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

[maxor]

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 alpha1-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.

The following ranking is interesting: http://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

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

Clomipramine acts as a functional (potent!) inhibitor of acid sphingomyelinase (FIASMA): http://en.wikipedia.org/wiki/FIASMA
Some interesting graphs regarding antidepressant FIASMAs: http://d-nb.info/1011278227/34

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

[CeremonyNewOrder]

I tried it but it did nothing for me and the side effects were awful but of course you may be different. 

[CrazyRedhead]

 

39 minutes ago, maxor said:

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

I was on 250mg for awhile and didn't have many side effects, except for a little dry mouth.

However, for me personally, it didn't do much, if anything, for my depression or OCD......We're all different though, so you might have a better experience with it than I did.

Edited March 6, 2018 by CrazyRedhead

[maxor]

1 hour ago, CeremonyNewOrder said:

I tried it but it did nothing for me and the side effects were awful but of course you may be different. 

What were those side effects?

[mikl_pls]

I was on 225 mg for a little while and had nothing but side effects too. My side effects were blurry vision, urinary retention (bad!), weight gain (30 lb in just a couple of months), and worsening of depression.

[Catwoman]

I'm starting it in a few weeks. I've read those articles on Psychotropical too. 
I've been reading up on reviews from Dutch people (I'm Dutch so that makes sense ;-))who took it or who are taking it. 
Clomipramine really gets mixed opinions. I don't know what to make of it, so I decided to try. In the past I've been happy with Luvox (fluvoxamine) and Lexapro (escitalopram), but both SSRI's stopped working. Currently decreasing Luvox so I can start clomipramine. I hope it will be the answer to the recurring intrusive thought I have.  In the past Luvox and Lexapro were miracles for me. According to my pdoc, going on clomipramine is the next step....

[maxor]

On 3/14/2018 at 1:25 PM, Catwoman said:

I'm starting it in a few weeks. I've read those articles on Psychotropical too. 
I've been reading up on reviews from Dutch people (I'm Dutch so that makes sense ;-))who took it or who are taking it. 
Clomipramine really gets mixed opinions. I don't know what to make of it, so I decided to try. In the past I've been happy with Luvox (fluvoxamine) and Lexapro (escitalopram), but both SSRI's stopped working. Currently decreasing Luvox so I can start clomipramine. I hope it will be the answer to the recurring intrusive thought I have.  In the past Luvox and Lexapro were miracles for me. According to my pdoc, going on clomipramine is the next step....

Have you already started?

Did you have sexual sides on SSRIs? And what about zombification: anhedonia, indifference, apathy...?

Dutch.. hee? Time to annex you again :=D ^^

[maxor]

You might wanna Clomipramine with Luvox for higher CMI blood concentrations:

https://www.ncbi.nlm.nih.gov/pubmed/8666564

http://www.dr-bob.org/cgi-bin/pb/mget.pl?post=/babble/20130222/msgs/1038888.html#1038888

On 3/6/2018 at 6:11 PM, CrazyRedhead said:

 

I was on 250mg for awhile and didn't have many side effects, except for a little dry mouth.

However, for me personally, it didn't do much, if anything, for my depression or OCD......We're all different though, so you might have a better experience with it than I did.

What medication did help you?

Edited April 7, 2018 by maxor

[maxor]

On 3/7/2018 at 1:37 PM, mikl_pls said:

I was on 225 mg for a little while and had nothing but side effects too. My side effects were blurry vision, urinary retention (bad!), weight gain (30 lb in just a couple of months), and worsening of depression.

I am sorry to hear that. What did help you?

[mikl_pls]

1 hour ago, maxor said:

I am sorry to hear that. What did help you?

It's hard to say. Nothing really has completely helped me. I've begged my pdoc to let me undergo ECT, but she doesn't seem to want to let me. If I experience a major relapse on the current combo I'm on, I'm going to probably look at TMS as an alternative to ECT if she doesn't let me go for ECT (if my insurance will pay for it). I can't seem to stop cycling in and out of depression though which is the other problem. Nothing has stopped my cycling. It has slowed down drastically from how rapid it used to be, but it's still pretty rapid (switches every 2-4 weeks or so).

[CrazyRedhead]

14 hours ago, maxor said:

What medication did help you?

So far, nothing has really helped....I was looking into TMS therapy,  but  I can't afford the co-pay.

[Catwoman]

On 8-4-2018 at 12:20 AM, maxor said:

Have you already started?

Did you have sexual sides on SSRIs? And what about zombification: anhedonia, indifference, apathy...?

Dutch.. hee? Time to annex you again :=D ^^

No didn't start yet. I'm still on a 100 mg of Luvox. I'm doing a little better with less intrusive thoughts so I keep postponing the switch to clomi. 

On sertraline I did have some sexual side effects (no libido and trouble with orgasms). On both high and low doses. 
Over the period of decreasing Luvox my libido decreased as well, but when I was on it in the early days I wasn't having any problems at all.
Now that I'm back on 100 mg I have to admit that my sex drive did return. 
 

[Persona_Is_Life]

It worked really well for my OCD. I started to notice a change at 25mg and we went up to 150mg. It was a great med but sue to some cognitive fog we went off it. I had minimal side effects. Just like with Luvox though, it aggravated my insomnia. This could be typical of any ADs with me, so keep that in mind. It helped me through the worst of my OCD and I haven't been back to that bad of a state in a while even though I'm not taking anything for it currently. 

I liked it. 

[mellifluous]

i really want to try this as it would reduce the number of meds i take overall if i could take one thing only for OCD. my psychiatrist won't give it to me because it can be lethal.

Edited May 18, 2018 by mellifluous

[Persona_Is_Life]

On 5/18/2018 at 4:46 PM, mellifluous said:

i really want to try this as it would reduce the number of meds i take overall if i could take one thing only for OCD. my psychiatrist won't give it to me because it can be lethal.

Lethal how?

[HydroCat]

1 hour ago, Persona_Is_Life said:

Lethal how?

In case of overdose it might be, so it is less "safe" than newer meds.

[CrazyRedhead]

7 hours ago, Persona_Is_Life said:

Lethal how?

Maybe she means "lethal" as in an overdose situation?.....Not sure....

But TCAs (like clomipramine) in general are considered more toxic than SSRIs in overdose.

Here's an informative article comparing SSRIs and TCAs.......Scroll down until you see the section under "Toxicity and safety"...:      http://www.emedexpert.com/compare/ssris-vs-tca.shtml

Edited May 20, 2018 by CrazyRedhead

[mellifluous]

Exactly as hydrocat and redhead suggested. 

I have a history of attempts and though none have been via overdose, my psychiatrist doesn't think it worth the risk in giving me something I potentially could OD on and succeed. 

[jt07]

I tried clomipramine for OCD. It is not really the gold standard for depression, but it once was the gold standard for OCD. I think now it is less so the gold standard since SSRIs came along and are proving helpful, especially at high doses. And to be honest, I personally found that SSRIs (especially citalopram/escitalopram)

[Catwoman]

Yes, have to agree with Jt07 that the newer meds (SSRI's for OCD I mean) have proven quite effective. With less side effects. Clomipramine is scaring the **** out of me actually. 
I really wish escitalopram / Lexapro still worked. Essentially, clomipramine is a SNRI. In the last two years I've been on three SSRI's and none of them did the trick anymore. Luxox and Lexapro were amazing for me when I first took them. 

My pdoc is still recommending Anafranil but I can't see how it could work. It will just do the same as SSRI's (concerning serotonin) but with more side effects probably.

 

[CrazyRedhead]

10 minutes ago, Catwoman said:

 My pdoc is still recommending Anafranil but I can't see how it could work. It will just do the same as SSRI's (concerning serotonin) but with more side effects probably.

IMO, I think Anafranil is at least worth a try .....If the side effects become too much for you, you can always discontinue it.

Edited May 23, 2018 by CrazyRedhead

[Ethansmom]

Hi All, 

This might be the next med i try if trintellix doesnt work. It seems kind of scary to try an "older" drug". Is anyone currently on this? And do you find it helps a lot with anxiety and panic. I need a med to crush these symptoms. I do go to therapy weekly, AND take Klonopin daily, but need something else.

[CrazyRedhead]

14 hours ago, Ethansmom said:

Hi All, 

This might be the next med i try if trintellix doesnt work. It seems kind of scary to try an "older" drug". Is anyone currently on this? And do you find it helps a lot with anxiety and panic. I need a med to crush these symptoms. I do go to therapy weekly, AND take Klonopin daily, but need something else.

