![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 13 to 37 of 37. Go back in thread:
Posted by Sad Panda on May 22, 2004, at 5:48:33
In reply to Re: wash-out before maoi, posted by King Vultan on May 21, 2004, at 12:25:12
> >
> > You need some H1 blockade to set your mind into sleep mode & some 5-HT2A blockade to keep it there. :)
> >
> > Cheers,
> > Panda.
> >
> >
>
> Hey there Panda,
>
> I know Remeron has those characteristics, but after my negative experience with trazodone, I am done with sedating antidepressants, as I have found nortriptyline difficult to tolerate also. I am getting some H1 blockade from the Benadryl I am currently taking but wake up several times a night. I've already decided to ask my pdoc about stuff like Halcion or Restoril, which I can take every other night or whatever is necessary to avoid any dependency/tolerance issues. I am not going to take the damned atypical antipsychotic he had brought up at my last visit. It's too expensive, and I have grave misgivings about this class of drugs being prescribed for people with unipolar depression who are just suffering insomnia because of their AD meds.
>
> Todd
>
>Hi Todd,
What sort of bad rections did you have to trazodone & nortriptyline? I am against the atypical AP for sleep for unipolar people, but they may be a good option for bipolar people needing sleep & mood stabization.
Cheers,
Panda.
Posted by King Vultan on May 22, 2004, at 11:35:33
In reply to Re: wash-out before maoi » King Vultan, posted by Sad Panda on May 22, 2004, at 5:48:33
>
> Hi Todd,
>
> What sort of bad rections did you have to trazodone & nortriptyline? I am against the atypical AP for sleep for unipolar people, but they may be a good option for bipolar people needing sleep & mood stabization.
>
> Cheers,
> Panda.
>
I found nortriptyline dreadfully sedating, and it also had a dual depressant/antidepressant action. I would go down in the dumps at first on a dosage increase, but then my spirits would gradually rise. Trazodone was a pure depressant for me and made me feel so depressed and out of sorts the next day after taking it that I dumped it after just a few days.I'm not sure what's going on with these drugs, but because I get such an immediate and positive response from SSRI type drugs (in as little as four hours with 25-50 mg Zoloft in a depressed and recently unmedicated state), perhaps my system is just geared more for this kind of drug than these atypical antidepressants. Nortripyline, at least, is a selective norepinephrine reuptake inhibitor, on top of the other things it does, and I'm convinced this is the only reason it had any antidepressant efficacy. Trazodone has very little direct effect on either serotonin or norepinephrine reuptake. I expect I would also react very badly to Serzone, which has a very similar pharmacology.
Todd
Posted by fuji on May 22, 2004, at 12:00:13
In reply to Re: wash-out before maoi » fuji, posted by King Vultan on May 21, 2004, at 7:26:26
It's interesting because most things sedate me whether they should or not. Provigil and coffee put me out like a light. So far the only thing that keeps me awake is anxiety but even then it's not that bad. Prozac, wellbutrin and effextor never keep me awake. Actually they are more like sleeping pills. Maybe I can go to sleep for the next 5 weeks!!
It seems that more people take Nardil. Any parnate folks out there with a couple of cents to throw in???
Posted by Questionmark on May 22, 2004, at 14:58:25
In reply to I feel your pain. (Have MAOI sex question too), posted by PhoenixGirl on May 21, 2004, at 22:14:26
> I wanted to ask the other people here who have taken MAOIs -- How does it affect your libido and sexual function?
For me, and for most people, Nardil has a negative effect on libido, but Parnate has a tremendously positive effect on libido and sexual function and pleasure.
Posted by Questionmark on May 22, 2004, at 15:01:50
In reply to Re: wash-out before maoi » Sad Panda, posted by King Vultan on May 22, 2004, at 11:35:33
>
>
> >
> > Hi Todd,
> >
> > What sort of bad rections did you have to trazodone & nortriptyline? I am against the atypical AP for sleep for unipolar people, but they may be a good option for bipolar people needing sleep & mood stabization.
> >
> > Cheers,
> > Panda.
> >
>
> I found nortriptyline dreadfully sedating, and it also had a dual depressant/antidepressant action. I would go down in the dumps at first on a dosage increase, but then my spirits would gradually rise. Trazodone was a pure depressant for me and made me feel so depressed and out of sorts the next day after taking it that I dumped it after just a few days.
>
> I'm not sure what's going on with these drugs, but because I get such an immediate and positive response from SSRI type drugs (in as little as four hours with 25-50 mg Zoloft in a depressed and recently unmedicated state), perhaps my system is just geared more for this kind of drug than these atypical antidepressants. Nortripyline, at least, is a selective norepinephrine reuptake inhibitor, on top of the other things it does, and I'm convinced this is the only reason it had any antidepressant efficacy. Trazodone has very little direct effect on either serotonin or norepinephrine reuptake. I expect I would also react very badly to Serzone, which has a very similar pharmacology.
>
> Toddi'm the exact same way: w/ antihistamines (other antihistamines-- never tried a TCA or trazadone) and SSRIs.
Posted by Sad Panda on May 23, 2004, at 1:33:07
In reply to Re: wash-out before maoi » Sad Panda, posted by King Vultan on May 22, 2004, at 11:35:33
>
>
> >
> > Hi Todd,
> >
> > What sort of bad rections did you have to trazodone & nortriptyline? I am against the atypical AP for sleep for unipolar people, but they may be a good option for bipolar people needing sleep & mood stabization.
