![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 21 of 21. This is the beginning of the thread.
Posted by temoigneur on March 29, 2008, at 19:48:24
I cried as i relayed this email to my mom, the one next to myself, who has probably most deeply felt the pain of my illness. If I can be helped, there is surely hope for all of us..
Sent to the American Psychiatric Association, in response to an anecdotal report of a lady with similar response to memantine..
Hi, I'm a 29 yr Male, with an extensive psychiatric history. My life was profoundly changed with initiation of memantine therapy, around October of last year.
I was diagnosed by a neurologist at 16 with Tourette syndrome: it was of acute symptomatic onset.
From that point on, the next decade, may be described at times, as a tormenting battle with OCD, severe GAD, and major depression with psychotic features.
Eventually diagnosed as schizo-affective, my condition was sometimes exacerbated by trials of pharmaceuticals.
I deteriorated from being a healthy, relatively well adjusted child, even a provincial medalist in Piano, to a semi-vegetative, episodically catatonic, cadaver.
Between the acute onset of my illness in my mid-teens, up until the initiation of memantine treatment, this past October, I was hospitalized in psychiatric wards, eight times, with a mean stay of approx. one month.
In my case, symptom remission was almost immediate, and dramatic, upon introduction of memantine.
Poly-pharmacy obscures its effects, but upon initiation, it felt as if.. a dischordant, frail psyche, had been replaced by a robust, dynamic, intellect. Like a butterfly emerging from a cocoon, I gracefully flew from the torment, masochism, and agony, to a beautiful place, where in my mind, it is often 34 degrees Farenheight, where I sit in pristine view of the Napa Valley vineyards, .. indeed, mine is a waterfront home in ... oh don't ruin my moment, what's that district on the north side of the Golden Gate Bridge..
Unable, for long, to piece together a coherent train of thought - since age 15, I have returned to school, full time. I study math, and chemistry, through an online school. I am near the top of my first year Biology class, the one course I could get into this semester, at a local college.
As the tired cliche goes, every day is a gift, and my fervent passion is to enter psychiatry, and help the unknown heroes that have no voice, or know any significant hope.
As with anyone given so much more than they could ever hope for, I am happy to share any part of my story, in any place it may be of use.
I have waited until the present to share my story, because there were environmental factors that needed to be resolved, before retrospect would become more objective.
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. 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, related, theory on memantine, in line with the first, is being studied at Stanford, It is that memantine may regulate abnormal glutamergic transmission, as I understand, one of the most important molecules, 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.
I have, however, 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=ObssessedArticle 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.4
While 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/articledetai
Article 4.
Citation from 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
***
Here's a list of my current medications, all in use since Oct/07:
Memantine 30mg, Dexedrine 60mg, Modafinil 300mg, Abilify 5mg, Prozac 20mg, Clonazepam 1mg
Modafinil and Dexedrine** were introduced with Memantine, I had been on each of the other three agents for a minimum of ~ 3 months.
**
When I initially took dexedrine, before starting memantine, it seemed to help substantially, for 2 - 3 days. In retrospect, I was in a high functioning manic phase, which was always followed by a crash into amphetamine psychosis, lasting 2 - 4 weeks.
Because of this, my psychiatrist raised my antipsychotic dose, and dexedrine would work as well as anything can in combination with an elephant tranquilizer. Again, this would last for about two days, then its effect would seem negligible.
30mg Memantine, at night, from initation this past Oct, has completely eliminated tolerance.
When I started memantine, I was on a high dose of Abilify, (30mg), so it would have been hard to speculate whether memantine was making a difference with the psychosis.I have, however, since been able to taper down to 5mg, with no recurrent mania or psychosis, and have experienced a return of all intellectual function, save the effects of 1mg clonazepam, which I am still tapering off of.
One thing of tremendous interest to me, is my acute sensitivity to msg - monosodiumGLUTAMATE.
Before memantine, I was overwhelmed much of the time, and made little attempt to look into possible dietary triggers.After starting treatment, however, I realized that I was likely having a reaction to msg.. I think.
After eating Chinese food, in particular, I become dysfunctional in about 20 minutes. The paranoia, fear, looping, religious obsessions, they all come back at roughly 40%, and taper off over the course of 2 - 4 hrs.
With no background in biochemistry, I haven't been able to look into this very deeply, but if anyone could explain how this might tie into the glutamate theories Ive pasted, I would be extremely grateful. I think the answer is probably staring me right in the face, I'm just too tired, and have no knowledge of the jargon etc..
I did read that msg is thought by some to be a neuro-toxin capable in sensitive indivuals, of over-exciting neurons, ending in cell death.
