Posted by Mike P. Sinn on August 28, 2012, at 16:56:21
In reply to Re: Memantine Insomnia Ready To Can, posted by bulldog2 on April 21, 2008, at 8:25:11
Dear Person Reading These Words,
I've suffered from major depression for decades and found the neurochemical means of overcoming this. I tried about every other possible approach prior to finding a solution for my problem. Lots of these things reduced my desire for death, but nothing made me actually want to be alive... until last week.
MY EXPERIENCE COMBINING MEMANTINE (~30mg/day), WELLBUTRIN (300mg/day), AND ADDERALL (10mg/day):
Life is sooooooo much easier. I have tons of spare brain capacity now that I used to devote to constantly hypothesis about the infinite reasons that everyone hated me.
I had no idea to what extent I was living in constant fear of everyone. Now, the only thing I'm afraid of is dying (an activity I used to look forward to).
Starting to take it was like the 1st time I put on glasses. I had no idea how clear and beautiful the world was to normal people.
HOW (I Think) MEMANTINE WORKS:
This is my interpretation of the literature. Please let me know if I'm wrong about something here. It's very possible.
Your brain cells (neurons) have these little keyholes in them (called NDMA receptors). Normally, glutamate molecules (or keys) floating around in your brain will bind to these receptors (analogous to a key unlocking a door). The door in the neuron is called a calcium ion channel. It lets a bunch of calcium ions rush into the neuron.
Calcium flux through NMDARs is thought to be critical in synaptic plasticity, a cellular mechanism for learning and memory. However, allowing high levels of calcium ions to enter the cell activates a number of enzymes that damage cell structures. This may be the mechanism by which Alzheimer's disease damages the brain. It is also likely the mechanism by which tolerances are built towards Adderall, wellbutrin, and other dopminergic stimulants.
The anti-alzheimer's disease drug called Memantine blocks this neurotoxic process. It clogs up the keyholes (NDMA receptors) so the glutamate molecules can't get in there to open the calcium ion channel (the door). This prevents the neuronal damage and resulting psychological degeneration.
Again, this is just what I pieced together from reading those little helpful sayings on the back of sugar packets. I am not a neuroscientist, so please correct me if I'm wrong.
STUDIES (It never hurts to re-cite these, does it?):
Note that there are studies showing Memantine to be ineffective by itself at lower dose between 5-20mg.
Cognition-enhancing and anxiolytic effects of memantine.
These data indicate that high, stable doses of memantine improved cognition and exhibited a potential anxiolytic response in normal mice.
The combined effects of memantine and fluoxetine on an animal model of obsessive compulsive disorder.
The present study investigates the effect of fluoxetine and memantine alone and in combination in a mouse model of compulsive behavior. In this model, compulsive scratching is induced by a subcutaneous injection of serotonin or a serotonin releasing agent, compound 48-80, in the back of the neck. The effects of the memantine and fluoxetine combination were found to synergistic, specifically as defined by an isobologram.
Effects of glutamate-related drugs on marble-burying behavior in mice: implications for obsessive-compulsive disorder.
We examined the effects of glutamate-related drugs on marble-burying behavior, which is an animal model of OCD. The uncompetitive N-methyl-d-aspartate (NMDA) antagonists memantine (10 mg/kg, i.p.) and amantadine (30 mg/kg, i.p.) significantly inhibited marble-burying behavior without affecting locomotor activity in mice.
Obsessive compulsive disorder
A Single-Blinded Case-Control Study of Memantine in Severe Obsessive-Compulsive Disorder
Conclusions: This study provides preliminary supportive evidence for the effectiveness of memantine as a glutamatergic augmenting agent in severe OCD. Future randomized double-blind placebo-controlled trials are warranted.
Differential Efficacy of Memantine for Obsessive-Compulsive Disorder vs. Generalized Anxiety Disorder: An Open-Label Trial.
Conclusions: These results suggest that memantine may have preferential efficacy in the treatment of OCD versus GAD. These preliminary findings warrant larger, placebo-controlled studies in OCD.
Memantine augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial.