> >
> > Cheers,
> > Panda.
> >
>
> I found nortriptyline dreadfully sedating, and it also had a dual depressant/antidepressant action. I would go down in the dumps at first on a dosage increase, but then my spirits would gradually rise. Trazodone was a pure depressant for me and made me feel so depressed and out of sorts the next day after taking it that I dumped it after just a few days.
>
> I'm not sure what's going on with these drugs, but because I get such an immediate and positive response from SSRI type drugs (in as little as four hours with 25-50 mg Zoloft in a depressed and recently unmedicated state), perhaps my system is just geared more for this kind of drug than these atypical antidepressants. Nortripyline, at least, is a selective norepinephrine reuptake inhibitor, on top of the other things it does, and I'm convinced this is the only reason it had any antidepressant efficacy. Trazodone has very little direct effect on either serotonin or norepinephrine reuptake. I expect I would also react very badly to Serzone, which has a very similar pharmacology.
>
> Todd
>
>Trazodone, Serzone & Nortriptyline are all 5-HT2A & Alpha-1 NE blockers, I'd be interested to know which receptor blockade causes you grief. A Remeron trial could be revealing, it stands out from the other sedating AD's because it doesn't block Alpha-1 NE.
Have you tried the other antihistamine for sleep like Phenergan & Polaramine? Phenergan might be bad, I think it would hit a bunch of receptors.
Cheers,
Panda.
Posted by King Vultan on May 24, 2004, at 8:03:25
In reply to Re: wash-out before maoi » King Vultan, posted by Sad Panda on May 23, 2004, at 1:33:07
> >
>
> Trazodone, Serzone & Nortriptyline are all 5-HT2A & Alpha-1 NE blockers, I'd be interested to know which receptor blockade causes you grief. A Remeron trial could be revealing, it stands out from the other sedating AD's because it doesn't block Alpha-1 NE.
>
> Have you tried the other antihistamine for sleep like Phenergan & Polaramine? Phenergan might be bad, I think it would hit a bunch of receptors.
>
> Cheers,
> Panda.
>
>
>My theory is that it is these drugs' blockade of 5HT-1 receptors that is responsible. For trazodone I have a reference showing these Ki values in order of strength:
alpha-1..... 12 +/- 0.2
5-HT2A..... 20 +/- 1
5-HT1A..... 29 +/- 1
alpha-2..... 106 +/- 2Furthermore, the trazodone metabolite mCPP shows these Ki values:
5-HT1A..... 16 +/- 0.2
alpha-1..... 97 +/- 3
5-HT2A..... 110 +/- 3So for the parent molecule, the 5-HT1A blockade is the 3rd most powerful--and of roughly the same order of magnitude as the alpha-1 blockade. For mCPP, the 5-HT1A blockade is by far the most powerful.
So what does this mean? I'm not sure, but I bring it up because the 5-HT1A receptor seems like a strange one for an antidepressant to be blockading. After all, the presynaptic 5-HT1A receptor is the initial target and the postsynaptic 5-HT1A receptor is the ultimate target for SSRIs to stimulate. To me, it doesn't sound like a great idea to be blockading this receptor, but trazodone--and Serzone, which has a very similar pharmacology--obviously work as antidepressants for some people. My theory is that this weird 5-HT1A blockade business is one of the reasons these drugs are viewed by some as marginal antidepressants. I also think that someone like myself who reacts very strongly and quickly to an SSRI will have a greater chance of finding Serzone and trazodone to be disappointing.
As for nortriptyline, I don't have statistical data, but in the receptor chart in "Psychotropic Drugs", its Ki for 5-HT1 blockade, represented by ++, is higher than most of the tricyclics, and it also has only a relatively weak blockade of serotonin reuptake to counterbalance it (its most powerful effect is its blockade of NE reuptake). I found nortriptyline to have kind of a dual action, as in one way I was getting a lift, and in another I was going down in the dumps. There was enough lift, however, that there was a net antidepressant effect.
None of this appears to apply to Remeron, which my book shows has zero effect on blockading 5-HT1A receptors. I'm more optimistic that this drug would have antidepressant effects for me, but I am not enthusiastic about trying it due to possible oversedation and weight gain problems.
Todd
Posted by Sad Panda on May 24, 2004, at 8:38:15
In reply to Re: wash-out before maoi, posted by King Vultan on May 24, 2004, at 8:03:25
> > >
> >
> > Trazodone, Serzone & Nortriptyline are all 5-HT2A & Alpha-1 NE blockers, I'd be interested to know which receptor blockade causes you grief. A Remeron trial could be revealing, it stands out from the other sedating AD's because it doesn't block Alpha-1 NE.
> >
> > Have you tried the other antihistamine for sleep like Phenergan & Polaramine? Phenergan might be bad, I think it would hit a bunch of receptors.
> >
> > Cheers,
> > Panda.
