Akathisia and Tardive Dyskinesia

[tetaoh]

I am curious as to the approach commonly used to treat akathisia that can’t be avoided (maybe because switching medications isn’t an option). My understanding is that beta blockers, benzos and benztropine are first line, but what do you actually do to typically handle it with your patients? Are there non-pharmacological approaches that you try? I think there might be some evidence for high dosage vitamin B6 and N-acetylcysteine, for example.


I am also wondering about another topic related to the side effects of antipsychotics, mainly the prevention of tardive dyskinesia in patients that you know will have to be on antipsychotics indefinitely. I was curious if you typically take any preventative measures against tardive dyskinesia in these patients? I know there are medication that can somewhat ameliorate symptoms if they persist after discontinuation of the drug, or if the patient has to remain on it despite the TD, but is there anything that’s been shown to help actually to prevent it (other than lowest dose possible and only when necessary)? I’m sure it would be difficult to pinpoint given longitudinal studies would be required. I know that some of the antioxidant supplements that have been tried such as N-acetylcystein, alpha lipoic acid, coenzyme q-10 and vitamin E as well as branch chain amino acids have some decent evidence in rats and humans to help with symptoms. I’ve always thought that if TD is a result of chronic oxidative damage to dopaminergic neurons, won’t the same antioxidants that help with symptoms once TD has set in might also be useful in preventing the damage in the first place?


Anyway, just curious what folks actually do in practice for both akathisia and prevention of TD.

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[hamstergang]

I’ve always thought that if TD is a result of chronic oxidative damage to dopaminergic neurons, won’t the same antioxidants that help with symptoms once TD has set in might also be useful in preventing the damage in the first place?

I don't have answers for you and am interested in them as well.

I am posting only to warn you that this sort of seemingly logical thinking too often doesn't pan out when dealing with the brain. It's a very complex organ with so much going on, so even when it seems clear that things should be a certain way, they very well may not be.

 

[MacDonaldTriad]

For akathisia,

#1, low the dose if you can
#2, beta blockers (watch out for asthma)
#3, benzos (not very effective on the subjective sense of restlessness)
#4, and way way down the list, anticholinergics, not very effective

As far as TD, I have seen several antioxidant fads come and go without any one of them showing enough efficacy to survive. The second generation antipsychotics mask TD without progressing it in most cases. When clozapine was the only atypical antipsychotic, one of its indications was TD even in patients without psychosis.

 

[milesed]

I agree with above post^.
I've seen benzos used with some success in reducing severity of TD. I've also seen lots more TD and acute dystonic reactions from Abilify than other SGAP's.

 

[tetaoh]

I agree with above post^.
I've seen benzos used with some success in reducing severity of TD. I've also seen lots more TD and acute dystonic reactions from Abilify than other SGAP's.

Are you seeing the increase in TD at doses used for adjunct for depression, or just schizophrenia dosing? Do you expect to see the same trend of more TD for Latuda and Saphris as well?

 

[MacDonaldTriad]

Well, it has taken two decades to be fairly sure second generation antipsychotics have less TD liability, but there is almost nothing comparing SGAs. Even if someone had data on the latest 2, it is far too early to be sure.

Unless there is something radically different about SGAs’ TD vs FGAs’ TD, it is mostly related to lifetime exposure. High dose is worse than low dose, but low dose for a long time can be as bad as brief high dose. Think of it a pack years for antipsychotics.

 

[birchswing]

Well, it has taken two decades to be fairly sure second generation antipsychotics have less TD liability, but there is almost nothing comparing SGAs. Even if someone had data on the latest 2, it is far too early to be sure.

Unless there is something radically different about SGAs’ TD vs FGAs’ TD, it is mostly related to lifetime exposure. High dose is worse than low dose, but low dose for a long time can be as bad as brief high dose. Think of it a pack years for antipsychotics.

I had read that as well:
http://www.orpdl.org/durm/drug_articles/evaluations/seroquel_due.pdf

I was put on 50 mg Seroquel about 15 years ago to help with Tourette's tics. I don't think it helped at all, and I do now have some TD symptoms (which of course are hard to distinguish from Tourette's--at least for me). My concern now is that the Seroquel is masking possible TD. And because I couldn't handle Seroquel in the day (I don't know how anyone could) I take it at bedtime, which means I've become accustomed to it regulating my sleep--even though that was not the original indication, although I know for some people it is.

 

[Merovinge]

Are you seeing the increase in TD at doses used for adjunct for depression, or just schizophrenia dosing? Do you expect to see the same trend of more TD for Latuda and Saphris as well?

