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Re: MAOIs, benzos, etc. » paulk

Posted by Elizabeth on June 29, 2001, at 8:44:13

In reply to Re: MAOIs, benzos, etc. » Elizabeth, posted by paulk on June 28, 2001, at 5:11:25

> >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 rapdily.

> 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 labelling (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. 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. MAO begins to return to normal levels within a few days; the two-week washout period recommended between stopping MAOIs and starting other serotonergic ADs is really very conservative.

> Hmmm – I have had the same effect on higher dosages of Effexor – 150mg/day

That's consistent with the reciprocal interaction model (considering the dose-dependent effects of Effexor on NE reuptake).

> I’ve only seen this dosing scheme suggested for Nardil??

It's actually in the labelling for Nardil. But there are an awful lot of errors in the labelling 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.?

> If the idea is to bring down the level of MAO and then maintain it there; it makes sense. That is the pills knock out so much MAO enzyme – after which you just need to knock out what the body replaces – thus a lower dose. I’m going to have to dig into this deeper.

For one thing, MAO is regenerated faster than one might expect. When you drop down to 15 or 30 mg, you might not experience an immediate clinical effect (and MAO levels won't increase too much in a single day), but in the long-term, an altered equilibrium will be established where you have a level of MAO inhibition less than what is required keep neurotransmitters from being metabolised sufficiently to maintain the cellular changes thought to be responsible (hand wave, hand wave) for the antidepressant effects of these drugs. (Are you with me here? < g >)

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.

> Now, if the drug has a dual MAO plus a GABA effect. I could see that the MAO level could be maintained at a low dose, but to maintain a higher level of GABA might require a higher dose, which would explain return of panic attacks.

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 return

(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.)

> (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).

> 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.

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.)

> He may have been getting them from 2 or three doctors at once.

That's a hallmark of drug abuse (although it doesn't prove drug abuse, it's highly suggestive). My guess is that he was trying to self-medicate his moods (to less-than-adequate effect) with benzos. This can be tempting, as they are fast-acting and have few side effects compared to lithium and most anticonvulsants and antidepressants (and certainly compared to all currently used antipsychotics).

> Probably not the best medicine for a Biopolar – but he seemed to enjoy his manias – might have just wanted to be able to sleep and return to his mania the next day.

That's not uncommon. Bipolars are notorious for going off their meds because they miss the manias and don't feel "productive" in a normal mood. It would be nice if mild hypomania were sustainable, but for most people it isn't.

> >I guess I'm confused. What sort of anxiety were you taking it for? (Any diagnosis?)
>
> GAD with mixed depression – probably better called atypical depression in my case.

GAD covers a lot of territory. Can you be specific?

> I define anxiety as fear/worry – some people try to control fear by avoiding the stimulus, others by fighting it (sounds like fight / flight adrenalin). I have done a bit of both – getting irritable /angry has the advantage of giving the illusion of being in control.

Perhaps anxious people who have a "control freak" < g > response or personality type are likelier than others to have weird reactions when the anxiety is relieved?

> At times I have had panic attacks –light headed, heart palpitations, shaky hands and voice.

That's common in depression, especially atypical, anxious, or mood-reactive depression.

> But I can go long times with out those symptoms – and will get quite irritable if I feel I’m getting pushed into a situation that will cause me anxiety.

That's, I suspect, a temperamental 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.

> I wonder if depression is an adaptation to anxiety – hypersomnia, not eating, less active, fatigue, low self estemem would all help a cave man avoid anxiety producing situations.

I think that hypersomnia and lethergy in atypical depression could be avoidance responses, yes. (Atypical depression is most commonly associated (by definition, but also by statistical study of symptom clusters that tend to occur together) with overeating, not undereating.)

> First time – half pill in the morning – that evening I had rebound anxiety – and even edgy the next day.

Wow. You seem to be very sensitive to benzos. (Half of what strength pill, BTW?) I think that if a drug has that profound effect on you, it's not too surprising that you will experience a rebound effect. I also would hazard a guess that perhaps this type of rebound puts certain people at increased risk for addiction.

-elizabeth


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