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Dr. Bob is Robert Hsiung, MD,
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Posted by linkadge on May 20, 2010, at 18:36:23
In reply to Re: Gone with trimipramine, posted by bulldog2 on May 18, 2010, at 17:38:26
keep mind mind folks that drugs like mianserin & ritanserin are well established antidepressants with no appreciable affinity for monoamine reuptake.
Linkadge
Posted by Bob on May 20, 2010, at 18:36:23
In reply to Re: Gone with trimipramine, posted by linkadge on May 18, 2010, at 20:30:50
> The TCA's antidepressant effect is (at least partly) due to interaction with opioid receptors. The TCA's display delta agonist like effects, as well as interaction with kappa receptors.
>
> Linkadge
Would any of those actions at opioid, kappa, or delta receptors have anything to do with their putative pain relieving attributes? From most of the reading I've done (and from what my doctor says) the anti-pain properties come from the presence of dual action on serotonin and norepinephrine only. I'm taking nortriptyline now, but it doesn't seem to reduce pain much.
Posted by Bob on May 20, 2010, at 18:36:23
In reply to Re: Gone with trimipramine, posted by linkadge on May 18, 2010, at 20:35:58
> keep mind mind folks that drugs like mianserin & ritanserin are well established antidepressants with no appreciable affinity for monoamine reuptake.
>
>
> Linkadge
From what I understand, Mianserin has been largely superceded by mirtazapine so I guess that would explain why it doesn't seem to be prescribed as an AD these days, but why is it no one is using ritanserin?
Posted by SLS on May 20, 2010, at 18:36:23
In reply to Re: Gone with trimipramine, posted by linkadge on May 18, 2010, at 20:30:50
> The TCA's antidepressant effect is (at least partly) due to interaction with opioid receptors. The TCA's display delta agonist like effects, as well as interaction with kappa receptors.
>
> LinkadgeThank you very much for the info. I was able to come up with a recent abstract on Medline based upon what you said. I imagine you have seen it already, but just in case you haven't, here is the URL:
http://www.ncbi.nlm.nih.gov/pubmed/19828880
Doesn't kappa stimulation produce dysphoria?
- Scott
Posted by SLS on May 20, 2010, at 18:36:23
In reply to Re: Gone with trimipramine, posted by linkadge on May 18, 2010, at 20:35:58
> keep mind mind folks that drugs like mianserin & ritanserin are well established antidepressants with no appreciable affinity for monoamine reuptake.
I might be wrong, but I think ritanserin by itself is not so effective as an antidepressant, although it might make a good augmenter. I doubt that we will ever see it marketed, though. As monotherapy, I don't think there are any indications that it would be appropriate for. I'm all but sure that the patent has expired, and no drug company would want to develop it. As a (non-selective) 5-HT2 receptor antagonist, it might even be effective in treating the negative symptoms of schizophrenia, but would not be a sufficient treatment for the entire symptom cluster.
- Scott
Posted by med-amorphosis on May 20, 2010, at 18:36:24
In reply to Re: Gone with trimipramine, posted by ed_uk2010 on May 18, 2010, at 15:44:06
> I wouldn't expect trimipramine to produce any serious interactions with isocarboxazid. It sounds like a reasonable choice.
>
> Trimipramine is quite sedating. It is particularly suitable for depression with insomnia.Well after my 1st night at 50mg (my appologies, but im desperate. Im not encouraging others to self increase dosage) and I awoke earlier than I have for a long long time. I was asleep by 12:30 and up at 9. Thats good for me. I expected to wake feeling hung over from starting trimipramine, especially as I combining with clonazepam. But I felt refreshed if anything. Nothing like clomipramine (yuck!-SSRI-in-disguise) Yes trimipramine knocks you out but sleep isn't foggy-I vaguely remembered dreams on waking. I hardly ever dream, unless they're nightmares.
I also must remember that there is still lofepramine in my system. That needs to be rid of before I can make any trully acurate reports.
Anyone know how long it takes 'till there is neg amounts in the blood and/or lofepramine's NRI effect diminishes?
Posted by med-amorphosis on May 20, 2010, at 18:36:24
In reply to Re: Gone with trimipramine, posted by bulldog2 on May 18, 2010, at 17:38:26
> > Trimipramine has the same opioid like effects as other TCA's. Even though it doesn't inhibit monoamine uptake, who says this matters?
> >
> > Trimipramine has affniity for MAO-B as well as the DAT transporter. It also shares the common affinity for monoamine receptors (acetylcholine, serotonin, histamine etc.)
> >
> > I would strongly hesitate in saying that surmontil is not an antidepressant just because it doesn't inhibit the classic monoamines (serotonin, norepinephrine).
