[Snipped]

Thanks for the above explanation and the interesting story below.  While on the
subject of benzodiazepines, I know that they are CNS depressants, but does this
mean that they can also cause depression in the clinical (i.e. psychiatric)
sense, or does it just mean that they make you sleepy and in large enough doses
could cause respiratory depression or whatever?  If you are taking an
antidepressant but are also anxious, is there any likelihood of the benzo
counteracting the effect of the AD?  Another thought:  I've read that the drug
reserpine can cause depression.  Is it considered a CNS depressant?  In other
words, is there any relationship between a drug being a CNS depressant in the
hypnotic sense and causing depression in the psychiatric sense of the word?

  While on the

    They make you sleepy, but aren't much in the way of respiratory
depressants in and of themselves (though in combination with other
depressant {*filter*} they can add to the effect).  So far as depression
goes they are pretty neutral.  Alprazolam/Xanax in fairly high doses
has some antidepressant properties.

 If you are taking an

   Not much of one.  I use them both together in patients all the
time-- the benzo while we wait a month of the SSRI to get fully kicked
in.

   No.  It causes affective depression but isn't a "CNS depressant."
Which seems odd but reflects the two completely different senses of the
word as used in medicine.  The latter term generally refers to level of
consciousness and respiratory function.  It has little or nothing to do
with with affective depression (sadness/anhedonia/phycomotor
retardation etc).

In other

word?

    No, not really.  Though there are some {*filter*} (most notably {*filter*})
which are famous for having both actions in chronic use.

                                   Steve Harris, M.D.

A better example of a CNS depressant is amitriptyline - marketed as an
antidepressant, and much more of a CNS depressant than, say, alprazolam.

(I've never heard of alprazolam being used for depression; how high a dose are we
talking?)

"Depress" just means "to decrease the activity of" - which is odd if you consider
the phrase "agitated depression." :-)

-elizabeth

writes:

    Hard to say.  Certainly not on a milligram/milligram basis!
Tricyclics are not classical CNS depressants like {*filter*}.  At low
doses their mental effects are probably mostly anticholinergic.  At
overdoses people typically go though a restless e{*filter*}ment phase before
slipping into coma (animals do this with barbs, but people less often).

   Upwards of 5 mg a day and usually 10-15.  A LOT.

    Yeah, "depression" is used as short for:

1) depression of respiratory drive
2) depression of alertness (sleepiness)
3) depression of ability to focus attension (aka delerium).  
4) depression of affect/mood

"Aggitated depression" refers to people with the last two losses.
Classic CNS depressants cause the first three, and after chronic use,
often all four.   Tricyclic antidepressants often cause #2 while
atempting to reverse #4.

What {*filter*} would be used to treat agitated depression?  And is this like anxiety
with depression?  What about people whose anxiety (or fear) doesn't seem to be
completely supressed by benzodiazepines?.  For the past couple weeks I've been
very sad and frightened and have been on Zoloft and clonazepam.  The clonazepam
helps some, but only partially.  Are there {*filter*} that work more specifically on
fear than anxiety?  I'm reproducing an article I'd saved below on fear and the
amygdala from the London Times.  Do benzos act on the amygdala?

February 22 1998        The Sunday Times

      Science finds key to beating fear

               by Steve Connor
            Science Correspondent

SCIENTISTS have found the seat of fear in the
brain, proving that one of the most potent
human emotions has a chemical basis and
raising the prospect of a new generation of
{*filter*} that could make man fearless.

In a ground-breaking study, researchers have
shown how the electrical circuitry of the
brain is altered by an individual's exposure
to frightening experiences.

The study will increase our understanding of
how fear can overwhelm the normal functioning
of the brain and open the way to the
development of effective treatments to combat
panic attacks, anxiety and phobias.

Scientists found that the emotion of fear is
biochemically manufactured in tiny pathways
between nerve cells in a small, almond-shaped
structure within the brain called the
amygdala, which is thought to be central to
the processing of other primal emotions.

A key finding is that certain connections
between the nerve cells within the amygdala
become strengthened when someone learns to
fear something. This raises the rate at which
nervous signals can flow through the brain's
fear centre, and so increases the intensity of
the emotion. In this way the scientists have
shown that, emotionally, the brain can learn
from experience.

Patricia Shinnick-Gallagher, professor of
pharmacology and toxicology at the University
of Texas, who led one of the two research
teams, says it is the first time anybody has
shown that the experience of fear has a
physical impact on the wiring of the brain.

