What's the relative safety/neurotoxicity of ADHD medications (Stimulants, Strattera, Wellbutrin, Guanfacine, etc...) versus other psychiatric medications (SSRIs, tricyclics, MAOIs, mood stabilizers, antipsychotics, benzos, etc...)?

What's the relative safety/neurotoxicity of ADHD medications (Stimulants, Strattera, Wellbutrin, Guanfacine, etc...) versus other psychiatric medications (SSRIs, tricyclics, MAOIs, mood stabilizers, antipsychotics, benzos, etc...)?

Good question.
I can mainly speak for Ritalin as I have researched it more. It has been around for over 50 years and considered to be among the safest psychiatric drugs on the market. I am not as sure of the other adhd drugs but would not be surprised if they would be somewhere in that category. The safety record for ADHD drugs in general is pretty good. Some will have side effects but that is true of any medication. For some aspirin is a deadly substance.

Hope this answers a little.
Dizfriz

I will have let others speak on the non adhd drugs as I have done no significant research on them.

Generally speaking, the ADHD meds responsible for catecholamine release (amphetamines, pemoline) are considered more neurotoxic than those drugs whose primary activity is at the DA/NE transporter, such as methylphenidate or even cocaine. For example, a by-product from the breakdown of released dopamine is H2O2, a powerful oxidizer. Obviously, because no dopamine is released with MPH, there is no real source of oxidative stress. This is not to say that MPH has no toxicity, but it is certainly less of a neurotoxin than the amphetamines.

Wellbutrin is considered to have little neurotoxicity, as is the case with most SSRI's and tri/tetracyclics. Some of the antipsychotics are potent neurotoxins, and can result in irreversible damage. Long-term benzodiazepine use can result in conformational changes at certain GABA receptor subunits. Long-term benzodiazapine use can also reduce plasma testosterone levels, as it binds to peripheral benzodiazepine receptor sites in the testes and adrenal cortex. Additionally, testosterone is considered a "neuromodulator", and may play an important role in cognition.

Generally speaking, the ADHD meds responsible for catecholamine release (amphetamines, pemoline) are considered more neurotoxic than those drugs whose primary activity is at the DA/NE transporter, such as methylphenidate or even cocaine.

Dextroamphetamine doesn't actually cause catecholamine release until high doses. However, methamphetamine does cause release at even low-to-medium doses.


For example, a by-product from the breakdown of released dopamine is H2O2, a powerful oxidizer. Obviously, because no dopamine is released with MPH, there is no real source of oxidative stress. This is not to say that MPH has no toxicity, but it is certainly less of a neurotoxin than the amphetamines.

Interesting point.

Wellbutrin is considered to have little neurotoxicity, as is the case with most SSRI's and tri/tetracyclics.

I wasn't aware that tetra/tricyclics have negligible neurotoxicity. Especially considering they have a low therapeutic index.

Is it possible that even though neurotoxicity may be low, SSRIs, tri/tetracyclics, SNRIs, and MAOIs still cause damage in long-term usage?

But if I'm understanding you correctly, all antidepressants (SSRI, SSRE, SNRI, tetra/tricylics) except MAOIs would be very safe as none of them cause catecholamine release. Then again, MAOIs don't cause catecholamine release either. But they aren't re-uptake inhibitors and mainly inhibit MAO-A/B enzymes.

Also note that tricylics have a high rate of side effects compared to amphetamines, SSRIs, and so on. Then again, side effects don't always equate to neurotoxicity in the long-term, as side effects may disappear after a few weeks anyway.


Some of the antipsychotics are potent neurotoxins, and can result in irreversible damage.

Is this mainly part of the typical vs. atypical antipsychotics difference? I wasn't aware that atypical antipsychotics or any of mood stabilizers are potent neurotoxins. Typical antipsychotics, however, seem to be unsafe for long-term use.

Long-term benzodiazepine use can result in conformational changes at certain GABA receptor subunits. Long-term benzodiazapine use can also reduce plasma testosterone levels, as it binds to peripheral benzodiazepine receptor sites in the testes and adrenal cortex. Additionally, testosterone is considered a "neuromodulator", and may play an important role in cognition.

Then again, SSRIs have also shown to decrease testosterone. The tricyclics and even the MAOIs would also cause this. Even stimulants can lower testosterone. Indeed adderall lowers prolactin levels and may cause a slow decrease in testosterone indirectly.

Secondly, what's your view on Klonopin. To me it seems to be a good choice for anxiety and is less problematic than the other benzos.

Here's a biased article on the topic:
http://www.antipsychiatry.org/drugs.htm

Content seems worrying, but obviously the source is horrible.

