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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 12 of 12. This is the beginning of the thread.
Posted by ace on March 3, 2004, at 20:50:02
I remember when I started Anafranil ages back, it caused a sever depression after 2/3 days on 25mg.
Has anyone ever experienced this and, if so, does the depression pass, and the AD effect take over?
Cheers,
Ace
Posted by Thereishope on March 3, 2004, at 21:00:40
In reply to Anyone suffer paradoxical depression with TCAs?, posted by ace on March 3, 2004, at 20:50:02
I experienced this with Zoloft. In my case the anxiety, depression, derealization became worst. I stuck it out for over a month...Ugh...I don't even want to think about that time in my life.
> I remember when I started Anafranil ages back, it caused a sever depression after 2/3 days on 25mg.
>
> Has anyone ever experienced this and, if so, does the depression pass, and the AD effect take over?
>
> Cheers,
> Ace
Posted by socialdeviantjeff on March 3, 2004, at 22:21:41
In reply to Re: Anyone suffer paradoxical depression with TCAs? » ace, posted by Thereishope on March 3, 2004, at 21:00:40
After 2 days of Amitriptaline and Desimpramine, I had a full blown psychotic episode. I was depressed for several days after discontinuation.
Posted by King Vultan on March 4, 2004, at 8:17:25
In reply to Anyone suffer paradoxical depression with TCAs?, posted by ace on March 3, 2004, at 20:50:02
> I remember when I started Anafranil ages back, it caused a sever depression after 2/3 days on 25mg.
>
> Has anyone ever experienced this and, if so, does the depression pass, and the AD effect take over?
>
> Cheers,
> Ace
IMO, SSRIs would be more likely to cause a paradoxical depression than tricyclics in general. Why? The initial target of SSRIs is the presynaptic serotonin 1A receptor, which is inhibitory. Blocking serotonin reuptake causes these receptors to be pummelled with serotonin. If a person is so depressed that their serotonin neurons aren't really firing anyway, a person won't notice any immediate change in mood, but if a person's serotonin neurons are still firing at a moderate level, the stimulation of these inhibitory 1A receptors may cause the serotonin neuron to slow down its firing rate, triggering a worse depression.I have taken both SSRIs and tricyclics and looked into their psychopharmacology in some detail, and my opinion is that the tricyclics are less likely to cause a paradoxical depression, this because of their blockade of norepinephrine reuptake. That be said, Anafranil is the lone TCA that is also an SSRI, but it is much less selective than are typical SSRIs. The other tricyclics either blockade both serotonin and norepinephrine reuptake (amitriptyline, imipramine) or selectively inhibit norepinephrine reuptake (nortriptyline, desipramine, protriptyline).
Todd
Posted by Sad Panda on March 4, 2004, at 11:19:41
In reply to Re: Anyone suffer paradoxical depression with TCAs?, posted by King Vultan on March 4, 2004, at 8:17:25
> > I remember when I started Anafranil ages back, it caused a sever depression after 2/3 days on 25mg.
> >
> > Has anyone ever experienced this and, if so, does the depression pass, and the AD effect take over?
> >
> > Cheers,
> > Ace
>
>
> IMO, SSRIs would be more likely to cause a paradoxical depression than tricyclics in general. Why? The initial target of SSRIs is the presynaptic serotonin 1A receptor, which is inhibitory. Blocking serotonin reuptake causes these receptors to be pummelled with serotonin. If a person is so depressed that their serotonin neurons aren't really firing anyway, a person won't notice any immediate change in mood, but if a person's serotonin neurons are still firing at a moderate level, the stimulation of these inhibitory 1A receptors may cause the serotonin neuron to slow down its firing rate, triggering a worse depression.
>
> I have taken both SSRIs and tricyclics and looked into their psychopharmacology in some detail, and my opinion is that the tricyclics are less likely to cause a paradoxical depression, this because of their blockade of norepinephrine reuptake. That be said, Anafranil is the lone TCA that is also an SSRI, but it is much less selective than are typical SSRIs. The other tricyclics either blockade both serotonin and norepinephrine reuptake (amitriptyline, imipramine) or selectively inhibit norepinephrine reuptake (nortriptyline, desipramine, protriptyline).