"I guess you could say we have described the
seat of fear in the brain.

"We can now determine the actual mechanisms
underlying fear and can specifically design
{*filter*} to treat patients who cannot exert
control over their fears," she said.

The latest findings on how the amygdala
handles fear stem from the work of Professor
Joseph LeDoux, a leading authority on the
emotional nature of the brain at the Center
for Neural Science at New York University.

He discovered that rats conditioned to a
frightening or painful situation developed
more intense neural communication in the
amygdala than those who were not. The rats
were given a small electric shock following
the sound of a buzzer.

They learnt to be fearful of the sound of the
buzzer. "We are born with the ability to be
afraid but we learn about most things that
make us afraid," said LeDoux.

Professor Barrie Gunter, a psychologist at the
University of Sheffield, said that fear was
one of the most basic emotions and evolved as
a vital survival reflex.

It provoked a range of physical responses -
including increased adrenaline production and
raised heart rate - which improved an animal's
ability to defend itself or to escape from
danger.

"It's a way of learning to cope with our
environment and we still have this vestigial
need to face up to challenging situations,"
Gunter said.

Excessive fear can, however, be crippling. In
wartime, exposure to repeated terror has
caused total psychiatric collapse among
soldiers. In the second world war, more than
half a million American soldiers were treated
for mental illness provoked by uncontrollable
fear.

In civilian life, psychological disorders such
as anxiety and phobias are often untreatable.
Valium, the most popular anti-anxiety drug,
carries a risk of serious side-effects, from
loss of balance to hallucinations. The
discovery of the amygdala's fear circuitry now
offers scientists a specific target to design
{*filter*} that affect only the fear centre of the
brain, leaving other functions unimpaired.

The amygdala lies at the base of the brain and
is considered one of its most ancient
structures, which first evolved many millions
of years ago, long before the evolution of the
"higher" centres of the brain in the cortex
responsible for thinking and consciousness.

LeDoux believes that humans are at a point in
their evolutionary history where the emotions
created by the amygdala overwhelm the thinking
brain in the cortex. In the future, he said,
this balance could shift away from emotion,
but this would take thousands of years and in
the meantime the only way of repressing
unwanted fear would be to develop new {*filter*}.

"We have shown that the amygdala is like the
hub in the centre of a wheel of fear. If we
understand the pathways of fear, it will
ultimately lead to better control," said
LeDoux.

For agitated depression, sedating antidepressants are usually preferred,
sometimes in combination with an antipsychotic.  (Risperdal, Zyprexa, and
Seroquel are the safest antipsychotics available in the U.S. at present.)
Examples of sedating antidepressants are imipramine, amitriptyline,
nortriptyline, doxepin, maprotiline, and mirtazapine (Remeron).

Is there something in particular that has you feeling fearful, and what other
symptoms do you have?

"Agitation" isn't terribly well defined, I don't think, but the connotation is
that it's more severe than "anxiety."

One other thing you might consider: antihypertensive {*filter*}, particularly
clonidine and the beta-adrenergic blockers (atenolol, propranolol, pindolol,
nadolol, etc.).  Clonidine is used quite a lot (around here, anyway) for
agitation in children, in particular.

The amygdala connection, unfortunately, is nothing new and hasn't proven too
fruitful in the quest for treatments for debilitating fear.

Good luck, eh?

-elizabeth

   The classic best ones are MAO inhibitors such as Nardil.  However,
due to safety concerns, SSRIs are generally tried first.  These days,
only the psychiatrists have much experience using MAO inhibitors.

   I would say anxious depression is a subset of the aggitated sort.

   They aren't getting enough benzodiazepines.  With enough benzos you
can convert even small wild animals (foxes) to tame ones.  In fact,
there is a classic study along that line.

  For the past couple weeks I've been

   Same thing, more or less.  Benzodiazepines are the drug of choice,
followed for chonic use by SSRIs, and MAO inhibitors.   Busapr has
effects, but they are mild and generally people who need benzos don't
get much kick from Buspar ("I get no kick from Bu-spar/  Mere {*filter*}
doesn't thrill me at all...").

    Yes.  Just out of curiosity, and for my own private series-- are
you Jewish?  I have seen a very large number of Ashkenazi with terrible
anxiety-- whether genetic or cultural/environmental, I cannot, of
course, tell.  I think with some pet scanning there's a fascinating
paper to be written on the Jewish amygdala (preface by Woody Allen).
Why is New York the only state in the union where benzodiaezpines
require a triplicate prescription?  There's a story here waiting to be
told, but it'll probably take Jewish phychiatrists to tell it (I mean,
other than Freud, who on the basis of his study of mostly Viennese
Jewish women, seems to have more or less decided that anxiety was the
key to most non-schizophrenic mental illness).