P.S. I can't believe there are medical doctors actually part of this "movement."

^^^^I am pretty sure this site was created by the Church of Scientology...

I haven't seen conclusive studies on SSRI's/TCA's and neurotoxicity, but then again, I haven't looked all that hard. The long-term effects are virtually unknown. In regards to the antipsychotics, yes the old ones were much worse. Some of the new atypicals, like olanzapine might even have neuroprotective properties (check out: http://cat.inist.fr/?aModele=afficheN&cpsidt=16001021)

My example of the toxicity associated with catecholamine release was only in reference to the stimulants, as oxidative stress is just one cause of neurotoxicity. Also, downregulation/upregulation can occur with both cocaine and MPH, so they are not completely devoid of toxicity. Tachyphylaxis is common with both cocaine and MPH, and a loss of transport proteins could likely occur over time, with high chronic doses.

Also, keep in mind, d-amphetamine is actually a more potent releaser of NE than methamphetamine. It has an IC50 of ~7nM, whereas methamphetamine has an affinity of ~12nM (the lower the number, the higher the affinity). This is probably why dexedrine is more physically stimulating than methamphetamine, as norepinephrine is strongly associated with wakefulness. However, yes you are right, d-amphetamine will only release dopamine at high dosages, whereas methamphetamine can release dopamine at virtually any dose. There is little question that dexedrine is significantly less neurotoxic than methamphetamine. This is one reason I will not take Desoxyn with any real frequency.

wellbutrin, Vyvanse, and Cymbalta HELP NEEDED PLEASE

<HR style="COLOR: #d1d1e1" SIZE=1><!-- / icon and title --><!-- message -->ok .

1. wellbutrin: reuptakes norepinephrine and dopamine
2. vyvanse:: reuptakes norepinephrine and dopamine
3. cymbalta: reuptakes norepinephrine and serotonin
4. herbal supplements l tyrosine and vitamines: norepinephrine dopamine an serotonin. i also take klonopin

ok so is this to much of the receptors being released to the point of nerotoxicty or is it safe

also ive been a dextromethorphan addict for 3 an a half years which release serotonin and dopamine so could my recptors be burt out dxm is an atnogist of nmda. so someone please help me out here. is it possible i have brain damage from all the dxm use because long term use can cause damage to cells in the brain.

^^^^I am pretty sure this site was created by the Church of Scientology...

I haven't seen conclusive studies on SSRI's/TCA's and neurotoxicity, but then again, I haven't looked all that hard. The long-term effects are virtually unknown. In regards to the antipsychotics, yes the old ones were much worse. Some of the new atypicals, like olanzapine might even have neuroprotective properties (check out: http://cat.inist.fr/?aModele=afficheN&cpsidt=16001021)

My example of the toxicity associated with catecholamine release was only in reference to the stimulants, as oxidative stress is just one cause of neurotoxicity. Also, downregulation/upregulation can occur with both cocaine and MPH, so they are not completely devoid of toxicity. Tachyphylaxis is common with both cocaine and MPH, and a loss of transport proteins could likely occur over time, with high chronic doses.

Also, keep in mind, d-amphetamine is actually a more potent releaser of NE than methamphetamine. It has an IC50 of ~7nM, whereas methamphetamine has an affinity of ~12nM (the lower the number, the higher the affinity). This is probably why dexedrine is more physically stimulating than methamphetamine, as norepinephrine is strongly associated with wakefulness. However, yes you are right, d-amphetamine will only release dopamine at high dosages, whereas methamphetamine can release dopamine at virtually any dose. There is little question that dexedrine is significantly less neurotoxic than methamphetamine. This is one reason I will not take Desoxyn with any real frequency.


