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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 17 of 17. This is the beginning of the thread.
Posted by Phoenix1 on June 17, 2008, at 23:48:43
Does anyone have anything good or bad to say about clomipramine (Anafranil) for depression and anxiety? I've previously only responded to Nardil, after trying at least 10 different AD's, and many many more combo's/cocktails.. My response to Nardil was very positive, but it's not an option anymore after it was implicated in a serious neurological accident I had.
So my depression and anxiety have relapsed in a bad way since I stopped Nardil. Pdoc is starting me on clomipramine, with the goal being high-dose, plasma level monitored treatment. I'm not too excited. I had a bad experience with nortriptylline. It made me cognitively useless, extremely tired, basically a zombie. And it didn't help the depression.
I guess I'm looking for some encouragement about starting the clomip., but if anyone has had a bad experience, I'd like to hear it as well. Also, I know everyone responds differently, butif anyone has taken both of these drugs, I'd be interested in hearing how you thought they compared even though their mechanisms are very different..
I feel like I'm at the end of the line here. Not many more options. Actually, no more options except for ECT, which I would not consent to. I would desperately like to go back on Nardil, but it's not going to happen any time soon. I really miss it...
Phoenix
Posted by Phillipa on June 18, 2008, at 0:22:28
In reply to Clomipramine vs. Nardil, posted by Phoenix1 on June 17, 2008, at 23:48:43
Phoenix is there any way you can get another doc and go back on nardil it seems so unfair as you were doing great what happened was not your fault. Do you have OCD? Anafranil as I'm sure you know is mainly used for that. My heart goes out to you. Love Phillipa
Posted by SLS on June 18, 2008, at 4:46:22
In reply to Clomipramine vs. Nardil, posted by Phoenix1 on June 17, 2008, at 23:48:43
Clomipramine (Anafranil) produces side effects that resemble both typical anticholinergic TCAs and typical SSRIs. How's that for fun? It is considered to be a "dirty" drug in this way. However, clomipramine might be the most potent antidepressant; second only to the MAOIs. It cannot be discounted that some of the drug's "dirtiness" contributes to its therapeutic effect.
Do you really have much of a choice?
The answer to that question is probably yes, but since you are here now, you might as well allow your doctor to take his shot. If things don't turn out well, you can always research the many drugs and drug combinations that you have not yet tried.
Can you describe the nature and symptoms of your depression?
- Scott
Posted by Phoenix1 on June 18, 2008, at 11:12:18
In reply to Re: Clomipramine vs. Nardil » Phoenix1, posted by SLS on June 18, 2008, at 4:46:22
Hi Scott,
Could you explain Clomipramine's dirtiness? I'm a little confused on it's primary mechanism even after browsing Pub Med. It seems to be a strong SRI with NE reuptake inhibition from it's major active metabolite. And it has a weak effect on dopamine too, right? And then the fun side effects caused by it's anticholingeric and antimuscarinic effects...
I've been on the med merry go round for almost 10 years. I have unipolar depression and GAD. I would guess that my depression would fall into the atypical class. Low mood with some reactivity to positive events, vegetative synptoms, sensitivity to criticism, etc. The GAD manifests itself in constant physical anxiety, extreme insomnia, rumination.
SSRI's make the anxiety worse. Meds that have a strong NE effect seem to make things much worse too (venlafaxine, bupropion. Dopaminergics have a neutral effect, but don't improve either my depressive or anxious symptoms.
Nardil, on the other hand was my first and only clear positive response to an AD. I felt normal, functional, and calm the whole time I was on it.
What, neurochemically speaking, would explain such a positive response to an MAOI, but negative responses to all other classes? Does this suggest some sort of trace amine deficiency that the other AD's don't touch? If that is the case, then I doubt any other class of drugs will help me. I know it's oversimplistic to choose a drug based on mechanisms, but I'm trying to figure out what the next rational choice is to avoid another round of unsuccessful trials...
Thanks for your help!
Phoenix
> Clomipramine (Anafranil) produces side effects that resemble both typical anticholinergic TCAs and typical SSRIs. How's that for fun? It is considered to be a "dirty" drug in this way. However, clomipramine might be the most potent antidepressant; second only to the MAOIs. It cannot be discounted that some of the drug's "dirtiness" contributes to its therapeutic effect.
