

I just learned a new adjective for receptor affinities - "promiscuous," as in Clomipramine will grab the *** of any receptor it sees, even if it latches on particularly tight to SERT. There is a whole grab bag of stuff there, the serotonin antagonism is good, but antihistamine + anticholinergic is no thank you. However due to the unbelievably high potency of Clomipramine, it seems the side effects/benefits may be questionable?

Actually the Wikipedia page analyses this point about the extreme potency. Clomipramine is a potent SNRI at a dose of 10 mg/ day, but the _typical_ dosage is 50-250!!! mg/day. I really wonder how Clomipramine, the REAL SNRI, would compare to one of the most commonly prescribed medications, venlafaxine (Effexor) if it were used at this low dosage.

The vastly higher dosage raises questions - did it go this high because it was only FDA-approved for use against OCD? (technically it is OFF-LABEL as an antidepressant). Do its other properties, i.e. serotonin antagonism, show really significant benefit at these higher dosages?

Here is Dr. Gillman's take: https://psychotropical.info/tca-intro/ actually he has two pages on Clomipramine, and two on TCAs in general. I say that Clomipramine is a real SNRI because of Dr. Gillman's analysis of venlafaxine shows it fails to suppress the tyramine reaction.


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## SSRIManiac (Jun 14, 2014)

I'm gonna ask my doctor about Clomipramine. All these new generation medications including atypical antipsychotics and SSRI's are making people worse in my opinion.

The new "one size" fits all scheme big pharma is pushing seems to be the antipsychotics. I don't know how Abilify or Vraylar can treat social anxiety, but that's the **** I get every time I go see a new doctor for suggestions..

Now, getting back to Clomipramine, is it more potent than Paroxetine? Paxil is supposed to be the most potent SSRI, so much that it almost resembles a TCA type of drug, e.g. the anticholinergic and muscarinic effects. It's the only one that worked for my social anxiety at a sufficient level. Venlafaxine didn't do much for neither depression or anxiety, certainly not anything for my OCD type symptoms.


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## RCMC (Feb 5, 2017)

The reasons why the new antidepressants like SSRIs usually fail to treat SA because socialization include very accurate verbal and nonverbal interactions between individuals in which it is impossible to do so if you still have a little bit social anxiety. You have to be 100% anxiety free so that you can enjoy the socialization and then continue to do so and then form friendships, social bonds. To make this happen, only the robust ones, the old antidepressants can help you achieve. It is because they include much more acting sites and neurotransmitters, therefore giving you much more side effects. But if you want to be social, you must be social anxiety free. You have no choice but try the old medicines. Old is not equal to bad, especially in the treatment for complicated social anxiety disorder. Complicated medicines treat complicated disorders.


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## Hordak (May 5, 2017)

*REVIEW: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated*
https://psychotropical.info/wordpre...eview_TCAs_pharmacol_interactions_updated.pdf


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## Hordak (May 5, 2017)

Thank you for your answer! 



Pharmville said:


> I have a big problem with motivation and energy


Welcome to the club :boogie



Pharmville said:


> Clomipramine is much more sedating than the SSRIs and SNRIs I've tried. This is felt immediately after dosing. When I first started on it I would be ready for bed at 10 pm (taken at 9pm) compared to my normal 1 am. Definitely not activating. This medicine would be very useful for someone with insomnia IMO. I also didn't experience any SSRI startup anxiety that I had from Zoloft one time.


Sedating stuff often causes weight gain... did you experience any weight gain?



Pharmville said:


> Yes to the zombie stuff a la: indifference, amotivation, apathy, lethargy.... common with all SRIs in my experience. this is why my doc is considering adding Bupropion.


Was it the same level of zombie stuff as with SSRIs? or less?
SRI induced zombie state is really annoying...
:blank


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## Hordak (May 5, 2017)

SSRIManiac said:


> *I'm gonna ask my doctor about Clomipramine.* All these new generation medications including atypical antipsychotics and SSRI's are making people worse in my opinion.


please keep us posted...



SSRIManiac said:


> Venlafaxine didn't do much for neither depression or anxiety, certainly not anything for my OCD type symptoms.


The hype around venlafaxine surprises me again and again... fascinating!