d-amphetamine will only release dopamine at high doses your wrong

Dextroamphetamine affects dopamine and serotonin levels in the caudate (http://en.wikipedia.org/wiki/Caudate_nucleus), and norepinephrine in the hippocampus (http://en.wikipedia.org/wiki/Hippocampus). Because dextroamphetamine is a substrate analog at monoamine transports, at all doses, dextroamphetamine prevents the reuptake of these neurotransmitters,<SUP class=reference id=cite_ref-Kuczenski_29-0>[30] (http://en.wikipedia.org/wiki/Dextroamphetamine#cite_note-Kuczenski-29)</SUP> causing them to remain in the synaptic cleft for a prolonged period (inhibiting monoamine reuptake in rats with a norepinephrine (http://en.wikipedia.org/wiki/Norepinephrine) to dopamine (http://en.wikipedia.org/wiki/Dopamine) ratio (NE:DA) of about 1:1 and a norepinephrine to 5-hydroxytryptamine (http://en.wikipedia.org/wiki/Serotonin) ratio (NE:5HT) of about 1:10<SUP class=reference id=cite_ref-30>[31] (http://en.wikipedia.org/wiki/Dextroamphetamine#cite_note-30)</SUP>). At some point, when doses are high, and the concentration of dextroamphetamine is high enough,<SUP class=reference id=cite_ref-Kuczenski_29-1>[30] (http://en.wikipedia.org/wiki/Dextroamphetamine#cite_note-Kuczenski-29)</SUP> dextroamphetamine will enter nerve cells and cause release of monoamines from the cytoplasmic dopamine pool (as opposed to 'protected' vesicular stores).<SUP class=reference id=cite_ref-31>[32] (http://en.wikipedia.org/wiki/Dextroamphetamine#cite_note-31)</SUP> In such high concentrations, dextroamphetamine will cause the norepinephrine, dopamine and serotonin (http://en.wikipedia.org/wiki/Serotonin) (5HT) transporters to reverse their direction of flow. This inversion leads to a release of these transmitters from the vesicles to the cytoplasm and from the cytoplasm to the synapse (releasing monoamines in rats with ratios of about NE:DA = 1:3.5 and NE:5HT = 1:250), causing increased stimulation of post-synaptic receptors.

d-amphetamine will only release dopamine at high doses your wrong.

If you had actually read what I wrote, I clearly stated, "d-amphetamine will only release dopamine at high dosages". Also, posting things straight from online sources helps no one. If you do, you need to cite your reference...

d-amphetamine will only release dopamine at high dosages, whereas methamphetamine can release dopamine at virtually any dose.

If you had actually read what I wrote, I clearly stated, "d-amphetamine will only release dopamine at high dosages". Also, posting things straight from online sources helps no one. If you do, you need to cite your reference...

d-amphetamine is Dextroamphetamine and no at high doses it will only release dopamine. wow yo. its an add/adhd medication all add/adhd medications release dopamine. if it didnt it wouldnt be perscribed for hdhd

Did the mods merge two threads? hmm...*confused*

Contrapunctus: I've collected all the threads on the topic that I think you might enjoy:

Neurotoxicity:
http://addforums.com/forums/showthread.php?t=52642
http://addforums.com/forums/showthread.php?t=52908
http://addforums.com/forums/showthread.php?t=52735

Neuroprotection:
http://addforums.com/forums/showthread.php?t=48296

I haven't seen conclusive studies on SSRI's/TCA's and neurotoxicity, but then again, I haven't looked all that hard.

Alright, let me know if you run into anything.

The long-term effects are virtually unknown.

Yes, it seems so. That's the worrisome part.

In regards to the antipsychotics, yes the old ones were much worse. Some of the new atypicals, like olanzapine might even have neuroprotective properties (check out: http://cat.inist.fr/?aModele=afficheN&cpsidt=16001021)

That's interesting


My example of the toxicity associated with catecholamine release was only in reference to the stimulants, as oxidative stress is just one cause of neurotoxicity. Also, downregulation/upregulation can occur with both cocaine and MPH, so they are not completely devoid of toxicity. Tachyphylaxis is common with both cocaine and MPH, and a loss of transport proteins could likely occur over time, with high chronic doses.

But do we have a definition of "high chronic doses"?

Also, keep in mind, d-amphetamine is actually a more potent releaser of NE than methamphetamine. It has an IC50 of ~7nM, whereas methamphetamine has an affinity of ~12nM (the lower the number, the higher the affinity). This is probably why dexedrine is more physically stimulating than methamphetamine, as norepinephrine is strongly associated with wakefulness. However, yes you are right, d-amphetamine will only release dopamine at high dosages, whereas methamphetamine can release dopamine at virtually any dose. There is little question that dexedrine is significantly less neurotoxic than methamphetamine. This is one reason I will not take Desoxyn with any real frequency.

Good point. However, check this out:
http://addforums.com/forums/showpost.php?p=593882&postcount=3
http://addforums.com/forums/showpost.php?p=609237&postcount=5

d-amphetamine is Dextroamphetamine and no at high doses it will only release dopamine. wow yo. its an add/adhd medication all add/adhd medications release dopamine. if it didnt it wouldnt be perscribed for hdhd

Let me explain.

ADHD medications increase dopamine. However, most do this by inhibiting the reuptake of dopamine i.e. they PREVENT dopamine from going back into "storage" so dopamine is available outside the storage where it can be "used."

Some medications, such as methamphetamine at all doses, and dextroamphetamine at high doses, reverse the transporter and actually cause the RELEASE of dopamine.