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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by viper1431 on August 1, 2009, at 2:56:37
I was reading this site and this particular part has me interested, table 3.7
http://www.preskorn.com/books/ssri_s3.html#tab3-7I was wondering if anyone happens to know the figures if imipramine was in that table ?
I'm mostly interested in Usually Effective Dose (mg/day)* and the Inhibition of 5-HT Uptake Pump (%) part.cheers
Posted by SLS on August 1, 2009, at 6:18:43
In reply to imipramine ) Inhibition of 5-HT Uptake Pump (%), posted by viper1431 on August 1, 2009, at 2:56:37
> I was reading this site and this particular part has me interested, table 3.7
> http://www.preskorn.com/books/ssri_s3.html#tab3-7
>
> I was wondering if anyone happens to know the figures if imipramine was in that table ?
> I'm mostly interested in Usually Effective Dose (mg/day)* and the Inhibition of 5-HT Uptake Pump (%) part.
>
> cheersMaybe you can ask Bulldog for more information:
http://www.dr-bob.org/babble/20090721/msgs/909504.html
Traditionally:
100-200mg for outpatients.
200-300mg for inpatients.I would target 150mg first, starting at 25-50mg.
I need 300+ mg because I am severely depressed and a rapid metabolizer (CYP P450 2D6). I am currently taking 150mg of nortriptyline, which is quite high.
- Scott
Posted by Brainbeard on August 18, 2009, at 4:31:06
In reply to Re: imipramine ) Inhibition of 5-HT Uptake Pump (%), posted by SLS on August 1, 2009, at 6:18:43
I can't find it right now, but Dr. Ken Gillman had a table suggesting that imipramine was in between citalopram (Celexa, less strong) and fluvoxamine (Luvox, stronger!) as for SRI potency.
I have been wondering myself how much imipramine would be necessary to reach the usual 80% 5HT receptor occupation. I don't know how 5HT receptor affinity relates to drug concentration, but if 50mg of citalopram is enough to reach about 80% 5HT occupancy, and 150mg of fluvoxamine is enough, and imipramine ranks in between, might it be that about 75mg of imipramine might be enough for some serious SRI? Or am I being an irresponsible amateur dumb *ss here?
Posted by Brainbeard on August 18, 2009, at 4:32:07
In reply to Re: imipramine ) Inhibition of 5-HT Uptake Pump (%), posted by Brainbeard on August 18, 2009, at 4:31:06
Sorry, I wasn't completely clear: according to Gillman, imipramine is *less* strong than citalopram, but *stronger* than fluvoxamine.
Posted by sowhysosad on September 15, 2009, at 22:00:46
In reply to Re: imipramine ) Inhibition of 5-HT Uptake Pump (%), posted by Brainbeard on August 18, 2009, at 4:31:06
> I can't find it right now, but Dr. Ken Gillman had a table suggesting that imipramine was in between citalopram (Celexa, less strong) and fluvoxamine (Luvox, stronger!) as for SRI potency.
According to Preskorn it has less affinity for the serotonin uptake pump than all of the SSRI's but is equal to venlafaxine.
> I have been wondering myself how much imipramine would be necessary to reach the usual 80% 5HT receptor occupation. I don't know how 5HT receptor affinity relates to drug concentration, but if 50mg of citalopram is enough to reach about 80% 5HT occupancy, and 150mg of fluvoxamine is enough, and imipramine ranks in between, might it be that about 75mg of imipramine might be enough for some serious SRI? Or am I being an irresponsible amateur dumb *ss here?
It has stronger affinity for the noradrenaline uptake pump than for serotonin. Presumably you'd need to achieve almost 100% occupancy of the noradrenaline pump before the serotonin kicked in.
Certainly when I took 150mg I felt the agitated panicky noradrenaline effects but couldn't discern any serotonin.
It's active metabolite, desipramine, is also an NRI not an SSRI/SNRI, so I wonder if that would also affect things?