> >
> > After all, its this flawed logic that produces the so called "tianeptine paradox"
> >
> >
> > Linkadge
>
> Yes it is possible it might have ad properties. There also was someing wikipedia that inidcated it might have strong neuropletic properties.Well I can say that the Surmontil brand is ONLY marketed as an AD here, or with associated anxiety. How can you question its AD abilities when its been used and marketed as such for so long?
Posted by hyperfocus on May 20, 2010, at 18:36:24
In reply to Re: Gone with trimipramine » ed_uk2010, posted by med-amorphosis on May 19, 2010, at 14:10:15
I also have this kind of paradoxical sleep, but with amitriptyline. Many days I sleep less and wake up more refreshed, much better than when I fall asleep with benzos or Risperdal. A few times I woke up after three or four hours feeling great physically. Maybe TCAs promote more REM sleep? Sleep on benzos feels shallow.
Posted by med-amorphosis on May 20, 2010, at 18:36:24
In reply to Re: Gone with trimipramine, posted by hyperfocus on May 19, 2010, at 15:22:08
> I also have this kind of paradoxical sleep, but with amitriptyline. Many days I sleep less and wake up more refreshed, much better than when I fall asleep with benzos or Risperdal. A few times I woke up after three or four hours feeling great physically. Maybe TCAs promote more REM sleep? Sleep on benzos feels shallow.
Yeah its odd. I took 25mg 2hrs ago before dinner. I'm still up, feel slightly sedated, very calm yet not at all drowsy. Yet if I laid down I know I could fall asleep. I also had a strange energizing effect after waking after my 1st dose taken at 8pm last night. I woke just after 9pm, went online, listened to some musice then took another 25mg before midnight. I was asleep shortly after. NO 'doziness' at all yet.
Posted by bulldog2 on May 20, 2010, at 18:36:25
In reply to Re: Gone with trimipramine » bulldog2, posted by med-amorphosis on May 19, 2010, at 14:16:47
> > > Trimipramine has the same opioid like effects as other TCA's. Even though it doesn't inhibit monoamine uptake, who says this matters?
> > >
> > > Trimipramine has affniity for MAO-B as well as the DAT transporter. It also shares the common affinity for monoamine receptors (acetylcholine, serotonin, histamine etc.)
> > >
> > > I would strongly hesitate in saying that surmontil is not an antidepressant just because it doesn't inhibit the classic monoamines (serotonin, norepinephrine).
> > >
> > > After all, its this flawed logic that produces the so called "tianeptine paradox"
> > >
> > >
> > > Linkadge
> >
> > Yes it is possible it might have ad properties. There also was someing wikipedia that inidcated it might have strong neuropletic properties.
>
> Well I can say that the Surmontil brand is ONLY marketed as an AD here, or with associated anxiety. How can you question its AD abilities when its been used and marketed as such for so long?I think my point has been misunderstood. This med might be a wonderful ad. I however was reading in wikipedia about this med being tested on 28 people as a neuropletic med and it seems to have done a good job. Read the wikipedia article about surmontil and it is in the bottom half. This might be a good ad for someone with anxiety issues. Kill two birds with one stone.
Posted by SLS on May 20, 2010, at 18:36:25
In reply to Re: Gone with trimipramine, posted by bulldog2 on May 19, 2010, at 16:13:14
> I think my point has been misunderstood. This med might be a wonderful ad. I however was reading in wikipedia about this med being tested on 28 people as a neuropletic med and it seems to have done a good job. Read the wikipedia article about surmontil and it is in the bottom half. This might be a good ad for someone with anxiety issues. Kill two birds with one stone.
Amoxapine (Asendin) is a tricyclic with moderate neuroleptic properties. It is a relative of loxapine. It was thought that this drug, too, could serve a dual purpose. It never became popular, even though it was touted as working faster than other TCAs to treat depression.
- Scott
Posted by linkadge on May 20, 2010, at 18:36:25
In reply to Re: Gone with trimipramine » linkadge, posted by SLS on May 19, 2010, at 7:16:52
Kappa stimulation can produce acute dysphoria, but long term adminitration may reduce the responsivity of the kappa receptors to dynorphin.
Kappa receptor agonists might also have analgesic and mood stabilizing effects.
Linkadge
Posted by linkadge on May 20, 2010, at 18:36:25
In reply to Re: Gone with trimipramine, posted by SLS on May 19, 2010, at 7:27:00
Ritanserin was/is an effective antidepressant (as effective as any) from the abstracts I have read. I also read that ritanserin inhibits dopamine reuptake. See:
http://www.nature.com/mp/journal/v5/n6/full/4000804a.html
Similar effectiveness to amitriptyline:
http://www.biopsychiatry.com/ritanserinvamitrip.htm
I think there is still this assumption that just because it is not a serotonin/norepinephrine reuptake inhibitor, it is not an effective antideressant.