I'm certainly not a pdoc, but I would suggest asking your doc about trying at least one of the SSRIs, or an SNRI, before trying the clomipramine,  if the Trintellix doesn't work out...........Simply because TCAs like clomipramine do have the potential of causing more side effects.

(SSRIs: Prozac, Zoloft, Lexapro, Celexa, Luvox, Paxil...............SNRIs: Effexor, Cymbalta)

In general, TCAs are usually a second-line treatment if an SSRI or an SNRI doesn't work, although it does depend on the doc....Some docs will prescribe TCAs more than others.

Of course, you should talk to your doc about what med would be best for you to try, if the Trintellix fails.

Edited May 25, 2018 by CrazyRedhead

[Pete6]

Hi there,

New to this forum. I have been taking clomipramine (anafranil) for the past 4 months. I started on 75mg and am now taking 150mg, divided in 2 dosages. I was diagnosed with OCPD (Obsessive compulsive personality disorder) over a year ago and initially i was given Luvox. It helped very little and I asked my pdoc to try anafranil. My experience is quite positive since it has given me back the will to live however, I still have ups and downs. There are days to weeks where i feel almost normal and there are days that my obsessive thoughts and compulsions are back making me feel miserable. I try to say to myself that ocd does fluctuate and never forget that but it's hard! Anyway, do give it a try I definitely recommend it! 

[Persona_Is_Life]

50 minutes ago, Pete6 said:

Hi there,

New to this forum. I have been taking clomipramine (anafranil) for the past 4 months. I started on 75mg and am now taking 150mg, divided in 2 dosages. I was diagnosed with OCPD (Obsessive compulsive personality disorder) over a year ago and initially i was given Luvox. It helped very little and I asked my pdoc to try anafranil. My experience is quite positive since it has given me back the will to live however, I still have ups and downs. There are days to weeks where i feel almost normal and there are days that my obsessive thoughts and compulsions are back making me feel miserable. I try to say to myself that ocd does fluctuate and never forget that but it's hard! Anyway, do give it a try I definitely recommend it! 

Same. I did have good results with it. It was the only med where I began to understand what a sense of "calm" feels like. 

It was great for my OCD, especially after a Luvox nightmare. 

[Ethansmom]

THank you both. It’s good to hear you had good results with it! That’s the next med I will try.  I’ll keep u posted.

[Simba Cub]

Didn't touch my depression. I needed a maximum dose of an MAOI, various antipsychotics and mood stabilisers, electroshock and rTMS therapy.

[Ethansmom]

Oh wow. I feel like I’m so resistant to antidepressants and they make me so much worse. Benzos are the only thing that have worked so far.

[Catwoman]

For anyone who's interested in this thread:  I started with 25 mg of clomipramine yesterday evening. I also took 25 mg of fluvoxamine (going to cross taper, my pdoc wants to follow guidelines and not combine these two). I woke at at 4:00 in the morning, was having heart palpitations and couldn't fall asleep again. Felt really restless and at 6:00 even wide awake!

I think I can say that fluvoxamine (Luvox) was doing something for me between 50 and 100 mg. Since clomipramine is essentially an SNRI with around 80% SERT occupancy (even at doses between 10 and 25 mg) I really really hope that this will be the last med change I have to make.

I'm getting incredibly desperate after 14 years of the same intrusive thought. It only got better with the first try Luvox (2 years) and the 6 years on Lexapro. 
So maybe it is possible with clomi as well....

Edited July 11, 2018 by Catwoman

[CrazyRedhead]

32 minutes ago, Catwoman said:

So maybe it is possible with clomi as well....

Good luck with the clomipramine...!!......Keep in mind that you may have to titrate up to higher dose for the OCD...

When I tried it I was up to about 250mg if I remember correctly.....

[Catwoman]

17 hours ago, CrazyRedhead said:

Good luck with the clomipramine...!!......Keep in mind that you may have to titrate up to higher dose for the OCD...

When I tried it I was up to about 250mg if I remember correctly.....

Thanks!! I'll try to go up to 75 mg. My pdoc said I could stay on 25 mg for the next 12 days, but if I can handle side effects I can titrate faster.
My intrusive thoughts are much worse since I took the first pill. I'm a little shaky and my legs are feeling stiff. This could be from the Luvox since I've gone down from 50 mg to 25 mg. But maybe it's stress and side effects from Anafranil as well. I don't know, but I'm not happy....
I just hope it will help me.

[mikl_pls]

1 hour ago, Catwoman said:

I'll try to go up to 75 mg. My pdoc said I could stay on 25 mg for the next 12 days, but if I can handle side effects I can titrate faster

According to Epocrates, clomipramine can be titrated by 25 mg every 4-7 days as tolerated to a max of 100 mg in the first 2 weeks. Just throwing that tidbit of info out there. Good luck with it!

[Catwoman]

1 hour ago, mikl_pls said:

According to Epocrates, clomipramine can be titrated by 25 mg every 4-7 days as tolerated to a max of 100 mg in the first 2 weeks. Just throwing that tidbit of info out there. Good luck with it!

Thanks! Today the third pill, so why not going up to 50 mg upcoming monday? If I can tolerate side effects that is....and the pdoc wants me to go and have an EKG because I'm having heart palpitations.
I had these before so I'm not worried, but apparently clomipramine increases risk on heart failure? 

[CrazyRedhead]

1 hour ago, Catwoman said:

I had these before so I'm not worried, but apparently clomipramine increases risk on heart failure? 

Risk of cardiac complications is a possible side effect for all TCAs in general, not just clomipramine:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434967/      (Scroll down to the sub-heading "TCAs")

I do think getting a baseline EKG would be a good idea for you.

Edited July 12, 2018 by CrazyRedhead

[Catwoman]

On 12-7-2018 at 1:23 PM, CrazyRedhead said:

Risk of cardiac complications is a possible side effect for all TCAs in general, not just clomipramine:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434967/      (Scroll down to the sub-heading "TCAs")

I do think getting a baseline EKG would be a good idea for you.

I'm having the EKG next week. I'm not that worried, but it is annoying to have that restless feeling in my chest. 

I'm not sure if I want to continue....I'm having awfull crying spells, mood swings and the intrusive thougt is back full force....

[mikl_pls]

12 hours ago, Catwoman said:

I'm not sure if I want to continue....I'm having awfull crying spells, mood swings and the intrusive thougt is back full force....

Well, in my experience, for what it's worth, on clomipramine, even at near the max dose of 225 mg, my depression, anxiety, and OCD actually got worse. In fact, as the dose got higher, everything got way worse, and I had nothing but side effects (urinary retention, sexual side effects, dry mouth, constipation, etc.) That was just my experience with it. I did try to give it a good college try, too, about 4 months or so, for it to work, but I just absolutely couldn't stand the side effects, especially the urinary retention and extreme constipation, and the worsening of depression was almost the death of me, literally.

But I'm not by any means trying to scare you away from trying it. I'm just telling you what my experience was with it in case you start to notice a similar pattern with side effects (worsening depression, anxiety, OCD, etc.) as you increase the dose. I would definitely give it a good, earnest try! It's an extremely good antidepressant for those for whom it works.

Edited July 14, 2018 by mikl_pls

[Catwoman]

11 hours ago, mikl_pls said:

Well, in my experience, for what it's worth, on clomipramine, even at near the max dose of 225 mg, my depression, anxiety, and OCD actually got worse. In fact, as the dose got higher, everything got way worse, and I had nothing but side effects (urinary retention, sexual side effects, dry mouth, constipation, etc.) That was just my experience with it. I did try to give it a good college try, too, about 4 months or so, for it to work, but I just absolutely couldn't stand the side effects, especially the urinary retention and extreme constipation, and the worsening of depression was almost the death of me, literally.

But I'm not by any means trying to scare you away from trying it. I'm just telling you what my experience was with it in case you start to notice a similar pattern with side effects (worsening depression, anxiety, OCD, etc.) as you increase the dose. I would definitely give it a good, earnest try! It's an extremely good antidepressant for those for whom it works.

Hey Mik, thanks for replying!
Today physical side effects are less than yesterday. I noticed low blood pressure and urinating takes longer. On this dose no dry mouth yet and no increase in appetite. I'm dreading the weight gain, if that's ever going to happen, but I think I could do more exercise once the intrusive thoughts are going away.
I think clomipramine is really 'attacking' me on emotional and psychological levels, including the OCD thoughts worsening. 