>
> Todd
>Clomipramine is a potent NE reuptake inhibitor too. Clomipramine, Imipramine, Amitriptyline, Dothepin & Doxepin are very similar in their NE reuptake blocking ability.
Cheers,
Panda.
Posted by King Vultan on March 4, 2004, at 12:56:23
In reply to Re: Anyone suffer paradoxical depression with TCAs? » King Vultan, posted by Sad Panda on March 4, 2004, at 11:19:41
> >
>
> Clomipramine is a potent NE reuptake inhibitor too. Clomipramine, Imipramine, Amitriptyline, Dothepin & Doxepin are very similar in their NE reuptake blocking ability.
>
> Cheers,
> Panda.
>
>In absolute terms, clomipramine's affinity for the NE reuptake transporter is roughly the same as that of amitriptyline and imipramine, but it is about an order of magnitude less than its affinity for blocking serotonin reuptake. OTOH, imipramine and amitriptyline block serotonin and norepinephrine reuptake at roughly the same order of magnitude.
I do not know what Dothepin is, but in vitro, doxepin is slightly weaker in absolute terms in its affinity for the NE reuptake transporter than any of the drugs listed above. In vivo, it is drastically weaker than any of these drugs because doxepin's main pharmacological action is blocking histamine H1 receptors, at which it is one of the most powerful drugs available. Because doxepin's action at blockading NE reuptake lies about three orders of magnitude below its histamine blockade (based on the dissociation constants generated from Richelson's and Seeman's classic studies), doxepin has little or no effect on blocking NE reuptake in the real world, at least at reasonable dosages.
Todd
Posted by SLS on March 4, 2004, at 14:44:05
In reply to Anyone suffer paradoxical depression with TCAs?, posted by ace on March 3, 2004, at 20:50:02
> I remember when I started Anafranil ages back, it caused a sever depression after 2/3 days on 25mg.
>
> Has anyone ever experienced this and, if so, does the depression pass, and the AD effect take over?
Protriptyline dramatically exacerbated my depression. Amoxapine made me feel mildly worse. The drug that made me feel the worst was moclobemide.What's up?
- Scott
Posted by sb417 on March 5, 2004, at 2:02:16
In reply to Re: Anyone suffer paradoxical depression with TCAs?, posted by King Vultan on March 4, 2004, at 8:17:25
> > > IMO, SSRIs would be more likely to cause a paradoxical depression than tricyclics in general. Why? The initial target of SSRIs is the presynaptic serotonin 1A receptor, which is inhibitory. Blocking serotonin reuptake causes these receptors to be pummelled with serotonin. If a person is so depressed that their serotonin neurons aren't really firing anyway, a person won't notice any immediate change in mood, but if a person's serotonin neurons are still firing at a moderate level, the stimulation of these inhibitory 1A receptors may cause the serotonin neuron to slow down its firing rate, triggering a worse depression.
>
>Todd, that is very interesting. How would you explain a somewhat favorable response to an ssri initially, but a severe worsening of the depression 10 days to two weeks after starting the ssri?
Posted by Sad Panda on March 5, 2004, at 3:55:35
In reply to Re: Anyone suffer paradoxical depression with TCAs?, posted by King Vultan on March 4, 2004, at 12:56:23
> > >
> >
> > Clomipramine is a potent NE reuptake inhibitor too. Clomipramine, Imipramine, Amitriptyline, Dothepin & Doxepin are very similar in their NE reuptake blocking ability.
> >
> > Cheers,
> > Panda.
> >
> >
>
> In absolute terms, clomipramine's affinity for the NE reuptake transporter is roughly the same as that of amitriptyline and imipramine, but it is about an order of magnitude less than its affinity for blocking serotonin reuptake. OTOH, imipramine and amitriptyline block serotonin and norepinephrine reuptake at roughly the same order of magnitude.