>
> Do you really have much of a choice?
>
> The answer to that question is probably yes, but since you are here now, you might as well allow your doctor to take his shot. If things don't turn out well, you can always research the many drugs and drug combinations that you have not yet tried.
>
> Can you describe the nature and symptoms of your depression?
>
>
> - Scott
Posted by Phoenix1 on June 18, 2008, at 11:20:03
In reply to Re: Clomipramine vs. Nardil » Phoenix1, posted by Phillipa on June 18, 2008, at 0:22:28
Hi Phillipa,
Thanks for your support. Unfortunately, the resounding medical opinion is that I cannot be put back on an MAOI until I try some other meds. My pdoc, a mood disorder specialist, and two neurologists have all given written opinions that an MAOI poses too great a risk for me neurologically speaking. Specifically, they want me to try Nefazodone (which I refused) and clomipramine (which I agreed to try). My understanding is that if I give tje clomipramine a fair chance, and it fails, I will get referred back to the mood disorder specialist who might consider putting me back on Nardil With the writyten opinions of all these doctors, no other pdoc will put me back on Nardil. These records will just follow me wherever I go.
And no, I don't have OCD. The clomipramine is supposed to be a good antidepressant with anxiolytic properties. I have my doubts though.
Phoenix
> Phoenix is there any way you can get another doc and go back on nardil it seems so unfair as you were doing great what happened was not your fault. Do you have OCD? Anafranil as I'm sure you know is mainly used for that. My heart goes out to you. Love Phillipa
Posted by Crotale on June 18, 2008, at 18:30:07
In reply to Re: Clomipramine vs. Nardil, posted by Phoenix1 on June 18, 2008, at 11:20:03
Phoenix,
It seems to me that just because you had a bad reaction to Nardil, doesn't mean a different MAOI (particularly a non-hydrazine MAOI like Parnate or selegiline) would automatically cause the same problem for you. This is based on my own experience.
Clomipramine is a very powerful serotonin-norepinephrine reuptake inhibitor (it's likely that its active metabolite, N-desmethylclomipramine, contributes to its therapeutic effect), but it's true that it does tend to have a lot of side effects. I actually tolerate MAOIs better than TCAs.
If you want to consider a less "dirty" TCA, you might consider one of the secondary amine compounds, like desipramine or nortriptyline. They tend to have milder anticholinergic and sexual side effects compared with their tertiary amine counterparts (e.g., imipramine, amitriptyline). (The active metabolite N-desmethylchlomipramine is the secondary amine counterpart of chlomipramine, but it isn't marketed itself as a separate medication.)
What I mean by secondary and tertiary amines is this:
A tricyclic compound consists of a core "tricyclic" structure (e.g., in imipramine and desipramine, the tricyclic core is iminodibenzyl, while in amitriptyline and nortriptyline it's dibenzocycloheptadiene) plus a side chain. The side chains typically look something like this:
|
CH2-CH2-CH2-N(CH2)2
(tertiary amine)or this:
|
CH2-CH2-CH2-N(CH3)(H)(secondary amine)
Often the secondary amine drugs are active metabolites of the similar tertiary amine compounds. For example, desipramine is N-desmethylimipraine (DMI); I think nortriptyline is similarly a metabolite of amitriyptyline.
Protriptyline, doxepin, and maprotiline all have modified tricyclic cores. Amoxapine has a very different side chain as well as a modified core structure. Trimipramine has the same iminodibenzyl core as imipramine but a very modified side chain. It's what I'd call a tertiary amine, but its side chain is altered in other ways.
Chlomipramine just adds a chlorine to the iminodibenzyl of imipramine. Doxepin adds an oxygen in the centre ring of the dicycloheptadiene from amitriptyline. Protriptyline is similar to nortriptyline except that there is one point of saturation (double bond) in the centre ring. Maprotiline adds an ethylene bridge across a six-atom centre ring; its side chain is standard secondary-amine. Trimipramine is really just imipramine with an extra methyl on the side chain:
|
CH2-CH(CH3)-CH2-N(CH2)2Amoxapine is somewhat different and has some dopamine antagonist activity. Its tricyclic structure is a bit too difficult for me to depict here, and I wasn't able to draw its side chain, which is a ring itself.
