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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 21 of 21. This is the beginning of the thread.
Posted by rod on June 30, 2005, at 17:30:52
Hi all,
I am womdering about this. many people talk about dopamine, and selegiline. But why arent the COMT Inhibitors more ofter discussed here? Are the unsuiteable for mood disorders? do they have some severe "side effects"?
I cant find much about COMT inhibitors investigated for depression/dysthymia.
Well..... today, I have seen my pdoc...
And I am giving COMTAN (Entacapone) a try. I have already taken it. But I wont say anything about it yet. Its too early.if it fails, I will have to stick to Peraictin and wait for new stuff to come out ......
bye
Roland
Posted by ed_uk on June 30, 2005, at 18:17:35
In reply to COMT Inhibitors for mood disorder?, posted by rod on June 30, 2005, at 17:30:52
Hi Roland,
>But why arent the COMT Inhibitors more ofter discussed here?
I posted about COMT inhibitors a while ago and no one replied!!
>And I am giving COMTAN (Entacapone) a try.
I'm very interested. Please share your experiences :-) Your experiences will be very valuable to many people on the board!
Kind regards
~Ed
Posted by linkadge on June 30, 2005, at 22:11:13
In reply to Re: COMT Inhibitors for mood disorder? » rod, posted by ed_uk on June 30, 2005, at 18:17:35
Surprisingly there are many medicinal herbs that act as COMT inhibitors. Quercetin, GreenTea, SJW, certain bioflananoids etc.
Pure catecholamine enhancement only seems to have a marginal impact on many peoples mood disorders.
I have also heard that the amount of catecholamine enhancement due to COMT inhibition is relatively small compared to that of either MAOI inhibition or DAT inhibition.
Linkadge
Posted by ben on July 1, 2005, at 12:05:20
In reply to Re: COMT Inhibitors for mood disorder?, posted by linkadge on June 30, 2005, at 22:11:13
Pharmacogenomics J. 2005;5(1):49-53.
The catechol-O-methyltransferase Val108/158Met polymorphism affects short-term treatment response to mirtazapine, but not to paroxetine in major depression.Szegedi A, Rujescu D, Tadic A, Muller MJ, Kohnen R, Stassen HH, Dahmen N.
Department of Psychiatry, Charite-University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany. armin.szegedi@charite.de
The catechol-O-methyltransferase (COMT) is a major degrading enzyme in the metabolic pathways of catecholaminergic neurotransmitters such as dopamine and norepinephrine. This study investigated whether the functionally relevant Val(108/158)Met gene variant is associated with differential antidepressant response to mirtazapine and/or paroxetine in 102 patients with major depression (DSM-IV criteria) participating in a randomized clinical trial with both drugs. In patients treated with mirtazapine, but not paroxetine, allelic variations in the COMT gene were associated with differential response. COMT(VAL/VAL) and COMT(VAL/MET) genotype carriers showed a better response than COMT(MET/MET)-bearing patients in the mirtazapine group. Moreover, carriers of the COMT(VAL/VAL) or COMT(VAL/MET) genotype had significantly greater HAMD-17 (Hamilton Rating Scale for Depression 17 item version) score reductions than COMT(MET/MET) homozygotes from week 2 to 6, respectively, in the mirtazapine group. Time course of response and antidepressant efficacy of mirtazapine, but not paroxetine, seem to be influenced in a clinically relevant manner by this allelic variation within the COMT gene.
PMID: 15520843 [PubMed - indexed for MEDLINE]
Posted by ed_uk on July 1, 2005, at 12:14:47
In reply to look at this abstract - thats interesting !, posted by ben on July 1, 2005, at 12:05:20
Hi Ben,
.........It would be great if we see more studies looking at the influence of genetics on drug response in future!
.........less trial and error in drug selection sounds good to me!
~Ed
Posted by rod on July 2, 2005, at 12:42:49
In reply to Re: COMT Inhibitors for mood disorder? » rod, posted by ed_uk on June 30, 2005, at 18:17:35
> I'm very interested. Please share your experiences :-)
mmkay Mr Ed :-p
Its day three on Entacapone. Yesterday I got into bed at aroung 03:00 am. I watched some movies. I enjoyed that.
But today, I woke up at 18:00 (pm) :-/ but it was a good deep sleep, and feel refreshed today. In general its not unusual for me to sleep that long. Its not the first time this has happened. :-)So far it feels like the other parkinson drugs, amantadine and Mirapex. Time will show if Entacapone is any different on the long term run.
But someting interseting is that Entacapone on its own does not have any antiparkinson activity. Its only working as an add on to L-Dopa therapy.
