Shown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by vanvog on March 19, 2013, at 12:59:47
In several threads on Psycho-Babble the 1mg/1kg rule has been generally acknowledged as an rule-of-thumb, 0,8 1,5mg/kg according to Chairman_MAO. I did some research on the internet and could find nothing of this sort anywhere else. Basically all Ive found is 1 outside source stating that MAO Inhibition, contrary to a wide-held assumption might not be all that important at all for the therapeutic effect of Parnate and we can assume that there are far more complicated psychopharmacological effects nobody seems to have found out anything about yet.
Based on a study with Phenelzin we know that a MAO inhibition of 80% or 85% seems to be significant for a positive therapeutic effect.This report examines the hypothesis that for phenelzine to be more effective than placebo it is necessary to achieve at least 80% inhibition of platelet MAO activity. This hypothesis was examined in the context of a double-blind comparison of phenelzine, amitriptyline and placebo in depressed patients. When phenelzine became significantly more effective than placebo at 4 weeks, the average MAO inhibition was 85%. By the 5th week, with MAO inhibition greater than 90%, phenelzine was significantly more effective than amitriptyline. A highly significant correlation was noted between improvement and MAO inhibition within the phenelzine group.
Heres the abstract of the study: http://www.ncbi.nlm.nih.gov/pubmed/7231652
Unfortunately, the following abstract doesnt contain anything relevant other than:
[] the rate of MAO inhibition at Week 2 was significantly correlated with clinical improvement at Week 2 and final response status. These findings could not be explained by other potentially moderating variables such as sex, age, endogenicity, recurrence, and incapacitation.
http://www.ncbi.nlm.nih.gov/pubmed/2298705
There is renewed interest in the clinical pharmacology of phenelzine sulfate and other monoamine oxidase (MAO) inhibitors. Newer clinical and analytic techniques recently have been applied to investigations of this class of drugs in man. The results show that drugs such as phenelzine are effective in nonendogenous depression and phobic disorders. Clinical response to phenelzine is related to platelet MAO inhibition and dosage per unit body weight. High percent MAO inhibition in platelets at two weeks is associated with greater improvement after a six-week course of treatment. Our data show that a safe, effective phenelzine dose in 1 mg/kg body weight per day. These results have delineated the pharmacologic and therapeutic effects of phenelzine and support a continuing role for MAO inhibitors in psychopharmacology.
http://www.ncbi.nlm.nih.gov/pubmed/365127
Unfortunately I cant get my hands on the following studies:
http://www.ncbi.nlm.nih.gov/pubmed/6736280
http://www.ncbi.nlm.nih.gov/pubmed/6865965
http://www.ncbi.nlm.nih.gov/pubmed/2008794
I dont have any access to the following study either, but a secondary source from a foreign Tranylcypromine manufacturer states that:
http://www.ncbi.nlm.nih.gov/pubmed/3922441
Extensive and controlled studies for a correlation of MAO inhibition (measured in the Platelets) and the therapeutic effect of Tranylcypromine do not exist. In a study with 14 Patients (20 to 60 mg/day Tranylcypromine) a correlation could not be established. Simpson at al. (1985) found 3 hours after a single dose of 10 mg Tranylcypromine a MAO inhibition in the platelets of 66% and 72% after 24 hours. They discussed that an explanation of therapeutic differences could not be given on the basis of the variability of the MAO inhibition alone because even with low doses high MAO inhibition could be achieved. They concluded that on the basis of clinical dose effect of Tranylcypromine there must be additional pharmacological effects of Tranylcypromine which contribute to the antidepressant effect.
(My own translation. English is not my first language but you should get the idea.)
Posted by SLS on March 19, 2013, at 13:45:06
In reply to Parnate Therapeutic Effect and MAOI Inhibition, posted by vanvog on March 19, 2013, at 12:59:47
What have you concluded?
What questions remain?
- Scott
Posted by vanvog on March 19, 2013, at 21:38:19
In reply to Re: Parnate Therapeutic Effect and MAOI Inhibition » vanvog, posted by SLS on March 19, 2013, at 13:45:06
My point is, we don't know how MAO inhibitors work for the most part. There might be many contributing mechanisms other than MAO inhibition itself so the reasoning "you have to take dose x to achieve inhibition of x%" which I came across on Psycho-Babble might be too simplistic or even wrong. I see it as an argument for higher doses in general because it appears to be that you get decent % of inhibition with very low doses. There might be other mechanisms we don't know about yet which kick in on significantly higher doses than 60 mg/day.
Posted by SLS on March 20, 2013, at 7:08:25
In reply to Re: Parnate Therapeutic Effect and MAOI Inhibition, posted by vanvog on March 19, 2013, at 21:38:19
> My point is, we don't know how MAO inhibitors work for the most part.
Can't the same be said of other antidepressants?
> There might be many contributing mechanisms other than MAO inhibition itself so the reasoning "you have to take dose x to achieve inhibition of x%" which I came across on Psycho-Babble might be too simplistic or even wrong.
I don't recall there being a consensus established on behalf of Psycho-Babble promoting a mechanism of action for MAOIs.
What is the accepted value for the minimum percentage of MAO inhibition deemed necessary for producing a clinical response?
> I see it as an argument for higher doses in general because it appears to be that you get decent % of inhibition with very low doses.
