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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 JohnX on October 13, 2001, at 12:14:00
Scott,
I'm looking over your med list. Maybe we can
reason through to find a pattern that will help
you reach an end to your search. This has worked
well for me. Maybe it is psychosomatic for me, but
my working theories seem to correlate well with
responses I get from various meds.My primary thing that keeps me going is the
fact that "I have felt better". Logic dictates
that my brain still has the capability of experiencing
well-being. My main problem has been keeping any
response going, and so I look into that and
try to understand why, and I think I come to some
good conclusions.So here are a couple of starter questions:
- What happened on d-amphetamine?
- What meds if any did you get some sort of
"response", and what transpired ?
- Was there ever a period of time that you
felt "cured" even if it was only for a few
hours or days or weeks?-John
Yo' list:
imipramine
desipramine
amoxapine
amitriptyline
nortriptyline
protriptyline
clomipramine
tranylcypromine
phenelzine
isocarboxazid
moclobemide
clorgyline
trazodone
lithium
carbamazepine
valproate sodium
lamotrigine
gabapentin
bupropion
indalpine
viqualine
pk-8059
nomifensine
adinazolam
modafinil
bromocriptine
triiodothyronine
thyroxine
d-amphetamine
methylphenidate
idazoxan
mirtazepine
clonazepam
risperidone
olanzapine
ziprasidone
perphenazine
paroxetine
venlafaxine
fluoxetine
lorazepam
triazolam
temazepam
zolpidem
chlorpromazine
fluphenazine
pemoline
chloral hydrate
selegiline
quetiapine
placebo
Posted by JohnX on October 13, 2001, at 12:38:55
In reply to Scott - medication responses?, posted by JohnX on October 13, 2001, at 12:14:00
Scott,After looking over your prior postings you had
information that indicated many contrary reactions
to meds. You also described that a pdoc indicated
that you have symptoms that may be consistent
with those for PTSD. PTSD is an extremely complicated
disorder and the shape of the body during a
depression (spicifically in the HPA axis) will
show paradox's to those who are normally depressed.One such test for this is a dexamethasone suppression
test. (I think there is a better one). A depressed
person is administerred the synthetic steroid
dexamethasone. Generally
people who have depression are dexamethasone
non-supressors (levels of corticosteroids don't
drop with dexamethasone administration), they have elavated levels of
corticosteroids and this causes a down regulation
of inhibitory receptors. But for people with
PTSD who are depressed the *opposite* is seen.
The subject will generally be a super-suppressor
of cortisol when tested with dexamethasone. I have
looked at this and other biological underpinnings
to PTSD to try and understand my bizzare med
reactions and I have also tried to understand
how existing treatments may help me.Anyways, the latest thinking is that CRF antagonists are
the best way to break a back-asswords feedback
loop in the HPA axis (hypothalamis,pituitary,
adrenal gland).Personally, I think there may be ways to
stablize the area of the brain that is most
likely impacted by chronic stress (the locus
coerulus). Without robust feedback response
mechanisms in the body, depression can be
very elusive to treat. But I think with a will
there is a way.Have you been tested for abonormalities
in your HPA as I discussed?-john
> Scott,
>
> I'm looking over your med list. Maybe we can
> reason through to find a pattern that will help
> you reach an end to your search. This has worked
> well for me. Maybe it is psychosomatic for me, but
> my working theories seem to correlate well with
> responses I get from various meds.
>
> My primary thing that keeps me going is the
> fact that "I have felt better". Logic dictates
> that my brain still has the capability of experiencing
> well-being. My main problem has been keeping any
> response going, and so I look into that and
> try to understand why, and I think I come to some
> good conclusions.
>
> So here are a couple of starter questions:
>
> - What happened on d-amphetamine?
> - What meds if any did you get some sort of
> "response", and what transpired ?
> - Was there ever a period of time that you
> felt "cured" even if it was only for a few
> hours or days or weeks?