I'll keep on trying for at least six weeks. I've read so much positive stuff about this medication....My worst fear is that it won't do anything because of being on SSRI's for 10 years. 
Luvox seemed to work for me in the last 6 months, so that's positive, but on the other hand I'm scared about things like downregulation, loss of receptors, physiological adaptation and increased metabolic degradation. I wish I knew what was going on.
Maybe it's a bit obsessive of me, but it's hard to handle the uncertainty. 

[mikl_pls]

1 hour ago, Catwoman said:

Today physical side effects are less than yesterday.

This is a good sign!

1 hour ago, Catwoman said:

I noticed low blood pressure and urinating takes longer.

This, however, probably is not a good sign, but hopefully this will subside with time.

1 hour ago, Catwoman said:

On this dose no dry mouth yet and no increase in appetite. I'm dreading the weight gain, if that's ever going to happen, but I think I could do more exercise once the intrusive thoughts are going away.

Some people actually experience decreased appetite and weight loss on clomipramine since it's such a potently serotonergic medication despite being a tertiary TCA and having relatively potent antihistaminergic properties. Its metabolite, N-desmethylclomipramine, is also a very potent norepinephrine reuptake inhibitor, so may offset the weight gain potential of its parent compound.

2 hours ago, Catwoman said:

I think clomipramine is really 'attacking' me on emotional and psychological levels, including the OCD thoughts worsening.

Why do you think this?

2 hours ago, Catwoman said:

I'll keep on trying for at least six weeks. I've read so much positive stuff about this medication....My worst fear is that it won't do anything because of being on SSRI's for 10 years.

I've read that clomipramine takes actually much longer than typical antidepressants. Like at the very soonest, it takes up to 8 weeks for people to get a response... Sometimes even longer! (I know that isn't what you want to hear...  I know when I read that when I was on it I was pretty bummed out...) But just hang in there and stay strong!

Just curious, what does being on an SSRI for so long have to do with clomipramine possibly not working? Usually a TCA is tried after many failed trials of first-line agents like SSRIs/SNRIs.

2 hours ago, Catwoman said:

Luvox seemed to work for me in the last 6 months, so that's positive, but on the other hand I'm scared about things like downregulation, loss of receptors, physiological adaptation and increased metabolic degradation. I wish I knew what was going on.
Maybe it's a bit obsessive of me, but it's hard to handle the uncertainty.

Actually, receptor downregulation is precisely what you want--that's the therapeutic effect of serotonergic antidepressants, and that's what is beneficial to anxiety and depressive disorders. Serotonergic antidepressants raise serotonin levels and indiscriminately stimulate all serotonin subtypes, causing them to downregulate. At first, this causes many of the negative side effects associated with antidepressants (anxiety, agitation, etc.), mostly due to excess stimulation of serotonin 5-HT_2A and 5-HT_2C receptors, which, in people with anxiety and depression, are already abnormally highly upregulated to begin with. Also, the presynaptic 5-HT_1A autoreceptors (which when stimulated with serotonin inhibits release of serotonin, hence being called an autoreceptor) tend to also be abnormally highly expressed in some depressed and anxious patients (usually tends to be a genetic thing). But as you take the antidepressant, the chronic stimulation of the elevated serotonin levels causes these receptors to decrease in expression, or as you said, "downregulate" over a period of several weeks (all subtypes do, but these in particular are the ones we're talking about). The 5-HT_2A receptors downregulate, decreasing anxiety and depression, and cause a release of dopamine in the prefrontal cortex. The 5-HT_2C receptors downregulate, decreasing depressive symptoms and allowing dopamine and norepinephrine release. The presynaptic 5-HT_1A autoreceptors downregulate, and the inhibition of serotonin release is disinhibited, and serotonin release is greatly enhanced. The postsynaptic 5-HT_1A receptors are stimulated by the enhanced serotonin release plus the increased serotonin levels from the antidepressant, causing a downstream release of dopamine.

As it turns out though, antagonizing or blocking the 5-HT_2A/2C receptors causes them to downregulate, too, and clomipramine happens to be a 5-HT_2A/2C antagonist. So while you're taking clomipramine, you are less likely to get the negative effects of excess serotonergic stimulation at these receptors (which I'm sure, by now, from taking SSRIs all these years, your serotonin receptors are downregulated enough to where you wouldn't experience them anyway... but I could be wrong, as you are experiencing OCD symptoms still, but that could be via another mechanism that isn't serotonergic...)

 

So I forget, have you talked to your pdoc about something other than an antidepressant for your OCD? Because there are plenty of other options for this that don't involve antidepressants, and they can be used as adjunctive treatment for people who don't respond adequately or not at all to antidepressants. I'm talking about things like antipsychotics, antiglutamatergic medicines like topiramate, lamotrigine, memantine, riluzole, N-acetylcysteine (NAC). Even dextroamphetamine apparently has been used for OCD in people with ADHD. 

 

[Iceberg]

@mikl_pls my doc agrees with you about this med taking longer than others...he said he doesn't give up until 3 months at a good dose (but obviously covering with other things in the meantime) 

[Catwoman]

Arrghhh quoting a post is giving me trouble right now.

Edited July 16, 2018 by Catwoman

[Catwoman]

On 14-7-2018 at 4:43 PM, mikl_pls said:

Just curious, what does being on an SSRI for so long have to do with clomipramine possibly not working? Usually a TCA is tried after many failed trials of first-line agents like SSRIs/SNRIs.

Actually, receptor downregulation is precisely what you want--that's the therapeutic effect of serotonergic antidepressants, and that's what is beneficial to anxiety and depressive disorders. Serotonergic antidepressants raise serotonin levels and indiscriminately stimulate all serotonin subtypes, causing them to downregulate. At first, this causes many of the negative side effects associated with antidepressants (anxiety, agitation, etc.), mostly due to excess stimulation of serotonin 5-HT_2A and 5-HT_2C receptors, which, in people with anxiety and depression, are already abnormally highly upregulated to begin with. Also, the presynaptic 5-HT_1A autoreceptors (which when stimulated with serotonin inhibits release of serotonin, hence being called an autoreceptor) tend to also be abnormally highly expressed in some depressed and anxious patients (usually tends to be a genetic thing). But as you take the antidepressant, the chronic stimulation of the elevated serotonin levels causes these receptors to decrease in expression, or as you said, "downregulate" over a period of several weeks (all subtypes do, but these in particular are the ones we're talking about). The 5-HT_2A receptors downregulate, decreasing anxiety and depression, and cause a release of dopamine in the prefrontal cortex. The 5-HT_2C receptors downregulate, decreasing depressive symptoms and allowing dopamine and norepinephrine release. The presynaptic 5-HT_1A autoreceptors downregulate, and the inhibition of serotonin release is disinhibited, and serotonin release is greatly enhanced. The postsynaptic 5-HT_1A receptors are stimulated by the enhanced serotonin release plus the increased serotonin levels from the antidepressant, causing a downstream release of dopamine.

As it turns out though, antagonizing or blocking the 5-HT_2A/2C receptors causes them to downregulate, too, and clomipramine happens to be a 5-HT_2A/2C antagonist. So while you're taking clomipramine, you are less likely to get the negative effects of excess serotonergic stimulation at these receptors (which I'm sure, by now, from taking SSRIs all these years, your serotonin receptors are downregulated enough to where you wouldn't experience them anyway... but I could be wrong, as you are experiencing OCD symptoms still, but that could be via another mechanism that isn't serotonergic...)

So I forget, have you talked to your pdoc about something other than an antidepressant for your OCD? Because there are plenty of other options for this that don't involve antidepressants, and they can be used as adjunctive treatment for people who don't respond adequately or not at all to antidepressants. I'm talking about things like antipsychotics, antiglutamatergic medicines like topiramate, lamotrigine, memantine, riluzole, N-acetylcysteine (NAC). Even dextroamphetamine apparently has been used for OCD in people with ADHD. 

 

Hi Mik, thanks for explaining! 
I knew a little bit about the working mechanism of SSRI's.  My first experience with Luvox was positive. After 6 weeks I noticed a decrease in intrusive thoughts and with 9 weeks I seemed to be in remission. I was a textbook example, though I had few side effects to begin with. On high dosages I had RLS but that was about it. 
Over two years I stopped taking Luvox twice. The last time I restarted it didn't seem to work very well and I switched to Lexapro. I thought this was an incredible medication, because after just 2/3 weeks I noticed the effect. It took me longer to stabilize though, but after two years I felt really really good and the intrusive thought didn't bother me anymore. My life was normal ;-)

About two years ago I had a major relapse and increased Lexapro from 5 mg to 15 mg over a few weeks.
It a horrible experience: crying spells, very emotional, mood swings, nightmares, ruminating and no concentration. 
(Very much like the first few days on clomipramine)

I decided to go off Lexapro, which was a difficult process and took me a few months.
After being off meds for four months I wasn't seeing any improvements and I couldn't function, so my gdoc let me go on Zoloft/sertraline.
I tried various doses, even went up to 250 mg, but it just wasn't doing the same as Luvox and Lexapro.

