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Dr. Bob is Robert Hsiung, MD,
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Posted by g_g_g_unit on October 5, 2010, at 0:11:16
In reply to Re: Clomipramine's Tail Is Smashing My Little Future » g_g_g_unit, posted by Brainbeard on October 4, 2010, at 13:58:36
Thanks for the encouragement, Mr Brainbeard! You truly are a pioneer, and I am honored to be trailing in your steps.
One question: I was thinking of asking my GP for a bethanechol script tomorrow, so I can obtain it online. How effective and broad-acting is it in relieving your anticholinergic side-effects? Forgive the revelation, but I suffer from a sensitive stomach as it is, and the constipation caused by the clomipramine is making it difficult to breathe clearly at times. I'm also experiencing chest pains.
It's strange that we are both experiencing sleep disturbances on the drug. One of my prime motivations in trying it was because of its reputed effectiveness against insomnia.
> G_g_g my comrade, don't give up yet! I'm biting my way through 225 freakin' milligrams of clomipramine and believe me, it's not a day at the beach. Don't see much therapeutic benefit either. But since I got here, I think I must endure for at least six more weeks and see wether clomipramine is the golden drug I have made it out to be. Actually, I'm not experiencing much brain fog anymore, and even the dry mouth seems to have gotten better. Remember, SRI's often need six weeks or more to become effective against OCD.
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Posted by Roslynn on October 5, 2010, at 10:35:45
In reply to Re: Clomipramine's Tail Is Smashing My Little Future » Brainbeard, posted by g_g_g_unit on October 5, 2010, at 0:11:16
Hi guys,
I just wanted to add that clomipramine has been a stimulating drug for me as well, and it's causing some insomnia. My pdoc was expecting it to be sedating and was very surprised at my reaction to it.
Roslynn
>
> It's strange that we are both experiencing sleep disturbances on the drug. One of my prime motivations in trying it was because of its reputed effectiveness against insomnia.
>
> > G_g_g my comrade, don't give up yet! I'm biting my way through 225 freakin' milligrams of clomipramine and believe me, it's not a day at the beach. Don't see much therapeutic benefit either. But since I got here, I think I must endure for at least six more weeks and see wether clomipramine is the golden drug I have made it out to be. Actually, I'm not experiencing much brain fog anymore, and even the dry mouth seems to have gotten better. Remember, SRI's often need six weeks or more to become effective against OCD.
> >
> >
> >
>
>
Posted by Brainbeard on October 5, 2010, at 10:38:29
In reply to Re: Clomipramine's Tail Is Smashing My Little Future » Brainbeard, posted by Roslynn on October 4, 2010, at 15:48:43
> Hi Brainbeard,
>
> Thank you for your message. I fear adding nortrip would increase my already terrible dry mouth. (I've taken it before.)
>
> Just for some background, my med combo is Clomipramine 50mg, Prozac 60mg, Seroquel 100mg, lithium 300mg and ativan 2-4 mg as needed. I am desperately trying to get off the seroquel as it causes me a lot of mental confusion.
>
>
>Dudette, if you're on 60mg of Prozac, your clomipramine is boosted like a rocket. Your blood levels of desmethylclomipramine, the metabolite working on noradrenaline and mostly responsible for dry mouth and cognitive blurring, are bound to be very high. Desmethylclomipramine gets eliminated through 2D6 enzymes, and Prozac is a major 2D6 inhibitor. So your dose of clomipramine is in fact a very high one. Did you have your blood levels checked? Your doc oughta check on them with this combo.
With 60mg of Prozac, 5-10mg instead of 25-50 of nortriptyline may already be enough for better sleep, since nortriptyline is also metabolized through 2D6.
Posted by Brainbeard on October 5, 2010, at 10:45:39
In reply to Re: Clomipramine's Tail Is Smashing My Little Future » Brainbeard, posted by g_g_g_unit on October 5, 2010, at 0:11:16
Me, a pioneer?! I'm taking a fifty year old drug!! ;)
Yeah, bethanechol, and you may be pleased to hear it, actually works far better for me against constipation than it does for dry mouth. It's superb for constipation. I just wish it would also make me drool, but the effects on dry mouth are subtle rather than dramatic.
Sleep disturbances... Yes, clomipramine inhibits 1A2, the enzyme group that breaks down melatonin, and thereby it could promote sleep. But its SRI can counter deep sleep. Clomipramine is probably too weak a 5HT2A-inhibitor to help out with that. I'm thinking of asking my p-doc to add mirtazapine (Remeron) for better sleep.
Hang in there, brother. This drug is/may be/oughta be/ worth its weight in gold.
Posted by Roslynn on October 5, 2010, at 11:52:38
In reply to 50mg clomipramine is a HIGH dose with 60mg Prozac » Roslynn, posted by Brainbeard on October 5, 2010, at 10:38:29
Brainbeard,
Thank you so much, I didn't realize this. No, my pdoc has not requested blood levels.
