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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 6 of 6. This is the beginning of the thread.
Posted by cumulative on August 21, 2007, at 18:02:03
Googling Nardil + REM ...
Very interesting. Like others I would expect this to be disastrous for cognitive function, subtle and apparent, but a great deal of studies have been able to find no impairment whatsoever. Actually, the bulk of antidepressant effect seems to kick in around the time that REM is completely inhibited ...
Thoughts?
From THE CASE AGAINST MEMORY CONSOLIDATION IN REM SLEEP
http://www.bbsonline.org/Preprints/OldArchive/bbs.vertes.html3.1. Monoamine oxidase inhibitors (MAOIs)
Of the antidepressants, the MAOIs have the strongest suppressive action on REM sleep. A number of early reports using normal and patient populations showed that MAOIs virtually completely (or completely) suppressed REM sleep for weeks to several months. In an initial study, Wyatt et al. (1969) reported that the MAOIs, isocarboxazid, pargyline hydrochloride, and mebanazine, reduced REM from about 20-25% of TST to 9.7%, 8.6% and 0.4% of TST, respectively, and that in one subject REM was virtually eliminated for two weeks.
In a subsequent report in anxious-depressed patients, Wyatt and co-workers (1971a) described the remarkable findings that the MAOI, phenelzine (Nardil), given at therapeutic doses, completely abolished REM sleep in six patients for periods of 14 to 40 days. There was a gradual decline in amounts of REM sleep for the first two weeks on the drug and a total loss of REM after 3-4 weeks. In a complementary study with narcoleptic patients, Wyatt et al. (1971b) reported that phenelzine completely abolished REM in 5 of 7 patients for the following lengths of time: 14, 19, 93, 102 and 226 days. They stated that: "The complete drug-induced suppression of REM sleep in these patients is longer and more profound than any previously described"; and further that "No adverse psychological effects were noted during the period of total rapid-eye-movement suppression".
Several other studies have similarly shown that MAOIs essentially abolish REM sleep. Akindele et al. (1970) reported that phenelzine completely eliminated REM sleep in four subjects (one normal and 3 depressed) for 2 to 8 weeks, and addressing possible behavioral consequences stated that "Far from this leading to disastrous effects on mental functions, as some might have proposed, clinical improvement began". Kupfer and Bowers (1972) showed that phenelzine abolished REM in 7 of 9 patients, and drastically suppressed it in remaining patients from pre-drug values of 23.1% and 24.8% of TST to 1.4% and 0.5% of TST, respectively. Finally, Dunleavy and Oswald (1973) reported that phenelzine eliminated REM in 22 depressed patients.
If REM sleep were involved in memory consolidation, it would seem that the total loss of REM with MAOIs for periods of several months to a year (Wyatt et al. 1969, 1971a, 1971b; Kupfer & Bowers 1972; Dunleavy & Oswald 1973) would affect memory. As indicated above, the loss of REM did not appear to be associated with any noticeable decline in cognitive functions in these largely patient populations. These studies, however, made no systematic attempt to assess the effects of MAOIs on cognition.
Other reports, however, have examined the actions of MAOIs, primarily phenelzine, on cognition/memory and described an essential lack of impairment (Rothman et al. 1962; Raskin et al. 1983; Georgotas et al. 1983, 1989). For example, Raskin et al. (1983) observed no adverse effects of phenelzine on a battery of 13 psychomotor and cognitive tasks in a heterogeneous population of 29 depressed patients. Similarly, Georgotas and colleagues (Georgotas et al. 1983, 1989) reported that elderly depressed patients given phenelzine for 2 to 7 weeks showed no alteration in several measures of cognitive function, and concluded that the lack of adverse effects with phenelzine suggests that it is preferable to TCAs (see below) in the treatment of depression in the geriatric population.
Posted by linkadge on August 21, 2007, at 19:40:19
In reply to Nardil completely suppresses REM sleep, posted by cumulative on August 21, 2007, at 18:02:03
Interesting. Yeah. You can produce an almost instintanious antidepresant effect in some of the most severly depressed individuals just by wakening them every time they begin to enter REM sleep. They knew this way back in the 70's.
Perhaps certain aspects of memory are consolidated during REM sleep. Ie perhaps mood related memory is processed during REM sleep.