Last year I wanted to try Luvox again. The result wasn't amazing, but by the end of December 2017 I did feel like I was improving. I think Luvox was working for me, but I still felt insecure and thought I could get better results from something else.

My pdoc wants to follow guidelines so clomipramine was the first thing she wants me to try. 
I asked her about other options and augmentation treatments, but she wants to take it slow and be as careful as possible.

The reason why I'm worried about clomi not working is because SSRI's used to work for me, but stopped working.  I know Anafranil is tried after two/three failed SSRI attempts, but SSRI's didn't really fail me in the first 8 years. Sertraline was a letdown and Luvox wasn't as great as with the first try.
It's really getting to me actually.....

I took some additional OTC supplements, but run out of all of them. Magnesium, high doses of NAC, bacopa,  ashwaghanda...all good quality. I didn't notice a big difference.
My pdoc thinks augmenting with Seroquel can be an option later on. With @browri I talked about Abilify and Rexulti as well as other anti-psychotics. 
I can't exactly remember how these act towards unwanted thoughts (Dopamine agonists, antagonists....confusing!!)

What I would really like is to end this annoying thought process. I have a massive aversion towards this obsession (or intrusive thought) and I haven't succeeded in turning it around, despite all the therapy and mindfulness. 

[mikl_pls]

8 hours ago, Catwoman said:

Hi Mik, thanks for explaining! 
I knew a little bit about the working mechanism of SSRI's.  My first experience with Luvox was positive. After 6 weeks I noticed a decrease in intrusive thoughts and with 9 weeks I seemed to be in remission. I was a textbook example, though I had few side effects to begin with. On high dosages I had RLS but that was about it. 
Over two years I stopped taking Luvox twice. The last time I restarted it didn't seem to work very well and I switched to Lexapro. I thought this was an incredible medication, because after just 2/3 weeks I noticed the effect. It took me longer to stabilize though, but after two years I felt really really good and the intrusive thought didn't bother me anymore. My life was normal ;-)

About two years ago I had a major relapse and increased Lexapro from 5 mg to 15 mg over a few weeks.
It a horrible experience: crying spells, very emotional, mood swings, nightmares, ruminating and no concentration. 
(Very much like the first few days on clomipramine)

I decided to go off Lexapro, which was a difficult process and took me a few months.
After being off meds for four months I wasn't seeing any improvements and I couldn't function, so my gdoc let me go on Zoloft/sertraline.
I tried various doses, even went up to 250 mg, but it just wasn't doing the same as Luvox and Lexapro.

Last year I wanted to try Luvox again. The result wasn't amazing, but by the end of December 2017 I did feel like I was improving. I think Luvox was working for me, but I still felt insecure and thought I could get better results from something else.

My pdoc wants to follow guidelines so clomipramine was the first thing she wants me to try. 
I asked her about other options and augmentation treatments, but she wants to take it slow and be as careful as possible.

The reason why I'm worried about clomi not working is because SSRI's used to work for me, but stopped working.  I know Anafranil is tried after two/three failed SSRI attempts, but SSRI's didn't really fail me in the first 8 years. Sertraline was a letdown and Luvox wasn't as great as with the first try.
It's really getting to me actually.....

I took some additional OTC supplements, but run out of all of them. Magnesium, high doses of NAC, bacopa,  ashwaghanda...all good quality. I didn't notice a big difference.
My pdoc thinks augmenting with Seroquel can be an option later on. With @browri I talked about Abilify and Rexulti as well as other anti-psychotics. 
I can't exactly remember how these act towards unwanted thoughts (Dopamine agonists, antagonists....confusing!!)

What I would really like is to end this annoying thought process. I have a massive aversion towards this obsession (or intrusive thought) and I haven't succeeded in turning it around, despite all the therapy and mindfulness. 

You could've gone into supratherapeutic doses of Luvox (> 300 mg) or Zoloft (well above 200 mg), but that's in the past now, possibly for another time. I'm sort of considering trying very high dose Zoloft (> 200 mg) for my OCD. It works for it very well, but the normal dose range just doesn't quite cut it. Sucks that RLS occurred with SSRIs. That can be mitigated with something like gabapentin or a dopamine agonist, though.

Abilify does quite well for me for a lot of my issues. I love Abilify quite a lot. It does seem to be a bit too stimulating for some, though.

 

[Catwoman]

1 hour ago, mikl_pls said:

You could've gone into supratherapeutic doses of Luvox (> 300 mg) or Zoloft (well above 200 mg), but that's in the past now, possibly for another time. I'm sort of considering trying very high dose Zoloft (> 200 mg) for my OCD. It works for it very well, but the normal dose range just doesn't quite cut it. Sucks that RLS occurred with SSRIs. That can be mitigated with something like gabapentin or a dopamine agonist, though.

Abilify does quite well for me for a lot of my issues. I love Abilify quite a lot. It does seem to be a bit too stimulating for some, though.

 

I went up to 250 mg with Zoloft. I can't remember how long I've been on that dose, but less than a month. I couldn't fall asleep because of the ringing in my ears...
With Luvox I didn't go up so high this time, I think 200 mg was the maximum, but because I wanted to try Anafranil we decided to go down. Things suddenly got better at 100 mg, stayed stable at 75 mg and even 50 mg was helping a little.

I stopped Luvox entirely because my pdoc says the Luvox+Anafranil combo is build on individual cases and there's not enough medical research to support it.  
Wednesday I'm going for the EKG. The heart palpitations are a lot less, but maybe they'll return once I go up in dose. 

I would like to try aripiprazole, but I'm not sure it can be taken with clomipramine?
Or are there other ap's to augment with TCA's?

[mikl_pls]

11 hours ago, Catwoman said:

I went up to 250 mg with Zoloft. I can't remember how long I've been on that dose, but less than a month. I couldn't fall asleep because of the ringing in my ears...

Oh yeah that's definitely not a side effect that can be tolerated...

I'm currently on 150 mg Zoloft and while I like it, I feel my OCD is not under control. I've been on 200 mg before, but it didn't help much better. I think I may ask my pdoc about going up to 250-300 mg or something.

11 hours ago, Catwoman said:

With Luvox I didn't go up so high this time, I think 200 mg was the maximum, but because I wanted to try Anafranil we decided to go down. Things suddenly got better at 100 mg, stayed stable at 75 mg and even 50 mg was helping a little.

Interesting...

11 hours ago, Catwoman said:

Wednesday I'm going for the EKG. The heart palpitations are a lot less, but maybe they'll return once I go up in dose.

Hopefully not!

11 hours ago, Catwoman said:

I would like to try aripiprazole, but I'm not sure it can be taken with clomipramine?
Or are there other ap's to augment with TCA's?

I don't see why aripiprazole couldn't be taken with clomipramine. The only interaction I could see is that they're both metabolized by CYP2D6, which could interfere with each others' metabolism and raise each others' blood levels, effectively raising their dosages, so lower doses of both drugs would possibly need to be used than normal, but that's about it. Pharmacodynamically, there's nothing wrong with combining the two.

[Catwoman]

5 hours ago, mikl_pls said:

I don't see why aripiprazole couldn't be taken with clomipramine. The only interaction I could see is that they're both metabolized by CYP2D6, which could interfere with each others' metabolism and raise each others' blood levels, effectively raising their dosages, so lower doses of both drugs would possibly need to be used than normal, but that's about it. Pharmacodynamically, there's nothing wrong with combining the two.

I couldn't find much about it with Google. Maybe because clomi is quite old and aripiprazole is a newer medication. 
I'll ask my pdoc next week, though adding something might not be necessary (if clomi  does the job)

It would be really fantastic to find something which stops the constant thinking of the same thought. I would love to have some piece and quiet.
It probably comes back into my mind because I can't stand it (white polar bear effect), but on the other hand it feels like an overactive thought mechanism which I can't influence.

Edited July 17, 2018 by Catwoman

[browri]

On 7/17/2018 at 6:45 AM, Catwoman said:

I couldn't find much about it with Google. Maybe because clomi is quite old and aripiprazole is a newer medication. 
I'll ask my pdoc next week, though adding something might not be necessary (if clomi  does the job)

It would be really fantastic to find something which stops the constant thinking of the same thought. I would love to have some piece and quiet.
It probably comes back into my mind because I can't stand it (white polar bear effect), but on the other hand it feels like an overactive thought mechanism which I can't influence.