Can you cite specific drugs and specific values?
> There might be other mechanisms we don't know about yet which kick in on significantly higher doses than 60 mg/day.
It has been a long time since I had my MAO activity assayed. I'm not sure that this is done anymore. At 60 mg/day, my MAO was about 90% inhibited. At that time, I responded well to 60 mg/day, but relapsed at 50 mg/day.
I have seen animal studies indicating that at high dosages, but not low dosages, Parnate downregulates 5-HT2a receptors and reduces tryptamine binding in the hippocampus and striatum.
http://www.ncbi.nlm.nih.gov/pubmed/7931218
http://www.ncbi.nlm.nih.gov/pubmed/8139763
- Scott
Posted by vanvog on March 21, 2013, at 16:27:57
In reply to Re: Parnate Therapeutic Effect and MAOI Inhibition » vanvog, posted by SLS on March 20, 2013, at 7:08:25
>Can't the same be said of other antidepressants?
Most PI sheets read like "While the mechanism of action of x, is unknown..."
Best I can do for MAOI Inhibition atm is a study with selegiline on rats: http://www.ncbi.nlm.nih.gov/pubmed/10418793I'm sure there are studies that show on little correlation between the theraputic effects of MAOIs and the % of inhibition. I just can't find any at the moment but that might be because Google is not my friend anyway.
Posted by vanvog on March 22, 2013, at 10:39:51
In reply to Re: Parnate Therapeutic Effect and MAOI Inhibition, posted by vanvog on March 21, 2013, at 16:27:57
I found a few more references in Psychotropic Drug Handbook 8e by Paul J. Perry, Bruce Alexander, Barry Liskow and C. Lindsay DeVane
"It is estimated that tranylcypromine 0.7 mg/kg per day equals phenelzine 1.0 mg/kg per day (Grasso, Perry, & Sherman, 1991)."
http://www.ncbi.nlm.nih.gov/pubmed/2008794
"A positive correlation exists between the degree of platelet MAO inhibition and clinical response for phenelzine ans isocarboaxid, but not necessarily tranylcypromine (Giller, 1980)" I couldn't find the study this part refers to.
"With a dose of phenelzine 60 mg/day for 6 weeks, 68% of patients with MAO inhibition greater than 80% responded favorably; 79% improved with greater than 90% inhibition. However, the response rate was only 44% in those achieving less than 80% inhibition, and the placebo improvement rate was only 32% (Robinson et al., 1978)
http://www.ncbi.nlm.nih.gov/pubmed/365127"[...] doses of phenelzine of 1 mg/kg per day and tranylcypromine of 0,7 mg/kg per day in most patients will usually produce the 80% or greater MAO inhibition necessary to attain an antidepressant response."
Posted by vanvog on March 24, 2013, at 13:53:35
In reply to Re: Parnate Therapeutic Effect and MAOI Inhibition, posted by vanvog on March 22, 2013, at 10:39:51
"The full therapeutic dose of tranylcypromine is no less than 0.8mg/kg/day, and can be 1.5-2mg/kg/day. The 60mg/day maximum dose is a fiction. It's really around 120-200mg/day, and any competent psychiatrist knows this."
by Chairman_MAO, I wanted to provide this quote initially but totally forgot about it.
Posted by cassandracomplex on March 25, 2013, at 12:32:31
In reply to Re: Parnate Therapeutic Effect and MAOI Inhibition, posted by vanvog on March 24, 2013, at 13:53:35
> "The full therapeutic dose of tranylcypromine is no less than 0.8mg/kg/day, and can be 1.5-2mg/kg/day. The 60mg/day maximum dose is a fiction. It's really around 120-200mg/day, and any competent psychiatrist knows this."
>
> by Chairman_MAO, I wanted to provide this quote initially but totally forgot about it.
>
> http://www.dr-bob.org/babble/20070219/msgs/734479.htmlReally? Because I see a MAOI expert (one of the founders of "atypical depression," has done numerous research studies - recently, one on Parnate + Dexedrine and now one on Parnate for bipolar) and I was pretty sure he said 60 mg to 120 mg was typical therapeutic use.
Has anyone here exceeded 120 mg? What was different about its side effect profile, if anything?
(Of course, there will always be fast metabolizers who need higher doses of meds in general but I've never known anyone who exceeded 120 mg of Parnate. If there was a partial response to 120 mg and side effects were tolerable, I can imagine that stimulant augmentation would be the next step rather than continuing to push the dose. I will be sure to ask him when I see him this week.)
Also, I wasn't aware that Parnate had a linear "mg by kg" response. When I weighed 100 lbs, I took 120 mg and now, at 115 lbs, I've been titrating onto it again and the therapeutic response has just kicked in at 70 mg. I have friends who weigh more than this who responded to lower doses (though none below 60 mg/day) but none exceeding 120/day, either.
Posted by damnthislife on April 10, 2013, at 13:13:43
In reply to Re: Parnate Therapeutic Effect and MAOI Inhibition » vanvog, posted by cassandracomplex on March 25, 2013, at 12:32:31
>
> Really? Because I see a MAOI expert (one of the founders of "atypical depression," has done numerous research studies
- Don't suppose you're in the Baltimore/Tri-state area, are you? I would love to find an expert on Atypical Depression (one that isn't afraid of MAOI's
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