Posted by bulldog2 on March 30, 2008, at 12:33:11
In reply to Memantine +glutamate ex.toxicty, dramatic recovery, posted by temoigneur on March 29, 2008, at 19:48:24
Can you separate out how the memantine has benefitted you outside of it's ability to prevent tolerance to stimulants? I to have tried stimulants with a very rapid tolerance to them. Adderall stoped working after two days and ritalin after several weaks of escalating doses.
Posted by SLS on March 30, 2008, at 12:38:05
In reply to Memantine +glutamate ex.toxicty, dramatic recovery, posted by temoigneur on March 29, 2008, at 19:48:24
Yay!
Thanks for all the information. Great post.
It might be interesting to try adding magnesium should you not be satisfied with your treatment response at some point. Also, it is possible that Lamictal would act synergistically to reduce glutamate activity. NMDA funtion is a bit complicated, but I know it relies on the input of other glutamatergic activity.
- Scott
Posted by undopaminergic on March 30, 2008, at 13:33:29
In reply to Memantine +glutamate ex.toxicty, dramatic recovery, posted by temoigneur on March 29, 2008, at 19:48:24
>
> So basically we have following NDMA antagonists:
> 1. Memantine (Akatinol/Axura)
> 2. Acamprosate (Campral)
> 3. Amantadine (Symmetrel/Amantix)
> 4. Magnesium (supplement)
>
>
> 3) Amantadine,
>
> 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.
I have extensive experience with amantadine. Unfortunately, I can't get it to work reliably and consistently. I've only been successful with it once, when I managed to induce a powerful stimulant/antidepressive - and even briefly hypomanic - response. This is remarkable because I can take high doses of stimulants without much of a response, and even that little response tends to dissipate due to tolerance.Therefore, it's particularly interesting to learn that some NMDA antagonists may be capable of reducing or preventing tolerance:
>
> 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.
>
> 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.
So that is one more reason to explore NMDA-antagonists, as I'm already in the process of doing. Previous brief trials of memantine have been promising, as noticeable antidepressive effects were noted.>
> The presence of OCD-schizotypal comorbidity is interesting given the role of glutamatergic dysfunction in both OCD and schizophrenia spectrum disorders.
Also interesting because I may have schizoid personality disorder, another schizophrenia spectrum disorder. It consist of emotional blunting, anhedonia, social withdrawal and other so-called negative schizophrenic symptoms.Indeed, one small study indicates that memantine might be useful in the treatment of negative symptoms:
http://www.ncbi.nlm.nih.gov/pubmed/17728110Quote: "Seven schizophrenia patients, were included in a six-week open-label study, with weekly increasing dosage (5, 10, 15, 20 mg) of memantine added to their on-going antipsychotic treatment. ... We found a significant improvement of the PANSS score ... after six weeks ..., with the most prominent improvement (21%) in negative signs sub-scale"
>
> I did read that msg is thought by some to be a neuro-toxin capable in sensitive indivuals, of over-exciting neurons, ending in cell death.
>The concern mainly applies to those with an immature (ie. infants) or damaged (mobile phone users?) blood-brain-barrier, which could allow the glutamate from MSG to enter the brain and cause excitotoxicity. There is similar concern about aspartame, which contains aspartate - another excitatory amino acid that also stimulates glutamate receptors, but not as potently as glutamate.
On the other hand, NMDA-antagonists can also cause neurotoxicity, at least in rats. The toxicity is initially reversible, but upon longer term treatment with potent NMDA-antagonists, damage to particularly the posterior cingulate and retrosplenial cortices results.
Posted by bulldog2 on March 30, 2008, at 17:50:36
In reply to Memantine +glutamate ex.toxicty, dramatic recovery, posted by temoigneur on March 29, 2008, at 19:48:24
It says one or two pills a day to prevent amphetemine tolerance. Did you need a full a full 30 mg of memantine to prevent amphetemine tolerance? How quickly did you titrate up to 30 mg?
Posted by undopaminergic on March 30, 2008, at 19:34:03
In reply to Re: Memantine +glutamate ex.toxicty, dramatic recovery, posted by bulldog2 on March 30, 2008, at 17:50:36
When I first tried memantine, I took too much, which resulted in a state of impaired thinking (maybe a hint of the dissociative states that NMDA-antagonists can produce), but tolerance quickly developed to that effect, within days. It may be a good idea to take the first doses of memantine at bedtime, or it might ruin your day. It is important not to dismiss it based on initial adverse effects, as I almost did.
Based on the half-life, which is about 3 days, it may be a good idea not to increase the dose more than about 5 mg a week.