>
> -John
>
> Yo' list:
>
> imipramine
> desipramine
> amoxapine
> amitriptyline
> nortriptyline
> protriptyline
> clomipramine
> tranylcypromine
> phenelzine
> isocarboxazid
> moclobemide
> clorgyline
> trazodone
> lithium
> carbamazepine
> valproate sodium
> lamotrigine
> gabapentin
> bupropion
> indalpine
> viqualine
> pk-8059
> nomifensine
> adinazolam
> modafinil
> bromocriptine
> triiodothyronine
> thyroxine
> d-amphetamine
> methylphenidate
> idazoxan
> mirtazepine
> clonazepam
> risperidone
> olanzapine
> ziprasidone
> perphenazine
> paroxetine
> venlafaxine
> fluoxetine
> lorazepam
> triazolam
> temazepam
> zolpidem
> chlorpromazine
> fluphenazine
> pemoline
> chloral hydrate
> selegiline
> quetiapine
> placebo
Posted by SLS on October 14, 2001, at 15:09:25
In reply to Scott - medication responses?, posted by JohnX on October 13, 2001, at 12:14:00
> I'm looking over your med list. Maybe we can
reason through to find a pattern that will help
you reach an end to your search. This has worked
well for me. Maybe it is psychosomatic for me, but
my working theories seem to correlate well with
responses I get from various meds.
Hi John.I really appreciate that you have taken an interest in me.
I guess I can give you an idea as to which drugs helped and which ones hurt. I am a DST non-suppressor.
These produced partial or brief improvement:imipramine
desipramine
amitriptyline
nortriptyline
tranylcypromine
phenelzine
clorgyline
venlafaxine
paroxetine
d-amphetamine
lamotrigine
gabapentin
bromocriptine
olanzapine
viqualine
thyroxineThese produced significant exacerbations:
amoxapine
protriptyline
triiodothyronine
bupropion
moclobemide
reboxetine
mirtazepine
idazoxanDrugs I haven’t tried:
nefazodone
citalopram
sertraline
fluvoxamine
topiramate
tiagabine
sibutramine
pramipexole
pergolide
amisulpride
1. Tricyclics have made me feel 100 percent well for two or three days beginning on the 13th day of treatment. The switch into depression is abrupt and dramatic.2. A combination of tranylcypromine + desipramine produced the only long-term remission I have ever experienced in the last 25 years. I was functionally 100 percent, but I experienced residual anhedonia. This remission lasted for 6 – 9 months before a dysphoric or mixed-state mania developed. These drugs were withdrawn, and I was treated with lithium and clonazepam. Lithium produced a mild antimanic effect. The addition of clonazepam helped a great deal. I relapsed into depression 8 weeks after the discontinuation of the antidepressants. My doctor elected to use only tranylcypromine. I received some mild benefit, but it was episodic and inadequate. Subsequent trials of the TRL + DMI were unsuccessful. I was taking lorazepam and triazolam for the entire nine-month period.
3. Several months later, I was switched from tranylcypromine to phenelzine. I experienced a dramatic improvement within two weeks. This state of normothymia lasted for about a month, and then waned. I was left in a mixed-state with some hypomanic features.
4. D-amphetamine can produce a moderate antidepressant effect that begins within an hour of the first dose. This response lasts for two or three hours before disappearing. I received no benefit from increasing the dosage or continuing the treatment for a few weeks.
5. Bromocriptine produced a mild improvement that lasted for three days immediately upon adding it to an ongoing trial of tranylcypromine + desipramine.
6. I received a small, but perceptible benefit upon adding thyroxine to a combination of tranylcypromine + desipramine + d-amphetamine.
7. Sulpiride produced a mild improvement within an hour of the first dose. It lasted several hours and then disappeared.
8. Modafinil produced a mild improvement within an hour of the first dose. It lasted for no more than an hour.
9. Placebo was no better than placebo.
Thanks for trying to brainstorm this stuff, John.
Sincerely,
Scott
- It seems that the brief 3-day response to various drugs is pervasive amongst people with TRD. For me, this has been the case with tricyclics, MAOIs, d-amphetamine, bromocriptine, and atypical neuroleptics. Not 2 days. Not 4 days. I am hoping that a drug like memantine will allow for these antidepressant responses to remain stable beyond this 3-day period.