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## Hordak (May 5, 2017)

Gillman fan said:


> Its potency as a serotonin reuptake inhibitor is drastically higher than... any other medication in existence.
> 
> Actually the Wikipedia page analyses this point about the extreme potency. Clomipramine is a potent SNRI at a dose of 10 mg/ day, but the _typical_ dosage is 50-250!!! mg/day. I really wonder how Clomipramine, the REAL SNRI, would compare to one of the most commonly prescribed medications, venlafaxine (Effexor) if it were used at this low dosage.
> 
> The vastly higher dosage raises questions - did it go this high because it was only FDA-approved for use against OCD? (technically it is OFF-LABEL as an antidepressant). Do its other properties, i.e. serotonin antagonism, show really significant benefit at these higher dosages?


I am glad you mention that. I was wondering about that too. So if Clomipramine has ~80% SERT occupancy at 10mg/day... does it also have that strong occupancy for other receptors at the same low dosage? Maybe it is being "overdosed" in general? (except maybe for OCD)



Gillman fan said:


> I just learned a new adjective for receptor affinities - "promiscuous," as in Clomipramine will grab the *** of any receptor it sees, even if it latches on particularly tight to SERT.


http://666kb.com/i/dqyfjc05nejmpmjcc.png


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## Pharmville (Feb 11, 2018)

Hordak said:


> Thank you for your answer!
> 
> Welcome to the club :boogie
> 
> ...


It's embarrassing but on my current med cocktail I gained about 50 lbs in a year. I blame the Mirtazapine. I'd say the zombiness of Clomipramine is the same as the SSRIs for me.


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## Hordak (May 5, 2017)

Pharmville said:


> It's embarrassing but on my current med cocktail I gained about 50 lbs in a year. I blame the Mirtazapine. I'd say the zombiness of Clomipramine is the same as the SSRIs for me.


 How is your general experience with Mirtazapine? Did you try different dosages (15, 30, 45mg)?


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## Pharmville (Feb 11, 2018)

Hordak said:


> How is your general experience with Mirtazapine? Did you try different dosages (15, 30, 45mg)?


I love it. It's the most sedating drug I've ever taken -probably tied with Trazodone. I get plenty of sleep because of it. Also, my anxiety is very tied to my GI system and when I get anxious I get nauseous. Mirtazapine's 5-HT3 antagonism really helps out with that -a property that it shares with the antiemetic ondansetron/Zofran, which I also take occasionally.

My first experience with Remeron/Mirtazapine was in combination with Cymbalta. This combination is called "limerick" rocket fuel and is similar to the Effexor + Remeron "California" rocket fuel. SNRI + Remeron = rocket fuel. I was on 60 mg of Cymbalta and 45 mg of Remeron. It's called rocket fuel because, well, it's really stimulating. I had to lower my Remeron back down to 15 mg because it was just too stimulating for me. At low doses Remeron is very sedating and at higher doses the noradrenergic effect increases dramatically.

When I was at Hopkins and they were tweaking my meds they decided to keep 15 mg of Remeron on board to help with my appetite, which I lose when I'm anxious. Unfortunately, it has contributed to a lot of weight gain. It's a very powerful appetite stimulatant.


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## Hordak (May 5, 2017)

Pharmville said:


> I love it. It's the most sedating drug I've ever taken -probably tied with Trazodone. I get plenty of sleep because of it. Also, my anxiety is very tied to my GI system and when I get anxious I get nauseous. Mirtazapine's 5-HT3 antagonism really helps out with that -a property that it shares with the antiemetic ondansetron/Zofran, which I also take occasionally.
> 
> My first experience with Remeron/Mirtazapine was in combination with Cymbalta. This combination is called "limerick" rocket fuel and is similar to the Effexor + Remeron "California" rocket fuel. SNRI + Remeron = rocket fuel. I was on 60 mg of Cymbalta and 45 mg of Remeron. It's called rocket fuel because, well, it's really stimulating. I had to lower my Remeron back down to 15 mg because it was just too stimulating for me. At low doses Remeron is very sedating and at higher doses the noradrenergic effect increases dramatically.
> 
> When I was at Hopkins and they were tweaking my meds they decided to keep 15 mg of Remeron on board to help with my appetite, which I lose when I'm anxious. Unfortunately, it has contributed to a lot of weight gain. It's a very powerful appetite stimulatant.


Very informative. thanks 
Do the sedating and stimulating effects cancel each other out at 30mg?


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## Hordak (May 5, 2017)

SSRIManiac said:


> Now, getting back to Clomipramine, is it more potent than Paroxetine?