Posted by Sigismund on March 31, 2008, at 2:44:38
In reply to Re: Memantine +glutamate ex.toxicty, dramatic recovery, posted by undopaminergic on March 30, 2008, at 19:34:03
Was your experience of it positive?
Did it do anything?
Anything you would like to add?
Posted by undopaminergic on April 2, 2008, at 5:28:39
In reply to Re: Memantine +glutamate ex.toxicty, dramatic recovery » undopaminergic, posted by Sigismund on March 31, 2008, at 2:44:38
> Was your experience of it positive?
>
> Did it do anything?
>
> Anything you would like to add?Yes, there were clear antidepressive/anti-anhedonic/stimulant effects. However, I only tried memantine briefly on a couple of occasions, so I don't know if the positive effects would last. I intend to try it again and more thoroughly.
Posted by cumulative on April 4, 2008, at 2:13:04
In reply to Re: Memantine +glutamate ex.toxicty, dramatic recovery, posted by undopaminergic on April 2, 2008, at 5:28:39
This will be a little long. Pardon the disorganization; I am inattentive.
30 mg is quite a bit. Isn't it impairing during the day, with that long half-life?
NMDA antagonism provokes dopamine release and there's one good-looking small trial showing good benefits for memantine in ADHD. 10mg was the typical working dose, it looks like. I believe there has in fact been some work that noted excitotoxicity in ADHD-type states. Know also that dopaminergic transmission actually lowers glutamate release in many parts of the brain, and one might also examine the apparently sometimes-antagonistic relationship between AMPA activity and NMDA activity, reminiscent of the relationship between nicotinic and muscarinic acetylcholine.
Magnesium has also seen to be useful in ADHD in some studies.
So as far as memantine preventing psychostimulant tolerance. I just am not sure of the mechanism. Does excitotoxic glutamate transmission provoke a downregulation of the dopamine receptors in the limbic system, for instance? Intuitively (maybe it's just me, but spend all your time reading about this stuff and after a while you gain an intutition about it) I think there may be something here.
This entire issue hinges on and is complicated by the idea that, with the psychostimulants, the initial mood boost/euphoric-type reactions, as well as probably an increase in motivation, have been linked to a stimulation of mesolimbic dopamine, to which tolerance develops very rapidly. OTOH, the concentrative benefits can often last much longer (many people can attain a therapeutic effect from dopaminergic stimulants for many years) and may even show sensitization. I roughly link this latter, different effect (which may actually be accompanied by mood-flattening, the "zombification" problems) to potentiation of prefrontal structures.
This also brings to mind ideas I have been having with regards to differences between those with hyperactive problems, and those with inattention.
Recent research suggests that hyperactivity may resolve over time, even aided by the psychostimulants -- probably a process of plasticity -- as concentrative abilities are developed. The issue here may often be something like too great of a ratio of limbic excitatory transmission (and development) in comparison to prefrontal transmission. Whereas those with inattention (or sluggish cognitive tempo), problems that more closely resemble the negative symptoms of schizophrenia, or even the mental-behavioral consequences of Parkinson's, may have a more problematic condition, a more global deficit/impairment of dopaminergic function -- more problematic because maintaining a potentiation of limbic dopamine seems nigh-impossible.
You always run up against that accursed homeostatic wall.
With inattention and a unmedicated zombie-like state, I often feel that the initial mood boost of the first few weeks is much more useful for concentration/motivation, a feeling of life, a sort of expansion of my being, than the concentrative effects that linger, which can make it easier to direct myself and get things done but still leave me with the problem of being a zombie.
So, with memantine, is it this initial mood boost that is preserved?
Again, I'm sorry for the ramble and I hope it interests someone.
Posted by bulldog2 on April 4, 2008, at 15:44:15
In reply to Re: Memantine +glutamate ex.toxicty, dramatic reco, posted by cumulative on April 4, 2008, at 2:13:04
There is one famous ex babbler andrewb that could never go past two days on adderall before it pooping out..On memantine 30 mg this problem abated and years later his adderall was still working.
Posted by cumulative on April 4, 2008, at 22:08:40
In reply to Re: Memantine +glutamate ex.toxicty, dramatic reco, posted by bulldog2 on April 4, 2008, at 15:44:15
That's really fantastic.
I'd be happily surprised if that dose didn't have a tendency to produce some cognitive impairment, though ...
Posted by bulldog2 on April 5, 2008, at 14:03:40
In reply to Re: Memantine +glutamate ex.toxicty, dramatic reco, posted by cumulative on April 4, 2008, at 22:08:40
> That's really fantastic.
>
> I'd be happily surprised if that dose didn't have a tendency to produce some cognitive impairment, though ...well his last post didn't seem to indicate that..He felt he might not need the adderall anymore but would always want the memantine..Seem to straighten out his dopamine issues.