(Amoxapine -- actually N-desmethyl-loxapine -- is a secondary amine, which is consistent with its pharmacology: it has very little effect on serotonin uptake.)
Amoxapine's centre ring has multiple points of saturation, as well as a N and a O. It also has a Cl- hanging off one of the side rings.
As I recall, protriptyline and maprotiline tend to be associated with increased risk of adverse effects -- cardiac arrhythmias in the case of protriptyline, seizures in the case of maprotiline. Amoxapine, of course, has some risk of extrapyramidal side effects as a consequence of its antipsychotic (i.e., dopamine antagonist) activity. In general, tertiary amines tend to be more active at the serotonin transporter than secondary amines.
Please tell me if you think this belongs more on PB-Neurotransmitters. I hope it will help people who are trying to decide whether to try a TCA and if so which one.
Posted by Phoenix1 on June 18, 2008, at 19:26:53
In reply to Re: Clomipramine vs. Nardil » Phoenix1, posted by Crotale on June 18, 2008, at 18:30:07
Hi Crotale,
Thanks for the thorough explanation of TCA's. It brought back some bad memories of first year organic chem, but I think I followed. :)
The idea, according to my pdoc, is that since I was so somnolent on nortriptylline, yet I have prominent anxiety, clomipramine balances anxiolytic effects with activating effects a bit better. This remains to be seen.
I agree with you that a bad experience with Nardil shouldn't rule out the other MAOI's for me. I wanted to try Parnate, I really did. Unfortunately, the overwhelming opinion from 2 pdocs and 2 neuros is that I should not go back on a MAOI except as a last resort. So I have to give clomipramine a try. Maybe it will work, who knowws? I'm not holding my breath though. Thanks again for your thoughtful response!
Phoenix.
Posted by Crotale on June 18, 2008, at 22:13:14
In reply to Re: Clomipramine vs. Nardil » Crotale, posted by Phoenix1 on June 18, 2008, at 19:26:53
Phoenix,
What dose of Nardil were you on, and what was your bad reaction?
I think clomipramine is liable to be more sedating than nortrip or MAOI, but we'll see. Good luck with that, or whatever you end up doing!
-Crotale
Posted by Tomatheus on June 19, 2008, at 0:46:00
In reply to Clomipramine vs. Nardil, posted by Phoenix1 on June 17, 2008, at 23:48:43
> Does anyone have anything good or bad to say about clomipramine (Anafranil) for depression and anxiety?
I experienced severe irritability after just one dose of the medication when I tried it during my last psychiatric hospitalization. As you know, everybody is different, and not everybody is going to respond to clomipramine in the same way that I did. This is especially true considering that clomipramine is typically prescribed to patients with mood and/or anxiety disorders such as major depressive disorder and obsessive-compulsive disorder, and my diagnosis is schizoaffective disorder. I took Nardil before I had my psychotic break and experienced a wonderful-but-short-lived remission on the medication. I ultimately stopped taking Nardil after I received a bad batch of it more than two years ago.
So, in a nutshell, I found clomipramine to be quite different from Nardil. However, I didn't give clomipramine enough of a chance to get any kind of idea as to what its overall effect would be in the long run, and I took it when I was suffering from a condition that had progressed significantly since the time that I took Nardil.
I hope this helps some.
Tomatheus
Posted by Tomatheus on June 19, 2008, at 1:34:27
In reply to Re: Clomipramine vs. Nardil » SLS, posted by Phoenix1 on June 18, 2008, at 11:12:18
> What, neurochemically speaking, would explain such a positive response to an MAOI, but negative responses to all other classes? Does this suggest some sort of trace amine deficiency that the other AD's don't touch?
High-activity variants of the MAO-A gene have been shown to be positively correlated with depressed suicide, major depressive disorder, and sleep disturbance in males (Du et al., 2002; Du et al., 2004). More recently, high levels of the MAO-A enzyme itself have been shown to be elevated in depressive patients (Meyer et al., 2006).