The combo was not intentional. My doc put me on clomipramine to try to bridge me over while I stopped Prozac in order to start an MAOI.
The thing is, I felt much better when the clomipramine was added to my cocktail, and I wasn't able to stop the Prozac anyway. So now I am on both those meds and I don't think my doc is thrilled with me. He thinks I'm bipolar and should take less antidepressant meds, not more. Complicated, huh?
Thank you so much for your info. I may ask my doc for 5mg of nortrip, maybe it will help me sleep.
Roslynn
>
> Dudette, if you're on 60mg of Prozac, your clomipramine is boosted like a rocket. Your blood levels of desmethylclomipramine, the metabolite working on noradrenaline and mostly responsible for dry mouth and cognitive blurring, are bound to be very high. Desmethylclomipramine gets eliminated through 2D6 enzymes, and Prozac is a major 2D6 inhibitor. So your dose of clomipramine is in fact a very high one. Did you have your blood levels checked? Your doc oughta check on them with this combo.
>
> With 60mg of Prozac, 5-10mg instead of 25-50 of nortriptyline may already be enough for better sleep, since nortriptyline is also metabolized through 2D6.
>
>
Posted by Brainbeard on October 5, 2010, at 14:30:14
In reply to Re: 50mg clomipramine is a HIGH dose with 60mg Prozac » Brainbeard, posted by Roslynn on October 5, 2010, at 11:52:38
Roslynn, more than welcome, and thank you for clearing that up.
Hm, Prozac is a med known to compromise sleep, so it's the first suspect for your sleep problem.
Couldn't you at least lower your Prozac dose?
You could also move over to a sleep-friendly SSRI like Luvox (fluvoxamine), although then you REALLY would have to have blood levels checked - or tread carefully - since Luvox boosts clomipramine exactly the other way around as does Prozac: it boosts the mother drug, i.e. clomipramine itself, while suppressing the noradrenergic metabolite. Sorry for all this metabolism talk, I'm in this dung too deep. (Sorry for saying 'dung', it's because 'sh*t' is censored.)
Remeron (mirtazapine) could help a lot too, especially if you also fancy becoming fat as an elephant. ;)
Posted by Roslynn on October 5, 2010, at 15:26:17
In reply to Re: 50mg clomipramine is a HIGH dose with 60mg Prozac, posted by Brainbeard on October 5, 2010, at 14:30:14
Hi Brainbeard,
Unfortunately I cannot lower the Prozac dose; I've tried several times and it brings back the depression very quickly.
I really want to get off Seroquel (which I use for sleep) and I'm hoping that my doc will write a script for the 5mg Nortrip. That should help. Weight gain has also been an issue for me with Seroquel.
Thank you for all the info you've given me!
Roslynn
>
> Couldn't you at least lower your Prozac dose?
>
> You could also move over to a sleep-friendly SSRI like Luvox (fluvoxamine), although then you REALLY would have to have blood levels checked - or tread carefully - since Luvox boosts clomipramine exactly the other way around as does Prozac: it boosts the mother drug, i.e. clomipramine itself, while suppressing the noradrenergic metabolite. Sorry for all this metabolism talk, I'm in this dung too deep. (Sorry for saying 'dung', it's because 'sh*t' is censored.)
>
> Remeron (mirtazapine) could help a lot too, especially if you also fancy becoming fat as an elephant. ;)
Posted by Brainbeard on October 5, 2010, at 15:42:26
In reply to Re: 50mg clomipramine is a HIGH dose with 60mg Prozac » Brainbeard, posted by Roslynn on October 5, 2010, at 15:26:17
Roslynn, if I gave a dollar to every person appreciating my comments, I would still be a rich man.
Problem getting a script for 5mg nortriptyline is that most doctors will think you're nuts and such a dose can only be placebo. A friend of mine started taking 25mg of nortriptyline for sleep at my advise and eventually, he got a script, but his doctor's convinced that the effect is totally in his head.
These people can only think in big numbers. My p-doc is the same, he's brilliant enough, but the same all the same. (Now that's a lot of same and I know it.) So that creates the situation that he's prescribing me low doses of meds at my request thinking that it won't hurt when it won't help. Who's fooling who, huh?
In my uneducated and totally biased and unfounded opinion, Seroquel is an inferior piece of marketed thin air.
Sleep tight.
Posted by SLS on October 5, 2010, at 16:12:24
In reply to Bethanechol for dry mouth and constipation, posted by Brainbeard on October 5, 2010, at 10:45:39
> Me, a pioneer?! I'm taking a fifty year old drug!! ;)
>
> Yeah, bethanechol, and you may be pleased to hear it, actually works far better for me against constipation than it does for dry mouth. It's superb for constipation. I just wish it would also make me drool, but the effects on dry mouth are subtle rather than dramatic.Bethanechol can also help with urinary retention resulting from the anticholinergic effects of certain antidepressants. It can prevent a trip to the hospital for a catheterization. Ouch.