Posted by JohnX on October 14, 2001, at 17:52:33
In reply to Re: Scott - medication responses? » JohnX, posted by SLS on October 14, 2001, at 15:09:25
> > I'm looking over your med list. Maybe we can
> reason through to find a pattern that will help
> you reach an end to your search. This has worked
> well for me. Maybe it is psychosomatic for me, but
> my working theories seem to correlate well with
> responses I get from various meds.
>
>
> Hi John.
>
> I really appreciate that you have taken an interest in me.
>
> I guess I can give you an idea as to which drugs helped and which ones hurt. I am a DST non-suppressor.
>
>
> These produced partial or brief improvement:
>
> imipramine
> desipramine
> amitriptyline
> nortriptyline
> tranylcypromine
> phenelzine
> clorgyline
> venlafaxine
> paroxetine
> d-amphetamine
> lamotrigine
> gabapentin
> bromocriptine
> olanzapine
> viqualine
> thyroxine
>
>
>
> These produced significant exacerbations:
>
> amoxapine
> protriptyline
> triiodothyronine
> bupropion
> moclobemide
> reboxetine
> mirtazepine
> idazoxan
>
>
>
> Drugs I haven’t tried:
>
> nefazodone
> citalopram
> sertraline
> fluvoxamine
> topiramate
> tiagabine
> sibutramine
> pramipexole
> pergolide
> amisulpride
>
>
>
>
> 1. Tricyclics have made me feel 100 percent well for two or three days beginning on the 13th day of treatment. The switch into depression is abrupt and dramatic.
>
> 2. A combination of tranylcypromine + desipramine produced the only long-term remission I have ever experienced in the last 25 years. I was functionally 100 percent, but I experienced residual anhedonia. This remission lasted for 6 – 9 months before a dysphoric or mixed-state mania developed. These drugs were withdrawn, and I was treated with lithium and clonazepam. Lithium produced a mild antimanic effect. The addition of clonazepam helped a great deal. I relapsed into depression 8 weeks after the discontinuation of the antidepressants. My doctor elected to use only tranylcypromine. I received some mild benefit, but it was episodic and inadequate. Subsequent trials of the TRL + DMI were unsuccessful. I was taking lorazepam and triazolam for the entire nine-month period.
>
> 3. Several months later, I was switched from tranylcypromine to phenelzine. I experienced a dramatic improvement within two weeks. This state of normothymia lasted for about a month, and then waned. I was left in a mixed-state with some hypomanic features.
>
> 4. D-amphetamine can produce a moderate antidepressant effect that begins within an hour of the first dose. This response lasts for two or three hours before disappearing. I received no benefit from increasing the dosage or continuing the treatment for a few weeks.
>
> 5. Bromocriptine produced a mild improvement that lasted for three days immediately upon adding it to an ongoing trial of tranylcypromine + desipramine.
>
> 6. I received a small, but perceptible benefit upon adding thyroxine to a combination of tranylcypromine + desipramine + d-amphetamine.
>
> 7. Sulpiride produced a mild improvement within an hour of the first dose. It lasted several hours and then disappeared.
>
> 8. Modafinil produced a mild improvement within an hour of the first dose. It lasted for no more than an hour.
>
> 9. Placebo was no better than placebo.
>
>
> Thanks for trying to brainstorm this stuff, John.
>
>
> Sincerely,
> Scott
>
>
> - It seems that the brief 3-day response to various drugs is pervasive amongst people with TRD. For me, this has been the case with tricyclics, MAOIs, d-amphetamine, bromocriptine, and atypical neuroleptics. Not 2 days. Not 4 days. I am hoping that a drug like memantine will allow for these antidepressant responses to remain stable beyond this 3-day period.Thanks for the information. I really
hope you can get something that sticks. My
list of meds was over about a 2.5 year span,
and nothing is more frustrating than having these
little blips of depressive relief only to relapse.I've been extremely fortunate to run into Lamictal.