Theoretically, individuals with high levels of either MAO-A or MAO-B might respond uniquely to the nonselective MAOIs Nardil, Parnate, and Marplan. Given the evidence for an association between high levels of MAO-A and depression, it could be the case that individuals like yourself who respond most favorably to MAOIs might be doing so because MAOIs are the only medications that truly address the problem of having abnormally high levels of MAO-A. Despite increasing monoamine neurotransmission, antidepressants such as the TCAs, SSRIs, and SNRIs might not be adequate treatments for those who respond uniquely to MAOIs (a group of patients who could conceivably include those with high levels of MAO-A) because such antidepressants do not reduce the levels of monoamine-oxidization byproducts such as ammonia and hydrogen peroxide.
Having said this, there is no way for me to conclusively say that you (or anybody else) has high MAO-A levels *and* will only be responsive to MAOIs. Individuals with high levels of MAO-A might conceivably respond well to medications other than MAOIs, so even if you are one of these individuals, the only way to determine what your response to various meds will be is through trial and error. Hopefully, the practice of psychiatry will one day involve less guesswork, but unfortunately, that day is not here yet.
Tomatheus
==
Du, L., Faludi, G., Palkovits, M., Sotonyi, P., Bakish, D., & Hrdina, P.D. (2002). High activity-related allele of MAO-A gene associated with depressed suicide in males. Genetics of Nervous System Disease, 13, 1195-1198. Abstract: http://www.neuroreport.com/pt/re/neuroreport/abstract.00001756-200207020-00025.htm;jsessionid=LZ4Q1CmvwgypvLj7tFy5fJgpNtRGVXBX1lXH8R7KFTTWQxhL22cn!-74786611!181195628!8091!-1
Du, L., Bakish, D., Ravindran, A., & Hrdina, P.D. (2004). MAO-A gene polymorphisms are associated with major depression and sleep disturbance in males. Molecular Neuroscience, 15, 2097-2101. Abstract: http://www.neuroreport.com/pt/re/neuroreport/abstract.00001756-200409150-00020.htm;jsessionid=LZ4G0fYwQlgTyNGcZCzGYvXqPrJGx9BszWth1TGCJCpqldsPMYNX!-74786611!181195628!8091!-1
Meyer, J.H., Ginovart, N., Boovariwala, A., Sagrati, S., Hussey, D., Garcia, A., et al. (2006). Elevated monoamine oxidase A levels in the brain: An explanation for the monoamine imbalance of major depression. Archives of General Psychiatry, 63, 1209-1216. Abstract: http://archpsyc.ama-assn.org/cgi/content/abstract/63/11/1209
Posted by SLS on June 19, 2008, at 4:53:52
In reply to Re: Clomipramine vs. Nardil » Phoenix1, posted by Tomatheus on June 19, 2008, at 1:34:27
Posted by Tomatheus on June 19, 2008, at 14:45:06
In reply to Re: Clomipramine vs. Nardil | Thank you for this. (nm) » Tomatheus, posted by SLS on June 19, 2008, at 4:53:52
Posted by Phoenix1 on June 19, 2008, at 18:24:51
In reply to Re: Clomipramine vs. Nardil, posted by Crotale on June 18, 2008, at 22:13:14
> Phoenix,
>
> What dose of Nardil were you on, and what was your bad reaction?
>
> I think clomipramine is liable to be more sedating than nortrip or MAOI, but we'll see. Good luck with that, or whatever you end up doing!
>
> -CrotaleHi Crotale,
I went as high as 90mg on Nardil, but was at 75 when things hit the fan.I had a hypertensive crisis that the ER misdiagnosed as conversion disorder. The treatment delay resulted in a form of encephalopathy called PRES. (See my earlier posts here: http://www.dr-bob.org/babble/20080519/msgs/830220.html ) I still have neurologic sequelae. Since they don't know what caused the hypertensive crisis (I'm sure it wasn't dietary), and PRES is extremely rare, they won't let me go back on Nardil.)
I'm finding that even 10mg of Clomipramine is quite sedating, but the sedation doesn't help my anxiety. I also feel spaced out, quite like my previous SSRI experiences. But I guess I have to give it some more time. I think my biggest fear is that it will actually be effective, but that I will be miserable with the side effects...
