Posted by paulk on June 29, 2001, at 19:29:43
In reply to Re: MAOIs, benzos, etc. » paulk, posted by Elizabeth on June 29, 2001, at 8:44:13
> > >No, the increase in neurotransmitter concentrations takes place immediately.
> >
> > This is not at all what my doctor told me???
>
> "Immediately" is imprecise: what I mean is that it doesn't take a few weeks (or even days) for the increase in monoamine levels to be observable; as with reuptake inhibitors, this effect happens rapidly.
>I was told it takes about three weeks to knock out enough MAO to raise the level of monoamines. I experienced the loss of accommodation I always notice with an increase in seritonin level at about 3-4 wks. I saw a decrease in BP the first couple of days that seems to correlate with the short half-life of the drug comes on in the first 30min and goes away in 3-4 hours.
> > He said that the reason they ramp the drug up to 60mg/day is that it takes some time to knock out enough MAO to effect the monoamines – after that, the MAO level can be kept low by a lower dosage that is only knocking out the amount that the body is replacing.
>
> This idea hasn't been borne out by practice. Despite the labeling (which hasn't been changed much since the drug's original approval in 1959, BTW), current clinical experience seems to support the continued use of the effective initial dose in maintenance therapy.Sort of what my doctor just told me yesterday – the drug is so cheap – and there doesn’t seem to be a problem with knocking out too much of the MAO so why not just keep the dose up for an incremental improvement.
>I don't know of any evidence supporting the idea that a lower maintenance dose is clinically effective. A dose of around 45 mg/day typically results in 80% inhibition of MAO, incidentally.
That’s not enough from what I understand.
>MAO begins to return to normal levels within a few days;
Yes, but getting down to 90% can take much longer – 80% probably is not enough to do any good.
Think of a flooded basement up to the first floor with water still coming in through the walls – you turn on a small pump that has to pump out the basement AND any water that is still coming in.
After three weeks you get 90% of the water out - now the water comes in a bit quicker so you approch an equilibrium. If you turn off the pump it takes very little time for the water to go back up to 80%.
The monoamines only start to increase after the MAOs are down to about 90% This explains the slow onset of the drug – especially when you realize that the monoamines need to be higher for another 3 – 6 weeks for the drug to reach maximum effectiveness.
>the two-week washout period recommended between stopping MAOIs and starting other serotonergic ADs is really very conservative.I sort of though so – I asked about that and my doc said it had more to do with lawyers – in theory you should be able to switch between MAOIs without waiting – probably the attitude is that it would cost a lot to study – so they go ultra conservative and reduce risk of a lawsuit and reserve an extra excuse.
> It's actually in the labelling for Nardil. But there are an awful lot of errors in the labeling for Nardil. It's an old drug. They really should just rewrite the product monograph entirely, but who wants to waste the time and money on that when a drug is old, off-patent, not very popular in the first place, etc.?
Not to mention the liability costs of doing so. If it weren’t for all the lawsuits, I bet it would have been rewritten already.
> Also, as I noted, although monoamine concentrations increase rapidly in response to MAO inhibition, increased MA concentrations are not directly responsible for the clinical effects of monoaminergic antidepressants.I would have to see numbers on this – the body is replaces MAO constantly – but sort of slowly – to reach a steady state of 90% is supposed to take weeks. The tertiary effect of the increase in neuro-transmitters is immediate AND long term – I respond in a better mood quite rapidly to SSRIs. There is evidence that while the Seritonin levels are higher, new neurons are formed (I think it was near the hippocampus) and over the course of weeks to many months cause long-term changes one could think of as healing. For atypicals like myself – there is probably some genetic or endocrine system defect that makes effective treatment it a lifelong deal.
> The increase in GABA levels occurs via a similar mechanism to that responsible for increases in monoamine levels: phenelzine (as well as many other hydrazine-related compounds) inhibits an enzyme that catalyses a major metabolic pathway of GABA. Allowing this enzyme to returnI have looked for this GABA effect written somewhere – where did you see it? (not in the PDR of course)
>
> (BTW, in case this is of any relevance, I have primary depression, while the panic may be primary or it may result from the depression and other factors. It's definitely not the case that my depression is the result of panic disorder, because I was depressed long before I ever had a panic attack.)Atypical depression?
>
> > (That’s a lot of ifs, but I don’t remember seeing that the increase in GABA was due to the missing MAO – so I could imagine that it could have a different dose dependency than the increase in Monoamines.)
>
> That's right. Non-hydrazine MAOIs, like Parnate and selegiline, don't increase GABA. Phenelzine inhibits GABA transaminase (the enzyme alluded to above -- this mechanism is analogous to MAO inhibition and makes phenelzine a novel anxiolytic).I’m confused – if we inhibit GABA transaminase – wouldn’t there be an increse in GABA?
>
> > My hunch, which could easily be wrong, but I hope to find the answers, is that the lowBP is not caused by the increase in Monoamines, but is a different effect of the drug.
>
> It's caused by NE increase, though not directly.I’m Confused again – I would think that an increase in NE would cause an increase in BP – as happens with Effexor????
>
> About your friend...
>
> > It was my understanding that he had been using only benzos for the last 5 years.
>
> That explains why he was doing poorly. A person with severe bipolar disorder needs to be on, at a minimum, a mood stabiliser of some sort. (Often they need a combination of multiple mood stabiliers, antidepresants, antipsychotics, and/or benzos.)Yes – but he loved his manic state – couldn’t work or anything, but seemed not to get psychotic or nasty at the top – just outrageous and uninhibited -
> thing -- an individual trait -- perhaps related to the atypical depression. It's not the anxiety itself, but how you react to it. Atypical depressives are said to be "mood-reactive" in that they can sometimes be cheered up; they also tend to be unusually sensitive or emotionally reactive as a trait, even when not depressed.
Yep – that’s me. Even the very small dose of Clonazepam sure helps dampen the reactivity – just enough to keep me from moving from appropriately angry to feeling threatened and escalating the conflict. My wife had to adjust to it – she used to depend on me blowing up and eventually feeling guilty. She would even light the fuse to move the blame on to me. Now that doesn’t work anymore.
-Paulk
poster:paulk
thread:65795
URL: http://www.dr-bob.org/babble/20010625/msgs/68391.html