Posted by Robert_Burton_1621 on February 22, 2015, at 8:17:37
In reply to Re: Itching: Temazepam, Parnate or Amitriptyline? » Robert_Burton_1621, posted by ed_uk2010 on February 17, 2015, at 14:16:52
> Cetirizine is a potent antihistamine, so good luck.>
Itching resolved! I only need to take one tablet every second day. No side-effects, either.
> How are you doing?>
Thanks for asking, Ed.
Well, my recent (self-assessed) depression scores were:
19/2/14
oHDRS= 35
oMADRS = 4722/2/14
oHDRS= 29 (severe > or = 28)
oMADRS= 35 (severe > or = 35)I have progressed up to 80mg daily, as of today. I am having no side-effects to speak of. But there has been no improvement in mood. There is transient improvement in focus and motivation when I first take my dose (and for that reason I'm spreading the tablets out through the day), but my affect remains blunted and my anticipatory anhedonia is disabling. Psychomotor retardation has slightly improved, though, and I am keeping my appointments.
I also managed to go the gym for the first time in 10 weeks. I was very apprehensive about this, since I had little confidence I would have the sufficient drive to do anything. But my trainer was perceptive and took me at a slow pace. I did manage to do some low-intensity weight and core training. This was reasurring, though it resulted in no improvement in mood or my "default" state.
I am now approaching my third week on parnate. But I understand that it may still be considered early (ish) days.
I have read some interesting speculative research (a bit old now) which attempts to explain the reported "delay" in clinical onset of MAOIs even though brain levels of catecholamines and 5-HT become elevated pretty quickly. The first explanation for this "lag" which I have read is (if I understand it correctly) that the mechanism of action of MAOIs is more complex than merely elevating dopamine, noradrenaline and serotonin. The inhibition of MAO also results in the elevation in the brain of levels of trace amines. These amines have a "marked" effect on uptake and/or release of catecholamines and 5-HT at nerve endings and/or may act as neuromodulators through direct actions on receptors for the catecholamines and 5-HT. Changes in pre- and post-synaptic receptors may occur *subsequent* to the increased levels of catecholamines, 5-HT and the trace amines. Therefore, "[t]hese delayed effects may be associated with the lag between administration of the MAO inhibitors and onset of clinical effect."
See, "Insights into the Mechanisms of Action of the MAO Inhibitors Phenelzine and Tranylcypromine" (1992) J Psych Neurosci 17(5).
The other hypothesis posits, as a cause of or contributor to this "lag", a critical role for 5-HT. The hypothesis is that acute administration of large doses of tranylcypromine preferentially increases (extra-cellular - not sure what significance this qualification has?) 5-HT levels in the midbrain (dorsal + median) raphe nuclei, as compared to the frontal cortex. Apparently, "these nuclei contain the cell bodies and dendrites of most serotonergic neurones that project to the forebrain." Thus, according to the hypothesis, "this characteristic regional selectivity,. . ., may be relevant to understanding [tranylcypromine's] mechanism of action, and particularly,[its] delayed clinical effects."
See, "Effects of single and chronic treatment with tranylcypromine on extracellular serotonin in rat brain" (1994) Europ J Pharmaco 263.
Perhaps supporting the role of 5-HT in the delayed onset, I read that an old case report relates how a patient improved rapidly with the addition of lithium to parnate. The explanation for this rapid response in improvement was suggested to be related to lithium's putative capacity to enhance serotonergic activity "synergistically" with the serotonergic effect of an MAOI.
See, "Rapid Antidepressant Effect of Addition of Lithium to Tranylcypromine" (1986) J Clin Psychopharm 6(3).
Needless to say, I don't possess the competence to assess the merits of these theories, but they cropped up when I did a few searches seeking information on when parnate can be expected to kick in.
Any thoughts?
poster:Robert_Burton_1621
thread:1075968
URL: http://www.dr-bob.org/babble/20150129/msgs/1076980.html