This pulled me out of some severe dispair, but
I don't believe I am anywhere near cured. I
still have some really crummy days. And it does
interfere in psychological ways. For example I'll
string together a number of good days and make
obligations thinking I'm fine, but then I'll hit
a slump and feel hopeless and paralyzed (like this
morning).Memantine was where I was going with this too.
It seems as though you should be able to at least
get some sort of sustained anti-depressant response
on something strong like d-amphetamine.Have you had a chance to try memantine, or
are the logistics getting in the way? PS
those meds like clonodine and guanfacine
inhibit NMDA transmission. I say just go
to the source (glutamate).There is a cheat to this which may work but
seems a little dangerous is to use
dextromethorphan in combo with a drug that
supresses cyp2d6 like quinidine (or maybe
Paxil?). See US patent 5,863,927. www.uspto.gov.In high doses the nmda antagonists can be dangerous as glutamate
stimulates gaba neurons in some areas of the brain.Memantine appears to be the least problematic due
to its "competitiveness" that we talked about.
You may also want to look into Baclofen. You
can get this in the US, it is also an anti-spasmodic.
If you go on medline you will also see a lot
of references to Baclofen (a GabaB agonist) preventing
addiction (which hopefully in our cases can mean
no poop-out).I really wish the best for you Scott. Please
don't give up, you haven't tried everything and
neither have I. But it seems apparent that for
the number of meds you have run through (which
you are correct, makes me look like a light
weight), that alternative answers are needed.PS. have you been screened for metabolism
of liver enzymes (like poor cyp 2d6 metabolizer,
etc)?Btw, I had some luck with Serzone, and I think
this has both to due with its alpha-1 antagonism
and its 5ht-2 antagonism. Again, it made me drowsy
but all of a sudden I could take stimulates like
caffeine and get a consistent buzz. I would consider
taking Serzone again if I could take a medication
that would alleviate the drugged out problem.
The other thing I would wonder is how I would
respond to any med I took *before* taking lamictal
if I now added it to lamictal. Maybe serzone
wouldn't zone me out.Good Luck,
-john
Posted by JohnX on October 14, 2001, at 20:48:39
In reply to Re: Scott - medication responses? » SLS, posted by JohnX on October 14, 2001, at 17:52:33
> > > I'm looking over your med list. Maybe we can
> > reason through to find a pattern that will help
> > you reach an end to your search. This has worked
> > well for me. Maybe it is psychosomatic for me, but
> > my working theories seem to correlate well with
> > responses I get from various meds.
> >
> >
> > Hi John.
> >
> > I really appreciate that you have taken an interest in me.
> >
> > I guess I can give you an idea as to which drugs helped and which ones hurt. I am a DST non-suppressor.
> >
> >
> > These produced partial or brief improvement:
> >
> > imipramine
> > desipramine
> > amitriptyline
> > nortriptyline
> > tranylcypromine
> > phenelzine
> > clorgyline
> > venlafaxine
> > paroxetine
> > d-amphetamine
> > lamotrigine
> > gabapentin
> > bromocriptine
> > olanzapine
> > viqualine
> > thyroxine
> >
> >
> >
> > These produced significant exacerbations:
> >
> > amoxapine
> > protriptyline
> > triiodothyronine
> > bupropion
> > moclobemide
> > reboxetine
> > mirtazepine
> > idazoxan
> >
> >
> >
> > Drugs I haven’t tried:
> >
> > nefazodone
> > citalopram
> > sertraline
> > fluvoxamine
> > topiramate
> > tiagabine
> > sibutramine
> > pramipexole
> > pergolide
> > amisulpride
> >
> >
> >
> >
> > 1. Tricyclics have made me feel 100 percent well for two or three days beginning on the 13th day of treatment. The switch into depression is abrupt and dramatic.