                                             Steve Harris, M.D.

Well, it's a relief to know that I'm generally taking the right {*filter*} then,
given that my psychiatrist put me on Zoloft and clonazepam (and I also got some
Xanax from my family doctor).  My psychiatrist also recommended that I take
Neurontin (gabapentine) saying that although my EEG was basically normal, there
was some abnormality in the voltage, especially in the temp{*filter*}lobe region
(don't ask me what all this means, I'm just repeating what he said as best as I
remember it).  I'm wondering if I should get another opinion regarding the
Neurontin, although from what I've read on the Net about it, it seems pretty
safe.

Well, I just took another Xanax after reading that.  It does seem to help, but
will tolerance develop?  If I really need it I'm not so concerned about
"{*filter*}ion," but I'd be somewhat concerned if I had to take more and more to get
relief, if only because it requires a prescription and I'd be afraid my doctor
wouldn't give it to me.  I've been on the Zoloft for about two and a half weeks,
and am now up to 150 mg/day.  After a few more weeks might the Zoloft also have
an anti-anxiety effect allowing me to reduce the dosage of the benzos?

"....so tell me why should it be true/ that I get a kick out of you.

"Some get a kick from {*filter*}/ But I am sure that if I took even one sniff it
would bore me terrifically, too/ but I get a kick out of you.

"Some get a kick from a plane/ Often at night I go up for a flight but I just
fall asleep when I do/ but I get a kick out of you."

Nice to lighten things up a little :)

Well, as far as I know, no, but I read an interesting article that I'm
reproducing part of below on the unusually large difference between verbal and
performance IQs in Ashkenazi Jews, and as my verbal IQ is almost 40 points
greater than my performance IQ as measured by taking the WAIS three times, I
wonder if there might be some connection between this and some emotional
problems I've had, or if there might be some Jewish ancestry in my family.

---------

The average IQ of Ashkenazi Jewish children is about I SD above that of white
controls.... Equally interesting is the disproportion of verbal and performance
tests, with verbal IQ much higher than performance IQ....The correlation between
verbal and performance tests is about 0.77 in the general population, hut only
0.31 among Jewish children. Differences of
10-20 points have been found in samples of Jewish children; there is no other
group that shows anything like this size difference.

---------

I'll send you the article in an email.

I don't know.  Why?  If there are that many anxious Jews you'd think they'd want
them available OTC  :)

I'm not sure I understand what you're saying here.  Based on your observations
of anxiety in Ashkenazi Jews, do you tend to agree with Freud?  I mean why did
you say "other than Freud"?  Or are you saying that because Freud had already
made up his mind on the subject that it would be better to have someone else
study it to make sure that you're getting an unbiased point of view?

True; but tricyclic plasma levels vary so much among individuals anyway....

Anticholinergic and sedative (anti-H1 and -alpha1), the degree depending on
the specific drug (amitriptyline has the worst repuatation).  I was referring
to tricyclic intoxication, yeah (phenobarbital, for example, isn't much of a
CNS depressant at low enough doses, but everybody recognizes that it is one).

I guess that is a lot. :-} Do they know (or have some sort of speculation)
why it works that way?  (i.e., what it does that makes it an antidepressant)

-elizabeth

writes:

Oh, guh-roovy.  What I'd like to know is what emotion is appropriate when
confronted with evidence that the popular press actually thinks that the
whole human race would be better off on some kind of Soma?  Here's your
warlord armed with chemical weapons, here's your local prison camp with
1% of the population and rising, there's your kid being marched around in
uniform and indoctrinated to obey orders without question, but don't
worry, be happy, today there are {*filter*} to MAKE you like the established
order, and tomorrow they'll come up with electrodes and things to make
you obey them too, but you WON'T BE AFRAID!!!

There's nothing wrong with the human capacity to fear, except that you
can't really be afraid all the time, and with all the nuts armed with
technology they plan to use on you, you SHOULD be afraid all the time.

   I've got news for you all: SOMA is here already.  Except that the
name had already been taken by cardisoprodol, so they called the new
stuff "Xanax."  A milligram is worth a damn.

                                        Steve Harris, M.D.