> >
> >
> >
>
> My theory is that it is these drugs' blockade of 5HT-1 receptors that is responsible. For trazodone I have a reference showing these Ki values in order of strength:
>
> alpha-1..... 12 +/- 0.2
> 5-HT2A..... 20 +/- 1
> 5-HT1A..... 29 +/- 1
> alpha-2..... 106 +/- 2
>
> Furthermore, the trazodone metabolite mCPP shows these Ki values:
>
> 5-HT1A..... 16 +/- 0.2
> alpha-1..... 97 +/- 3
> 5-HT2A..... 110 +/- 3
>
> So for the parent molecule, the 5-HT1A blockade is the 3rd most powerful--and of roughly the same order of magnitude as the alpha-1 blockade. For mCPP, the 5-HT1A blockade is by far the most powerful.
>
> So what does this mean? I'm not sure, but I bring it up because the 5-HT1A receptor seems like a strange one for an antidepressant to be blockading. After all, the presynaptic 5-HT1A receptor is the initial target and the postsynaptic 5-HT1A receptor is the ultimate target for SSRIs to stimulate. To me, it doesn't sound like a great idea to be blockading this receptor, but trazodone--and Serzone, which has a very similar pharmacology--obviously work as antidepressants for some people. My theory is that this weird 5-HT1A blockade business is one of the reasons these drugs are viewed by some as marginal antidepressants. I also think that someone like myself who reacts very strongly and quickly to an SSRI will have a greater chance of finding Serzone and trazodone to be disappointing.
>
> As for nortriptyline, I don't have statistical data, but in the receptor chart in "Psychotropic Drugs", its Ki for 5-HT1 blockade, represented by ++, is higher than most of the tricyclics, and it also has only a relatively weak blockade of serotonin reuptake to counterbalance it (its most powerful effect is its blockade of NE reuptake). I found nortriptyline to have kind of a dual action, as in one way I was getting a lift, and in another I was going down in the dumps. There was enough lift, however, that there was a net antidepressant effect.
>
> None of this appears to apply to Remeron, which my book shows has zero effect on blockading 5-HT1A receptors. I'm more optimistic that this drug would have antidepressant effects for me, but I am not enthusiastic about trying it due to possible oversedation and weight gain problems.
>
> Todd
>I was aware of Traz & mCPP blocking 5-HT1A, but I didn't know Nortriptyline did, I haven't seen that anywhere on the net. I think the AD abilities of Remeron would be similar to Traz & Serzone, that is, it's only an AD to a handfull of people. I like Remeron mostly as a sleep tablet, but it also is a great anti-nausea drugs & counters SRI anorgasmia. I hate that it blocks Alpha-2 NE, that effect just irritates me so much, I guess nothing is perfect. :) Ever find any data on benadryl & phenergan?
Cheers,
Panda.
Posted by zeugma on May 24, 2004, at 13:25:56
In reply to Re: wash-out before maoi, posted by King Vultan on May 24, 2004, at 8:03:25
> > >
> >
> > Trazodone, Serzone & Nortriptyline are all 5-HT2A & Alpha-1 NE blockers, I'd be interested to know which receptor blockade causes you grief. A Remeron trial could be revealing, it stands out from the other sedating AD's because it doesn't block Alpha-1 NE.
> >
> > Have you tried the other antihistamine for sleep like Phenergan & Polaramine? Phenergan might be bad, I think it would hit a bunch of receptors.
> >
> > Cheers,
> > Panda.
> >
> >
> >
>
> My theory is that it is these drugs' blockade of 5HT-1 receptors that is responsible. For trazodone I have a reference showing these Ki values in order of strength:
>
> alpha-1..... 12 +/- 0.2
> 5-HT2A..... 20 +/- 1
> 5-HT1A..... 29 +/- 1
> alpha-2..... 106 +/- 2
>
> Furthermore, the trazodone metabolite mCPP shows these Ki values:
>
> 5-HT1A..... 16 +/- 0.2
> alpha-1..... 97 +/- 3
> 5-HT2A..... 110 +/- 3
>
> So for the parent molecule, the 5-HT1A blockade is the 3rd most powerful--and of roughly the same order of magnitude as the alpha-1 blockade. For mCPP, the 5-HT1A blockade is by far the most powerful.
>
> So what does this mean? I'm not sure, but I bring it up because the 5-HT1A receptor seems like a strange one for an antidepressant to be blockading. After all, the presynaptic 5-HT1A receptor is the initial target and the postsynaptic 5-HT1A receptor is the ultimate target for SSRIs to stimulate. To me, it doesn't sound like a great idea to be blockading this receptor, but trazodone--and Serzone, which has a very similar pharmacology--obviously work as antidepressants for some people. My theory is that this weird 5-HT1A blockade business is one of the reasons these drugs are viewed by some as marginal antidepressants. I also think that someone like myself who reacts very strongly and quickly to an SSRI will have a greater chance of finding Serzone and trazodone to be disappointing.The azapirones- buspirone and gepirone- are 5-HT 1A agonists, and they are even more marginal antidepressants than trazodone and the soon to be discontinued Serzone. The azapirones have even worse pharmacokinetics than trazodone and Serzone - i.e. shorter half lives, and some people claim that this is the reason they have exhibited so little success when treating depression- or anxiety, for that matter. We will see when gepirone is released in an ER formulation, but from what I have heard buspirone ER was not a notable success.
As for nortriptyline, nobody has ever claimed it is a marginal antidepressant. So maybe for a good proprtion of people its antiserotonergetic effects are therapeutic?