Posted by Brainbeard on September 16, 2009, at 8:42:46
In reply to Re: imipramine ) Inhibition of 5-HT Uptake Pump (%), posted by sowhysosad on September 15, 2009, at 22:00:46
> According to Preskorn it [imipramine, BB] has less affinity for the serotonin uptake pump than all of the SSRI's but is equal to venlafaxine.
That ain't right. Are you sure Preskorn said that? Got a link? Look at the table in this article by Gillman: http://www.psychotropical.com/Dual_action_drugs.shtml. Imipramine has an affinity for 5HT between 1.3 and 20, whereas venlafaxine has an affinity between 7.5 and 102 (the lower the number, the higher the affinity). Imipramine is obviously a much more potent SRI than venlafaxine (Effexor).
Ah, here is the article I was referring to: http://www.psychotropical.com/Antidepressants_Receptor_affinities_1.shtml
Gillman gives this list:
'Potency as 5 HT reuptake inhibitors (highest to lowest)
Paroxetine 0.13 Clomipramine 0.28
Sertraline 0.29 Fluoxetine 0.81
Citalopram 1.16 Imipramine 1.4Fluvoxamine 2.2 Amitriptyline 4.3
Dothiepin 8.6 Venlafaxine 8.9'Here you can see that fluvoxamine (Luvox) ranks lower than imipramine for SRI potency, while venlafaxine ranks absolute lowest of all the SRI's. Venlafaxine is a bit of a mystery, since it is known to be able to cause serotonin syndrome, while its affinity for 5HT (serotonin) is actually pretty weak. There may be some other, unknown mechanism at play.
> It [imipramine, BB] has stronger affinity for the noradrenaline uptake pump than for serotonin. Presumably you'd need to achieve almost 100% occupancy of the noradrenaline pump before the serotonin kicked in.No, imipramine is a moderate SRI, so the serotonin will kick in soon enough. At the usual therapeutic doses (say, 150mg), full SRI will certainly be at play.
> Certainly when I took 150mg I felt the agitated panicky noradrenaline effects but couldn't discern any serotonin.
Despite your experience, the fact that imipramine causes sexual dysfunction in therapeutical doses illustrates that it has potent SRI action. The sexual dysfunction is a typical effect of SRI. Fluvoxamine causes the least sexual dysfunction of all (S)SRI's, which is not surprising seeing that it is weaker than imipramine.
> It's active metabolite, desipramine, is also an NRI not an SSRI/SNRI, so I wonder if that would also affect things?
The NRI, which is indeed strong with imipramine, might overshadow the SRI (which doesn't mean that it's not there).
Cheers,
Brainbeard
Posted by sowhysosad on September 16, 2009, at 11:54:19
In reply to Re: imipramine ) Inhibition of 5-HT Uptake Pump (%), posted by Brainbeard on September 16, 2009, at 8:42:46
> > According to Preskorn it [imipramine, BB] has less affinity for the serotonin uptake pump than all of the SSRI's but is equal to venlafaxine.
>
> That ain't right. Are you sure Preskorn said that? Got a link?http://www.preskorn.com/books/omd_s6.html
Figures 6.3 and 6.4 on that page.
> Despite your experience, the fact that imipramine causes sexual dysfunction in therapeutical doses illustrates that it has potent SRI action.Good point. I think I had some problems in that area, plus some erectile dysfunction which I believe was caused by hypotension.
> Fluvoxamine causes the least sexual dysfunction of all (S)SRI's, which is not surprising seeing that it is weaker than imipramine.A lot of people claim escitalopram causes the least but - in line with your reasoning - some data show it's a fairly weak (but very selective) SRI.
> The NRI, which is indeed strong with imipramine, might overshadow the SRI (which doesn't mean that it's not there).Yeah, you could well be right.
Posted by Brainbeard on September 16, 2009, at 13:06:04
In reply to Re: imipramine ) Inhibition of 5-HT Uptake Pump (%) » Brainbeard, posted by sowhysosad on September 16, 2009, at 11:54:19
>
> http://www.preskorn.com/books/omd_s6.html
>
> Figures 6.3 and 6.4 on that page.I can't find the potency data for imipramine anywhere on the page!
