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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 5 of 5. This is the beginning of the thread.
Posted by ed_uk on January 13, 2005, at 13:00:17
Hello,
Considering the potential neurotoxicity of the amphetamines (Adderall, Dexedrine etc).... is it safest to have a trial of methylphenidate (Ritalin, Concerta) first and to only use Adderall/Dexedrine if methylphenidate is ineffective or intolerable??? What do you think?
To all those who take stimulants long term.....
Do you take any other drugs or supplements in attempt to prevent/reduce the risk of neurotoxicity?
Ed.
Posted by lars1 on January 14, 2005, at 13:13:04
In reply to Psychostimulant Neurotoxicity, posted by ed_uk on January 13, 2005, at 13:00:17
> Considering the potential neurotoxicity of the amphetamines (Adderall, Dexedrine etc).... is it safest to have a trial of methylphenidate (Ritalin, Concerta) first and to only use Adderall/Dexedrine if methylphenidate is ineffective or intolerable??? What do you think?
I think so. Ricaurte and McCann(1) seem to think so, too; they write, "From a clinical standpoint, when chronic use of a psychostimulant is indicated (e.g., in ADHD, narcolepsy), it would seem prudent to prescribe methylphenidate rather than amphetamine, since methylphenidate appears to lack the DA neurotoxic potential that has been well documented for amphetamine." Unfortunately, my pdoc does not think so. He says that Adderall works better for adults, and he won't let me even try methylphenidate. :-(
From what I read, the main disadvantage of methylphenidate is that it is more likely than amphetamine to cause anxiety. Therefore, I have to wonder how a methylphenidate + benzo combo would compare for safety and effectiveness.
Another option would be methylphenidate + amphetamine. There is some evidence(2) that this combo would be safer than amphetamine alone.
As you know, there are also lots of non-stimulant alternatives: Wellbutrin, Strattera, Provigil, MAO inhibitors, etc.
Best regards,
LarsP.S. Is this question just hypothetical? I thought that you weren't able to get psychostimulants prescribed where you live.
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(1) Brain Res. 1997 Aug 29;767(1):172-5.
Methylphenidate and brain dopamine neurotoxicity.Yuan J, McCann U, Ricaurte G.
Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, MD 21224, USA.To further evaluate the dopamine (DA) neurotoxic potential of the widely prescribed psychostimulant, methylphenidate, mice were treated with various doses (range: 10-120 mg/kg) and treatment schedules of methylphenidate (every 2 h x 4 or twice daily x 4). Higher doses of methylphenidate produced intense stereotypy, as well as short- (5-day), but not long- (2-week), term depletions of striatal DA axonal markers. By contrast, amphetamine caused not only intense stereotypy, but also profound, long-lasting, dose-related DA deficits. These findings indicate that results of studies of amphetamine neurotoxicity using short (5-day) post-drug survival periods are potentially misleading. Further, the present findings confirm and extend previous results indicating that methylphenidate, unlike amphetamine, lacks DA neurotoxic potential, and strongly suggest that DA efflux, although perhaps necessary, is not sufficient for the expression of amphetamine-induced DA neurotoxicity.
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(2) J Pharmacol Exp Ther. 2003 Mar;304(3):1181-7.
Methylphenidate alters vesicular monoamine transport and prevents methamphetamine-induced dopaminergic deficits.Sandoval V, Riddle EL, Hanson GR, Fleckenstein AE.
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, USA.It has been hypothesized that high-dose methamphetamine treatment rapidly redistributes cytoplasmic dopamine within nerve terminals, leading to intraneuronal reactive oxygen species formation and well characterized persistent dopamine deficits. We and others have reported that in addition to this persistent damage, methamphetamine treatment rapidly decreases vesicular dopamine uptake, as assessed in purified vesicles prepared from treated rats; a phenomenon that may contribute to aberrant intraneuronal dopamine redistribution proposedly caused by the stimulant. Interestingly, post-treatment with dopamine transporter inhibitors protect against the persistent dopamine deficits caused by methamphetamine; however, mechanisms underlying this phenomenon have not been elucidated. Also of interest are findings that dopamine transporter inhibitors, including methylphenidate, rapidly increase 1) vesicular dopamine uptake, 2) vesicular monoamine transporter-2 (VMAT-2) ligand binding, and 3) VMAT-2 immunoreactivity in a vesicular subcellular fraction prepared from treated rats. Therefore, we hypothesized that methylphenidate post-treatment might protect against the persistent striatal dopamine deficits caused by methamphetamine by rapidly affecting VMAT-2 and vesicular dopamine content. Results reveal that methylphenidate post-treatment both prevents the persistent dopamine deficits and reverses the acute decreases in vesicular dopamine uptake and VMAT-2 ligand binding caused by methamphetamine treatment. In addition, methylphenidate post-treatment reverses the acute decreases in vesicular dopamine content caused by methamphetamine treatment. Taken together, these findings suggest that methylphenidate prevents persistent methamphetamine-induced dopamine deficits by redistributing vesicles and the associated VMAT-2 protein and presumably affecting dopamine sequestration. These findings not only provide insight into the neurotoxic effects of methamphetamine but also mechanisms underlying dopamine neurodegenerative disorders, including Parkinson's disease.