From what I have read: Yes, it's the most potent SRI on the market, but it's not "selective", whatever that means :boogie ^^


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## SSRIManiac (Jun 14, 2014)

Hordak said:


> SSRIManiac said:
> 
> 
> > Now, getting back to Clomipramine, is it more potent than Paroxetine?
> ...


That means it's a messier scattered type drug that isn't primarily selective for SERT w/o other actions. Though, I think its greatest affinity binding properties may be serotonin it may have other mechanisms that cause more side effects. Don't know if a low dose should be considered. You can add it to most antidepressant drugs.


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## genuris (Feb 28, 2018)

How do you think, will it be helpful for bipolar depression with psychomotor retardation (sluggish thougts, slow thinking), apathy, anergy ? (SSRI,SNRI doesn't work)


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## Hordak (May 5, 2017)

SSRIManiac said:


> That means it's a messier scattered type drug that isn't primarily selective for SERT w/o other actions. Though, I think its greatest affinity binding properties may be serotonin it may have other mechanisms that cause more side effects. Don't know if a low dose should be considered. You can add it to most antidepressant drugs.


Yes, but on the other hand: Paroxetine for example also hits muscarinic receptors and is called selective... and maybe hitting more stuff is the reason why Clomipramine is more effective?


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## Hordak (May 5, 2017)

genuris said:


> How do you think, will it be helpful for bipolar depression with psychomotor retardation (sluggish thougts, slow thinking), apathy, anergy ? (SSRI,SNRI doesn't work)





> Mania: Clomimipramine can trigger mania in bipolar individuals and can cause rapid cycling from depression to mania. The mania can be severe and can progress to psychosis, delusions, paranoia, hostility and aggression and violence.
> 
> Source: http://www.anti-depressants.com/drugs/tricyclic/clomipramine/


Not sure if it's the right thing for bipolar... ^^


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## porkpiehat (Feb 13, 2017)

Can this be taken with an MAOI? I need a replacement for trazodone for sleep and to antagonize the 5ht2a-c with my but I see that it has strong SERT activity. Low doses maybe?


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## Hordak (May 5, 2017)

porkpiehat said:


> Can this be taken with an MAOI? I need a replacement for trazodone for sleep and to antagonize the 5ht2a-c with my but I see that it has strong SERT activity. Low doses maybe?


It has strong SERT activity even at 10mg...

https://www.drugs.com/interactions-check.php?drug_list=702-0,1839-1190


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## Hordak (May 5, 2017)

*and up*

and up :smile2:


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## SSRIManiac (Jun 14, 2014)

porkpiehat said:


> Can this be taken with an MAOI? I need a replacement for trazodone for sleep and to antagonize the 5ht2a-c with my but I see that it has strong SERT activity. Low doses maybe?


Hell no!
Chlomipramine is a very high conductor of serotonin, arguably one of the most potent.
There is Doxipin Mirtazepine and Nefazodone that are sedating AD's.


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## SSRIManiac (Jun 14, 2014)

I still don't know if I should try Clomipramime someday. Not a lot of positive stories about it. 

I did very well with Paroxetine with its muscarinic anticholinegic effects and of course high SERT affinity.

In theory, Clomipramime would be similar or even better for anxiety and OCD.


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## Hordak (May 5, 2017)

SSRIManiac said:


> I still don't know if I should try Clomipramime someday.
> 
> I did very well with Paroxetine with its muscarinic anticholinegic effects and of course high SERT affinity.
> 
> In theory, Clomipramime would be similar or even better for anxiety and OCD.


Do it! Try it  :yes
It's a powerful versatile drug.

On the German Forum (psychic.de) there is a woman with panic disorder, depression and SAD. Sie didn't respond very well to most antidepressants _(SSRIs, SSNRIs, Atypicals, Tetracyclics, Pregabalin, Olanzapine, Quetiapine, Baclofen... pretty much the full program)_, even combinations didn't help. I suggested to her that she should try Clomipramine... she has been now for about 6 or 7 weeks on Clomipramine and feels better than ever. Full Remission seems possible. I will keep you posted. 

Of course this is the experience of one person and not the general rule, but nonetheless encouraging and promising... :wink



> Not a lot of positive stories about it.


That's because it isn't prescribed that often...


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## Hordak (May 5, 2017)

Anyone else on Clomipramine...?


