Posted by Jonathan on August 28, 2000, at 19:15:38
In reply to Ondansetron: For SSRI fatigue and memory loss, posted by AndrewB on August 22, 2000, at 9:49:47
> Ondansetron may be very effective for SSRI induced memory loss.
>
> Myself and another person have taken it and noted it creates a clear headed arousal.
>
> Studies on specific populations have shown it effective at ameliorating fatigue and improving memory.
>
> Ondansetron is a 5HT3 serotonin receptor antagonist. Overstimulation of the 5HT3 receptor, I speculate, may often be at the root of SSRI induced fatigue, fogginess and memory loss.
>
> I have not noticed any side effects with ondansetron.
>
> It is fast acting, working within an hour.
>Andrew,
Thanks. This is a fascinating idea. Where did you find this information?
I'm a little puzzled because SSRI-induced fatigue and memory impairment are slow in onset and seem to persist for weeks after discontinuation. I forget where (guess why!), but am almost sure I remember reading somewhere that this slow time-course matches an SRI-induced decline and recovery in dopamine and/or noradrenaline turnover in the pre-frontal cortex. As far as I know the 5-HT3 receptor has an immediate modulating effect on cholinergic neurotransmission, consistent with the rapid action of ondansetron. Although reducing 5-HT3 receptor activity below that normally resulting from endogenous serotonin levels undeniably enhances cognitive performance, I've not seen evidence for the reverse: a *rapid-onset* cognitive decline caused by increased 5-HT3 activity when an SRI increases serotonin above its normal endogenous level. The crucial test will come when the same person has tried ondansetron both when taking and when not taking an SSRI.
The reason I'd like to know is because my pdoc told me about a year ago (incorrectly, in my view) that Prozac cannot cause cognitive impairment: since there's also no such thing as adult ADD here in the UK, he attributed my symptoms entirely to depression. In April I discontinued venlafaxine (Effexor), and persuaded a new pdoc to prescribe reboxetine instead, because Effexor at 225 mg/day seemed to cause even greater cognitive impairment than 20 mg/day Prozac had (Effexor is supposed not to be as bad as Prozac in this respect, but we're comparing a high dose of Effexor with a low dose of Prozac, in terms of SRI activity) -- It afected me so badly that it took me no less than eight months to notice that we spell "Efexor" differently here!
Reboxetine has recently stopped working so well, so I'm seeing yet another pdoc soon (no. 5) and am concerned that he may recommend switching back to an SRI. It would be great if I could go prepared with evidence that not only can serotonin cause cognitive impairment, but this side-effect is so well characterized that we even know which receptor is responsible (namely 5HT-3?).
By the way, both my original depressive episode (Feb. '99) and the recent relapse followed a few weeks after accidental injuries which would have raised my levels of CRF, ACTH and cortisol. Do you think that an AD that elevates dopamine levels, such as low-dose amisulpride, would be a good way to get my HPA axis back to normal quickly, and perhaps even get reboxetine working again? I'm reluctant to give it up because, as well as being the only antidepressant I've tried that really works for me, it's the only one that has no significant side-effects (which probably shows how dysfunctional my noradrenergic system must be).
Jonathan.
poster:Jonathan
thread:43509
URL: http://www.dr-bob.org/babble/20000822/msgs/43947.html