Phoenix
Posted by Phoenix1 on June 19, 2008, at 18:40:18
In reply to Re: Clomipramine vs. Nardil » Phoenix1, posted by Tomatheus on June 19, 2008, at 1:34:27
Wow, thanks Thomatheus. That's fascinating. And I appreciate the references you linked to. Interesting reading!
Phoenix
I agree with you, unfortunately, that the only way to find out if a given drug will be effective is to try it. As I'm sure you know, the revo
> > What, neurochemically speaking, would explain such a positive response to an MAOI, but negative responses to all other classes? Does this suggest some sort of trace amine deficiency that the other AD's don't touch?
>
> High-activity variants of the MAO-A gene have been shown to be positively correlated with depressed suicide, major depressive disorder, and sleep disturbance in males (Du et al., 2002; Du et al., 2004). More recently, high levels of the MAO-A enzyme itself have been shown to be elevated in depressive patients (Meyer et al., 2006).
>
> Theoretically, individuals with high levels of either MAO-A or MAO-B might respond uniquely to the nonselective MAOIs Nardil, Parnate, and Marplan. Given the evidence for an association between high levels of MAO-A and depression, it could be the case that individuals like yourself who respond most favorably to MAOIs might be doing so because MAOIs are the only medications that truly address the problem of having abnormally high levels of MAO-A. Despite increasing monoamine neurotransmission, antidepressants such as the TCAs, SSRIs, and SNRIs might not be adequate treatments for those who respond uniquely to MAOIs (a group of patients who could conceivably include those with high levels of MAO-A) because such antidepressants do not reduce the levels of monoamine-oxidization byproducts such as ammonia and hydrogen peroxide.
>
> Having said this, there is no way for me to conclusively say that you (or anybody else) has high MAO-A levels *and* will only be responsive to MAOIs. Individuals with high levels of MAO-A might conceivably respond well to medications other than MAOIs, so even if you are one of these individuals, the only way to determine what your response to various meds will be is through trial and error. Hopefully, the practice of psychiatry will one day involve less guesswork, but unfortunately, that day is not here yet.
>
> Tomatheus
>
> ==
>
> Du, L., Faludi, G., Palkovits, M., Sotonyi, P., Bakish, D., & Hrdina, P.D. (2002). High activity-related allele of MAO-A gene associated with depressed suicide in males. Genetics of Nervous System Disease, 13, 1195-1198. Abstract: http://www.neuroreport.com/pt/re/neuroreport/abstract.00001756-200207020-00025.htm;jsessionid=LZ4Q1CmvwgypvLj7tFy5fJgpNtRGVXBX1lXH8R7KFTTWQxhL22cn!-74786611!181195628!8091!-1
>
> Du, L., Bakish, D., Ravindran, A., & Hrdina, P.D. (2004). MAO-A gene polymorphisms are associated with major depression and sleep disturbance in males. Molecular Neuroscience, 15, 2097-2101. Abstract: http://www.neuroreport.com/pt/re/neuroreport/abstract.00001756-200409150-00020.htm;jsessionid=LZ4G0fYwQlgTyNGcZCzGYvXqPrJGx9BszWth1TGCJCpqldsPMYNX!-74786611!181195628!8091!-1
>
> Meyer, J.H., Ginovart, N., Boovariwala, A., Sagrati, S., Hussey, D., Garcia, A., et al. (2006). Elevated monoamine oxidase A levels in the brain: An explanation for the monoamine imbalance of major depression. Archives of General Psychiatry, 63, 1209-1216. Abstract: http://archpsyc.ama-assn.org/cgi/content/abstract/63/11/1209
>
Posted by Crotale on June 19, 2008, at 23:19:05
In reply to Re: Clomipramine vs. Nardil » Crotale, posted by Phoenix1 on June 19, 2008, at 18:24:51
> I went as high as 90mg on Nardil, but was at 75 when things hit the fan.
Ah. Why (if I may ask) did you keep increasing it after, as you say, things hit the fan?