@mikl_pls for OCD, shouldn't more antagonism be used instead of agonism? My concern with the aripiprazole augmentation solution is that it has ~60% intrinsic activity at the D₂ receptor, and it's been known to potentially increase compulsive behaviors in some situations like compulsive gambling or shopping. Not sure if it would have the same effect on @Catwoman's pure "O", but I would think dopamine antagonists would be preferrable in this case to quiet ones thoughts. This would be why quetiapine would be beneficial and it's also why I suggested she talk to her doctor about brexpiprazole, because it has a lower intrinsic activity at the dopamine receptors of ~40-45% which should theoretically calm thoughts more effectively than aripiprazole. Although I suppose with aripiprazole there is the option to going to the higher doses (10mg+) which may provide enough blocking activity, but brexpiprazole would definitely be more calming because it has more potent antagonistic effects at the 5HT_2A and 5HT_1A receptors than aripiprazole.

I've also heard of risperidone being used as augmentation to treat OCD similarly to quetiapine. It has a higher risk of prolactin elevations, but it would have a similar calming effect and would likely lead to less weight gain than quetiapine. My partner takes just 0.25mg of risperidone with 10mg of escitalopram and finds that he really likes the way it calms his thoughts. He finds that he can focus better because his "internal monologue" is less distracting.

[mikl_pls]

57 minutes ago, browri said:

@mikl_pls for OCD, shouldn't more antagonism be used instead of agonism? My concern with the aripiprazole augmentation solution is that it has ~60% intrinsic activity at the D₂ receptor, and it's been known to potentially increase compulsive behaviors in some situations like compulsive gambling or shopping. Not sure if it would have the same effect on @Catwoman's pure "O", but I would think dopamine antagonists would be preferrable in this case to quiet ones thoughts. This would be why quetiapine would be beneficial and it's also why I suggested she talk to her doctor about brexpiprazole, because it has a lower intrinsic activity at the dopamine receptors of ~40-45% which should theoretically calm thoughts more effectively than aripiprazole. Although I suppose with aripiprazole there is the option to going to the higher doses (10mg+) which may provide enough blocking activity, but brexpiprazole would definitely be more calming because it has more potent antagonistic effects at the 5HT_2A and 5HT_1A receptors than aripiprazole.

I've also heard of risperidone being used as augmentation to treat OCD similarly to quetiapine. It has a higher risk of prolactin elevations, but it would have a similar calming effect and would likely lead to less weight gain than quetiapine. My partner takes just 0.25mg of risperidone with 10mg of escitalopram and finds that he really likes the way it calms his thoughts. He finds that he can focus better because his "internal monologue" is less distracting.

I think it could be a possible augmenting agent simply because there has been research done with it with successful results, but I do agree with you about there being issues with compulsivity/impulsivity issues with it.

In addition to Rexulti (brexpiprazole), quetiapine, and risperidone, I think that ziprasidone could be another good choice that would have even less liability to cause weight gain than quetiapine and risperidone, and less liability to produce elevated prolactin than risperidone, especially.  

[browri]

39 minutes ago, mikl_pls said:

I think it could be a possible augmenting agent simply because there has been research done with it with successful results, but I do agree with you about there being issues with compulsivity/impulsivity issues with it.

In addition to Rexulti (brexpiprazole), quetiapine, and risperidone, I think that ziprasidone could be another good choice that would have even less liability to cause weight gain than quetiapine and risperidone, and less liability to produce elevated prolactin than risperidone, especially.  

+1 on the ziprasidone suggestion at least from a tolerability and pharmacology standpoint. Definitely would be less likely to increase prolactin or weight. Not sure how good it would be for obsessive rumination unfortunately, as I've never taken it before.

[mikl_pls]

1 hour ago, browri said:

+1 on the ziprasidone suggestion at least from a tolerability and pharmacology standpoint. Definitely would be less likely to increase prolactin or weight. Not sure how good it would be for obsessive rumination unfortunately, as I've never taken it before.

It definitely helped me with my OCD when I took it the first time.

[Catwoman]

On 20-7-2018 at 3:29 PM, browri said:

@mikl_pls for OCD, shouldn't more antagonism be used instead of agonism? My concern with the aripiprazole augmentation solution is that it has ~60% intrinsic activity at the D₂ receptor, and it's been known to potentially increase compulsive behaviors in some situations like compulsive gambling or shopping. Not sure if it would have the same effect on @Catwoman's pure "O", but I would think dopamine antagonists would be preferrable in this case to quiet ones thoughts. This would be why quetiapine would be beneficial and it's also why I suggested she talk to her doctor about brexpiprazole, because it has a lower intrinsic activity at the dopamine receptors of ~40-45% which should theoretically calm thoughts more effectively than aripiprazole. Although I suppose with aripiprazole there is the option to going to the higher doses (10mg+) which may provide enough blocking activity, but brexpiprazole would definitely be more calming because it has more potent antagonistic effects at the 5HT_2A and 5HT_1A receptors than aripiprazole.

I've also heard of risperidone being used as augmentation to treat OCD similarly to quetiapine. It has a higher risk of prolactin elevations, but it would have a similar calming effect and would likely lead to less weight gain than quetiapine. My partner takes just 0.25mg of risperidone with 10mg of escitalopram and finds that he really likes the way it calms his thoughts. He finds that he can focus better because his "internal monologue" is less distracting.

I like what you're writing about the low dose of risperidone. It's not that my thoughts are all over the place, but the thought keeps pulling me towards it and distracts me. It literally intrudes everywhere I go and with everything I do. Interfering every thought or activity in my mind. 

What I've never accomplished is taking distance from the intrusive word. It has a big negative charge, I hate it and I'm resisting it. The opposite happens: it sticks to my consciousness, like it's superglued. I need to become accustomed to this intrusive word and stop paying attention to it.  If I don't respond, the thought will go away (habituation process). 
SSRI's just made the thought go away, but never removed the negative feelings. Moreover, I get anxious when I notice the thought 'breaking through'. 
It's not because I'm so scared about the meaning of the intrusive word. My problem is that I think I'm never going to stop thinking about this, which leads to fears of going through it again and again and never think like 'normal' people do.

Anyway, how could medications help with the habituation process, especially anti-psychotics?

[Catwoman]

Tomorrow I'm seeing my pdoc. She's probably increase the dose, I think she wants me on 75mg. No idea if this is going to be enough.

I'm feeling OK, I'm sleeping again and no restless legs!!
An occasional hot flush and a higher heart rate than I'm used to, but the EKG wasn't showing anything out of the ordinary.

About anti-psychotics:
-Ziprasidone isn't available in my country
-Brexiprazole might be too new and I'm not sure if my pdoc is willing to try it
-Quetiapine was mentioned first....I'm worried that it will make me gain weight and make me sleepy during the day!
-Aripiprazole might be too activating or stimulating? That could help me with some issues, but it could work against me if it increases obsessive thoughts and intrusive words.
-Risperidone....I would be concerned about weight gain, but I thought olanzapine was the biggest offender in that area?

[mikl_pls]

On 7/23/2018 at 9:21 AM, Catwoman said:

Tomorrow I'm seeing my pdoc. She's probably increase the dose, I think she wants me on 75mg. No idea if this is going to be enough.

I'm feeling OK, I'm sleeping again and no restless legs!!
An occasional hot flush and a higher heart rate than I'm used to, but the EKG wasn't showing anything out of the ordinary.

About anti-psychotics:
-Ziprasidone isn't available in my country
-Brexiprazole might be too new and I'm not sure if my pdoc is willing to try it
-Quetiapine was mentioned first....I'm worried that it will make me gain weight and make me sleepy during the day!
-Aripiprazole might be too activating or stimulating? That could help me with some issues, but it could work against me if it increases obsessive thoughts and intrusive words.
-Risperidone....I would be concerned about weight gain, but I thought olanzapine was the biggest offender in that area?

Sorry I didn't respond before you saw your pdoc... I haven't been able to get on here until now.

How did your pdoc appointment go? What did your pdoc end up doing with your dose? Any antipsychotic prescribed?

Yeah, quetiapine + clomipramine = snooze fest + ballooning up rapidly.

Aripiprazole, while it may be activating and stimulating, which may depend on the dose (low doses tend to be more stimulating than higher doses, but YMMV), has been studied for and found effective for OCD, although it doesn't have an official indication for it here in the US. It could be worth a try, ya know?