> >
> > 2. A combination of tranylcypromine + desipramine produced the only long-term remission I have ever experienced in the last 25 years. I was functionally 100 percent, but I experienced residual anhedonia. This remission lasted for 6 – 9 months before a dysphoric or mixed-state mania developed. These drugs were withdrawn, and I was treated with lithium and clonazepam. Lithium produced a mild antimanic effect. The addition of clonazepam helped a great deal. I relapsed into depression 8 weeks after the discontinuation of the antidepressants. My doctor elected to use only tranylcypromine. I received some mild benefit, but it was episodic and inadequate. Subsequent trials of the TRL + DMI were unsuccessful. I was taking lorazepam and triazolam for the entire nine-month period.
> >
> > 3. Several months later, I was switched from tranylcypromine to phenelzine. I experienced a dramatic improvement within two weeks. This state of normothymia lasted for about a month, and then waned. I was left in a mixed-state with some hypomanic features.
> >
> > 4. D-amphetamine can produce a moderate antidepressant effect that begins within an hour of the first dose. This response lasts for two or three hours before disappearing. I received no benefit from increasing the dosage or continuing the treatment for a few weeks.
> >
> > 5. Bromocriptine produced a mild improvement that lasted for three days immediately upon adding it to an ongoing trial of tranylcypromine + desipramine.
> >
> > 6. I received a small, but perceptible benefit upon adding thyroxine to a combination of tranylcypromine + desipramine + d-amphetamine.
> >
> > 7. Sulpiride produced a mild improvement within an hour of the first dose. It lasted several hours and then disappeared.
> >
> > 8. Modafinil produced a mild improvement within an hour of the first dose. It lasted for no more than an hour.
> >
> > 9. Placebo was no better than placebo.
> >
> >
> > Thanks for trying to brainstorm this stuff, John.
> >
> >
> > Sincerely,
> > Scott
> >
> >
> > - It seems that the brief 3-day response to various drugs is pervasive amongst people with TRD. For me, this has been the case with tricyclics, MAOIs, d-amphetamine, bromocriptine, and atypical neuroleptics. Not 2 days. Not 4 days. I am hoping that a drug like memantine will allow for these antidepressant responses to remain stable beyond this 3-day period.
>
> Thanks for the information. I really
> hope you can get something that sticks. My
> list of meds was over about a 2.5 year span,
> and nothing is more frustrating than having these
> little blips of depressive relief only to relapse.
>
> I've been extremely fortunate to run into Lamictal.
> This pulled me out of some severe dispair, but
> I don't believe I am anywhere near cured. I
> still have some really crummy days. And it does
> interfere in psychological ways. For example I'll
> string together a number of good days and make
> obligations thinking I'm fine, but then I'll hit
> a slump and feel hopeless and paralyzed (like this
> morning).
>
> Memantine was where I was going with this too.
> It seems as though you should be able to at least
> get some sort of sustained anti-depressant response
> on something strong like d-amphetamine.
>
> Have you had a chance to try memantine, or
> are the logistics getting in the way? PS
> those meds like clonodine and guanfacine
> inhibit NMDA transmission. I say just go
> to the source (glutamate).
>
> There is a cheat to this which may work but
> seems a little dangerous is to use
> dextromethorphan in combo with a drug that
> supresses cyp2d6 like quinidine (or maybe
> Paxil?). See US patent 5,863,927. www.uspto.gov.
>
> In high doses the nmda antagonists can be dangerous as glutamate
> stimulates gaba neurons in some areas of the brain.
>
> Memantine appears to be the least problematic due
> to its "competitiveness" that we talked about.
> You may also want to look into Baclofen. You
> can get this in the US, it is also an anti-spasmodic.
> If you go on medline you will also see a lot
> of references to Baclofen (a GabaB agonist) preventing
> addiction (which hopefully in our cases can mean
> no poop-out).
>
> I really wish the best for you Scott. Please
> don't give up, you haven't tried everything and
> neither have I. But it seems apparent that for
> the number of meds you have run through (which
> you are correct, makes me look like a light
> weight), that alternative answers are needed.
>
> PS. have you been screened for metabolism
> of liver enzymes (like poor cyp 2d6 metabolizer,
> etc)?