Linkadge
Posted by linkadge on May 20, 2010, at 18:36:26
In reply to Re: Gone with trimipramine » bulldog2, posted by med-amorphosis on May 19, 2010, at 14:16:47
Think of it this way: Surmontil could have potent dopaminergic effects on account of
1) 5-ht2a/c receptor antagonism
2) Muscarinic antagonism
3) MAO-B inhibition
4) DAT inhibition
5) 5-ht2a/c antagonism
6) Opioid bindingYes it does have some d2 antagonsm, but this would indirectly shunt more dopamine to d1/d3 etc.
Linkadge
Posted by SLS on May 20, 2010, at 18:36:26
In reply to Re: Gone with trimipramine, posted by linkadge on May 19, 2010, at 18:16:00
> I think there is still this assumption that just because it is not a serotonin/norepinephrine reuptake inhibitor, it is not an effective antideressant.
I can only hope that this is not true of our scientists.
As far as ritanserin is concerned, I am not convinced that it is as effective as the other drugs that we use for depression. I think if it were really that effective, more placebo controlled trials of its use in depression would have been published. I don't think I have come across a single study that looked at ritanserin as a treatment for major depressive disorder as diagnosed using DSM criteria. For now, I guess it ia a moot point. I don't think we will see it any time soon.
- Scott
Posted by linkadge on May 20, 2010, at 18:36:26
In reply to Re: Gone with trimipramine, posted by SLS on May 19, 2010, at 18:55:40
I don't see any reason why it would be less effective. Ritanserin was more of a research drug, true, but without evidence to suggest that it is inferior, I don't see why I would conclude so.
The reasons why one drug proves to be utilized more clinicaly is not always as strightforward as one might think.
Linkadge
Posted by SLS on May 20, 2010, at 18:36:26
In reply to Re: Gone with trimipramine, posted by linkadge on May 19, 2010, at 20:10:49
> I don't see any reason why it would be less effective.
However, it is so few times that we can yet predict the therapeutic value of a drug based upon what we think we know. Strattera and reboxetine suck for depression, yet they had the "right" properties to be effective according to what are probably outdated and impotent theories.
It seems that we have two head-to-head comparisons of ritanserin to another drug for treating depression. There is the one you cited that speaks of depression without stating the use of DSM criteria, and another for a DSM diagnosis of dysthymia. In the latter study, ritanserin was found to be inferior to imipramine. I don't know how relevant this is, though, as dysthymia is a different disorder than major depressive disorder. The former study fails to describe the relative potencies of its two test drugs. One thing seems clear. Ritanserin has not been thoroughly evaluated for treating major depression. You may be right about ritanserin.
> The reasons why one drug proves to be utilized more clinicaly is not always as strightforward as one might think.
You sure are right about that. Clorgyline is a prime example. This drug might be the most effective antidepressant yet tested, but it languishes in the laboratory because no one would want to develop a drug without a patent.
- Scott
Posted by med-amorphosis on May 20, 2010, at 18:36:26
In reply to Re: Gone with trimipramine » med-amorphosis, posted by linkadge on May 19, 2010, at 18:19:23
> Think of it this way: Surmontil could have potent dopaminergic effects on account of
>
> 1) 5-ht2a/c receptor antagonism
> 2) Muscarinic antagonism
> 3) MAO-B inhibition
> 4) DAT inhibition
> 5) 5-ht2a/c antagonism
> 6) Opioid binding
>
> Yes it does have some d2 antagonsm, but this would indirectly shunt more dopamine to d1/d3 etc.
>
> Linkadge
>
>
>
>
>
>
>Thanks. So your saying trimipramine is/could be more (directly/inderectly) dopaminergic than anything else? If so thats interesting as it was his next offer after I highlighted my loss of pleasure in everything, even things I normally love even if I'm down. Fishing is one, but last trip I just wanted to go home allmost strait away. Being around nature is normally theraputic.
med
Posted by SLS on May 20, 2010, at 18:36:27
In reply to Re: Gone with trimipramine, posted by SLS on May 20, 2010, at 6:26:16
> > The reasons why one drug proves to be utilized more clinicaly is not always as strightforward as one might think.
> You sure are right about that. Clorgyline is a prime example. This drug might be the most effective antidepressant yet tested, but it languishes in the laboratory because no one would want to develop a drug without a patent.I hope that the recent discovery that clorgyline reverses heart failure fuels interest in bringing irreversible MAO-A inhibitors to market.