Risperidone is not quite as prone to causing weight gain as quetiapine or olanzapine. The way I understand it, as far as weight gain goes, the hierarchy is clozapine > olanzapine > quetiapine > risperidone. The main things you gotta worry about with risperidone is hyperprolactinemia and EPS, but with 0.25-0.5 mg, you probably won't have much of an issue with the latter.

[Catwoman]

57 minutes ago, mikl_pls said:

Sorry I didn't respond before you saw your pdoc... I haven't been able to get on here until now.

How did your pdoc appointment go? What did your pdoc end up doing with your dose? Any antipsychotic prescribed?

Yeah, quetiapine + clomipramine = snooze fest + ballooning up rapidly.

Aripiprazole, while it may be activating and stimulating, which may depend on the dose (low doses tend to be more stimulating than higher doses, but YMMV), has been studied for and found effective for OCD, although it doesn't have an official indication for it here in the US. It could be worth a try, ya know?

Risperidone is not quite as prone to causing weight gain as quetiapine or olanzapine. The way I understand it, as far as weight gain goes, the hierarchy is clozapine > olanzapine > quetiapine > risperidone. The main things you gotta worry about with risperidone is hyperprolactinemia and EPS, but with 0.25-0.5 mg, you probably won't have much of an issue with the latter.

The appointment went....well...blah....I had to cry a few times, because I felt incredibly emotional yesterday. My menstrual period was about to start. OCD gotten worse as well, so I'm having the unwanted thought almost continuously. And I can't turn around how I respond to this. 
I told her about this and I asked her about anti-psychotics, but I she didn't answer any of my questions. I thought: "Can't you see I need something to block this thought right now?"
I'm seeing her again next Monday. She prescribed 35 mg of clomipramine for the next two tweeks.  I need to increase to 75 mg in the upcoming weeks.  I wonder when I'm going to do the blood test to see how the levels in my blood are. I just really really really hope this med will help, because I'm so scared right now

[echolocation]

just wanted to throw in my 2 cents re: risperidone for general calming of OCD type stuff. i'm on 0.75 mg daily, and it gives me a lot of relief from intrusive thoughts and brain spirals. i've honestly noted no side effects from it (including weight gain), but in general i'm not too prone to serious side effects from medication.

i hear you about how scary it is to feel like things are getting worse. i hope you find relief soon. take care. ?

[Catwoman]

14 hours ago, echolocation said:

just wanted to throw in my 2 cents re: risperidone for general calming of OCD type stuff. i'm on 0.75 mg daily, and it gives me a lot of relief from intrusive thoughts and brain spirals. i've honestly noted no side effects from it (including weight gain), but in general i'm not too prone to serious side effects from medication.

i hear you about how scary it is to feel like things are getting worse. i hope you find relief soon. take care. ?

Thanks!

I'm not sure how anxious I am. I just have this thought coming up again and again. I know I shouldn't resist, fight or trying to suppress  it, but I haven't managed this yet, so I keep doing it. 

What I would like from an anti-psychotic in any case is not sedation. I just feel a little tense. I wonder if an AP can stop this continuous thought.  Although it's not a racing thought or 'monkey-brain'.
Silence, that would be nice.

There must be some kind of neurochemical or biological process in the brain going on which keeps repeating this intruding thought.
I wonder how it works. Everything we do and think is done by our brain, right? So what causes it, what happens? And which drug could stop this if suppressing the thought is counterproductive?

On the internet I read that clomipramine / Anafranil can work within 4 weeks. But I'm not sure on which dose. I'm at 35 mg so that's really low after 2,5 weeks.

Edited July 26, 2018 by Catwoman

[CrazyRedhead]

7 hours ago, Catwoman said:

On the internet I read that clomipramine / Anafranil can work within 4 weeks. But I'm not sure on which dose. I'm at 35 mg so that's really low after 2,5 weeks.

The max dose of clomipramine for OCD is 250mg/day........You have quite a bit of room to go up......I would suggest asking your pdoc what the target dose is for you.

More info on clomipramine dosages here:  https://www.drugs.com/dosage/clomipramine.html

[Catwoman]

11 minutes ago, CrazyRedhead said:

The max dose of clomipramine for OCD is 250mg/day........You have quite a bit of room to go up......I would suggest asking your pdoc what the target dose is for you.

More info on clomipramine dosages here:  https://www.drugs.com/dosage/clomipramine.html

I'm supposed to go to 75 mg in a few weeks and stay there for some time. Hopefully it will kick in. I'll probably have a blood test as well to check the clomipramine levels.

[browri]

On 7/25/2018 at 12:35 PM, echolocation said:

just wanted to throw in my 2 cents re: risperidone for general calming of OCD type stuff. i'm on 0.75 mg daily, and it gives me a lot of relief from intrusive thoughts and brain spirals. i've honestly noted no side effects from it (including weight gain), but in general i'm not too prone to serious side effects from medication.

i hear you about how scary it is to feel like things are getting worse. i hope you find relief soon. take care. ?

If my partner were on here, he would certainly second this. He's been taking 0.25mg of risperidone for a few months now. At first he said that he didn't like the way it made him feel but after a few weeks, he commented to me that he adjusted to it more and that he actually enjoyed how much more calm and collected his brain was. Keep in mind he's somewhere on the Bipolar 2 spectrum but also has irrefutable ADHD. He's told me once or twice the 4.5 years we've been together that he does sometimes experience rumination that he can't quiet. But he has also commented that a lot of that has changed since adding the 0.25mg of risperidone. He's never even tried other APs and he's never done beyond that dose. He's currently also takes the risperidone with 50mg of Vyvanse and 10mg of escitalopram. He doesn't really like the escitalopram though and feels like it's pooped out on him.

[Catwoman]

17 hours ago, browri said:

 He's currently also takes the risperidone with 50mg of Vyvanse and 10mg of escitalopram. He doesn't really like the escitalopram though and feels like it's pooped out on him.

From all that I've read on forums and research it seems that all SSRI's will poop-out sooner or later. I liked escitalopram a lot, though in the first year I still had ups and downs (with intrusive thoughts that it), but in the following years it felt like complete remission. After 6 years it suddenly stopped working and going back to 15 mg didn't do anything.
Your partner could try to go up to 15 or 20 mg?

I've read a lot of scary stuff about risperidone, but with such a low dose as 0.25 or even 0.50 I might not get all the scary side effects.
My doctor probably thinks I should wait because I'm still only taking clomipramine for three weeks and she might be right, but another 3 weeks feels like a very long waiting period right now....
I just want some quietness in my thoughts....

Edited July 30, 2018 by Catwoman

[browri]

7 hours ago, Catwoman said:

From all that I've read on forums and research it seems that all SSRI's will poop-out sooner or later. I liked escitalopram a lot, though in the first year I still had ups and downs (with intrusive thoughts that it), but in the following years it felt like complete remission. After 6 years it suddenly stopped working and going back to 15 mg didn't do anything.
Your partner could try to go up to 15 or 20 mg?

I've read a lot of scary stuff about risperidone, but with such a low dose as 0.25 or even 0.50 I might not get all the scary side effects.
My doctor probably thinks I should wait because I'm still only taking clomipramine for three weeks and she might be right, but another 3 weeks feels like a very long waiting period right now....
I just want some quietness in my thoughts....

He's actually tried going to 15mg before but he doesn't tolerate it. Doesn't like the way that it makes him feel. Spacey and such. It makes him feel more tired too. Not a surprise. Fatigue was the usual for me on escitalopram.

[echolocation]

risperidone is very unlikely to give you the more serious side effects (movement issues, prolactin levels changing) at under 1 mg. my pdoc told me he rarely sees patients with those side effects at those doses when i expressed concern about it.

[Catwoman]

22 hours ago, browri said:

He's actually tried going to 15mg before but he doesn't tolerate it. Doesn't like the way that it makes him feel. Spacey and such. It makes him feel more tired too. Not a surprise. Fatigue was the usual for me on escitalopram.

I recall feeling quite lethargic in the mornings on escitalopram, but I was so used it that I thought it was just me. I had trouble waking up, couldn't get up early and it took me the whole morning to get going. Once I was up and running I didn't have much trouble. 

[Catwoman]

11 hours ago, echolocation said:

risperidone is very unlikely to give you the more serious side effects (movement issues, prolactin levels changing) at under 1 mg. my pdoc told me he rarely sees patients with those side effects at those doses when i expressed concern about it.

