Posted by Marty on July 28, 2008, at 0:17:50
In reply to Extremely depressed, advices needed!, posted by Maximus on July 27, 2008, at 13:38:53
Hi Maximus,As you already know we can only speculate very oversimplistic and naive theory about what's going on. But here's a cute (naive) idea I can come with on the top of my head:
Norepinephrine (NE). You have 2 drugs interacting with those receptor: Lithium which decrease the release of NE and Duloxetine which inhibit its reuptake. Here's how I can imagine NE to be implicated in your crash...
1. BEFORE Lowering Lithium : Lithium decrease the NE 'signal' while Duloxetine amplify it. Your NE receptors are desensitized by the 'increased NE' level caused by Duloxetine in your synaptic gap.
The desensitization level stabilize to a "Lithium(-NE)+Duloxetine(+NE)" sensitivity. Your brain adapts itself to this 'new' level of NE activity.
2. AFTER Lowering Lithium : Lithium NE release inhibition is decreased and so NE release increase. NE receptors desensitize more than before and to an extend greatly magnifigned by the NE reuptake inhibition induced by Duloxetine. More NE release + not-yet-stabilized level of NE desensitization (no dulling/flatening reuptake inhbition receptor desensitization induced effet yet) = Feeling better, feeling more alive. Yet your BP is crawling back and you sense it, but somethings feels better. = in part NE.3. After RISING Lithium again : Let's call this the 'NE Crash'. Your NE receptors are way more desensitized than while you was in #1 by what happened in #2 and so now rising your Lithium to #1 level brings back an NE release inhibition that your NE-numb receptors find hard to deal with. ... And here you have your NE Crash.
If this is happening AND significant at all it could only be a part of the whole thing. Lithium and Duloxetine both plays also with Serotonin where Li increase its synthesis and Duloxetine inhibit its reuptake.. that's just another thing one could try to see how it played into what's happening to you. Could it be possible that 5-HT2a/2c sensitized while your lithium holiday and now that the serotonergic effect of lithium is back those 2a/2c are hitten too strongly for your brain taste ? Not sure how your antipsychotic modulate this in his 5-HT2 antagonist role. I find it harder to theorize on 5-HT than NE since in mood disorders I find NE nature/role to be way less dichotomous than 5-HT or dopamine.SOOOO... If true what does it mean for you ? (after all that's what important, not the intellectual mast*rbation part)
... I think it means your receptors are readapting to your therapeutic dosage of Lithium and while it does that you feel the pain. NE or not, I think that's true for 'something' and probably ALOT OF THINGS. (NE Upregulation, 5-HT Downregulation and some more profound neuronal plasticity... etc). Time could be all you need to feel better. But while it happen I wonder if there's something 'Bp safe' for you that could ease the pain ..What is your precise Dx and do you switch easily into (hypo)mania ?
/\/\arty
poster:Marty
thread:842353
URL: http://www.dr-bob.org/babble/20080727/msgs/842510.html