Tardive Dyskinesia in Low Potency FGA, High Potency FGA, and SGA

[AD04]

According to Stahl, "concomitant use of anticholinergic agents does not lessen the ability of the conventional antipsychotics to cause tardive dyskinesia."

1. Do you know if low potency FGA (with more intrinsic anticholinergic properties) have lower likelihood of causing tardive dyskinesia compared to high potency FGA?

2. When SGA have lower likelihood of causing tardive dyskinesia, is it mainly due to the lower dopamine receptors affinity compared to FGA, instead of the former's anticholingeric properties?

3. Speaking about dopamine receptors affinity, I've read that all antipsychotic medications are about equally effective in treating positive symptoms and disorganization. Wouldn't something with higher dopamine receptors affinity be better for treating positive symptoms?

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[MacDonaldTriad]

1. No, or not significantly so given equal potent dosing for equal amounts of exposure
2. No, no, there are relatively high affinity D2 SGAs that have much less TD liability compared to low potency FGAs. You are failing to look at 5HT2a/D2 affinity ratios
3. No, if you give enough of the low potency drugs to block the same D2, the job is done about the same.

 

[splik]

anticholinergic properties of neuroleptics lessen parkinsonism; they neither treat nor prevent tardive dyskinesia (though bizarrely you often see people on anticholinergics for this reason).

low potency neuroleptics (for example aliphatic phenothiazines) have a slightly lower affinity for D2 receptors. It is the affinity for D2 receptors and the % saturation that are associated with the risk of tardive dyskinesia. The highest risk is for the high potency butyrophenones like haloperidol (with a 5% annual risk)

SGAs (with the exception of high dose risperidone) do have a lower risk of TD (but you can see people developing it even at lower doses even with seroquel). They don't have a lower affinity for D2 receptors (in fact some, like abilify have an affinity that is even greater than dopamine for the D2 receptor). But they fast-dissociate from D2 receptors, which is to say they dissociate about 100x faster from the receptors than the older drugs.

I think most people would disagree with the statement all neuroleptics are equally effective at suppressing positive symptoms of psychosis; this is patently not the case. You also have to balance this against causing terrible disabling brain damage in the form of dyskinesias, dementia etc I consulted on a case recently where I opined that the individual had developed frontal lobe syndrome as a result of treatment with neuroleptics. We still prescribe way too high doses of neuroleptics despite evidence not supporting it. It was worse in the past when it was not unusual for pts to be routinely racked up to 120mg of haldol!, completely saturating their D2 receptors, with no additional gain in control of psychosis.

There is a little under 15% of patients who do not benefit at all from any neuroleptics whatsoever

 

[clausewitz2]

anticholinergic properties of neuroleptics lessen parkinsonism; they neither treat nor prevent tardive dyskinesia (though bizarrely you often see people on anticholinergics for this reason).

low potency neuroleptics (for example aliphatic phenothiazines) have a slightly lower affinity for D2 receptors. It is the affinity for D2 receptors and the % saturation that are associated with the risk of tardive dyskinesia. The highest risk is for the high potency butyrophenones like haloperidol (with a 5% annual risk)

SGAs (with the exception of high dose risperidone) do have a lower risk of TD (but you can see people developing it even at lower doses even with seroquel). They don't have a lower affinity for D2 receptors (in fact some, like abilify have an affinity that is even greater than dopamine for the D2 receptor). But they fast-dissociate from D2 receptors, which is to say they dissociate about 100x faster from the receptors than the older drugs.

I think most people would disagree with the statement all neuroleptics are equally effective at suppressing positive symptoms of psychosis; this is patently not the case. You also have to balance this against causing terrible disabling brain damage in the form of dyskinesias, dementia etc I consulted on a case recently where I opined that the individual had developed frontal lobe syndrome as a result of treatment with neuroleptics. We still prescribe way too high doses of neuroleptics despite evidence not supporting it. It was worse in the past when it was not unusual for pts to be routinely racked up to 120mg of haldol!, completely saturating their D2 receptors, with no additional gain in control of psychosis.

There is a little under 15% of patients who do not benefit at all from any neuroleptics whatsoever

I was curious what you made of proposals involving every other day dosing of neuroleptics for folks in early psychosis who had a fairly high degree of functioning prior to onset of symptoms to avoid just the sort of problems you are describing.

 

[AD04]

Thanks for the replies.

Stahl's only showed the binding affinities for SGA (maybe I missed the ones for FGA), so I incorrectly assumed the affinity of FGA was higher.

What is a good source that shows that binding properties for FGA and SGA?

 

[FlowRate]

He probably threw that in for people who conflate tardive dyskinesias with dystonias.

 

[hamstergang]

What is a good source that shows that binding properties for FGA and SGA?

The most comprehensive I could find: Antipsychotic - Wikipedia (the comparison of medications section has a chart on binding affinities).

 

[HarryMTieboutMD]

anticholinergic properties of neuroleptics lessen parkinsonism; they neither treat nor prevent tardive dyskinesia (though bizarrely you often see people on anticholinergics for this reason).

low potency neuroleptics (for example aliphatic phenothiazines) have a slightly lower affinity for D2 receptors. It is the affinity for D2 receptors and the % saturation that are associated with the risk of tardive dyskinesia. The highest risk is for the high potency butyrophenones like haloperidol (with a 5% annual risk)

SGAs (with the exception of high dose risperidone) do have a lower risk of TD (but you can see people developing it even at lower doses even with seroquel). They don't have a lower affinity for D2 receptors (in fact some, like abilify have an affinity that is even greater than dopamine for the D2 receptor). But they fast-dissociate from D2 receptors, which is to say they dissociate about 100x faster from the receptors than the older drugs.

I think most people would disagree with the statement all neuroleptics are equally effective at suppressing positive symptoms of psychosis; this is patently not the case. You also have to balance this against causing terrible disabling brain damage in the form of dyskinesias, dementia etc I consulted on a case recently where I opined that the individual had developed frontal lobe syndrome as a result of treatment with neuroleptics. We still prescribe way too high doses of neuroleptics despite evidence not supporting it. It was worse in the past when it was not unusual for pts to be routinely racked up to 120mg of haldol!, completely saturating their D2 receptors, with no additional gain in control of psychosis.

There is a little under 15% of patients who do not benefit at all from any neuroleptics whatsoever

So do you think this in part explains the differential rates of TD between the FGAs and SGAs?

 

[MacDonaldTriad]

and the 5HT blockade may be responsible for this rapid dissociation so both can be right, or neither could end up being it as far as we know. Theories always precede accepted fact. The whole SGA thing comes down to dissociating D2 blockade from EPS. A first generation drug had to make rats stiff or else it wasn't developed.

 

[birchswing]

Have you all seen the commercials for iloperidone?

It's such a sneaky commercial it just as easily could be for CCHR (scientology front).

It says sponsored by Vanda Pharmaceuticals, but I assumed it was a fake name.

It seems like it's a commercial against psychiatric drugs causing akathisia.

And the web-site it takes you to still doesn't tell you it's an ad for a drug. But it is to get you to have your doctor prescribe iloperidone. Supposedly it's akathisia profile is almost non-existent, but looks risky for prolonged qt syndrome.

I know akathisia and TD aren't the same thing, but I didn't feel this merited its own thread.

It's very confusing . . . the message of the ad is so unclear. I would have guessed that it was legal action against drug manufacturers. If it were a product, I would have guessed an add-on product to stop akathisia.

But instead, it's an ad for an entirely different antipsychotic--whose side effects could just as easily be vilified in another dystopian ad.



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