10 replies to this topic

[InquilineKea]

Basically, I'm quite interested in this, since antipsychotics decrease dopamine levels, and I'm pretty concerned about the neurotoxicity of the dopamine-increasing Adderall I take.

I haven't read much into antipsychotics yet, but their effects aren't pretty at all. Giving antipsychotics to elderly patients *significantly* increases their chances of both death and cardiac abnormalities.

Edited by inquilinekea, 09 January 2011 - 07:39 AM.

[tlm884]

Basically, I'm quite interested in this, since antipsychotics decrease dopamine levels, and I'm pretty concerned about the neurotoxicity of the dopamine-increasing Adderall I take.

I haven't read much into antipsychotics yet, but their effects aren't pretty at all. Giving antipsychotics to elderly patients *significantly* increases their chances of both death and cardiac abnormalities.

Please note my response is complete speculation and I am just providing a theory.

As we age, dopamine producing neurons die and dopamine receptors lessen in number and basically, the dopamine pathways are already greatly diminished say when we are 90. Assuming that atleast some antipsychotics blocked Dopamine receptors outside the brain, say in the heart. So we are getting older, our hearts have been beating for 90 years and there is probably some sort of myopathy, or hypertrophy, or some cardiac disease process going on. Dopamine can increase cardiac output. So throw an antipsychotic into the mix and your blocking dopamine from stimulating an already weakened heart. Heart gets weaker, you die.

Dopamine also controls other vital processes in the brain. For example, motor control. This is the reason that antipsychotics can cause Parkonsions like symptoms. Or your pleasure centers. Your old, you know your going to die, you have very little pleasures in your life, throw in an antipsychotic and all pleasure is gone. Maybe they just give up and die?

[chrono]

This is a pretty general question. Are you asking about typical or atypical antipsychotics? The relevant characteristics will likely be pretty different, perhaps even among drugs within these two classes. Undesirable effects like neuro or cardiotoxicity could also be due to other MOAs, so your best bet would probably be to start searching pubmed for a specific substance.

How various antipsychotics combine with adderall is another question you'd probably want to look into, if your question is a practical one. Crazymeds and ADDForums might have some discussions on this, but take them with a grain of salt, of course.

Edited by chrono, 11 January 2011 - 04:51 AM.

[InquilineKea]

Well, I'm not intending to combine antipsychotics with Adderall. That defeats the purpose of both of them at once. I'm just curious about if antipsychotics are toxic in the way "opposite" of Adderall toxicity. Of course, it's also possible that their toxicities act on entirely different routes from each other.

Mostly talking about typical antipsychotics since those are the ones that decrease dopamine.

[Application]

Anti-psychotics both typicals and most newer atypicals decrease various dopamines (di, d2 etc) leading to risk of Parkinsonian type neurological disorders involving movement and cognition secondary to the decreased dopamine activity.

Adderall is not linked to permanent neurological diseases under conditions of normal use far as I know. Abuse of amphetamines, on the other hand, can lead to desensitization of dopamine receptors to normal stimulation from everyday life. The brains compensation for excess dopamine leaves people in a chronically under stimulated state- symptoms being depressed and ADHD like, not parkinsonian.

Well, I'm not intending to combine antipsychotics with Adderall. That defeats the purpose of both of them at once. I'm just curious about if antipsychotics are toxic in the way "opposite" of Adderall toxicity. Of course, it's also possible that their toxicities act on entirely different routes from each other.

Mostly talking about typical antipsychotics since those are the ones that decrease dopamine.

[Application]

I would make an educated guess that the increased death risk among elderly is due to the weight gain and metabolic effects of the newer anti-psychotics, not neurotoxicity.

Basically, I'm quite interested in this, since antipsychotics decrease dopamine levels, and I'm pretty concerned about the neurotoxicity of the dopamine-increasing Adderall I take.

I haven't read much into antipsychotics yet, but their effects aren't pretty at all. Giving antipsychotics to elderly patients *significantly* increases their chances of both death and cardiac abnormalities.

[Delta Gamma]

Forgive my lack of a source, but a large portion of neuroleptics negative effects could be due to their negative effects on glucose metabolism through antagonistic actions on receptors such as D2. Of course thats a bit of a simplistic answer, but antipsychotics tend to hit a massive number of targets.

There is also some evidence that they can impair other metabolic pathways as well, if memory serves a large number of them inhibit fatty acid metabolism which could easily play a role.

I'll post more when I'm free.