>
> A lot of people claim escitalopram causes the least [sexual dysfunction] but - in line with your reasoning - some data show it's a fairly weak (but very selective) SRI.Well, I think you mean citalopram (Celexa) - that indeed is a rather weak SSRI. Escitalopram (Lexapro) on the other hand is truly the most selective and potent SSRI. I suspect that claims about less sexual side-effects are the result of marketing hype and myth-building rather than an accurate representation of reality. Since escitalopram is the strongest SSRI, it is bound to have the strongest serotonergic side-effects, i.e. the worst sexual dysfunction of all SSRI's.
(People sometimes forget, while scapegoating the SSRI's, that the older tricyclic clomipramine, which is a highly potent SRI, also is able to cause big time sexual dysfunction. Clomipramine was worse in this regard for me than any SSRI I've been on.)There are forum discussions supportive of my reasoning that Lexapro should rather be worse than better when it comes to sexual dysfunction: http://www.drugs.com/forum/featured-conditions/longterm-lexapro-sexual-side-effects-33868.html (beware, this discussion has a wild tale about Lexapro lingering in the liver for more than a year - hilarious!); http://www.topix.com/forum/drug/lexapro/TD58CPM2FST9IN7NM; http://www.dr-bob.org/babble/20040412/msgs/336801.html...
Posted by sowhysosad on September 16, 2009, at 20:07:44
In reply to Re: imipramine ) Inhibition of 5-HT Uptake Pump (%), posted by Brainbeard on September 16, 2009, at 13:06:04
> I can't find the potency data for imipramine anywhere on the page!
Oops! Botched link! Try figures 6.3 and 6.4 here:
http://www.preskorn.com/books/omd_s6.html#fig6-3
> Escitalopram (Lexapro) on the other hand is truly the most selective and potent SSRI.
I can't find any data for escitalopram but do I recall reading it's not the most potent SRI in terms of affinity for the serotonin uptake pump - sertraline or paroxetine would claim that title.
The only sources I can find claiming escitalopram is the most potent SSRI are Lundbeck's own literature, and forums where the claim isn't backed up with any data.
Its selectivity - not affinity - for the 5-HT pump is what makes it unusual amongst SSRI's as far as I'm aware.
I may well be wrong though - does anyone have any data?
> I suspect that claims about less sexual side-effects are the result of marketing hype and myth-building rather than an accurate representation of reality.Again I've no hard evidence but, anecdotally, some people on Babble claim it's caused them the least sexual sides of all the SRI's.
Certainly sexual issues were minimal for me at 10mg, but more troublesome at 20. Still way better than fluoxetine or paroxetine in that respect though.
Posted by Brainbeard on September 17, 2009, at 12:43:44
In reply to Re: imipramine ) Inhibition of 5-HT Uptake Pump (%) » Brainbeard, posted by sowhysosad on September 16, 2009, at 20:07:44
Preskorn seems to rely on different research findings than Gillman concerning imipramine's potency as an SRI.
I couldn't find comparative data on the SSRIs' affinity for 5HT including escitalopram anywhere. The claim that it has the highest affinity is all over the internet, but indeed without backup references.
Posted by sowhysosad on September 17, 2009, at 20:53:13
In reply to Re: imipramine ) Inhibition of 5-HT Uptake Pump (%), posted by Brainbeard on September 17, 2009, at 12:43:44
> Preskorn seems to rely on different research findings than Gillman concerning imipramine's potency as an SRI.
Yeah, there's quite a bit of variation in data depending on which source you believe.
But sertraline or paroxetine always seem to come out tops in terms of SRI potency regardless of the source.
> I couldn't find comparative data on the SSRIs' affinity for 5HT including escitalopram anywhere. The claim that it has the highest affinity is all over the internet, but indeed without backup references.
It could just be people repeating Lundbeck's marketing blurb, or confusing "potency" with "selectivity".
This is the end of the thread.
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