Posted by temoigneur on March 29, 2008, at 15:49:36
In reply to Re: Happy Ending :P - OCD/major depression/psychosis » temoigneur, posted by johnj on March 28, 2008, at 19:14:27
> How did you get your doc to prescribe it? Do you have any side effects? Do you have any thoughts on how it might be working? Thank you.
>
> johnjHi John, I did have to take a round-about route to get the drug.. I live in Vancouver BC, and I hoped the boarder, to a Washington state nurse-practitioner, who I had seen previously to get Abilify. I was just lucky that he is very liberal in his prescribing practices, - I took the Rx to my family doc in Canada, and, fortunate again.. he was willing to re-write it so it would be covered up here.
There's two theories about what memantine might be doing. With my negligeable knowledge of biochemistry.. I perceive them to be distinct mechanisms, but they might well involve the same active molecule..
the first, like the previous poster suggested, addresses preventing dexedrine tolerance.. When I initially took dexedrine, It would work well for 2 - 3 days, but in retrospect, I was a high - functioning manic.. and this was always followed by a crash into amphetamine psychosis, lasting 2 - 4 weeks.
Because of this, my pdoc raised my antipsychotic dose, and dexedrine would work as well as anything can in combination with those elephant tranquilizers, again for about two days, then I would have no effect at all.
30mg Memantine, at night, from initation this past Oct, has completely eliminated tolerance. This is a theory on how that works. Taken from a public drug bulletin board, I have no idea about the source.
Article 1.
Amphetamine tolerance is caused by excess Ca++ influx through the NMDA receptor gated calcium channels on the outer membranes of the dopamine cells bodies in the ventral tegental area, one of two areas in the brain with concentrations of dopamine producing neurons.
As alluded to above, taking an appropriate NMDA (partial) antagonist will prevent the development of a tolerance for the effects of an amphetamine or amphetamine-like stimulant. Also, by preventing excess Ca++ influx into the neuron, an NMDA antagonist will prevent associated brain alterations and damage (excitotoxicity).Studies have indicated that amphetamine tolerance is prevented by exogenous or endogenous agents that are able to inhibit excess Ca++ influx into the neuron through the gated calcium channels on the neuronal membrane that have NMDA subtype glutamate receptors.Glutamate , the bodys major excitatory neurotransmitter, opens the gated calcium ion channels upon attaching to the NMDA receptor. A number of other receptors are also expressed on these calcium channels, which, when stimulated, either facilitate or inhibit glutamates action.
It is also important that agents that inhibit calcium channel activity not also cause deficient Ca++ influx. For example, ketamine is a full NMDA receptor antagonist, that prevents excess Ca++ influx and amphetamine tolerance. But being a full NMDA antagonist, ketamine in excessive doses results in deficient Ca++ influx. This could be one of the reasons it leaves K-user in a state of disassociation.
So basically we have following NDMA antagonists:
1. Memantine (Akatinol/Axura)
2. Acamprosate (Campral)
3. Amantadine (Symmetrel/Amantix)
4. Magnesium (supplement)
Two of them have minimal (or none) side effects and have been identified (and verified by one anecdotal person, which has been taking amphetamine-type stimulants and NDMA antagonist with same beneficial effects for a period of 2 years) as preventing amphetamine tolerance: 1) Memantine and 2) Acamprosate.1) Memantine is a partial NMDA antagonist that effectively puts an upper limit on Ca++ influx without compromising healthy levels of Ca++ influx. Memantine is not available in the US at this time. It is in stage 3 trials for Alzheimers disease. US approval may come within the next 2 years. Memantine is now approved in the European Union for the treatment of Alzheimers. It has been marketed in Germany since 1978 for the treatment of dementia and other cognitive disorders. It comes in 10mg tablets. One or two tablets/day are sufficient to prevent amphetamine tolerance, overactivity of the NMDA receptor and consequent free radical stress inside the neuron. The most expensive option though.