>
> As for nortriptyline, I don't have statistical data, but in the receptor chart in "Psychotropic Drugs", its Ki for 5-HT1 blockade, represented by ++, is higher than most of the tricyclics, and it also has only a relatively weak blockade of serotonin reuptake to counterbalance it (its most powerful effect is its blockade of NE reuptake). I found nortriptyline to have kind of a dual action, as in one way I was getting a lift, and in another I was going down in the dumps. There was enough lift, however, that there was a net antidepressant effect.
>
> None of this appears to apply to Remeron, which my book shows has zero effect on blockading 5-HT1A receptors. I'm more optimistic that this drug would have antidepressant effects for me, but I am not enthusiastic about trying it due to possible oversedation and weight gain problems.
>
> ToddI found nortriptyline sedating enough, so I am not going near Remeron myself. The real mystery about nortriptyline is that it is the only AD with a true therapeutic window. This window cannot be based solely on its NRI effects, or adding Strattera would have resulted in loss of antidepressant effect. (?- is this reasoning off the mark? I mention it because Strattera definitely seemed to boost nortriptyline's AD effects.)
I am going to call my pdoc later and ask him to have a script called in for clomipramine. I am probably more depressed on 50 mg nortriptyline than I was on 75 mg, and sleeping worse, so i want to try the experiment of adding clomipramine and seeing if I can get a stronger AD effect from clomipramine alone than I did from nortriptyline. Then I would like to eliminate the Strattera and try a stimulant for my ADD instead.
What does your book tell you about the receptor blocking affinities of clomipramine? Probably both 5HT-1A and 5HT 2A blockade is therapeutic for me. The great experiment will be to see what 5HT reuptake inhibition does for me, since I have never taken one long enough to determine the nature of its effects. My hope is that the other actions of clomipramine will make the SRI effects tolerable.
>
Posted by cybercafe on May 25, 2004, at 1:39:28
In reply to Re: I feel your pain. (Have MAOI sex question to » PhoenixGirl, posted by Questionmark on May 22, 2004, at 14:58:25
> > I wanted to ask the other people here who have taken MAOIs -- How does it affect your libido and sexual function?
>
>
> For me, and for most people, Nardil has a negative effect on libido, but Parnate has a tremendously positive effect on libido and sexual function and pleasure.2nd time around, parnate seems to have no positive effect on libido... either because of a tiny dose of abilify, ritalin, or because i actually have a couple girlfriends so sex really isn't anything i think about anymore, it's just something i do... hmmm... tough to answer
Posted by gardenergirl on May 25, 2004, at 10:00:44
In reply to Re: I feel your pain. (Have MAOI sex question to, posted by cybercafe on May 25, 2004, at 1:39:28
I had libido issues when I started on Nardil, but after about 4 months, they went away. Pleasant surprise!
gg
Posted by King Vultan on May 25, 2004, at 14:21:31
In reply to Re: wash-out before maoi » King Vultan, posted by zeugma on May 24, 2004, at 13:25:56
>
> What does your book tell you about the receptor blocking affinities of clomipramine? Probably both 5HT-1A and 5HT 2A blockade is therapeutic for me. The great experiment will be to see what 5HT reuptake inhibition does for me, since I have never taken one long enough to determine the nature of its effects. My hope is that the other actions of clomipramine will make the SRI effects tolerable.
> >
>
>Clomipramine
NE reuptake............+++
5HT reuptake........+++++
DA reuptake..............+
Blockade 5HT1.........+
Blockade 5HT2.......+++
Blockade ACh.........+++
Blockade H1...........+++
Blockade alpha-1....+++
Blockade alpha-2......+
Blockade D2............++where each + represents a difference of one order of magnitude for Ki, ranging from
+++++ represents Ki = 0.1-1.0
+ represents Ki = 1000-10000
Todd
Posted by zeugma on May 25, 2004, at 18:46:57
In reply to Re: wash-out before maoi » zeugma, posted by King Vultan on May 25, 2004, at 14:21:31
>
> >
> > What does your book tell you about the receptor blocking affinities of clomipramine? Probably both 5HT-1A and 5HT 2A blockade is therapeutic for me. The great experiment will be to see what 5HT reuptake inhibition does for me, since I have never taken one long enough to determine the nature of its effects. My hope is that the other actions of clomipramine will make the SRI effects tolerable.
> > >
> >
> >
>
> Clomipramine
>
> NE reuptake............+++
> 5HT reuptake........+++++
> DA reuptake..............+
> Blockade 5HT1.........+
> Blockade 5HT2.......+++
> Blockade ACh.........+++
> Blockade H1...........+++
> Blockade alpha-1....+++
> Blockade alpha-2......+
> Blockade D2............++
>
> where each + represents a difference of one order of magnitude for Ki, ranging from
>
> +++++ represents Ki = 0.1-1.0
> + represents Ki = 1000-10000
>
>
> Todd
>Thank you for the info. My pdoc said I could swap nortrip for clomip one-to-one. That was a lot of my reason for wanting to try clomip instead of my lex samples in the first place. The TCA depressant/antidepressant combo (monoamine reuptake blockade vs. H1/5HT blockade) is why I think I responded to nortrip, and is the clue I will follow as i experiment with clomipramine.
By the way, do you think clomipramine + stimulant comes as close to an MAOI as is possible without actually taking one? My thought is that it might COMBINE the attributes of Parnate and Nardil. (In this comparison I would also include the GABAergic effects of the clonazepam I also take.)