[InquilineKea]

Wow I just found this paper:

The Influence of Chronic Exposure to Antipsychotic Medications on Brain Size before and after Tissue Fixation: A Comparison of Haloperidol and Olanzapine in Macaque Monkeys

It is unclear to what degree antipsychotic therapy confounds longitudinal imaging studies and post-mortem studies of subjects with schizophrenia. To investigate this problem, we developed a non-human primate model of chronic antipsychotic exposure. Three groups of six macaque monkeys each were exposed to oral haloperidol, olanzapine or sham for a 17–27 month period. The resulting plasma drug levels were comparable to those seen in subjects with schizophrenia treated with these medications. After the exposure, we observed an 8–11% reduction in mean fresh brain weights as well as left cerebrum fresh weights and volumes in both drug-treated groups compared to sham animals. The differences were observed across all major brain regions (frontal, parietal, temporal, occipital, and cerebellum), but appeared most robust in the frontal and parietal regions. Stereological analysis of the parietal region using Cavalieri's principle revealed similar volume reductions in both gray and white matter. In addition, we assessed the subsequent tissue shrinkage due to standard histological processing and found no evidence of differential shrinkage due to drug exposure. However, we observed a pronounced general shrinkage effect of 20% and a highly significant variation in shrinkage across brain regions. In conclusion, chronic exposure of non-human primates to antipsychotics was associated with reduced brain volume. Antipsychotic medication may confound post-mortem studies and longitudinal imaging studies of subjects with schizophrenia that depend upon volumetric measures.

[outsider]

Wow I just found this paper:

The Influence of Chronic Exposure to Antipsychotic Medications on Brain Size before and after Tissue Fixation: A Comparison of Haloperidol and Olanzapine in Macaque Monkeys

It is unclear to what degree antipsychotic therapy confounds longitudinal imaging studies and post-mortem studies of subjects with schizophrenia. To investigate this problem, we developed a non-human primate model of chronic antipsychotic exposure. Three groups of six macaque monkeys each were exposed to oral haloperidol, olanzapine or sham for a 17–27 month period. The resulting plasma drug levels were comparable to those seen in subjects with schizophrenia treated with these medications. After the exposure, we observed an 8–11% reduction in mean fresh brain weights as well as left cerebrum fresh weights and volumes in both drug-treated groups compared to sham animals. The differences were observed across all major brain regions (frontal, parietal, temporal, occipital, and cerebellum), but appeared most robust in the frontal and parietal regions. Stereological analysis of the parietal region using Cavalieri's principle revealed similar volume reductions in both gray and white matter. In addition, we assessed the subsequent tissue shrinkage due to standard histological processing and found no evidence of differential shrinkage due to drug exposure. However, we observed a pronounced general shrinkage effect of 20% and a highly significant variation in shrinkage across brain regions. In conclusion, chronic exposure of non-human primates to antipsychotics was associated with reduced brain volume. Antipsychotic medication may confound post-mortem studies and longitudinal imaging studies of subjects with schizophrenia that depend upon volumetric measures.

Wow 20% is a pretty big number. I read somewhere that antipsychotics basically puts you in a hibernating state which would account for the glucose/fat changes in metabolism and other related problems.

[Application]

A key component to the cardiac and metabolic problems is that Olanzapine and other newer anti-psychotics dramatically increase appetite.

Wow I just found this paper:

The Influence of Chronic Exposure to Antipsychotic Medications on Brain Size before and after Tissue Fixation: A Comparison of Haloperidol and Olanzapine in Macaque Monkeys

It is unclear to what degree antipsychotic therapy confounds longitudinal imaging studies and post-mortem studies of subjects with schizophrenia. To investigate this problem, we developed a non-human primate model of chronic antipsychotic exposure. Three groups of six macaque monkeys each were exposed to oral haloperidol, olanzapine or sham for a 17–27 month period. The resulting plasma drug levels were comparable to those seen in subjects with schizophrenia treated with these medications. After the exposure, we observed an 8–11% reduction in mean fresh brain weights as well as left cerebrum fresh weights and volumes in both drug-treated groups compared to sham animals. The differences were observed across all major brain regions (frontal, parietal, temporal, occipital, and cerebellum), but appeared most robust in the frontal and parietal regions. Stereological analysis of the parietal region using Cavalieri's principle revealed similar volume reductions in both gray and white matter. In addition, we assessed the subsequent tissue shrinkage due to standard histological processing and found no evidence of differential shrinkage due to drug exposure. However, we observed a pronounced general shrinkage effect of 20% and a highly significant variation in shrinkage across brain regions. In conclusion, chronic exposure of non-human primates to antipsychotics was associated with reduced brain volume. Antipsychotic medication may confound post-mortem studies and longitudinal imaging studies of subjects with schizophrenia that depend upon volumetric measures.

Wow 20% is a pretty big number. I read somewhere that antipsychotics basically puts you in a hibernating state which would account for the glucose/fat changes in metabolism and other related problems.

[onetimevisit]

InquilineKea you bring up a very interesting topic, a topic that could hold tremendous value to those who hunt knowledge.
But you surely would know that info like this isnt published. I did not, i do regret my indiscretion. Cognitive dissidants makes it rather hard to comphrehend the whole, and without that understanding its tempting to follow the science and your heart.

I accept what is, maybe i will be able to demonstrate that at some point, i do support many measures. Anyway commerce is my only real interest, My word is my Bond.

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