> I had a hypertensive crisis that the ER misdiagnosed as conversion disorder. The treatment delay resulted in a form of encephalopathy called PRES. (See my earlier posts here: http://www.dr-bob.org/babble/20080519/msgs/830220.html )
I'm confused; I thought the PRES was the result of too-rapid discontinuation of Nardil. (I sympathize; I had a terrible time when I had to go off Nardil extremely rapidly.)
Well, anyway, it sucks that you got misdiagnosed with "conversion disorder." That's just the sort of thing doctors do to psych patients.
> I still have neurologic sequelae. Since they don't know what caused the hypertensive crisis (I'm sure it wasn't dietary), and PRES is extremely rare, they won't let me go back on Nardil.)
It seems to me that it wasn't the Nardil but too-rapid discontinuation of the Nardil that caused the PRES....
How bad was the hypertensive crisis? (That is, how high was BP?)
> I'm finding that even 10mg of Clomipramine is quite sedating, but the sedation doesn't help my anxiety.
I found that with the sedation from TCAs also. (The sedative effect is mainly, I think, because they are antihistamines.) I had better luck with secondary-amine TCAs (desipramine, nortriptyline, etc.) -- less sedating and less anticholinergic side effects (constipation, dry mouth, etc.) -- although I ended up having to go off desipramine b/c of a seizure (unfortunately, because it was working rather well for me).
> I also feel spaced out, quite like my previous SSRI experiences. But I guess I have to give it some more time. I think my biggest fear is that it will actually be effective, but that I will be miserable with the side effects...
If it is effective, a different TCA might work as well with milder side fx...just a thought. Best of luck to you.
Crotale
Posted by Tomatheus on June 19, 2008, at 23:49:16
In reply to Re: Clomipramine vs. Nardil » Tomatheus, posted by Phoenix1 on June 19, 2008, at 18:40:18
> Wow, thanks Thomatheus. That's fascinating. And I appreciate the references you linked to. Interesting reading!
You're welcome, and thanks for your response.
Tomatheus
Posted by Phoenix1 on June 21, 2008, at 12:10:37
In reply to Re: Clomipramine vs. Nardil » Phoenix1, posted by Crotale on June 19, 2008, at 23:19:05
> Ah. Why (if I may ask) did you keep increasing it after, as you say, things hit the fan?*Sorry, I should have been mire ckear on this. I went up to 90mg, had bad orhostatic hypotension, then reduced to 75mg.
>
> I'm confused; I thought the PRES was the result of too-rapid discontinuation of Nardil. (I sympathize; I had a terrible time when I had to go off Nardil extremely rapidly.)
>*I agree, I think the PRES was indirectly caused by Nardil withdrawal. Pdoc strongly disagrees, but then it's probably a CYA thing. The problem is that if he were to agree that the discontinuation caused it, I would have a good chance of being allowed to re-start it, which is what I want.
> Well, anyway, it sucks that you got misdiagnosed with "conversion disorder." That's just the sort of thing doctors do to psych patients.*Yup, the first ER treated me with total contempt and prejudice the minute I told them I was on an MAOI for depression. They dismissed my suggestion that I was having a hypertensive crisis. I even told them the standard treatment was chlorpromazine or nifedipine, but no action... Is it an unwritten rule that psych patients get a lower standard of care in the ER?
> It seems to me that it wasn't the Nardil but too-rapid discontinuation of the Nardil that caused the PRES....*Exactly! Man I wish the docs would see this is the case.
> How bad was the hypertensive crisis? (That is, how high was BP?)
*190/110 on admission. When I told them it was a hypertensive crisis, the doc said "I see blood pressures like this all day."
> I found that with the sedation from TCAs also. (The sedative effect is mainly, I think, because they are antihistamines.) I had better luck with secondary-amine TCAs (desipramine, nortriptyline, etc.) -- less sedating and less anticholinergic side effects (constipation, dry mouth, etc.) -- although I ended up having to go off desipramine b/c of a seizure (unfortunately, because it was working rather well for me).
> If it is effective, a different TCA might work as well with milder side fx...just a thought. Best of luck to you.
*Thanks for the suggestion. I'll ask about desipramine. I found nortriptylline intensely sedating.
Phoenix
This is the end of the thread.
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
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