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## GlasgowGuy (Jan 7, 2018)

Been on 50 mg of Clomipramine a day for 5 weeks now. Mainly for depression, OCD and anxiety.
Would say that my Social Anxiety has been helped somewhat, my depression a little
but my OCD has over the last couple of weeks got worse.

Going to increase dose tomorrow hopefully Pdoc will let me go up to 100mg a day. 
Believe that its to early to tell if its going to work or not. 50 mg a day is a low dose
and i believe higher doses are needed especially for OCD.


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## Hordak (May 5, 2017)

GlasgowGuy said:


> Been on 50 mg of Clomipramine a day for 5 weeks now. Mainly for depression, OCD and anxiety.
> Would say that my Social Anxiety has been helped somewhat, my depression a little
> but my OCD has over the last couple of weeks got worse.
> 
> ...


Thanks for the info! Please keep us posted... :yes


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## versikk (Nov 25, 2013)

Hordak said:


> Thanks für the info! Please keep us posted... :yes


:nerd:


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## Hordak (May 5, 2017)

versikk said:


> :nerd:


\o


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## SteveOReno (May 2, 2018)

*TCAs are not safe*



Hordak said:


> It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system; so that speaks for itself.


The World Health Organization needs to update their list (i.e. delete CLOMIPRAMINE) because it is not safe:
New research has revealed compelling evidence of a link between long-term use of anticholinergic medications like TCAs and dementia. Although many studies have investigated this link, this was the first study to use a long-term approach (over seven years) to find that dementias associated with anticholinergics may not be reversible even years after drug use stops. Anticholinergic drugs block the action of acetylcholine, which transmits messages in the nervous system. In the brain, acetylcholine is involved in learning and memory.

Not to mention the very long list of side effects.


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## CopadoMexicano (Aug 21, 2004)

Ive taken a similar drug TCA desipramine back in 2010 but nothing. Im treatment resistant for depression. I also take clonazepam for panic attacks and anxiety as needed. Ive heard from doctors that untreated anxiety leads to dementia later in life because it builds up lesions in the brain due to all stress over time on the body. One of my aunts has dementia with lewy bodies due to untreated anxiety over the years and has parkinsons.


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## Hordak (May 5, 2017)

SteveOReno said:


> The World Health Organization needs to update their list (i.e. delete CLOMIPRAMINE) because it is not safe:
> New research has revealed compelling evidence of a link between long-term use of anticholinergic medications like TCAs and dementia. Although many studies have investigated this link, this was the first study to use a long-term approach (over seven years) to find that dementias associated with anticholinergics may not be reversible even years after drug use stops. Anticholinergic drugs block the action of acetylcholine, which transmits messages in the nervous system. In the brain, acetylcholine is involved in learning and memory.
> 
> Not to mention the very long list of side effects.


Correlation does not imply causation?


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## Hordak (May 5, 2017)

CopadoMexicano said:


> Ive taken a similar drug TCA desipramine back in 2010 but nothing. Im treatment resistant for depression. I also take clonazepam for panic attacks and anxiety as needed. Ive heard from doctors that untreated anxiety leads to dementia later in life because it builds up lesions in the brain due to all stress over time on the body. One of my aunts has dementia with lewy bodies due to untreated anxiety over the years and has parkinsons.


Desipramine is an NRI... maybe you need both: SRI + NRI...?


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## CopadoMexicano (Aug 21, 2004)

Hordak said:


> Desipramine is an NRI... maybe you need both: SRI + NRI...?


I thought desipramine was a tca>?: https://en.wikipedia.org/wiki/Desipramine


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## Hordak (May 5, 2017)

CopadoMexicano said:


> I thought desipramine was a tca>?: https://en.wikipedia.org/wiki/Desipramine





> The tricyclic antidepressants TCAs are a group of drugs of similar structure (hence their tag of TCA, which refers to their arrangement in three-rings), but they are markedly heterogeneous in terms of their pharmacological actions. Some of them can be considered as mis-classified in that they are not actually antidepressants at all. They therefore illustrate that although the structural similarity of drugs may be close, their pharmacological actions can be very different. For instance, clomipramine is a close structural analogue of chlorpromazine, but their effects could hardly be more different.
> 
> source: https://psychotropical.info/tca-intro/


Greetings, Hordak


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## Hordak (May 5, 2017)

CopadoMexicano said:


> I thought desipramine was a tca>?: https://en.wikipedia.org/wiki/Desipramine


from your link:



> Desipramine, sold under the brand name Norpramin and Pertofrane among others, is a tricyclic antidepressant (TCA) which is used in the treatment of depression.[6] *It acts as a relatively selective norepinephrine reuptake inhibitor*, though it does also have other activities such as weak serotonin reuptake inhibitory, α1-blocking, antihistamine, and anticholinergic effects. The drug is not considered a first-line treatment for depression since the introduction of selective serotonin reuptake inhibitor (SSRI) antidepressants, which have fewer side effects and are safer in overdose.
> 
> source: https://en.wikipedia.org/wiki/Desipramine


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## SteveOReno (May 2, 2018)

Hordak said:


> Correlation does not imply causation?


Correlation does imply causation, but it may not prove causation. The large number of patients in the research study (3400) and the long study time (10 years) supports their conclusion quite firmly. See footnote 20 in the Wikipedia article.

On another note, the list of side effects for clomipramine (50-100 total side effects), does not include Lethargy, but it does include Depersonalization. Why is that?


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## CopadoMexicano (Aug 21, 2004)

Hordak said:


> from your link:


thanks for the clarification. :smile2:


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## SteveOReno (May 2, 2018)

I was referring to footnote 20 of the article on TCA.

Gray, Shelly L.; Anderson, Melissa L.; Dublin, Sascha; Hanlon, Joseph T.; Hubbard, Rebecca; Walker, Rod; Yu, Onchee; Crane, Paul K.; Larson, Eric B. (1 March 2015). "Cumulative Use of Strong Anticholinergics and Incident Dementia"


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## Hordak (May 5, 2017)

SteveOReno said:


> Correlation does imply causation, but it may not prove causation. The large number of patients in the research study (3400) and the long study time (10 years) supports their conclusion quite firmly. See footnote 20 in the Wikipedia article.


How strong is that "link"? _(without having read the article)_
How many people on anticholinergics get "dementia" compared to the placebo-group?



SteveOReno said:


> but it does include Depersonalization. Why is that?


I don't know.


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## Hordak (May 5, 2017)

CopadoMexicano said:


> thanks for the clarification. :smile2:


you are welcome :yes


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## SteveOReno (May 2, 2018)

If you take an anticholinergic every day for several years, and are older than 70 years, your odds of dementia go up about 50%.
Older people may be at much greater risk from medications because their kidneys don't eliminate drugs as well, their bodies don't heal as well, etc.

What is really surprising is that common antihistamines, like chlorpheniramine, were part of the study because they are anticholinergic. So over the counter meds can increase dementia risks. [email protected]#%^*&. Yes indeed!

Of course, SSRIs have been shown to increase QT intervals and arrhythmias, which increase the risk of heart attack.
But there are a lot of things that can kill you, so don't worry too much. Your meds may have a lot more positives than negatives.


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## Hordak (May 5, 2017)

SteveOReno said:


> If you take an anticholinergic every day for several years, and are older than 70 years, your odds of dementia go up about 50%.


Do you know the absolute numbers?



SteveOReno said:


> But there are a lot of things that can kill you, so don't worry too much. Your meds may have a lot more positives than negatives.


:yes


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## SteveOReno (May 2, 2018)

The published data of the study results was non-trivial. However, I took some of the numbers out of the study for your convenience.
They divided 3,434 people over the age of 65 into 5 categories: no use, very low use, low use, medium low use, and fifth was everyone from medium to high use.
Total number of people with dementia at the end of the study was 797 (23%).
Total number of people with medium to high use of anticholinergic (most common - doxepin) was 558.
Total number of people with dementia at the end and medium to high use of anticholinergic was 184 (33%).


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## Hordak (May 5, 2017)

SteveOReno said:


> The published data of the study results was non-trivial. However, I took some of the numbers out of the study for your convenience.
> They divided 3,434 people over the age of 65 into 5 categories: no use, very low use, low use, medium low use, and fifth was everyone from medium to high use.
> Total number of people with dementia at the end of the study was 797 (23%).
> Total number of people with medium to high use of anticholinergic (most common - doxepin) was 558.
> Total number of people with dementia at the end and medium to high use of anticholinergic was 184 (33%).


Thanks. It would be interesting to see a study concerning young people. Hope they make one in the near future...