- Scott
Posted by linkadge on October 6, 2010, at 20:50:05
In reply to Re: Bethanechol for dry mouth and constipation, posted by SLS on October 5, 2010, at 16:12:24
Posted by Brainbeard on October 7, 2010, at 14:18:31
In reply to Re: can bethanechol help blurry vision? (nm), posted by linkadge on October 6, 2010, at 20:50:05
Posted by g_g_g_unit on October 11, 2010, at 1:51:21
In reply to wouldn't know (nm) » linkadge, posted by Brainbeard on October 7, 2010, at 14:18:31
Is it just me or does clomipramine possibly have the worst cognitive side-effects of any legitimate AD? It feels like the drug is punching holes in my brain, which is quite a feat, given that I was severely depressed before trialling it. 90% of my vocabulary is missing; when I try and think simple, everyday thoughts, it's like my brain lacks the language to fill in what I'm thinking.
Posted by Brainbeard on October 11, 2010, at 5:55:16
In reply to dumb drug, posted by g_g_g_unit on October 11, 2010, at 1:51:21
> Is it just me or does clomipramine possibly have the worst cognitive side-effects of any legitimate AD? It feels like the drug is punching holes in my brain, which is quite a feat, given that I was severely depressed before trialling it. 90% of my vocabulary is missing; when I try and think simple, everyday thoughts, it's like my brain lacks the language to fill in what I'm thinking.
Wow, that's pretty cool.
OK, I'm only kidding...
Well, the TCA's do tend to cause much more cognitive dumbing than the newer antidepressants. Your ability to think and speak may (partially) recover in the course of treatment; when I was on 75mg of clomipramine two years ago, I suffered from much worse cognitive dumbing than I do now on 225mg!
Posted by SLS on October 11, 2010, at 7:00:27
In reply to Re: dumb drug, posted by Brainbeard on October 11, 2010, at 5:55:16
> > Is it just me or does clomipramine possibly have the worst cognitive side-effects of any legitimate AD? It feels like the drug is punching holes in my brain, which is quite a feat, given that I was severely depressed before trialling it. 90% of my vocabulary is missing; when I try and think simple, everyday thoughts, it's like my brain lacks the language to fill in what I'm thinking.
> Well, the TCA's do tend to cause much more cognitive dumbing than the newer antidepressants. Your ability to think and speak may (partially) recover in the course of treatment; when I was on 75mg of clomipramine two years ago, I suffered from much worse cognitive dumbing than I do now on 225mg!
Yes. I was going to suggest giving clomipramine a bit more time and focus less on the cognitive side effects that are more robust at the beginning of treatment. Cognitive impairment might be the consequence on the anticholinergic effects of clomipramine. However, things like having trouble with word finding and brain fog can just as easily be attributed to its pro-serotonergic actions.
I may be a bit premature in my suggestion.
What are you being treated for and why was clomipramine started? How long are you on it and what dosage are you at. Sorry if these are redundant questions.
- Scott
Posted by kizzie2 on October 11, 2010, at 7:05:44
In reply to Re: dumb drug, posted by Brainbeard on October 11, 2010, at 5:55:16
Hi Brainbeard - I also take anafranil.
I really really struggle with it at first - terrible side effects but these eventually settle down and im left with muscle spasms, dry mouth, tiredness and constipation.I am currently taking 50mg which twice in the past has helped me regain stability. This time that hasnt happened. (I am unable to take more than 50mg because of side effects including my blood pressure going very low.)
You mentioned that previously you used 75mg so just wondered if you think you need more now because it loses efficiency over time. just wondering if that is what has happened to me.
Thanks
Kizzie
Posted by g_g_g_unit on October 11, 2010, at 7:42:50
In reply to Re: dumb drug » Brainbeard, posted by SLS on October 11, 2010, at 7:00:27
Oh no, your questions are by no means redundant! I appreciate the support . .
I suffer from major depressive disorder, OCD and inattentive ADD.
the clomipramine was begun with the hopes of treating the OCD and depression. I've been taking 75mg for just over four weeks now. I've seen a modest improvement in my depression, a very slight improvement in my OCD, with an unfortunate exacerbation of my ADD (I feel uncomfortably hyperactive, and am experiencing a lot less impulse control).
>
> Yes. I was going to suggest giving clomipramine a bit more time and focus less on the cognitive side effects that are more robust at the beginning of treatment. Cognitive impairment might be the consequence on the anticholinergic effects of clomipramine. However, things like having trouble with word finding and brain fog can just as easily be attributed to its pro-serotonergic actions.
>
> I may be a bit premature in my suggestion.
