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 These drugs were withdrawn, and I was treated with lithium and clonazepam.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
poster:JohnX
thread:81196
URL: http://www.dr-bob.org/babble/20011007/msgs/81311.html