Posted by King Vultan on May 26, 2004, at 12:42:39
In reply to thanks for the info, and another ? » King Vultan, posted by zeugma on May 25, 2004, at 18:46:57
>
> By the way, do you think clomipramine + stimulant comes as close to an MAOI as is possible without actually taking one? My thought is that it might COMBINE the attributes of Parnate and Nardil. (In this comparison I would also include the GABAergic effects of the clonazepam I also take.)
>
>Well, clomipramine is basically an SSRI with a powerful affinity for serotonin and a relatively low selectivity ratio for 5HT over NE reuptake, meaning that it is also relatively strong as far as increasing norepinephrine transmission. In that respect, I suppose if you added a stimulant, it might come closer to an MAOI than most of the conventional SSRIs, but the same might be said of adding a stimulant to either imipramine or amitriptyline. Both of these blockade NE and 5HT reuptake at roughly the same order of magnitude. You could also make a case for adding a stimulant to Effexor to attempt to simulate an MAOI.
Todd
Posted by Sad Panda on May 27, 2004, at 11:46:34
In reply to Re: wash-out before maoi » zeugma, posted by King Vultan on May 25, 2004, at 14:21:31
>
> >
> > What does your book tell you about the receptor blocking affinities of clomipramine? Probably both 5HT-1A and 5HT 2A blockade is therapeutic for me. The great experiment will be to see what 5HT reuptake inhibition does for me, since I have never taken one long enough to determine the nature of its effects. My hope is that the other actions of clomipramine will make the SRI effects tolerable.
> > >
> >
> >
>
> Clomipramine
>
> NE reuptake............+++
> 5HT reuptake........+++++
> DA reuptake..............+
> Blockade 5HT1.........+
> Blockade 5HT2.......+++
> Blockade ACh.........+++
> Blockade H1...........+++
> Blockade alpha-1....+++
> Blockade alpha-2......+
> Blockade D2............++
>
> where each + represents a difference of one order of magnitude for Ki, ranging from
>
> +++++ represents Ki = 0.1-1.0
> + represents Ki = 1000-10000
>
>
> Todd
>Hi Todd,
If one + equals a range of 1000-10000, then I would say that + and ++ are would be clinically insignificant. Do you think you could put up some data for the other TCA's? I am fascinated that clomipramine gets a ++ for D2 blockade & I'd also like to see the comparison of the different TCA's that this book offers.
Cheers,
Panda.
Posted by zeugma on May 27, 2004, at 20:17:25
In reply to Re: wash-out before maoi » King Vultan, posted by Sad Panda on May 27, 2004, at 11:46:34
> >
> > >
> > > What does your book tell you about the receptor blocking affinities of clomipramine? Probably both 5HT-1A and 5HT 2A blockade is therapeutic for me. The great experiment will be to see what 5HT reuptake inhibition does for me, since I have never taken one long enough to determine the nature of its effects. My hope is that the other actions of clomipramine will make the SRI effects tolerable.
> > > >
> > >
> > >
> >
> > Clomipramine
> >
> > NE reuptake............+++
> > 5HT reuptake........+++++
> > DA reuptake..............+
> > Blockade 5HT1.........+
> > Blockade 5HT2.......+++
> > Blockade ACh.........+++
> > Blockade H1...........+++
> > Blockade alpha-1....+++
> > Blockade alpha-2......+
> > Blockade D2............++
> >
> > where each + represents a difference of one order of magnitude for Ki, ranging from
> >
> > +++++ represents Ki = 0.1-1.0
> > + represents Ki = 1000-10000
> >
> >
> > Todd
> >
>
> Hi Todd,
>
> If one + equals a range of 1000-10000, then I would say that + and ++ are would be clinically insignificant. Do you think you could put up some data for the other TCA's? I am fascinated that clomipramine gets a ++ for D2 blockade & I'd also like to see the comparison of the different TCA's that this book offers.
>
> Cheers,
> Panda.Clomipramine's ++ for D2 blockade is actually unsurprising, given its remarkable structural resemblance to chlorpromazine {Thorazine}; clomipramine actually resembles a cross between imipramine and chlorpromazine, and early investigators seem to have fully expected this drug to be an antipsychotic (of course, all of the tertiary amine TCA's were first tested as AP's, as they all appear on paper to be minor variations on the Thorazine theme).
As to TCA + stimulant simulating an MAOI, while this may crudely be true, on reflection I am more doubtful. I wonder if any who have been on this combination can report on its effects. I also think (simply going on my experiences with nortriptyline and atomoxetine, and KV's contrasting impressions of desipramine and nortriptyline) that the three major tertiary amine TCA's have significant differences between them, and that Effexor would be in a class of its own.
>
>
Posted by Sad Panda on May 29, 2004, at 0:31:22
In reply to TCA-Thorazine resemblances, and more » Sad Panda, posted by zeugma on May 27, 2004, at 20:17:25
> > >
> > > >
> > > > What does your book tell you about the receptor blocking affinities of clomipramine? Probably both 5HT-1A and 5HT 2A blockade is therapeutic for me. The great experiment will be to see what 5HT reuptake inhibition does for me, since I have never taken one long enough to determine the nature of its effects. My hope is that the other actions of clomipramine will make the SRI effects tolerable.