- Scott
Posted by bulldog2 on May 20, 2010, at 18:36:27
In reply to Re: Gone with trimipramine, posted by SLS on May 20, 2010, at 7:25:12
> > > The reasons why one drug proves to be utilized more clinicaly is not always as strightforward as one might think.
>
> > You sure are right about that. Clorgyline is a prime example. This drug might be the most effective antidepressant yet tested, but it languishes in the laboratory because no one would want to develop a drug without a patent.
>
> I hope that the recent discovery that clorgyline reverses heart failure fuels interest in bringing irreversible MAO-A inhibitors to market.
>
>
> - Scott
>
>Yes I'll drink to that. The last thing that we need is another ssri or snri.
Posted by linkadge on May 20, 2010, at 18:36:27
In reply to Re: Gone with trimipramine, posted by SLS on May 20, 2010, at 6:26:16
This is a good point about straterra and reboxetine. On paper, they look like better antidepressants than trimipramine but who knows.
Here is an animal study in which olanzapine produced a faster onset of recovery from anhedonia than did amitriptyline. On paper, olanzapine is not an antidepressant, but in this study, it lead to a faster recovery of depressive symptoms than amitriptyline.
http://www.ncbi.nlm.nih.gov/pubmed/15967060
There are so many unknowns in the mechanisms of drug activity. There are so many targets for depression, HPA axis, neurotransimtters, neuromodulators, neurotrophic factors, circadian modulators, glutamate, substance p, galanin, neuropeptides, the list goes on.
Parnate (a wonder drug for some) made me more depressed. Its so hard to know will work for any one individual.
Linkadge
Posted by linkadge on May 20, 2010, at 18:36:27
In reply to Re: Gone with trimipramine » linkadge, posted by med-amorphosis on May 20, 2010, at 7:05:36
Some researchers speculate that the final common destination / target of any antidepressant agent is an enhancement of dopaminergic activity.
If you combine a number of targets that each affect dopamine on their own, then the net effect might be significant.
Linkadge
Posted by bulldog2 on May 20, 2010, at 18:36:28
In reply to Re: Gone with trimipramine, posted by linkadge on May 20, 2010, at 14:50:56
I also believe in the end that mood(s) reside in a certain part of the brain. What makes creating a universal AD virtually impossible is that every depressed persons brain chemistry is unbalanced in their own unique way. So right now you just keep trying ad after ad or different combos and hope you fix the unbalance.
So the question is can any one antidepressant of the future fix well over 90% of depressed people's depressive episodes. That would be the universal ad.
Posted by Bob on May 21, 2010, at 20:03:53
In reply to Re: olanzapine vs. amitriptyline, posted by linkadge on May 20, 2010, at 18:36:27
> This is a good point about straterra and reboxetine. On paper, they look like better antidepressants than trimipramine but who knows.
>
> Here is an animal study in which olanzapine produced a faster onset of recovery from anhedonia than did amitriptyline. On paper, olanzapine is not an antidepressant, but in this study, it lead to a faster recovery of depressive symptoms than amitriptyline.
>
> http://www.ncbi.nlm.nih.gov/pubmed/15967060
>
> There are so many unknowns in the mechanisms of drug activity. There are so many targets for depression, HPA axis, neurotransimtters, neuromodulators, neurotrophic factors, circadian modulators, glutamate, substance p, galanin, neuropeptides, the list goes on.
>
> Parnate (a wonder drug for some) made me more depressed. Its so hard to know will work for any one individual.
>
> Linkadge
Which would you rather take if they were hypothetically of roughly equal therapeutic value? I understand that olanzapine has those pesky weight gain and diabetes problems, but the amitriptyline has weight gain too, and those super-pesky anti-cholinergic effects.
Posted by Brainbeard on May 25, 2010, at 7:33:56
In reply to Re: olanzapine vs. amitriptyline » linkadge, posted by Bob on May 21, 2010, at 20:03:53
> Which would you rather take if they were hypothetically of roughly equal therapeutic value? I understand that olanzapine has those pesky weight gain and diabetes problems, but the amitriptyline has weight gain too, and those super-pesky anti-cholinergic effects.
I have 'till now shunned olanzapine, even though I have been frantically searching for a 5HT2A/C-antagonist that doesn't increase prolactin. But indeed, it being diabetogenic plus likely to induce weight gain have kept me off.I have been using low dose amitriptyline since many months now. I like the drug. I have been able to avoid weight gain so far.
A friend of mine has very good results with olanzapine. He takes it IN THE MORNING - and it stimulates him!! Can you believe that?
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Dr. Bob is Robert Hsiung, MD,
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