Anyway, I *do* feel it has some profound pro dopamine activity.And I will go more into detail, in the future, if it still has some good effect. Amantadine for example made me fatigued and apathic on the long term. I hope this will not happen with Entacapone....
bye
Roland
Posted by ed_uk on July 2, 2005, at 13:02:54
In reply to Re: COMT Inhibitors for mood disorder?, posted by rod on July 2, 2005, at 12:42:49
Hi Roland!
>In general its not unusual for me to sleep that long. Its not the first time this has happened. :-)
It's not unusual for me to sleep that long either!
>And I will go more into detail, in the future, if it still has some good effect.
Thank you :-D
>Amantadine for example made me fatigued and apathic on the long term. I hope this will not happen with Entacapone....
Did Mirapex make you tired too?
Bye Roli!
~Ed
Posted by rod on July 2, 2005, at 13:36:08
In reply to Re: COMT Inhibitors for mood disorder? » rod, posted by ed_uk on July 2, 2005, at 13:02:54
> Did Mirapex make you tired too?
no, bot really tired or sleepy. It was more like a downer on the long term... Other people have told that too, as if it would act like some kind of mood stabiliser....
bye
Roland
Posted by ed_uk on July 2, 2005, at 14:17:39
In reply to Re: COMT Inhibitors for mood disorder? » ed_uk, posted by rod on July 2, 2005, at 13:36:08
Hi Roland :-)
>It was more like a downer on the long term....
It made you more depressed? Are you interested in trying other dopamine agonists eg. cabergoline?
Kind regards
~Ed
Posted by rod on July 2, 2005, at 18:38:24
In reply to Re: COMT Inhibitors for mood disorder? » rod, posted by ed_uk on July 2, 2005, at 14:17:39
Hi Ed :-)
>
> >It was more like a downer on the long term....
>
> It made you more depressed?Not really depressed.
I dont find the right words for this.
Maybe the word "blah" is the right one for this feeling :-)
It was neiter great nor bad. An other person also said it made him a couch potato... I guess its due to downregulation of postsynaptic D receptors.
For me, Mirapex was a waste of time...> Are you interested in trying other dopamine agonists eg. cabergoline?
not at the moment. I think they are a waste of time for depression, because they seem to always "poop out"....
I havent seen any person on this board who found them effective for a longer period of time....
I like the COMT inhibitors better, because they do a lot more than just dopamine..
And hope they do the trick for me!mfg :-D
Roland
Posted by ed_uk on July 3, 2005, at 4:48:15
In reply to Re: COMT Inhibitors for mood disorder? » ed_uk, posted by rod on July 2, 2005, at 18:38:24
Hello Roli Roland :-P
>Maybe the word "blah" is the right one for this feeling :-)
Hehe, sounds like being on an SSRI!
>An other person also said it made him a couch potato...
.......and some people find it makes them fall asleep during the day :-(
>I havent seen any person on this board who found them effective for a longer period of time....
No, me neither. Ame Sans Vie benefitted for a while.......but I think it pooped out.
>And hope they do the trick for me!
Me too! I hope entacapone helps you.
mfg :-D
~Ed
Posted by SLS on July 3, 2005, at 8:57:08
In reply to Re: COMT Inhibitors for mood disorder? » ed_uk, posted by rod on July 2, 2005, at 18:38:24
Hi Roland!
If you search back in the PB archives, you might find a few submissions by AndrewB who had tried a COMT inhibitor. I can't remember which one. It could have been tolcapone for all I know. I don't think he received much benefit from it. I know he abandoned it at some point.
I had thought to attack my depression using COMT inhibitors over 20 years ago before there was such a thing. It might make sense to combine MAOI + COMTI. You would cover intracelullar and extracellular catabolization of catecholamines.
- Scott
Posted by linkadge on July 4, 2005, at 18:22:57
In reply to Re: COMT Inhibitors for mood disorder? » rod, posted by SLS on July 3, 2005, at 8:57:08
Well, indirectly I suppose.
It is known that green tea acts to increase norepinephrine leveles. This is why Green tea extract is used as a weight loss product.
I believe that green tea works to increase norepinephrine though COMT inhibiton. Quercetin is also a COMT inhibitor.
Linkadge
Posted by Sarah T. on July 4, 2005, at 20:23:48
In reply to I have tried an COMT inhibitor, posted by linkadge on July 4, 2005, at 18:22:57
Hi, Linkadge,
Which substance in green tea raises NE levels? I thought that the theanine in green tea was supposed to be calming, but raising NE levels would be activating, wouldn't it?