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## ladysmurf (Jan 3, 2012)

useless for me


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## Hordak (May 5, 2017)

ladysmurf said:


> useless for me


what was useful for you?


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## ladysmurf (Jan 3, 2012)

Hordak said:


> what was useful for you?


nothing. i never responded to MAOI's either...doctor's aren't sure why :frown2:


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## SSRIManiac (Jun 14, 2014)

I should of already been on Anafranil. =(
But I'm late to everything even my own experiences.
It will be the last drug before Parnate. If it works then it's gonna be great.


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## Hordak (May 5, 2017)

any other experiences?


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## Hordak (May 5, 2017)

SSRIManiac said:


> I should of already been on Anafranil. But I'm late to everything even my own experiences.
> It will be the last drug before Parnate. If it works then it's gonna be great.


 Go on! Don't waste time


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## ladysmurf (Jan 3, 2012)

Gillman fan said:


> I will point to this ranking here: slatestarcodex.com/2015/04/30/prescriptions-paradoxes-and-perversities/
> 
> These numbers are based on aggregated patient ratings.
> Top 4 drugs:
> ...


seriously?? all those were useless from me...where do you get your info from??


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## 546617 (Oct 8, 2014)

I wanna try this medication for anxiety.

It was found that clomipramine lowers CRH mRNA expression in the PVN by 74%, regardless of stressor conditions.
https://www.ncbi.nlm.nih.gov/pubmed/15214866


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## Hordak (May 5, 2017)

KurdishFella said:


> I wanna try this medication for anxiety.
> 
> It was found that clomipramine lowers CRH mRNA expression in the PVN by 74%, regardless of stressor conditions.
> https://www.ncbi.nlm.nih.gov/pubmed/15214866


that means?


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## 546617 (Oct 8, 2014)

Hordak said:


> that means?


paraventricular nucleus (PVN) is a nucleus in the hypothalamus, it creates CRH. which is your body stress signal. By inhibiting that and as much as clomipramine does it will decrease the activity of its receptors, mainly CRHR1 which high level is heavily involved in anxiety. So by inhibiting CRH the activity of CRHR1 will decrease and anxiety lessen.


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## Hordak (May 5, 2017)

KurdishFella said:


> paraventricular nucleus (PVN) is a nucleus in the hypothalamus, it creates CRH. which is your body stress signal. By inhibiting that and as much as clomipramine does it will decrease the activity of its receptors, mainly CRHR1 which high level is heavily involved in anxiety. So by inhibiting CRH the activity of CRHR1 will decrease and anxiety lessen.


interesting!


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## Hordak (May 5, 2017)

SSRIManiac said:


> I still don't know if I should try Clomipramime someday. Not a lot of positive stories about it.
> 
> I did very well with Paroxetine with its muscarinic anticholinegic effects and of course high SERT affinity.
> 
> In theory, Clomipramime would be similar or even better for anxiety and OCD.


So how is your Clomipramine experiment going?


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## lily (Nov 9, 2018)

GlasgowGuy said:


> Been on 50 mg of Clomipramine a day for 5 weeks now. Mainly for depression, OCD and anxiety.
> Would say that my Social Anxiety has been helped somewhat, my depression a little
> but my OCD has over the last couple of weeks got worse.
> 
> ...


this could depend on the individual



SteveOReno said:


> The World Health Organization needs to update their list (i.e. delete CLOMIPRAMINE) because it is not safe:
> New research has revealed compelling evidence of a link between long-term use of anticholinergic medications like TCAs and dementia. Although many studies have investigated this link, this was the first study to use a long-term approach (over seven years) to find that dementias associated with anticholinergics may not be reversible even years after drug use stops. Anticholinergic drugs block the action of acetylcholine, which transmits messages in the nervous system. In the brain, acetylcholine is involved in learning and memory.
> 
> Not to mention the very long list of side effects.


but this is bad news. this is the one I'm trying, on 50mg today. I better switch to another medication especially when I was told I need to take a blood test if I go any higher


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## lily (Nov 9, 2018)

in this case, I'd like to stay with trying SSRI first, like fluoxetine (Prozac) for the OCD especially and secondly, eye contact anxiety (social anxiety). Any opinions?
could you get dementia or other hard to get rid of if you withdraw from it withdrawal effects as I quoted on 50mg? if 50mg is enough for me?


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## lily (Nov 9, 2018)

should I be scared off this medication?


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