>
> What are you being treated for and why was clomipramine started? How long are you on it and what dosage are you at. Sorry if these are redundant questions.
>
>
> - Scott
>
>
>
Posted by SLS on October 11, 2010, at 9:27:02
In reply to Re: dumb drug » SLS, posted by g_g_g_unit on October 11, 2010, at 7:42:50
I am not sure if a response to clomipramine follows the same pattern as that seen with SSRIs when treating OCD, but it often takes a higher dosage and more time for the OCD to remit. I would continue to titrate your dosage of clomipramine upwards very slowly. What you might want to do is to discuss setting a target dosage and establishing a time-line for evaluating its effectiveness. Taking tests to assay blood levels of clomipramine/desmethylclomipramine might be helpful along away. Most people do well with nortriptyline for depression when they take 75mg. Yet, I need 150mg because I am a rapid-metabolizer. Blood tests helped confirm this so that I did not miss an opportunity to respond to nortriptyline by being chronically underdosed.
- Scott
Posted by Conundrum on October 11, 2010, at 11:12:03
In reply to Re: dumb drug » Brainbeard, posted by SLS on October 11, 2010, at 7:00:27
What about taking a muscarinic agonist? could that help?
Posted by SLS on October 11, 2010, at 12:32:12
In reply to Re: dumb drug, posted by Conundrum on October 11, 2010, at 11:12:03
> What about taking a muscarinic agonist? could that help?
Atomoxetine (Strattera) perhaps.
- Scott
Posted by ed_uk2010 on October 11, 2010, at 14:17:53
In reply to dumb drug, posted by g_g_g_unit on October 11, 2010, at 1:51:21
>Is it just me or does clomipramine possibly have the worst cognitive side-effects of any legitimate AD?
Nope, that would be amitriptyline ;-)
Posted by Brainbeard on October 11, 2010, at 15:54:58
In reply to Re: dumb drug » g_g_g_unit, posted by ed_uk2010 on October 11, 2010, at 14:17:53
> >Is it just me or does clomipramine possibly have the worst cognitive side-effects of any legitimate AD?
>
> Nope, that would be amitriptyline ;-)Exactly! Here's a chance to lose that remaining 10 percent of your vocabularly, G_g_G! ;)
Posted by g_g_g_unit on October 11, 2010, at 19:43:21
In reply to Re: dumb drug, posted by Conundrum on October 11, 2010, at 11:12:03
> What about taking a muscarinic agonist? could that help?
I'm trying to get my pdoc interested in Memantine for the OCD. In that regard, there's this . .
The non-competitive NMDA receptor antagonist memantine, currently prescribed for the treatment of Alzheimer's disease, is assumed to prevent the excitotoxicity implicated in neurodegenerative processes. Here, we investigated the actions of memantine on hippocampal function and signalling. In behavioural experiments using the water maze, we observed that memantine (at 2 mg/kg) reversed scopolamine-induced learning deficits in mice. When acutely applied to mouse hippocampal slices, memantine caused a significant upward shift in the population spike input-output relationship at 10 and 100 μM, and a corresponding downward shift in latency, indicative of overall enhanced synaptic transmission. This action was blocked by the muscarinic antagonist scopolamine (10 μM) but not by the NMDA antagonist MK-801 (10 μM) or the GABA antagonist bicuculline (20 μM). Further, memantine occluded potentiation induced by 50 nM carbachol (CCh), while enhancing inhibitory actions of CCh at 1 μM, suggesting additive actions. As anticipated for an NMDA antagonist, 100 μM (but not 10 μM) memantine also inhibited tetanus-induced long-term potentiation (LTP), and NMDA-induced Ca^{2+} signals were blocked in cultured hippocampal neurones at 10 μM (by 88%).
Overall, our data suggest actions of memantine beyond NMDA receptor antagonism, including stimulating effects on cholinergic signalling via muscarinic receptors. These interactions with the cholinergic system are likely to contribute to memantine's therapeutic potential.
Posted by Brainbeard on October 12, 2010, at 2:41:35
In reply to Re: dumb drug » Conundrum, posted by g_g_g_unit on October 11, 2010, at 19:43:21
Memantine seems to have some dirty side-effects though, potentially. Cardiac trouble if you belong to an unhappy 1 percent of users.
Posted by SLS on October 12, 2010, at 7:23:58
In reply to Re: dumb drug » Conundrum, posted by g_g_g_unit on October 11, 2010, at 19:43:21
Posted by SLS on October 12, 2010, at 7:26:21
In reply to Re: dumb drug » Conundrum, posted by g_g_g_unit on October 11, 2010, at 19:43:21
I found 20mg of memantine to be a very clean drug. It was only when I raised the dosage did I experience cognitive disturbances. I felt drunk. However, I didn't continue with memantine to see if this side effect would disappear.
- Scott
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