Posted by bulldog2 on April 11, 2008, at 15:38:15
In reply to Re: Memantine +glutamate ex.toxicty, dramatic reco, posted by bulldog2 on April 5, 2008, at 14:03:40
I'm interested in starting memantine therapy to see if it does anything by itself. I respond to stimulants and opiates but tolerance issues develope quickly. I would like to add a stim or an opiate to memantine and see if i could get a sustained response.
Posted by Sigismund on April 12, 2008, at 18:55:01
In reply to Re: Memantine +glutamate ex.toxicty, dramatic reco, posted by cumulative on April 4, 2008, at 22:08:40
Does it make sense to ask if there are symptoms of excitotoxicty?
Is there some pattern to the symptoms of people who have it?
That sort of thing.
Posted by utca5utca on April 14, 2008, at 14:45:51
In reply to Memantine +glutamate ex.toxicty, dramatic recovery, posted by temoigneur on March 29, 2008, at 19:48:24
Two questions for temoigneur and undopaminergic (or anyone else who has taken Memantine):
(1) How rapid is Memantine's onset in relieving stimulant tolerance?
(2) Is it safe to start dosing at the 20mg range and titrate upwards from there? It seems low dose Memantine has proven ineffective for combating stimulant tolerance. I read undopaminergic's post about slowly titrating from 5mg. What was your experience, temoigneur? Did you go directly to 30mg? (Does anyone else have any experiences to share?)
If it's of use to anyone, here is a brief history of my life with stimulants:
I've been on various stimulants for the past seven years. Prior to stimulant usage, the only medications that have helped me over 13 years of medical treatment have been the combination of Prozac + Desipramine. (This combo worked incredibly well for nearly two years until it began to sputter and eventually stop working whatsoever. I have revisited the combo a couple of times in the years since, but to no avail.)
Adderall was the first stimulant to help me. (Ritalin and its cousins had no effect on me at all.) Adderall at 30mg/day gave me my life back. For seven months, I felt alive again.
After that seven month mark, tolerance quickly set in. My doctor increased the dosage and included Wellbutrin SR to the mix. Provigil was added shortly afterwards but not taken on any regular dosing cycle.
(Wellbutrin SR did have some beneficial effect, but it stopped working after about four months. Wellbutrin XL was tried, but had immediate negative effects. The effects of Provigil were very mildly beneficial, but at an almost imperceptible level.)
As time went on, the Adderall was becoming less and less effective and was also causing some very harsh crashing in the evenings. My doctor prescribed Klonopin to combat the crashing and panic attacks.
Not long afterwards, Dexedrine tablets and Dexedrine spansules were added so I could go off the Adderall for a while.
The Klonopin was preventing the harsh crashing, but it was also causing severe memory deterioration and cognitive impairment in general. (And continues to do so.)
I also became dependent on the Klonopin because of the fact that my stimulants won't work unless I take them with Klonopin. There seems to be some sort of synergistic relationship between the two. (Has anyone experienced anything similar?)
So, fast-forward to present day. My current intake of meds is roughly as follows:
- - - - - - - - - - - - - - - - - - -
* Dexedrine tablets (generic)
- 30mg in AM, 20mg in PM* Dexedrine Spansules (brand name)
- 15mg in AM* Adderall tablets (brand name)
- 15mg in AM, 15mg in PM* Klonopin tablets (generic)
- 2mg in AM, 2mg in PM- - - - - - - - - - - - - - - - - - -
This cocktail of stimulants and Klonopin are my only means of having some semblance of a functional life. Without them I am a total vegetable. The fact that tolerance continues to develop and dosages continue to increase terrifies me.
Adding to my frustration is the toll that this is taking on my bank account. Generic Adderall and generic Dexedrine spansules have very adverse effects on me, so I really have no other choice but to shell out more and more $$ for the brand name versions.
Anyway, that's my backstory. Apologies for the rambling.
Any input regarding my questions on Memantine or alternative methods for curbing my stimulant tolerance (or anything else in general) would be greatly appreciated.
Many thanks -utca.
Posted by Questionmark on April 28, 2008, at 11:33:52
In reply to Re: Memantine +glutamate ex.toxicty, dramatic recovery, posted by undopaminergic on March 30, 2008, at 13:33:29
This is probably stupid to say because you'd probably have realized if this would be helpful, but just in case it's of any value..., i would think that caffeine would be one of the best, if not THE best, substances for the "negative schizophrenic symptoms" you describe. Though i imagine caffeine and other stimulants are generally detrimental for schizophrenia spectrum conditions, if the "positive symptoms" were not a problem i think that caffeine might be a great tool.