> > > > >
> > > >
> > > >
> > >
> > > Clomipramine
> > >
> > > NE reuptake............+++
> > > 5HT reuptake........+++++
> > > DA reuptake..............+
> > > Blockade 5HT1.........+
> > > Blockade 5HT2.......+++
> > > Blockade ACh.........+++
> > > Blockade H1...........+++
> > > Blockade alpha-1....+++
> > > Blockade alpha-2......+
> > > Blockade D2............++
> > >
> > > where each + represents a difference of one order of magnitude for Ki, ranging from
> > >
> > > +++++ represents Ki = 0.1-1.0
> > > + represents Ki = 1000-10000
> > >
> > >
> > > Todd
> > >
> >
> > Hi Todd,
> >
> > If one + equals a range of 1000-10000, then I would say that + and ++ are would be clinically insignificant. Do you think you could put up some data for the other TCA's? I am fascinated that clomipramine gets a ++ for D2 blockade & I'd also like to see the comparison of the different TCA's that this book offers.
> >
> > Cheers,
> > Panda.
>
> Clomipramine's ++ for D2 blockade is actually unsurprising, given its remarkable structural resemblance to chlorpromazine {Thorazine}; clomipramine actually resembles a cross between imipramine and chlorpromazine, and early investigators seem to have fully expected this drug to be an antipsychotic (of course, all of the tertiary amine TCA's were first tested as AP's, as they all appear on paper to be minor variations on the Thorazine theme).
>
> As to TCA + stimulant simulating an MAOI, while this may crudely be true, on reflection I am more doubtful. I wonder if any who have been on this combination can report on its effects. I also think (simply going on my experiences with nortriptyline and atomoxetine, and KV's contrasting impressions of desipramine and nortriptyline) that the three major tertiary amine TCA's have significant differences between them, and that Effexor would be in a class of its own.
>
>
> >
> >
>
>The differences between desipramine & nortriptyline are similar to the differences between imipramine & amitriptyline. Imipiramine is a weak H1 & 5-HT2A blocker while amitriptyline is potent. Amitriptyline is also a milder SRI than imipramine & clomipramine & can be cautiously combined with MAOI's, although I can't imagine a benefit to this. I would think doxepin or nortriptyline would be the ideal TCA's for useage with MAOI's as both are 5-HT2A bloackers & NRI's with no real SRI activity.
Cheers,
Panda.
Posted by zeugma on May 29, 2004, at 8:49:24
In reply to Re: TCA-Thorazine resemblances, and more » zeugma, posted by Sad Panda on May 29, 2004, at 0:31:22
The differences between desipramine & nortriptyline are similar to the differences between imipramine & amitriptyline. Imipiramine is a weak H1 & 5-HT2A blocker while amitriptyline is potent. Amitriptyline is also a milder SRI than imipramine & clomipramine & can be cautiously combined with MAOI's, although I can't imagine a benefit to this. I would think doxepin or nortriptyline would be the ideal TCA's for useage with MAOI's as both are 5-HT2A bloackers & NRI's with no real SRI activity.
Cheers,
Panda.>>>Panda,
The idea was that AMI, IMI, or CMI combined with a stimulant would simulate an MAOI. I had wanted to switch to CMI because I had suffered a relapse of depression while on nortriptyline as my AD (there's also Strattera but that's another story) and I wanted to try CMI as lowering the dose of NOR made my sleep significantly worse, both in quantity and quality. That plan is in abeyance for now, as my pdoc put the NOR dosage back at 75 mg and plans to do another plasma level test on me after a month at that level again. The change this time is the elimination of buspirone 15 mg at night just before bed, with the goal, if that goes OK, of eliminating buspirone entirely (I now take 15 mg am). The previous goal was eliminating (his preference) or exchanging (my preference- for CMI) the NOR. As that worsened sleep, and didn't help with fatigue or depression, the NOR is going back up to where it was, and he says, depending on the plasma test, that I could go up to 100 mg.
Going back to NOR was my preference if CMI failed, as it definitely helps a LOT with sleep and I have LOTS of sleep problems (I would be fascinated I'm sure by the results of a sleep EEG, but I am short on funds and going to a sleep clinic is not an option currently). He is convinced that noradrenergic meds are the way to treat my depression, and now seems sure that serotonergetic meds would damage my sleep further. From what I've observed personally, and read about here, that is a justified assumption.
Posted by Sad Panda on May 29, 2004, at 13:07:02
In reply to Re: TCA-Thorazine resemblances, and more » Sad Panda, posted by zeugma on May 29, 2004, at 8:49:24
>> The idea was that AMI, IMI, or CMI combined with a stimulant would simulate an MAOI. I had wanted to switch to CMI because I had suffered a relapse of depression while on nortriptyline as my AD (there's also Strattera but that's another story) and I wanted to try CMI as lowering the dose of NOR made my sleep significantly worse, both in quantity and quality. That plan is in abeyance for now, as my pdoc put the NOR dosage back at 75 mg and plans to do another plasma level test on me after a month at that level again. The change this time is the elimination of buspirone 15 mg at night just before bed, with the goal, if that goes OK, of eliminating buspirone entirely (I now take 15 mg am). The previous goal was eliminating (his preference) or exchanging (my preference- for CMI) the NOR. As that worsened sleep, and didn't help with fatigue or depression, the NOR is going back up to where it was, and he says, depending on the plasma test, that I could go up to 100 mg.
