Hey all, just wanted to briefly share my experience here. I have ADHD, best described as the "Ring of Fire" subtype if you buy into the Amen Clinics' categorizations. My flavor comes with all the core features, along with anger, 'mood swings', brain fog, depression and anxiety, including terrible social anxiety making eye contact a painful experience. I've been on Namenda (memantine) for about a month and a half; I've been on Namenda XR 21 mg for about a month. While it does not seem to help directly with the core ADHD symptoms, it has almost entirely eliminated my depression and social anxiety (and I believe has decreased my anxiety in general). The effect has been so profound that a couple of days after switching to my current dosage and formulation (I started on the instant release, which btw is being discontinued in August), I seemed to experience at least a few hours of rapid synaptogenesis, in which my perceptions of the world seemed new (or encoded differently) and I felt that I was learning it all over again. During this period, novelty seemed to cause a euphoric sensation, which I found concerning but thankfully was short-lived and manageable by throttling the novelty, which otherwise might have been overwhelming. To a much lesser degree this process seems to continue (without euphoria), as I occasionally seem to relearn things that I had perceived differently when I was depressed. Also, I have found that my coordination has improved, best evidenced by my improved pool playing. For the first time in my life, I have been able to feel relatively normal and content, and comfortable around other people, becoming far more extroverted. I no longer constantly worry about being judged, and do not feel inferior to the people around me. Eye contact is pleasurable rather than painful, as is exerting my will and expressing my desires. I am able to truly enjoy physical and emotional intimacy now. I see people more for who they truly are (their pain, their anxiety, their joy, etc.). The list goes on, but I'll end it here.
My best guess regarding the mechanism by which memantine has been effective is this:
- proinflammatory cytokines/mediators cause astrocytes to downregulate glutamate transporters EAAT-1 and EAAT-2 (underactivity of EAAT-1 in general may explain my intolerance to (sub-)chronic aspartame exposure)
- Due to underactivity of these astrocytic glutamate transporters, either (1) excessive glutamate builds up in the synapses and causes oversaturation/downregulation/desensitization of the glutamate receptors, or (2) presynaptic release or synthesis of glutamate is downregulated to compensate. In light of the efficacy of memantine, (2) would seem to depend upon the use of presynaptic NMDA receptors to regulate release or synthesis, which is rather dubious, so I lean toward (1). If (2) were shown to be true, it would raise a concern regarding excitotoxicity.
- (Assuming (1) above) memantine reduces the effect of excessive glutamate on NMDA receptors, allowing them to function more normally, through e.g. upregulation/translocation/sensitization, turning down/off natural pathways guarding against excitotoxicity. In other words, shifting the balance of stimulation from tonic to phasic.
Of course, plenty of downstream effects on other neurotransmitter "systems" are then possible.
I am hoping the reason the remainder of my ADHD symptoms have not been resolved is due to the fact that I am merely dealing with one of the effects of reduced synaptic glutamate clearance. I am presently looking into ways to upregulate EAAT-1 or EAAT-2 or (less desirably) antagonize the various other glutamate receptors. In the meantime, I continue to use Vyvanse, albeit at a reduced dosage. I am hoping to try ceftriaxone (unfortunately only available via IV or IM routes) or celecoxib to see whether they treat my brain fog and hyperactivity and comfortably replace memantine, Vyvanse, and omega-3s.
In case anyone is curious, my current best guess at the etiology of my ADHD is the rs6565113 variant of the CDH13 (T-Cadherin) gene. This is statistically linked to ADHD and is likely to have significant inflammatory implications. (The state of knowledge regarding CDH13 is still rudimentary but highly intriguing.)
Btw, I have a naturally high level of testosterone and a very youthful appearance, and I am aware of the possibility that properly treating my ADHD will normalize these traits, but that price would be well worth paying.
I could go on, but I think I've covered all the big stuff. Btw for those who are interested in memantine but are unable to get it, you may consider trying gentian root, which I've found to be relaxing and likely also works via NMDA receptors.
I hope this helps someone! I'm sure there are lots of people out there who, like me, have tried the standard treatments for depression and anxiety and been gravely disappointed. I'd be happy to answer questions regarding my experiences or thought processes, so fire away but please stay on topic and don't get off into the weeds trying to show how smart you are.
EDIT: Forgot to mention, I do not seem to be experiencing any side effects. I tapered and stopped Cymbalta (which did not seem to help me) after starting memantine and this seems to have caused "brain zaps" which are still tapering off - I believe this is unrelated to the memantine but am mentioning it just in case.
EDIT: Also forgot to mention that (1) my sexual proclivities have normalized somewhat (no, I will not go into detail) and (2) I'm wondering whether an NMDA receptor agonist could be used (esp. intramuscularly) as a treatment for psychopathia/sociopathia, to increase their anterior cingulate gyrus activity and their sensitivity to others' feelings/opinions/reactions. Just a thought.
Edited by AlwaysLearning, 02 June 2014 - 12:53 AM.