>
> I do not know what Dothepin is, but in vitro, doxepin is slightly weaker in absolute terms in its affinity for the NE reuptake transporter than any of the drugs listed above. In vivo, it is drastically weaker than any of these drugs because doxepin's main pharmacological action is blocking histamine H1 receptors, at which it is one of the most powerful drugs available. Because doxepin's action at blockading NE reuptake lies about three orders of magnitude below its histamine blockade (based on the dissociation constants generated from Richelson's and Seeman's classic studies), doxepin has little or no effect on blocking NE reuptake in the real world, at least at reasonable dosages.
>
> Todd
>Hi Todd,
Data I have seen on the web indicates that Doxepin is actually the stongest of the Tertiary TCA's with with regard to NE reuptake blocking, however, they are all weak NE reuptake blockers when compared to their H1 blocking abilities.
Dothepin is sulphated Amitriptyline. (Doxepin is oxygenated Amitriptyline). It was Britans most popular TCA primarily becuase it is a weak A1 blocker & causes very minimal orthostatic hypotension, whoever, it is by far the most toxic of TCA's being about twice as toxic is Amitriptyline which itself is far more toxic than Clomipramine.
Cheers,
Panda.
Posted by King Vultan on March 5, 2004, at 11:11:36
In reply to Re: Anyone suffer paradoxical depression with TCAs? » King Vultan, posted by sb417 on March 5, 2004, at 2:02:16
> > > > IMO, SSRIs would be more likely to cause a paradoxical depression than tricyclics in general. Why? The initial target of SSRIs is the presynaptic serotonin 1A receptor, which is inhibitory. Blocking serotonin reuptake causes these receptors to be pummelled with serotonin. If a person is so depressed that their serotonin neurons aren't really firing anyway, a person won't notice any immediate change in mood, but if a person's serotonin neurons are still firing at a moderate level, the stimulation of these inhibitory 1A receptors may cause the serotonin neuron to slow down its firing rate, triggering a worse depression.
> >
> >
>
> Todd, that is very interesting. How would you explain a somewhat favorable response to an ssri initially, but a severe worsening of the depression 10 days to two weeks after starting the ssri?
I suppose one could imagine a case where a person has a small amount of serotonin available, and with the SSRI blocking reuptake, less serotonin is reabsorbed into the neuron and more makes it to its postsynaptic target (this is a postsynaptic receptor confusingly labeled as 1A also, but it is not inhibitory as is the presynaptic 1A autoreceptor). The stimulation of this receptor causes an immediate improvement in mood.However, some of the extra serotonin that is available from blocking reuptake also begins stimulating the presynaptic 1A autoreceptor. This has the effect of slowing down the firing rate of the serotonin neuron, causing an increase in depression, perhaps even to a point where a person is more depressed then before he began therapy.
Todd
Posted by sb417 on March 6, 2004, at 0:09:30
In reply to Re: Anyone suffer paradoxical depression with TCAs?, posted by King Vultan on March 5, 2004, at 11:11:36
Todd, thanks very much for that explanation. I do badly on ssri's, but the first time I took Celexa, I did well for about 12 days. After that, I became severely depressed, and regardless of how much I raised or lowered the dose over several months, I never benefited from that medicine. For me, Celexa is one of the worst medicines ever made. It's poison for me. It magnifies every aspect of my depression.
Posted by Thereishope on March 6, 2004, at 12:05:29
In reply to Re: Anyone suffer paradoxical depression with TCAs? » King Vultan, posted by sb417 on March 6, 2004, at 0:09:30
Went through the same thing with Paxil. Seven wonderful days...ahh...then day 8...AHHHHHH! Zoloft was horrible from day 1.
> Todd, thanks very much for that explanation. I do badly on ssri's, but the first time I took Celexa, I did well for about 12 days. After that, I became severely depressed, and regardless of how much I raised or lowered the dose over several months, I never benefited from that medicine. For me, Celexa is one of the worst medicines ever made. It's poison for me. It magnifies every aspect of my depression.
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