>
> Going back to NOR was my preference if CMI failed, as it definitely helps a LOT with sleep and I have LOTS of sleep problems (I would be fascinated I'm sure by the results of a sleep EEG, but I am short on funds and going to a sleep clinic is not an option currently). He is convinced that noradrenergic meds are the way to treat my depression, and now seems sure that serotonergetic meds would damage my sleep further. From what I've observed personally, and read about here, that is a justified assumption.
>
>Hi Zeugma,
You are saying that Clomipramine caused your sleep to detriorate? That's a little surprising as it is a stronger 5-HT2A blocker than Nortryptyline. Clomipramine is a weaker H1 blocker, so it would be less sedating initially.
Cheers,
Panda.
Posted by zeugma on May 29, 2004, at 13:39:05
In reply to Re: TCA-Thorazine resemblances, and more » zeugma, posted by Sad Panda on May 29, 2004, at 13:07:02
Hi Zeugma,
You are saying that Clomipramine caused your sleep to detriorate? That's a little surprising as it is a stronger 5-HT2A blocker than Nortryptyline. Clomipramine is a weaker H1 blocker, so it would be less sedating initially.
Cheers,
Panda.Panda,
Sorry if I expressed myself a little unclearly. When I visited my pdoc yesterday my regimen was 50 mg nortriptyline plus the other stuff (Strattera, buspirone, clonazepam). Four psychotropic meds in all, no CMI. I had experienced a relapse due to exogeneous factors (an incident precipitating depression) which led me to believe that I was still at risk for a prolonged major depressive episode which I dread. Besides, a month of major depression by itself can cause panic. Last month I saw my pdoc and said I felt my then-current meds weren't working right, and I mentioned fatigue as a primary symptom which was causing distress, and which I was convinced made vulnerable to this exogeneous depression.
We decided to lower the NOR first, as a likely culprit for fatigue. I mentioned CMI at this point, and he said that would be possible depending on how the dose reduction of NOR went. Well, there were the usual problems that come with reducing the dose of any med, which did not alarm me, as they are normal. But the sleep difficulties persisted, and not merely difficulty initiating sleep, but less restful sleep overall. And my energy level was as low as ever. Plus, my ADD symptoms started coming back, indicating that the NOR was potentiating the Strattera in some way. Depression is bad enough, but depression plus returned ADD goes beyond words. So he told me to put the NOR back where it was, at 75 mg. The idea is to help both the sleep and ADD symptoms.
The thing that surprised me most about my experience has been the fact that NOR reduction seemed to weaken the Strattera too. (The two drugs 'feel' very different to me despite the fact that they are both NET inhibitors, and my pdoc believes they work on different portions of the brain, so he strongly advocates their co-use in my case despite the apparent redundancy. He nodded knowingly when I told him about the NOR weakening the Strattera effect. On the other hand, my anxiety has been controlled by 1 mg clonazepam, and there have been only subtle signs of increased anxiety during the past month [NOR does have some kind of hard-to-characterize anxiolytic effect] unlike the not-subtle signs of returned ADD- I locked myself out of my apt. for the first time in years this month!).
All this is long-winded, and I need some coffee :) The upshot is that the next move will be, if the buspirone discontinuation goes through, the ratio of NOR to Strattera will be played with (i.e., raing NOR and lowering Strattera). The Strattera could be increasing my fatigue. Once the NOR, Strattera, and clonazepam are at their proper balance, then maybe a stimulant to deal with the fatigue. That's if all goes {reasonably) well.
Posted by zeugma on May 29, 2004, at 13:47:58
In reply to Re: TCA-Thorazine resemblances, and more » zeugma, posted by Sad Panda on May 29, 2004, at 13:07:02
as I said just now, I need coffee, so I am not going to be long-winded :) But drugs that affect serotonin in a way that increases synaptic availability can cause sleep disruption in people not disposed to this prior to taking the med. Hence the popularity of Remeron, trazodone, small doses of doxepin, etc., to counter SSRI sleep disruption. Well, I have sleep disruption to begin with, and so I think my pdoc is wary of introducing CMI at this point since simply lowering the NOR dose caused a return of these problems. CMI may be a stronger 2a blocker than NOR, but NOR has 2a blockade plus weaker SRI effect, and it is in fact supported by studies that NOR produces much less sleep disruption than CMI. CMI is in fact in a category of its own among TCA's for sleep disruption, although it probably causes less than SSRI's or Effexor.
Posted by Sad Panda on May 30, 2004, at 2:42:08
In reply to Re: TCA-Thorazine resemblances, and more » Sad Panda, posted by zeugma on May 29, 2004, at 13:39:05
> Sorry if I expressed myself a little unclearly. When I visited my pdoc yesterday my regimen was 50 mg nortriptyline plus the other stuff (Strattera, buspirone, clonazepam). Four psychotropic meds in all, no CMI. I had experienced a relapse due to exogeneous factors (an incident precipitating depression) which led me to believe that I was still at risk for a prolonged major depressive episode which I dread. Besides, a month of major depression by itself can cause panic. Last month I saw my pdoc and said I felt my then-current meds weren't working right, and I mentioned fatigue as a primary symptom which was causing distress, and which I was convinced made vulnerable to this exogeneous depression.