SUMMARY: In this open-label augmentation trial of memantine in treatment-resistant OCD, almost half the subjects had a meaningful improvement in symptoms. Our study was limited by its small size, presence of comorbidities, and lack of control. Large double-blind placebo-controlled trials are needed to further test our findings.
Memantine augmentation for refractory obsessive-compulsive disorder.
We report two cases of refractory obsessive-compulsive disorder treated with an augmentation of memantine at 15 mg/day. The first case did not benefit from such treatment, while the second showed immediate and substantial improvement.
A double-blind, placebo-controlled study of memantine in the treatment of major depression.
CONCLUSIONS: In an 8-week trial, the low-to-moderate-affinity NMDA antagonist memantine in doses of 5-20 mg/day was not effective in the treatment of major depressive disorder.
Note that in trials where higher doses were used it was effective for major depression, the minimum dose for depression is 30 or 40mg.
An open-label, flexible-dose study of memantine in major depressive disorder.
Memantine demonstrated early-onset efficacy in patients with MDD. The treatment was well tolerated. This study suggests that double-blind, placebo-controlled studies of memantine in depression are merited.
Double-blind, randomized comparison of memantine and escitalopram for the treatment of major depressive disorder comorbid with alcohol dependence.
CONCLUSIONS: These data provide new evidence for the safety and potential efficacy of memantine and escitalopram for major depressive disorder in patients with comorbid alcohol dependence.
Post traumatic stress disorder
Pilot trial of memantine in the treatment of posttraumatic stress disorder.
These data suggest potential positive treatment outcomes, both cognitively and psychiatrically, and provide rationale for future double-blind, placebo-controlled studies of memantine in PTSD.
A pilot evaluation of the safety, tolerability, pharmacokinetics, and effectiveness of memantine in pediatric patients with attention-deficit/hyperactivity disorder combined type.
CONCLUSIONS: This pilot study suggests that a memantine dose of 20 mg/day may be a safe and possibly effective treatment for pediatric ADHD. Further investigations of memantine in ADHD appear to be warranted.
Anyway, I wish I would have found this drug a decade or two ago. I could have been a much better person instead of the neurotic, selfish creature I was.
But I also wonder if I'm better than I would have been if i'd never had the psychological handicap. It seems like the other parts of my brain may have overdeveloped to compensate. It seems like taking this and deactivating my hyperactive amygdala might be like a runner taking off weights he'd worn on his legs his whole life.
Alternatively, maybe all the stress caused long-term irreparable brain damage. Fortunately, I don't care.
MY THEORY AS TO WHY I'VE NEVER HEARD OF MEMANTINE BEFORE:
Memantine was invented in 1968 so it's my understanding that it is no longer under patent. It's antidepressant effects were not discovered until its patent had expired. At that point, the cost to overcome the FDA's regulatory hurdles required to get approval of a new prescriptive usage may have exceeded the profit to made by selling it to the small fraction of the population that it could help. Hence, the FDA is still effectively discouraging psychiatrists to use this to help their patients. I'm fairly confident that many of the one million people who killed themselves last year may still be alive if the FDA cared as much about helping people as it did about protecting them from ineffective treatments.
WHAT DO YOU GUYS THINK?
Aside from insomnia, almost non-existent. PLEASE let me know if any of you have figured out any STRATEGIES FOR OVERCOMING THE INSOMNIA issue.
I take memantine in the morning and at lunch. I take 3mg melatonin and valerian root before bed. I excercise for 1 hour, 3 days a week. All of these things seem helpful.
I've titrated up to about 50 mg over a couple weeks. (Disclaimer: Note that this is faster than recommended and I do not suggest that anyone else do this.) At this point the antidepressand/antianxiety effects remain in force but the euphoria has decreased somewhat. If anyone has any causal theories, PLEASE SHARE THEM.
PLEASE SHARE YOUR THOUGHTS OR EXPERIENCES!
Visit thinkbynumbers.org where statistics-based reasoning > emotion-based intuition. (Is shameless self-promotion really so wrong?)
Here's a graph of my mood:
poster:Mike P. Sinn