Thanks! I really wonder what it is like to be on an anti-psychotic. I assume as an augment strategy it's usually a low dose. It's always a bit scary to start with something new. 
I'm seeing my pdoc tomorrow afternoon. I suspect she doesn't prescribe me anything new.
On the other hand, she's supposed to help me and must have some ideas on how to handle to increase in my obsessive thoughts.

[echolocation]

definitely stress to her that the increase in obsessive thoughts is bothering you and you want to do something about it. she might have some ideas on how to deal with it.

when i began taking my AP, it felt like a really drastic step to me. like before, i was just on an antidepressant, like ordinary people, but now something must really be wrong with me to need this. i didn't really accept that i was "really" mentally ill before going on risperidone. joining this community helped a lot. honestly, after starting risperidone, i didn't really notice feeling different. about a week after starting it, i realized that i had better focus and a quieter mind, like i did on my "good days". but it wasn't just good days, it was the medication. my baseline increased in quality, so what used to be my good days became my normal days. 

the augmenting dose is always low, usually far below the target dose for treating psychotic symptoms. APs are wonderful in that they have many uses beyond treating psychotic symptoms, and are often used for depression, rumination, and sleep among other things. taking an AP necessarily mean doesn't mean you are psychotic, it means you're exploring other avenues to treat symptoms.

hope your pdoc appt goes well! :-)

[browri]

On 7/31/2018 at 11:40 AM, echolocation said:

definitely stress to her that the increase in obsessive thoughts is bothering you and you want to do something about it. she might have some ideas on how to deal with it.

when i began taking my AP, it felt like a really drastic step to me. like before, i was just on an antidepressant, like ordinary people, but now something must really be wrong with me to need this. i didn't really accept that i was "really" mentally ill before going on risperidone. joining this community helped a lot. honestly, after starting risperidone, i didn't really notice feeling different. about a week after starting it, i realized that i had better focus and a quieter mind, like i did on my "good days". but it wasn't just good days, it was the medication. my baseline increased in quality, so what used to be my good days became my normal days. 

the augmenting dose is always low, usually far below the target dose for treating psychotic symptoms. APs are wonderful in that they have many uses beyond treating psychotic symptoms, and are often used for depression, rumination, and sleep among other things. taking an AP necessarily mean doesn't mean you are psychotic, it means you're exploring other avenues to treat symptoms.

hope your pdoc appt goes well! :-)

+1

[Catwoman]

Started with 50 mg yesterday after a few days on 45 mg. In about three weeks I'm supposed to go to 75 mg. My pdoc is on vacation now, so I wasn't prescribed more just to stay on the safe side.
50 mg is probably not a therapeutic dose, but I do feel better the last few days. I don't think it's kicked in already.

I can clearly notice the effects on noradrenaline:  heart palps, some hairloss, waking up early, feeling quite awake in the mornings....
I'm not feeling the usual serotonergic side effects like restless legs and teeth grinding. My dreams aren't as vivid. 

I'm not sure where to twitchy muscles are coming from. I had these on all three SSRI's, so I always thought them as serotonergic. But I'm not taking a high dose right now and the twitches are more noticeable.

I talked to my pdoc about the AP's but she wasn't willing to prescribe any just yet. I have to admit that I'll have to wait for clomipramine first to see what it will do. Maybe it's strong enough on its own.
 

[browri]

5 hours ago, Catwoman said:

Started with 50 mg yesterday after a few days on 45 mg. In about three weeks I'm supposed to go to 75 mg. My pdoc is on vacation now, so I wasn't prescribed more just to stay on the safe side.
50 mg is probably not a therapeutic dose, but I do feel better the last few days. I don't think it's kicked in already.

I can clearly notice the effects on noradrenaline:  heart palps, some hairloss, waking up early, feeling quite awake in the mornings....
I'm not feeling the usual serotonergic side effects like restless legs and teeth grinding. My dreams aren't as vivid. 

I'm not sure where to twitchy muscles are coming from. I had these on all three SSRI's, so I always thought them as serotonergic. But I'm not taking a high dose right now and the twitches are more noticeable.

I talked to my pdoc about the AP's but she wasn't willing to prescribe any just yet. I have to admit that I'll have to wait for clomipramine first to see what it will do. Maybe it's strong enough on its own.
 

This is why the combination of fluovaxamine+clomipramine may be better. Fluvoxamine will prevent clomipramine from being broken down into desmethylclomipramine (DMC) which is responsible for most of the noradrenergic effects.

The muscle twitchiness might be the antagonism of 5HT_2A leading to dopamine release when you aren't on a high enough dose of clomipramine to block dopamine receptors to compensate. You would need to get to therapeutic doses of 100-200mg/day before this happens. But looking at receptor affinities, you likely would need fluvoxamine for this to happen because DMC has a much lower affinity for the dopamine receptors than clomipramine and has twice the circulating concentrations in the blood than clomipramine when at steady state.

Likely you just need more time to adjust. I would continue working with your pdoc to try and get to the 100mg before you ask yourself how you're feeling.

[Catwoman]

On 6-8-2018 at 3:34 PM, browri said:

This is why the combination of fluovaxamine+clomipramine may be better. Fluvoxamine will prevent clomipramine from being broken down into desmethylclomipramine (DMC) which is responsible for most of the noradrenergic effects.

The muscle twitchiness might be the antagonism of 5HT_2A leading to dopamine release when you aren't on a high enough dose of clomipramine to block dopamine receptors to compensate. You would need to get to therapeutic doses of 100-200mg/day before this happens. But looking at receptor affinities, you likely would need fluvoxamine for this to happen because DMC has a much lower affinity for the dopamine receptors than clomipramine and has twice the circulating concentrations in the blood than clomipramine when at steady state.

Likely you just need more time to adjust. I would continue working with your pdoc to try and get to the 100mg before you ask yourself how you're feeling.

The strange thing is dat my pdoc never used the combination of clomipramine and fluvoxamine. While other pdocs in my country to use this combo with their patients.
I've come across a Dutch article which said the combo isn't based on comprehensive research, so that's why it's not in the treatment guidelines. My pdoc loves guidelines....but I'll suggest the combination to her again later this month because I actually had good results from fluvoxamine and almost no side effects.

The current side effects on 50 mg: muscle twitches, urination takes longer (kind of curious, that's only when I need to go in the middle of the night), more appetite and now and then a dry mouth. 
When waking up my legs are a little restless but nowhere near as restless as with SSRI's.

I'm staying on 50 mg for another two weeks because my pdoc is on her vacation and I don't want to increase the dose without being able to call her. My next appt is on the 27th

I think I feel some improvement concerning intrusive thoughts. Especially in situations with people around me and when I'm having a lot to do. My attention turns outward and I can let go of the unwanted thought.
Being alone (like today) I revert back to thinking 'it' almost all the time. 

So maybe clomi is helping me a little already, but it could be premature. I'm going into my fifth week, so it's it could be just my imagination.

[Persona_Is_Life]

On ‎7‎/‎12‎/‎2018 at 2:52 AM, Catwoman said:

Thanks!! I'll try to go up to 75 mg. My pdoc said I could stay on 25 mg for the next 12 days, but if I can handle side effects I can titrate faster.
My intrusive thoughts are much worse since I took the first pill. I'm a little shaky and my legs are feeling stiff. This could be from the Luvox since I've gone down from 50 mg to 25 mg. But maybe it's stress and side effects from Anafranil as well. I don't know, but I'm not happy....
I just hope it will help me.

I had those effects coming off of Luvox. To be fair, I did stop cold turkey. It stripped me of motivation and I had finals.

[Catwoman]

4 hours ago, Persona_Is_Life said:

I had those effects coming off of Luvox. To be fair, I did stop cold turkey. It stripped me of motivation and I had finals.

Yes, cold turkey isn't the best way to go ;-)
But I did that twice with Luvox in the first two years that I was taking it. I was doing so well and one day I forgot to pick up a new prescription. The next day everything was still fine and a week later I wasn't feeling bad at all, so I just thought: "oh well, I'm cured" ;-)

Nowadays I would go slowly. Coming off Lexapro was much harder, it took me about two months. 

[Persona_Is_Life]

19 hours ago, Catwoman said:

Yes, cold turkey isn't the best way to go ;-)
But I did that twice with Luvox in the first two years that I was taking it. I was doing so well and one day I forgot to pick up a new prescription. The next day everything was still fine and a week later I wasn't feeling bad at all, so I just thought: "oh well, I'm cured" ;-)

Nowadays I would go slowly. Coming off Lexapro was much harder, it took me about two months. 