Linkadge
Posted by FredPotter on August 22, 2007, at 22:23:53
In reply to Re: Nardil completely suppresses REM sleep, posted by linkadge on August 21, 2007, at 19:40:19
ECT also knocks out REM I believe. Also it's well-known that a night without sleep will temporarily alleviate depression. The trouble is one morning my little boy was sound asleep and his eyes were still. When I woke him he jumped and said he was dreaming about having a tooth out with a gigantic pair of pliers. So perhaps REM and dreams don't match exactly.
I'm on Nardil and my sleep is shallow and short without apparently any dreams, and I feel great
Posted by Girlnterrupted78 on August 23, 2007, at 3:00:34
In reply to Re: Nardil completely suppresses REM sleep, posted by linkadge on August 21, 2007, at 19:40:19
This stuff is really new for me, so I don't quite understand everything. But I did a search and found this:
CONCLUSIONS: Antidepressant response to phenelzine treatment does not depend on elimination of REM sleep or inhibition of SWA in non-REM sleep. In depressed patients, REM sleep is regulated independently from non-REM sleep and can be manipulated without altering the dynamics of SWA.
Just a question: Why would elimination of REM sleep have antidepressant effects? Does this have anything to do with neurotransmitters? My understanding is that depression might be caused by a depletion or a lack of serotonin, dopamine, norepinephrine, GABA, etc. What is the role of REM in here?
Thanks for the info
Posted by cumulative on August 23, 2007, at 15:10:51
In reply to Re: Nardil completely suppresses REM sleep » linkadge, posted by Girlnterrupted78 on August 23, 2007, at 3:00:34
No one's really sure. Like Fred said, sleep deprivation will produce rapid euphoria. High cortisol doesn't feel all that bad sometimes.
As for REM sleep? My working theory: maybe REM sleep is just a less-effective version of deep sleep, a less-developed deep sleep state, conferring less rest but (and here is the evolutionary reason) easier to wake up from say if a tiger jumps on your head.
That's a great abstract, thanks. Yeah, I was pretty spurious about the idea of the REM abolishing being completely responsible for Nardil's pretty unique antidepressant effect.
Obviously there's a lot we still have to learn about sleep rhythms and sleep cycles.
Posted by linkadge on August 23, 2007, at 22:17:12
In reply to Re: Nardil completely suppresses REM sleep » linkadge, posted by Girlnterrupted78 on August 23, 2007, at 3:00:34
Well, I wouldn't say this study actually proves that REM supression doesn't have antidepressant effect in some people, only that some people don't respond to REM supressors as antidepressants.
Different types of depression respond to different types of antidepressants. There are a few antidepressants that do not reduce REM sleep, (only two that I know of, namely bupropion and a TCA called trimipramine).
But, the thing is that there are types of depression for which those drugs are completely ineffective.
There is a link between the activity of the monoamines and REM sleep.
If you reduce REM sleep, you will actually increase serotonin in the hippocampus. (This is independant of the use of serotonergic drugs). Ie if you reduce REM sleep in an animal by non serotonergic drugs, you will still increase the serotonin content of the hippocampus.
There are other neurotransmitters that are altered by REM supression. Infact, continued REM supression produces a number of the same adaptive changes that are evident with long term AD administration, namely downregulation of 5-ht2a receptors, increased sensitivty of d2 receptors etc.
The mechanism of antidepressant effect of total sleep deprivation is not completely known but seems to involve many neurotransmitter systems. It seems to have a psychostimulant like effect. It can reduce hyperactive limbic metabolsm. It can increase the activity of monoamines. It can decrease the seizure threshold.
Complete relapse can happen if patients take even the shortest of naps. As little as 1 minaute of REM sleep recorded on and EEG can result in complete relapse.
I personally think that its got to do with affecting the cholinergic/monoaminergic ballance.
If you stress an animal, it will begin to show the exact same patterns of REM sleep that are evident in depresion. I think this is an adaptive responce. The brain is increasing the REM duration to try and put more brain processing into emotionally relavant material. (Ie to try and process the stressfull events). The REM induced increase in cholinergic activity reduces monoaminergic neurotransmission which makes it difficult to move forward.
Roughtly speaking cholinergic activity lets one reflect on previously established connections, wherase the monoamines promote the growth of new connections.
Linkadge
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