[free full text at http://jpet.aspetjournals.org/cgi/content/full/304/3/1181]
Posted by ed_uk on January 14, 2005, at 14:09:49
In reply to Re: Psychostimulant Neurotoxicity » ed_uk, posted by lars1 on January 14, 2005, at 13:13:04
Hi Lar,
Thank you for your reply! Thanks for the abstracts.
>Ricaurte and McCann(1) seem to think so, too; they write, "From a clinical standpoint, when chronic use of a psychostimulant is indicated (e.g., in ADHD, narcolepsy), it would seem prudent to prescribe methylphenidate rather than amphetamine, since methylphenidate appears to lack the DA neurotoxic potential that has been well documented for amphetamine."
Here is a summary of the UK NICE guidelines...
NICE guidance (methylphenidate). NICE has recommended (October 2000) that methylphenidate should be used as part of a comprehensive treatment programme for children and adolescents with a diagnosis of severe attention deficit/hyperactivity disorder (ADHD). Treatment should be initiated by a specialist in ADHD but may be continued by general practitioners, under a shared-care arrangement. When a child receiving methylphenidate shows improvement and the condition appears stable, treatment can be suspended periodically in order to assess the need for continuation of therapy.
........Dextroamphetamine (dexamfetamine) may be suitable for patients who don't respond to methylphenidate.
>He says that Adderall works better for adults, and he won't let me even try methylphenidate. :-(
Yes, most p-babblers seem to prefer Adderall. It's strange that he won't even let you try methylphenidate though. Will you pursue the subject further?
>From what I read, the main disadvantage of methylphenidate is that it is more likely than amphetamine to cause anxiety.
Yes, and anxiety is a big preoblem for me. What about you?
>Therefore, I have to wonder how a methylphenidate + benzo combo would compare for safety and effectiveness.
For some people, a benzo might be expected to negate some of the therapeutic benefits of the methylphenidate. Others have used the combination successfully however.
>Wellbutrin, Strattera, Provigil, MAO inhibitors, etc.
Which have you tried? What did you experience?
> Is this question just hypothetical? I thought that you weren't able to get psychostimulants prescribed where you live.
There is a small possibility that if I went to a private psychiatrist, a stim might be prescribed.
>Another option would be methylphenidate + amphetamine.
If a person responded better to amphetamine than methylphenidate, perhaps it would be useful to 'rotate' the two drugs eg. Adderall on a morning then methylphenidate in the afternoon.
Best Regards,
Ed.PS. I'm about to start some new threads about stims! Please reply if poss, I'm sure you will be interested!
Posted by banga on February 3, 2005, at 23:35:48
In reply to Re: Psychostimulant Neurotoxicity » lars1, posted by ed_uk on January 14, 2005, at 14:09:49
In terms of potential neurotoxicity of stims...somewhere someone mentioned that selegiline, being an antioxidant and neuroprotector, can ward this off. But what about supplements, like phosphatidylserine, Acetyl-L-Carnitine, alpha lipoic acid-to help with possible neurotoxicity of say Adderall?
Posted by lars1 on February 4, 2005, at 4:01:00
In reply to Re: Psychostimulant Neurotoxicity, posted by banga on February 3, 2005, at 23:35:48
Hi banga,
I'm interested in that question, too, and am hoping that others will reply. There have been studies showing that a variety of antioxidants can prevent amphetamine neurotoxicity in animals. N-acetyl-L-cysteine was discussed in a thread (http://www.dr-bob.org/babble/20050108/msgs/439943.html) that you have probably seen. I've pasted an abstract of another study below. Interestingly, one of the substances tested was ethanol. I never knew that vodka was an antioxidant! Unfortunately, in most of these studies, the antioxidant doses have been very large, so large that they might themselves be toxic. In the case of ethanol, the dose was the equivalent of several drinks for a human. Even vitamin E might not be safe; some studies have found increased death rates with vitamin E supplementation in humans. On the other hand, one of the abstracts on N-acetyl-L-cysteine claims that as little as 1 mg/kg had some benefit. (By way of comparison, the N-acetyl-L-cysteine tabs sold at my local natural food store are 600 mg.)
With best regards,
LarsNeuropharmacology. 1989 Oct;28(10):1145-50.
Methamphetamine-induced neuronal damage: a possible role for free radicals.
De Vito MJ, Wagner GC.
Department of Toxicology, Rutgers, State University, New Brunswick, New Jersey 08903.
The hypothesis that methamphetamine-induced neuronal damage is mediated by the production of free radicals was evaluated by pretreating rats with either antioxidants or a superoxide dismutase (SOD) inhibitor. It was found that methamphetamine (dose range 6.25-25.0 mg/kg) caused long-lasting depletions of dopamine and serotonin in the striatum and that pretreatment with the antioxidants, ascorbic acid (10-100 mg/kg), ethanol (1 g/kg), mannitol (2 g/kg), or vitamin E (2 g/kg), attenuated these depletions, whereas pretreatment with the superoxide dismutase inhibitor diethyldithiocarbamate (200-400 mg/kg) exacerbated the depletions. The alteration of this effect by four different antioxidants, as well as an inhibitor of superoxidase dismutase, indicated that oxygen-free radicals may have a role in the methamphetamine-induced neurotoxicity.
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