Jim McClintock's Bookmarks

Why are we having so many Black Box
Warnings for the use of psychiatric medications?

Simple answer: Many do not aim for, do not measure, and indeed don't seek
that mercurial Therapeutic
Window.

• Simply feels like you are toxic, it's just too much. You shouldn't feel
  stoned or drugged.

• Confusion, disorientation, cognitive stress, anxiety, self expression
  diminishes.

• If you feel these kind of symptoms for the first couple of days after
  starting a new med, usually no problem. If symptoms continue, urgency
  is called for and an adjustment is very likely necessary, - see your doc.

The Therapeutic
Window represents the body's ability to metabolize the medication
effectively. Several easy rules apply here:





1. If the medication is just right in dosage and duration you will
   feel that you are simply floating through that effective opening - no problem,
   and no, or very few, "side effects."
   
2. If the medication is too much, too high a dosage, you will have
   signs of toxicity, and will hit the top of the window - bump your head on the
   top of that window.
   
3. If the medication is too little, too low in dosage, it doesn't appear to be
   working at all, you can't get into the window, and your chin keeps hitting the
   sill at the bottom.

• New genetic studies show that many do not
  metabolize drugs at the same rates. Studies show that less than 50%
  of the population metabolizes medications at an average rate.

• Pharmacogenetic
  studies [regarding, in this case, 2D6 metabolic pathways] show that 5-7% of
  the population are very fast metabolizers and require more than expected doses
  to turn the therapeutic tide.

• Metabolism is not completely dependent on body size, and the old
  adage that body size, larger weight or height, suggests a need for more
  medications, is outdated.

• Also outdated is the cookie cutter dosage suggested by some based upon age.
  Each dose for each person must be reviewed at every medication check - Each
  individual's Therapeutic Window will tell
  the tale. Drug dosing, sometimes suggested on preliminary reports, can be
  misleading. Simply go low and slowly with everyone at the outset. Often psych
  medications are under and overdosed through the process of not establishing
  specific improvement criteria.
  
• With stimulant medications used for ADD: the top of the window can look like
  the bottom of the window, creating an apparent need for more medications in the
  real context of too much. Said another way, too much medication can diminish
  focus and attention.
  
• Noted repeatedly at CorePsychBlog: Drug
  interactions clearly effect the therapeutic window.
  
• As we have been regularly reporting here at CorePsychBlog: Metabolic issues,
  such a gluten
  sensitivity, bowel and liver
  problems also challenge the expected rate of metabolism.
  
• And see more here at
  Genelex on pharmacogenetics for antidepressants and antipsychotics.

What I am about to tell you is from my own experience, and is documented
somewhat indirectly in the drug interaction book on my website bookstore [Cozza
and Armstrong], but has not found it's way to the literature yet.
I say
"indirectly" because Vyvanse is not in there, only AMP as a class is
documented.

• It is a prodrug
  with a slow and forgiving delivery process: No heavy AM hit, no big
  drop in the PM
  

Likely the dose is not correct if it isn't working in the AM - at the correct
dose it works in .5 hr... and again we aren't looking for "feeling," but for
cognitive change.

If you are in the US you are most often talking *weed/marijuana* with
"hookah" use, - and weed, as other addictive substances, should be avoided if
you want the true fix.

Bottom line: breakfast of protein first, then any psych med after.

Second point: dosage may change that reaction and the post on water titration
may help.

Third point: Some people cannot take AMP meds.

I strongly recommend John Ratey's book: User's Guide to the Brain

http://astore.amazon.com/cpbks-20/detail/0375701079/103-7756357-1889446

- his work is cutting edge and he also would be a great resource for your
further investigations.

If the therapeutic window seems just too narrow and either up or down dosing
is insufficient - you very likely have a metabolic problem, or simply the wrong
medication for that symptom complex - from a defective 2D6 metabolic pathway [to
be measured by genetic testing with either Genelex [used by the Mayo Clinic and
available through our office] or Detoxigenomics [also available with our office
from Genova] ...or other metabolic testing indicated by our questionnaires and a
personal interview.

know John Ratey, who suggested intense exercise, but she is unable to follow
formal routine exercise. I do have her skating and bowling once a week via
special ed groups but know that's not enough. This is a young lady who can't
read her body; who never tires; can't tell hunger from full, etc. Extrememly
hyper/impulsive due to her brain injury as a tot.

The only time she is able to sit is when she perseverates on the compute

http://www.squidoo.com/vyvanse

Look for the therapeutic window, the top means it's too much, the bottom,
where you appear to be on this brief missive, is nada...it isn't working. We
look for the middle. You can't get out the window by going thru it, or bumping
against the window sill.

I completely agree with your psych about her start dose, and his observation
with you that she is a fast burner at a previous Adderall dose of 80mg. You do
already know she is fine with the AMP molecule, so she is not [as they say in
research], a *virgin [innocent from previous stimulant, -and, in this case, not
innocent from AMP stimulant] patient.*

So, with that foundation, 50mg Vyvanse would be expected to have a positive
effect on prefrontal cortical brain function [to coin a phrase!]. At the
previous DOE [duration of effectiveness] on the IR Adderall @ 3.5 hr, she was
slightly under-dosed. I have come to expect a solid 5-6 hr on the DOE with the
IR.

I would look for metabolic and nutritional components vigorously - and even
though she is smart and motivated, I am an anti-carb hound. Carbs mess up the
bowel, diminish effective metabolism, mess with the estrogen system [listen to
my podcast on PCOS and the other on estrogen dominance] and then can create
sleep problems, appetite and breakfast problems.

Bottom line: My experience at the Vyva