A relative of mine is currently taking Adderall for ADD.  My understanding
is that {*filter*} which promote neurotransmitter release (i.e. amphetamine,
fenfluramine) tend to be more neurotoxic than compounds which block
neurotransmitter reuptake (i.e. Ritalin, Prozac).  If this is the case, is
this significant when we're talking about the "therapeutic" dosages (10-20
mg of Ritalin vs. 10-20 mg of Adderall t.i.d.) used in psychiatry?  And,
does low-dose amphetamine taken daily for months or years have the potential
to produce neurotoxic effects similar to high-dose amphetamine taken
sporadically?  It seems that Adderall (mixture of d-amphetamine and
d,l-amphetamine) is becoming much more fashionable among psychiatrists and
patients for treatment of ADD, perhaps because the name "Ritalin" has such a
negative stigma attached to it, while few laypersons have heard of Adderall.

Any info is greatly appreciated!!

Dave

David,
long acting amphetamines like methamphetamine do cause neurotoxicity.  However,
short acting stimulants like methylphenidate (not the sustained release form)
have not been shown to cause neurotoxicity at therapeutic doses in any
scientific literature.  Perhaps short acting stimulants allow the neurons to
rebound even between doses; whereas long acting stimulants may totally deplete
catecholamines or cause neurotoxicity.
However, newer stimulants like modafinil and perhaps the antidepressant
bupropion may offer a safer alternative; especially since they lack the
sympathetic nervous system (pressor) effects as well.
Ed Modestino

However,

I wonder if d-amphetamine taken 2-3 times per day for ADD would result in
the same neurotoxicity as the longer-acting methamphetamine?  Also, I wonder
if tyrosine, phenylalanine, or tryptophan ingestion could block toxicity by
replenishing neurotransmitter stores?

I hope that modafinil will be investigated for effects on ADD.  It seems to
be a much safer and non-{*filter*}ive alternative to the dopaminergic
stimulants.  Thanks for the reply!

Dave

Please cite your references supporting the claim that methamphetamine is
neurotoxic at therapeutic doses.  My understanding (based on the scientific
literature I've seen on this question) is that amphetamines have shown
neurotoxicity only at monstrously high (i.e. completely UNREALISTIC) doses;
for example, the human equivalent of around 600 mg/day -an amount TEN TIMES
the recommended dosage ceiling!

Bob

Bob,
the mechanism they were discussing as being the actual etiology of
neurotoxicity of amphetamines does not represent theories that I am
familiar with.  Because they didn't respond with references, I am with you
and I think that neurotoxicity with therapuetic doses of speed is low.  
Modern research in the area focuses on oxidation damage.
Andy