Posted by ben on July 5, 2005, at 0:20:40
In reply to What substance in green tea? » linkadge, posted by Sarah T. on July 4, 2005, at 20:23:48
> Hi, Linkadge,
>
> Which substance in green tea raises NE levels? I thought that the theanine in green tea was supposed to be calming, but raising NE levels would be activating, wouldn't it?There is to few theanine in a cup of tea and you had to drink a huge green tea for reaching sufficient amounts of theanine. And whats the half life of theanine ? I dont know it but I guess not long enough because it is a xanthin-derivate ?!
best regards
Ben
Posted by linkadge on July 5, 2005, at 16:10:23
In reply to Re: What substance in green tea?, posted by ben on July 5, 2005, at 0:20:40
I don't think that theanine is the chemical which induces the NE increase. I am not sure what is.
Linkadge
Posted by rod on July 7, 2005, at 6:46:14
In reply to Re: COMT Inhibitors for mood disorder?, posted by rod on July 2, 2005, at 12:42:49
Ok.
The motivating, stimulating and mood brightening effect lasted about 2 days. then 1 added one tab at evening. Immediate positive effect. lasted 1 day. then, like the other Parkinsum drugs I tried I experienced fatigue, mental slowness and tiredness. Was like a downer after some days.
hmm I am not surprised they arent used to treat depressive symptoms..... because they do not seem work very well at all..
I can not recommend it. The positive effect lasts very short
mmmmkay, lets just forget the "dopamine agonists" ;-)
They are definately not the answer for me....
I am feeling better without it.I went off a day ago and the mental slownes and fatigues is subsiding....
Not that I am mentally fast without it. It just made these problems worse
Kind regards
Roland
Posted by ed_uk on July 7, 2005, at 14:01:54
In reply to Re: COMT Inhibitors? Entacapone is crap for me, posted by rod on July 7, 2005, at 6:46:14
Hi Roland,
>I experienced fatigue, mental slowness and tiredness. Was like a downer after some days.
:-(
Will you try a different type of drug instead?
Kind regards
~ed
Posted by rod on July 7, 2005, at 19:39:08
In reply to Re: COMT Inhibitors? Entacapone is crap for me » rod, posted by ed_uk on July 7, 2005, at 14:01:54
Hi Ed!
> Will you try a different type of drug instead?
hmm not really. for now, I reduce nortriptyline to 100mg and see how I do with it. and use periactin as needed etc... + all the other drugs
But I am thinking about a "new" approach. Maybe I will change a lot. But I will post about that later..
good night
Roland
Posted by rod on July 8, 2005, at 4:47:14
In reply to Re: COMT Inhibitors? Entacapone is crap for me » ed_uk, posted by rod on July 7, 2005, at 19:39:08
Well, the drug I am thinking about is Depakote/ine (valproic acid)
I have read it leads to increased dopamine release in the prefrontal cortex. Thats the point where my residual symptoms originate I guess. Depakine raises Dopamine activity in certain areas while it also lowers it in other areas. And decreases the activity of the cortisol stuff etc.. like Periactin, like Pentoxifylline and I guess also like Lyrica (there is no study about this. I just experience an anti stress effect)
I would drop Klonopin, Lyrica, Pentoxifylline and replace them with a low dose of Depakote/Depakine.
Well and maybe I am bipolar after all. Atypical. but maybe.
When I was 18/19 the symptoms was insomnia (which I treated with 1-3 beers) and depression (maybe because of the alcohol) with impaired memory, concentration etc.. might be the result of some kind of bipolar neurochmistry. I never had ruminting thoughts, early morning awakening etc.I am going nowhere if I dont change something. I feel relatively good, but still, I am not functioning. I have to do something. I have to change strategy. Now I try the "bipolar route"....
If I think back, almost 2 years ago, I started Lamictal monotherapy. well, while I was gradually increasing my dose, I gradually got "worse". Thats, I guess, when the "antidepressant" effect of Lamictal kicked in.
I have to try a mood stabiliser without any "robust" antidepressant capabiities.And futhermore, despite that I have not read it here, Valporate has a mild mood brightening effect for some people. 1 Monograph mentions this..
If I have the mental energy, I will post the abstracts which make me think Valporate its a good idea.
I hope it wont affect cognition negatively... but who knows.. I just have to give it a try... :-)
oh well,
I have to hurry, time to go to the script writer ;-D
bye
Roland> Hi Ed!
>
> > Will you try a different type of drug instead?
>
> hmm not really. for now, I reduce nortriptyline to 100mg and see how I do with it. and use periactin as needed etc... + all the other drugs
>
> But I am thinking about a "new" approach. Maybe I will change a lot. But I will post about that later..
>
> good night
>
> Roland
>
Posted by ed_uk on July 8, 2005, at 12:59:25
In reply to Re: COMT Inhibitors? Entacapone is crap for me, posted by rod on July 8, 2005, at 4:47:14
Hi Roli!
>And futhermore, despite that I have not read it here, Valporate has a mild mood brightening effect for some people.
A couple of babblers have reported that they find it mood brightening, many people seem to find it a bit 'depressogenic'.
Kind regards
~Ed
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