2) Acamprosate (n-acetyl-homo-taurine) analogue of the amino acid taurine. Alternatively, it may be termed as a carrier molecule for taurine, that allows taurine to readily cross the blood brain barrier, unlike taurine itself. Taurine is a NMDA receptor antagonist. Acamprosate is an investigational drug in the US, undergoing stage 2 (?) trials for the treatment of alcoholics. It is available in most European countries as a treatment for alcoholism, with great efficiacy. Cheaper than memantine, however efficiacy should be the same.
3) Amantadine, originally used in the treatment and prophylaxis of influenza infection and drug-induced Parkinsonism, also blocks NMDA receptors. Besides it is beneficial in traumatic head injury, dementia, multiple sclerosis,cocaine withdrawal and depression. Amantadine appears to act through several pharmacological mechanisms, none of which have been identified as the one chief mode of action. It is a dopaminergic, noradrenergic and serotonergic substance, blocks monoaminoxidase A and NMDA receptors, and seems to raise beta-endorphin/beta-lipotropin levels. I couldn't find what amount of the drug should be used to block NDMA. Cheaper than Acamprosate. No one has tested it yet, but I think it would be a good choice.
4) Magnesium is also an NMDA antagonist. Most people are deficient in magnesium, and stress reduces magnesium levels. Whether or not one takes amphetamines, magnesium supplementation is very important for mood, general well-being and keeping stress levels under control. It is also important to take magnesium in efficient form, with adequate bioavailability. The best type is magnesium glycinate (chelated) with bioavailability at around 80%. Second best is magnesium carbonate with (I don't remember exactly) bioavailability at little above 30%. Supplemented magnesium should be at 500 mg/day level. Also there is a study which shows that children who use amphetamine-type stimulants have bad magnesium/calcium balance. Calcium levels stay the same with amphetamine usage, but magnesium levels drop.
The article goes on to mention DXM, another NMDA antagonist, which I tried, and personally had negligeable success with, and was eventually hospitalized while on it.. it may have exacerbated OCD/schizo-xx tendencies, delusions in my case.
**Regarding the psychosis.. The second theory on memantine which is being studied at Stanford, is that it may regulate abnormal glutamergic transmission, as I understand, one of the most important molecules, (amino acid?) in neural function, found in brain scans to be abnormal, in both OCD, and various schizophrenia spectrum conditions.
When I started memantine, I was on a fairly high dose of Abilify, so it would have been hard to speculate whether memantine was making a difference with the psychosis, but I have been able to taper down to 5mg, with no recurrent mania or psychosis, and have experienced a return of all intellectual function, and joie de vivre:) save effects of 1mg clonazepam, which I am still tapering off of.
Article 2.
Neuropsychiatry
OCD primarily involves the brain regions of the striatum, the orbitofrontal cortex and the cingulate cortex. OCD involves several different receptors, mostly H2, M4, NK1, NMDA, and non-NMDA glutamate receptors. The receptors 5-HT1D, 5-HT2C, and the μ opioid receptor exert a secondary effect. The H2, M4, NK1, and non-NMDA glutamate receptors are active in the striatum, whereas the NMDA receptors are active in the cingulate cortex.
The activity of certain receptors is positively correlated to the severity of OCD, whereas the activity of certain other receptors is negatively correlated to the severity of OCD. Those correlations are as follows:Activity positively correlated to severity:
H2
M4
NK1
non-NMDA glutamate receptors
Activity negatively correlated to severity:
NMDA
μ opioid
5-HT1D
5-HT2C
The central dysfunction of OCD may involve the receptors nk1, non-NMDA glutamate receptors, and NMDA, whereas the other receptors could simply exert secondary modulatory effects.Pharmaceuticals that act directly on those core mechanisms are aprepitant (nk1 antagonist), riluzole (glutamate release inhibitor), and tautomycin (NMDA receptor sensitizer). Also, the anti-Alzheimer's drug memantine is being studied by the OC Foundation in its efficacy in reducing OCD symptoms due to it being an NMDA antagonist. One case study published in The American Journal of Psychiatry suggests that "memantine may be an option for treatment-resistant OCD, but controlled studies are needed to substantiate this observation. The drugs that are popularly used to fight OCD lack full efficacy because they do not act upon what are believed to be the core mechanisms.
source: http://www.reference.com/search?q=Obssessed
Article 3.