It was simultaneously the worst week ever in regards to my anxiety and the most insightful.

[Catwoman]

Not sure if I'm seeing real improvements just yet. I've started with 75 mg yesterday. It can take 8 weeks to work and I'm in the eight week now. 

My pdoc doesn't think I need to increase any further. She doesn't want me to go any higher, because 75 mg should work for my kind of issues.
I'm not sure if I agree with her. She says  dosages higher than 100 mg are only needed for severe depression.
I thought that high dosages of clomipramine are used for severe OCD, but maybe she meant that as well. 

I don't have severe OCD myself, but my issue is very chronic and refractory and I'm almost sure that the mechanism of reuptake inhibition isn't enough anymore.

I don't know how I can emphasize this to my pdoc.

If this doesn't work out I suspect she would rather have me go back to an SSRI and augment with an AAP.

Edited September 6, 2018 by Catwoman

[CrazyRedhead]

3 hours ago, Catwoman said:

 
My pdoc doesn't think I need to increase any further. She doesn't want me to go any higher, because 75 mg should work for my kind of issues.
I'm not sure if I agree with her. She says  dosages higher than 100 mg are only needed for severe depression.
I thought that high dosages of clomipramine are used for severe OCD, but maybe she meant that as well. 
 

Not to contradict your doc, but it is generally believed that higher doses of antidepressants are needed to treat OCD.

This link is from the International OCD Foundation.....If you scroll down, the page gives dosages of various ADs that might be used to treat OCD........The max dose for clomipramine is up to 250mg

https://iocdf.org/about-ocd/treatment/meds/

If the 75mg doesn't help, maybe you could convince her to go a bit higher.

[Catwoman]

26 minutes ago, CrazyRedhead said:

Not to contradict your doc, but it is generally believed that higher doses of antidepressants are needed to treat OCD.

This link is from the International OCD Foundation.....If you scroll down, the page gives dosages of various ADs that might be used to treat OCD........The max dose for clomipramine is up to 250mg

https://iocdf.org/about-ocd/treatment/meds/

If the 75mg doesn't help, maybe you could convince her to go a bit higher.

I think she'll let me go a bit higher, but only if side effects are tolerable.
At the moment on this dose the side effects are mild, so I don't see why I couldn't go up. 

I wonder why my pdoc is so reluctant....

[Iceberg]

Eh. Is it possible she just doesn't use TCAs that much and therefore isn't comfortable and is basically just dosing you off the suggested guidlines? I've had situations like that once or twice. And I tend to agree with @CrazyRedhead that its entirely possible to need a higher dose...the thing I looked at said the max was 250. That might be extreme but you get my point. One thing I've learned tho is that if a pdoc is really uncomfortable with a med(dose) pushing too hard can be counterproductive because they just get timid which means they may not be able to keep up with your symptoms. I know many people on here will disagree with this but I feel like things work better (in some, not all situations) if you stay near the doc's comfort zone

[CrazyRedhead]

7 hours ago, Catwoman said:

I think she'll let me go a bit higher, but only if side effects are tolerable.
At the moment on this dose the side effects are mild, so I don't see why I couldn't go up. 

I wonder why my pdoc is so reluctant....

I agree with @Iceberg , it's possible that she might not have a lot of experience using TCAs,  and maybe not as comfortable pushing the dose much higher...........If the 75mg doesn't help, and she won't go any higher, I'm not really sure what to advise....

Sorry I can't be of more help....I really do wish you the best........I am still severely suffering from OCD, although mine is a little different than yours  (constant obsessions and compulsive rituals).

Edited September 6, 2018 by CrazyRedhead

[Catwoman]

18 hours ago, Iceberg said:

Eh. Is it possible she just doesn't use TCAs that much and therefore isn't comfortable and is basically just dosing you off the suggested guidlines? I've had situations like that once or twice. And I tend to agree with @CrazyRedhead that its entirely possible to need a higher dose...the thing I looked at said the max was 250. That might be extreme but you get my point. One thing I've learned tho is that if a pdoc is really uncomfortable with a med(dose) pushing too hard can be counterproductive because they just get timid which means they may not be able to keep up with your symptoms. I know many people on here will disagree with this but I feel like things work better (in some, not all situations) if you stay near the doc's comfort zone

She's been working as a psychiatrist for a long time, but I have the feeling she has more experience in researching than working with actual patients. I find her difficult to talk to. Picture a patient sitting in a chair and a psychiatrist just listening and only responding with "hmhhmmm". She is not specialized in cognitive behavioral therapies, so I get that, but I'm always sharing everything I experience from the medication but not getting much of answer to my questions. Frustrating....

She likes following the guidelines, so that's why she wanted me to try clomipramine first. She had no explanation for the SSRI poop-outs I had and just says it's a shame that Lexapro doesn't work anymore. Very useful....*sigh*

I'm going to have the blood test for the clomipramine levels as well, she said we'll have to see from there on. 

[Catwoman]

Short update: I'm starting with 100 mg of clomipramine tomorrow.
Last June I began with 25 mg and I was slow with increasing due to side effects.

Now side effects don't really bother me that much. They also rotate...a few weeks of twitchy musles (legs mostly) , a few weeks of dry mouth, a few weeks of obstipation...
But I think my body adjusted quite well.

The question is: does it work for OCD?
In my case....it's not eliminating my intrusive thoughts completely at 75 mg.
I did make progress, but every few days (or sometimes weeks) I'm falling back.

When people are having an anxiety attack they can use a benzo as needed. 
But for intrusiving thoughts like mine getting more frequent (without panic) I don't think something 'as needed' / PRN exists.  I could use an add-on for when the clomipramine momentarily fails. 



 

[Persona_Is_Life]

Sounds like my Luvox experience. I was heading down the rabbit hole fast in terms of OCD. Luvox put the brakes on, but that's all it did. I didn't see any improvement. I stuck it out though for almost a year and only stopped when I realized I didn't have any motivation in me. 

 

Clomipramine was a godsend. I didn't think anything would help. I started to feel a bit at 25mg. It got better with each increase. I settled at about halfway with my germaphobia (still quite "dysfunctional" but it was a huge improvement for me). 

Give it a little more time. Maybe your sweet spot is higher up. If not, at least you tried. 

 

Good luck. 

[Catwoman]

5 hours ago, Persona_Is_Life said:

Sounds like my Luvox experience. I was heading down the rabbit hole fast in terms of OCD. Luvox put the brakes on, but that's all it did. I didn't see any improvement. I stuck it out though for almost a year and only stopped when I realized I didn't have any motivation in me. 

 

Clomipramine was a godsend. I didn't think anything would help. I started to feel a bit at 25mg. It got better with each increase. I settled at about halfway with my germaphobia (still quite "dysfunctional" but it was a huge improvement for me). 

Give it a little more time. Maybe your sweet spot is higher up. If not, at least you tried. 

 

Good luck. 

For me it's working a little better than Luvox.  Though my first med was also Luvox and back then in worked incredibly well.

Which dose of clomipramine were you on if I may ask?

[Persona_Is_Life]

19 hours ago, Catwoman said:

For me it's working a little better than Luvox.  Though my first med was also Luvox and back then in worked incredibly well.

Which dose of clomipramine were you on if I may ask?

I think I went up to 125mg. Stopped due to some cognitive difficulties (could be a number of things) but neuro doctor suggested going off of it. If things get really bad again, I wouldn't hesitate to request going back on it. 

[trophy]

Are cognitive side effects standard with clomipramine? It would be the next med for me to try if the current one doesn't work out.

[cakepop]

[deleted]

Edited April 7, 2019 by cakepop

[Persona_Is_Life]

4 hours ago, trophy said:

Are cognitive side effects standard with clomipramine? It would be the next med for me to try if the current one doesn't work out.

It could have been due to a few things, neuro decided that it was the Clomipramine causing it. 

4 hours ago, Gatorgirl said:

I never noticed any cognitive side effects and I’m on 200 mg. I don’t have any side effects at all actually. I don’t even notice if it’s helping though either.

That's my experience with Vistaril and Buspar. Haha. 

[Catwoman]

I don't notice any cognitive side effects either. 

But flushing (very red cheeks and warm face) seems to be the latest one. It's only happening at the end of the day after dinner. 

I'm also getting the impression that my blood sugar is dropping faster lately. After I've eaten something with lots of sugar I get very sleepy. Heavy eyelids and a a drowsy feeling. 
I can't remember I had this before or with other anti-depressants.

I'll stay at 100 mg for about three weeks and then re-evaluate.