>
> We decided to lower the NOR first, as a likely culprit for fatigue. I mentioned CMI at this point, and he said that would be possible depending on how the dose reduction of NOR went. Well, there were the usual problems that come with reducing the dose of any med, which did not alarm me, as they are normal. But the sleep difficulties persisted, and not merely difficulty initiating sleep, but less restful sleep overall. And my energy level was as low as ever. Plus, my ADD symptoms started coming back, indicating that the NOR was potentiating the Strattera in some way. Depression is bad enough, but depression plus returned ADD goes beyond words. So he told me to put the NOR back where it was, at 75 mg. The idea is to help both the sleep and ADD symptoms.
>
> The thing that surprised me most about my experience has been the fact that NOR reduction seemed to weaken the Strattera too. (The two drugs 'feel' very different to me despite the fact that they are both NET inhibitors, and my pdoc believes they work on different portions of the brain, so he strongly advocates their co-use in my case despite the apparent redundancy. He nodded knowingly when I told him about the NOR weakening the Strattera effect. On the other hand, my anxiety has been controlled by 1 mg clonazepam, and there have been only subtle signs of increased anxiety during the past month [NOR does have some kind of hard-to-characterize anxiolytic effect] unlike the not-subtle signs of returned ADD- I locked myself out of my apt. for the first time in years this month!).
>
> All this is long-winded, and I need some coffee :) The upshot is that the next move will be, if the buspirone discontinuation goes through, the ratio of NOR to Strattera will be played with (i.e., raing NOR and lowering Strattera). The Strattera could be increasing my fatigue. Once the NOR, Strattera, and clonazepam are at their proper balance, then maybe a stimulant to deal with the fatigue. That's if all goes {reasonably) well.
>
>
>I would still be keen to try Clomipramine, it would be so easy to swap to it & swap back if it was no good. Either way I would take the full blood tested doseage of Clomipramine or Nortriptyline & then you could have a lower doseage of Strattera & maybe take Klonopin PRN. Amitriptyline probably has the best balance between 5-HT & NE, but it's M1 blocking ability is brutual & probably not the best thing for a student trying to remember something or you like going to the toilet more than once a week. :)
Cheers,
Panda.
Posted by King Vultan on May 30, 2004, at 11:22:41
In reply to Re: wash-out before maoi » King Vultan, posted by Sad Panda on May 27, 2004, at 11:46:34
> >
>
> Hi Todd,
>
> If one + equals a range of 1000-10000, then I would say that + and ++ are would be clinically insignificant. Do you think you could put up some data for the other TCA's? I am fascinated that clomipramine gets a ++ for D2 blockade & I'd also like to see the comparison of the different TCA's that this book offers.
>
> Cheers,
> Panda.
>
>Well, it's a little tedious transcribing the receptor info just for one drug, let alone all of them. You may want to consider getting the book yourself, as it has a wealth of information in it. I actually got it because my local Barnes & Noble had it, and I was fascinated by the receptor chart. It is interesting, but bear in mind that it is based on classic studies from the 90's involving rodent tissue. I have other data derived from human cadaver tissue that suggests that the TCAs may be more serotonergic in people than they are in rats or mice. The pharmacology of psychotropic drugs does seem to vary depending on which particular study you are looking at.
Todd
Posted by zeugma on May 30, 2004, at 15:33:09
In reply to Re: TCA-Thorazine resemblances, and more » zeugma, posted by Sad Panda on May 30, 2004, at 2:42:08
yes I was curious about the effect of CMI, but first and foremost i want to be and stay well (as far as that's poss.), and it seems my pdoc knows what he's doing. my current depression is exogeneous, brought on by 'subsyndromal' depressive symptoms. now, look at this study:
http://ajp.psychiatryonline.org/cgi/content/full/156/8/1177
it shows how sensitive nortriptyline plasma levels are to the presence or not of 'subsyndromal' symptoms. i have not had plasma levels done on nortrip at 75 mg in years. things have changed a lot since then (concomitant meds, age, brand vs. generic) plus this study delimits a stricter window than most guidelines recommend.
Posted by Chairman_MAO on May 30, 2004, at 22:42:35
In reply to Re: TCA-Thorazine resemblances, and more » Sad Panda, posted by zeugma on May 29, 2004, at 13:39:05
In re: "emulating" an MAOI:
Reuptake inhibition and/or enhancement of release, speaking of antidepressants and stimulants, does not produce the same effect as MAO inhibition. MAO-A is present intraneuronally, and so inhibiton thereof produces a rise in the intraneuronal transmitter levels, not just those in the synaptic cleft. Perhaps this has to do with the MAOIs being so robust, or it could be simply that they're just damn potent mood elevators! I am not a neuropsychopharmacologist, so I cannot begin to tell you the relevance this has to anything pertitent to psyhcological health. In fact, I am not sure that human beings possess the epistemic faculties to ever comprehend it! :)
This obviously could be involved in the mechanics of adding TCAs and stimulants to MAOIs.
MAO-B, interestingly enough, is only present outside neurons. I _think_ all of this is correct, at least. There are plenty of people on here with more knowledge on this topic than I have. We need them in THIS discussion! My Effexor-crippled intellect can only muster so much strength tonight.
This is the end of the thread.
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.