Anecdotal account of remission of OCD/schizotypal symptoms correlated with Memantine treatment;
Add-On Memantine for Treatment-Resistant Obsessive-Compulsive Disorder
The N-methyl-D-aspartic acid (NMDA) receptor appears to be involved in the pathophysiology of several neuropsychiatric disorders, including schizophrenia and obsessive-compulsive disorder (OCD), both of which are believed to be associated with excess production of glutamate in the brain and hyperexcitation of glutamate receptors.1-4 In pediatric OCD patients, abnormally elevated concentrations of glutamate in the caudate have been observed; these levels decrease after treatment with paroxetine.4While currently available treatments, such as serotonin reuptake inhibitors, and cognitive-behavioral therapy are efficacious treatments of OCD, approximately 40% to 60% of patients experience significant reduction of symptoms, with many others demonstrating either partial or no response. Consequently, adjunctive treatments such as dopamine antagonists have been utilized in an effort to more effectively treat a wider range of patients. In severe, resistant cases, neurosurgery or deep brain stimulation may even be recommended.
Memantine is an NMDA receptor antagonist approved for moderate-to-severe Alzheimers disease. Now comes a report on the adjunctive use of memantine for treatment-resistant OCD.5
A 34-year-old woman with schizotypal personality disorder presented with incapacitating ego-dystonic obsessions, including fear of harm to her daughter and of losing her mind. She developed compulsive checking behavior to decrease the associated anxiety. Her history was notable for onset of obsessive-compulsive symptoms at 16 years of age, which remitted spontaneously 2 years later. Subsequent postpartum exacerbation of OCD symptoms associated with major depression occurred at 30 years of age.
The patient received adequate trials of paroxetine and sertraline; however, these were ineffective. Risperidone was added on, but due to marked akathisia, the drug had to be discontinued. At the time of presentation, oral clomipramine was initiated and titrated to 300 mg/day. Ten weeks later, there was still no significant clinical improvement, as evidenced by a Yale-Brown Obsessive Compulsive Scale (YBOCS) score of 35. Addition of the selective dopamine D2 antagonist sulpiride, up to 400 mg/day for 4 weeks, was also ineffective (YBOCS=34). At this point, it was decided to add memantine to the combination regimen of clomipramine 300 mg/day and sulpiride 400 mg/day. Memantine was started at 5 mg/day, then titrated to 20 mg/day within 2 weeks. Within 7 days, the patient reported initial relief. By day 21, there was a significant decline in symptom severity (YBOCS=22). Clinically, the patient reported a substantial reduction in the time occupied by OCD and distress, followed by increased control over obsessions. This improvement was maintained over the next 3 months, with no significant side effects.
This appears to be the first published report on the use of memantine as an adjunctive agent for treatment-resistant OCD, in this case in a patient with schizotypal personality disorder. The presence of OCD-schizotypal comorbidity is interesting given the role of glutamatergic dysfunction in both OCD and schizophrenia spectrum disorders. Controlled trials are indicated to more fully evaluate the potential utility of adjunctive memantine in treatment-resistant OCD. PP
source: http://www.primarypsychiatry.com/aspx/articledetail.aspx?articleid=119
Article 4.
Address in American Journal of Psychiatry for article on memantine for OCD by prominent OCD researcher/psychiatrist, Lorrin Koran, & others..
Am J Psychiatry. 2005 Nov ;162 (11):2191-2 16263867 (P,S,E,B,D) Memantine for Treatment-Resistant OCD.
[My paper] Michael Poyurovsky, Ronit Weizman, Abraham Weizman, Lorrin Koran
poster:temoigneur
thread:820264
URL: http://www.dr-bob.org/babble/20080316/msgs/820532.html