> Also interesting because I may have schizoid personality disorder, another schizophrenia spectrum disorder. It consist of emotional blunting, anhedonia, social withdrawal and other so-called negative schizophrenic symptoms.
>
Posted by undopaminergic on May 1, 2008, at 0:29:02
In reply to Re: Memantine +glutamate ex.toxicty, dramatic reco » undopaminergic, posted by Questionmark on April 28, 2008, at 11:33:52
For me, caffeine is not effective on its own (not even for promoting wakefulness), but may be useful in combination with dopaminergic stimulants (such as methylphenidate and modafinil) and memantine.
> This is probably stupid to say because you'd probably have realized if this would be helpful, but just in case it's of any value..., i would think that caffeine would be one of the best, if not THE best, substances for the "negative schizophrenic symptoms" you describe. Though i imagine caffeine and other stimulants are generally detrimental for schizophrenia spectrum conditions, if the "positive symptoms" were not a problem i think that caffeine might be a great tool.
>
> > Also interesting because I may have schizoid personality disorder, another schizophrenia spectrum disorder. It consist of emotional blunting, anhedonia, social withdrawal and other so-called negative schizophrenic symptoms.
> >
Posted by undopaminergic on May 1, 2008, at 1:37:37
In reply to Re: Memantine +glutamate ex.toxicty, dramatic reco, posted by utca5utca on April 14, 2008, at 14:45:51
> Two questions for temoigneur and undopaminergic (or anyone else who has taken Memantine):
>
> (1) How rapid is Memantine's onset in relieving stimulant tolerance?
>In my experience, memantine has an onset of action within 1-2 days. However, I currently don't have enough data to differentiate the stimulant-like actions of memantine itself from its potential efficacy against tolerance to (other) stimulants.
> (2) Is it safe to start dosing at the 20mg range and titrate upwards from there?
>The risk of serious adverse effects from starting at 20 mg is low, but the risk of encountering (less serious) side-effects (eg. cognitive impairment) is definitely higher than with a lower starting dose.
>
> Any input regarding my questions on Memantine or alternative methods for curbing my stimulant tolerance (or anything else in general) would be greatly appreciated.
>Examples of other potentially useful drugs are:
* selegiline and rasagiline
* sulpiride and amisulpride (generally low doses only)
* L-dopa and tyrosineOf course, combinations of the above are possible.
Posted by okydoky on June 20, 2008, at 14:16:27
In reply to Re: Memantine +glutamate ex.toxicty, dramatic reco, posted by undopaminergic on May 1, 2008, at 1:37:37
I've been reading about meantime because my other was prescribed it for dementia. It was interesting for me as I have recently noticed a stimulant tolerance. I have been taking Ritalin for about 14 years and never noticed any tolerance until a couple months ago. I started taking 20mg sr twice a day and stopped both because I was too depressed to care to take the second dose and the stimulation agitated me and created muscle tension. I was also interested in finding some relief for the cognitive impairment I have had for many years now basically since I stopped treating my depression with some exceptions. I continue to deteriorate both cognitively and mood.
I am also looking at changing the oxycontin I take to bupropione as it was suggested that the oxycntin could be interfering with the amineptine I was trying.
I also take klonopin sometimes and am currently taking Lyrica which I hope to be able to stop as soon as possible. I take it for certain symptoms of interstitial cystitis which are not usually present.I know this is rambling and will stop now.
Appreciate as always any suggestions. Many of you here have been very helpful already.
Thanks,oky
Posted by cumulative on July 11, 2008, at 15:40:47
In reply to Re: Memantine +glutamate ex.toxicty, dramatic reco, posted by okydoky on June 20, 2008, at 14:16:27
re: memantine, you should consider ceasing the methylphenidate before adding the memantine (resuming once you've been at the target dose for a few days), and also slowly titrating the memantine upwards (perhaps an increase of 2.5 mg daily) in the interest of avoiding the initial side effects which can include the agitation and tension you described. I experienced these as well early in my use of memantine, but they faded within days of each dose increase.
I currently take 20mg memantine (going to up it to 30mg) and it is a decent antidepressant. On Tuesday or so I should have the chance to trial adding lisdexamfetamine, so we will see if this does well for me. I am attempting to retain the psychostimulant mood boost (short of dumb euphoria), which I feel is probably more therapeutic for me than the later concentrative, but somewhat numbing (IME) effect.
Posted by okydoky on July 12, 2008, at 12:00:19
In reply to Re: okydoky, posted by cumulative on July 11, 2008, at 15:40:47
This is the end of the thread.
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