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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 8 of 8. This is the beginning of the thread.
Posted by Ben on September 29, 2011, at 14:38:52
I take Parnate 80 mg in the morning. I read several times that it is recommended to split the dose. Is it only about the short half-life?I`m looking at the irreversible inhibition of the MAO which can last 7 to 14 days so why we should split the dose?
Posted by Ben on September 29, 2011, at 14:44:02
In reply to Parnate --) to split or not?, posted by Ben on September 29, 2011, at 14:38:52
> I take Parnate 80 mg in the morning. I read several times that it is recommended to split the dose. Is it only about the short half-life?I`m looking at the irreversible inhibition of the MAO which can last 7 to 14 days so why we should split the dose?
Whats your experience and with a look on sleep too.
Posted by Chairman_MAO on September 29, 2011, at 19:24:38
In reply to Parnate --) to split or not?, posted by Ben on September 29, 2011, at 14:38:52
If you're at 80mg/day, you should probably go higher. Everyone's different.
You are dealing with a lot more than just MAO inhibition (which is actually semi-reversible).
With high-dose tranylcypromine, you're taking advantage of a synergy of its myriad metabolites and the parent compound (and other actions).
Shoot for 1.5mg/kg/day, max 200mg/day (as tolerated).
"Regarding the irreversible monoamine-oxidase inhibitor tranylcypromine, a few open-label
studies suggest an increase of therapeutic efficacy when raising the dose up to 100200 mg/d.In an original study
conducted by Amsterdam & Berwish, seven highly refractory
patients were given a dose increase to
90170 mg/d (mean: 112 mg ± 16 mg) [4].Four of the patients
achieved full remission and one patient remitted
partially. Treatment length ranged from two weeks to
four months. Interestingly, mild side effects, mainly hypotonia,
diminished at the maximum dose range. Tyramine-
induced reactions were not observed at all.Amsterdam
confirmed his own findings in a later publication
after expanding his sample to 14 subjects [5]. With a
mean dose of 128 mg/d (± 27 mg/d), 50% of patients
showed full remission and 21% showed partial remission.
Sympatholytic side-effects occurred frequently
(71 %), but mainly at moderate doses. In both of Amsterdams
studies, however, the previous unsuccessful
treatments had not been performed with tranylcypromine,
so these trials cannot be regarded as doseincrease
studies in the strict sense. The effectiveness of
ultra-high doses of tranylcypromine in treatment-refractory
patients has also been supported in several case
reports [46, 76, 90, 98].
■ Other antidepressants
A recent small-scale open study of 5 patients resistant to
different previous treatments found that 4 of 5 patients
responded (ΔHAMD ≥50%) to ultra-high-dose treatment
with venlafaxine (450600 mg/d) [61]. Tolerability
was also reported to be good.The small sample size and
long study period of six months, increasing probability
of spontaneous remissions, are major shortcomings of
this study.""Ultra-high dose
treatment of
tranylcypromine
sympathomimetic
(amphetaminergic)
effect compensates
sympatholytic side
effects""The irreversible MAO-I tranylcypromine might show
an increase of clinical efficacy in the ultra-high dose
range between 90 and 180mg/d suggesting a positive
dose-efficacy correlation. However, there seems to be a
flat relationship in the normal to high dose range when
MAO-inhibition is the main pharmacological mechanism
[4, 5]. The clinical effect of ultra-high dosages of
tranylcypromine is hypothesized to be related to an amphetaminergic
effect, which occurs in the high-dose
range.MAO-inhibition is not likely to be solely responsible
for the clinical effect in high-dose treatment since
a sufficient portion (90%) of MAO is already inhibited
by the administration of 10 mg tranylcypromine per day
[95]. This treatment is reported to be relatively safe with
side effects decreasing while doses increase. However,
when considering these open studies of ultra-high-dose
effectiveness of the MAO-I tranylcypromine, it is important
to note that before the double blind studies with fluoxetine
were carried out, this agent was regarded as a
promising candidate for high-dose treatment based on
the results of one open study"Sorry for the missing citations, if you want them I can get them for you.
Posted by Ben on September 30, 2011, at 0:57:27
In reply to Re: Parnate --) to split or not? » Ben, posted by Chairman_MAO on September 29, 2011, at 19:24:38
thanks for you great informations but at ultra high-doses isn't it acting so stimulant that you get too nervous and cant sleep any more?
Posted by europerep on September 30, 2011, at 7:47:17
In reply to Re: Parnate --) to split or not? » Chairman_MAO, posted by Ben on September 30, 2011, at 0:57:27
> thanks for you great informations but at ultra high-doses isn't it acting so stimulant that you get too nervous and cant sleep any more?
The question is whether you need a higher dose in the first place. Your opening post didn't sound like it, so I totally don't get ChairmanMAO's point that you *should* raise the dosage.
At any rate, the splitting up of doses of Parnate is, as far as I know, only about sleeping issues and insomnia. If you tolerate 80mg once a day, I think that's fine. And you said it, it's the pharmacodynamic half-life that counts, so you don't have to worry that your MAO levels are going up and down because you don't split the dose.
hope that helps.
ER
Posted by Chairman_MAO on October 1, 2011, at 15:18:54
In reply to Re: Parnate --) to split or not? » Ben, posted by europerep on September 30, 2011, at 7:47:17
> > thanks for you great informations but at ultra high-doses isn't it acting so stimulant that you get too nervous and cant sleep any more?
>Yeah, that can be a drawback. But I had that at the lower doses just as badly; didn't notice much of a difference between the two, honestly. I always had to take something to sleep, sometimes even clonidine + something else.
> The question is whether you need a higher dose in the first place. Your opening post didn't sound like it, so I totally don't get ChairmanMAO's point that you *should* raise the dosage.
>The point is that high-dose tranylcypromine is a different animal at the higher doses, because ...
> At any rate, the splitting up of doses of Parnate is, as far as I know, only about sleeping issues and insomnia.
... tranylcypromine gets metabolized into other active drugs. Certain side effects diminish at the higher doses. Take it however it helps; if yo uhave to take it all in the morning to avoid insomnia, go for it, but I found that to be a lackluster solution because _it's not just an MAO inhibitor_.
> day, I think that's fine. And you said it, it's >the pharmacodynamic half-life that counts, so you >don't have to worry that your MAO levels are going up and down because you don't split the dose.
This is an MAO inhibitor. There are no "MAO levels going up and down" of any significance. This is not like moclobemide. Not irreversible like the hydrazines are either, but this is a red herring.
Best of luck.
Posted by europerep on October 1, 2011, at 18:10:52
In reply to Re: Parnate --) to split or not?, posted by Chairman_MAO on October 1, 2011, at 15:18:54
> This is an MAO inhibitor. There are no "MAO levels going up and down" of any significance. This is not like moclobemide.
How does this differ from what I said?
Posted by Chairman_MAO on October 5, 2011, at 22:35:56
In reply to Re: Parnate --) to split or not? » Chairman_MAO, posted by europerep on October 1, 2011, at 18:10:52
I obviously misread what you said, because it doesn't differ at all.
This is the end of the thread.
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