>
> Btw, I had some luck with Serzone, and I think
> this has both to due with its alpha-1 antagonism
> and its 5ht-2 antagonism. Again, it made me drowsy
> but all of a sudden I could take stimulates like
> caffeine and get a consistent buzz. I would consider
> taking Serzone again if I could take a medication
> that would alleviate the drugged out problem.
> The other thing I would wonder is how I would
> respond to any med I took *before* taking lamictal
> if I now added it to lamictal. Maybe serzone
> wouldn't zone me out.
>
> Good Luck,
> -johnScott,
I forgot to mention one more candidate that I
had on my list and that is Acamprostate
(N-acetylhomotaurine). This is generally administered
to treat ethanol (i.e. booze) addiction, and is
used widely in Europe. I believe that it is on
its way to the US, but I haven't last checked
the status. Anyways, it appears to be both a
GabaB agonist (like baclofen) *and* a weak NMDA
receptor antagonist (like memantine).I've seen references to this being used to
treat TD.So here is a good list of potential med adjunct,
you were looking at similar things as me:- clonodine (Catapres) - > partial alpha-2 agonist,alpha-1 antagonist
- guanfacine (Tenex) - > alpha-2 agonist
- memantine (Akatinol) - > non-competitive nmda antagonist
- baclofen (????????) - > GabaB agonist (very different from other gaba meds)
- n-acetylhomotaurine - > Gaba agonist and NMDA antagonist.
(Acamprostate)I also believe meds with the following properties
are interesting (but beat around the bush..):- alpha-1 antagonists
- 5ht-2 anagonists
- 5ht-1 partial agonistsAlso, I don't remember if I saw beta-blockers
on your list?
- propranolol (Inderal) beta-blocker and 5ht-1 action
- pindolol (Visken) "partial" beta blocker and 5ht-1 actionI actually got manic on my Visken trial. It
made me anxious too. As I said, if there was
a norepinephrine deficiency in the LC than
a partial beta-agonist could induce anxiety.
Inderal always flattened my mood, plus it
stopped my racing heart when I was taking insane
combos of meds.I would like to see a med that is a clean partial
agonist at the pre-synaptic alpha-2 receptor.
Clonidine is a partial agonist (I think) at the
alpha-2 receptor but its blocking action at the
post-synaptic alpha-1 receptor causes drowsiness
for a lot of people. But we fall outside the
statistical norm, so "who knows?" (My favorite
quote from my 1st loser psychiatrist).I think a clean alpha-2 partial agonist
would help a lot of people.-john
Posted by JohnX on October 15, 2001, at 23:51:05
In reply to Re: Scott - medication responses?, posted by JohnX on October 14, 2001, at 20:48:39
Scott,I wanted to clarify an error regarding
clonidine (besides my perpetual mispelling).
It is a partial agonist of the
presynaptic alpha-2 receptor and an antagonist
at the post-synpaptic alpha-2 receptor (not
the alpha-1). Whoops.Regarding the 3-4 days magic number thingy,
it seems as though that is a typical amount
of time to up/down regulate beta-adrenoreceptors.
At least that's what my neurologist said when
he talked about Inderal. Don't know if there
is a correlation. But beta receptor down regulation is trademark sign of some older trycyclic antidepressants working.My thinking at least in regards to my own experience, is that I also get this very abrupt lift from depression, usually accompanied by
either excersize or caffeine digestion. I usually
get an anti-depressant response about 4 days after
I hit the right dose. Adderall, the stimulant,
poops out on me after 4 days.I read some interesting information about
poor "noradrenergic tone" and how clonodine could
help. The article was referring to childhood
trauma, but it could be easily extended to
cover a more broad based problem with noradrenergic tone.http://www.childtrauma.org/ptsd_child.htm
This may not be pertinent to you scenario, but as you may know, depression associated with a
history of trauma or other certain illnesses is
generally more treatment resistant. But it seems
as though researchers are making better strides
in this area.regards,
john
This is the end of the thread.
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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
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