It's somewhat poorly known that Abilify is the strongest D2 antagonist of SGA's which is likely why he is seeing more TD which we generally hypothesize to be related to degree of dopamine blockade. How the partial agonist action works in TD progression is pretty unclear to me. Abilify also has a pretty steep D2 affinity curve at lower doses so I would be significantly less worried about 2mg dosing than 10 or higher (nearly maxed D2 at 10), however it is certainly a possibility.

 

[PistolPete]

I have seen Abilify used at low doses (2.5mg, 5mg) in order to treat hyperprolactinemia since it binds so strongly to the D2 receptors and is kicking off the other typical antipsychotic. Of course the preference would be to lower the dose or switch altogether rather than be on 2 antipsychotics at the same time.

 

[milesed]

Are you seeing the increase in TD at doses used for adjunct for depression, or just schizophrenia dosing? Do you expect to see the same trend of more TD for Latuda and Saphris as well?

I see it at all doses of Abilify and don't see it yet with Saphris or Latuda (haven't had too many yet on those).

 

[liquidshadow22]

Do you guys think the risk for tardive dyskinesia requires CONSTANT usage- ie. 1 mg per day for 5 years may cause it vs 500 mg a day for 6 months- either fashion might cause brain damage and TD if taken in continuous fashion.

However, what about if a patient takes an antipsychotic for a low dosage for a few months , then waits a year, does the same thing, then waits another year off meds, takes another course. Do you think there is cumulative damage to dopaminergic neurons in the brain that occurs with even small doses for short periods of time? I guess I'm trying to see if drug holidays can eliminate the risk completely in theory.

 

[MacDonaldTriad]

Don’t even ask me to find it, but 30 years ago there was an article that showed that consistent low dose antipsychotics had less overall exposure to and there for less antipsychotic induced TD than patients who stopped their meds and then became exposed to periodic high dose treatment. The mantra was use the lowest effective dose you can (with no help suggesting how you determine this).

Now with second generation agents, obesity and diabetes is the new TD. There has always been an incidence of TD without schizophrenia or exposure to antipsychotics (although people with schizophrenia have a higher incidence of TD even without antipsychotic exposure as compared to the general population), but now we are really hidden in the clouds with the obesity epidemic. Can you imagine prosecuting “that man gave me a pill that made me fat!” ?

 

[milesed]

I was taught that it was a cumulative dose effect. Dose x years= risk with some groups more prone to developing it. You do what your pt needs, warn of risk, document it and attempt to deal with it of occurs. It's one of the few things psychiatrists are sued over.

 

[MacDonaldTriad]

TD was the #2 reason psychiatrists get prosecuted. #1 was boundary violations and still is. TD doesn’t happen overnight. Causing it isn’t a crime. Not recognizing it and addressing it in a timely manner is.

 

[liquidshadow22]

So you can't really answer my question because we don't really know what the pathophysiology is ? We don't know if there is some threshold that exists or if it is actually a cumulative effect.

 

[MacDonaldTriad]

If there is a threshold effect, the threshold seems to be zero for some people because TD was described by Kreaplin long before antipsychotics existed. It can also occur idiopathically in people without schizophrenia. If it is a cumulative effect, it varies very widely. A most people will not get TD no matter how much exposure there is.

 

[liquidshadow22]

A most people will not get TD no matter how much exposure there is.

However, didn't Yale do a study that showed that nearly 75- 80 % of people, on (typical?) antipsychotics for very long periods of time- 15-25 years, develop TD? ....From Wikipedia , sorry im lazy . "A study being conducted at the Yale University School of Medicine has estimated that "32% of patients develop persistent tics after 5 years on major tranquilizers, 57% by 15 years, and 68% by 25 years."[43]

If it's 70 % after that many years, then I think that says most people are NOT immune to developing this condition when exposed to an adequate amount of antipsychotic, whatever that mechanism may be.

 

[splik]

If there is a threshold effect, the threshold seems to be zero for some people because TD was described by Kreaplin long before antipsychotics existed. It can also occur idiopathically in people without schizophrenia. If it is a cumulative effect, it varies very widely. A most people will not get TD no matter how much exposure there is.

firstly there is a difference between TD and dyskinesia. The former implies a drug induced phenomenon, people can experience dyskinesias for other reasons. And although Kraepelin did describe abnormal movements in his dementia praecox patient, most of these movement share only a cursory resemblance to TD. The movements Kraepelin described were sterotyped and manneristic which is not characteristic of TD. Further, the description of dementia praecox really doesn't describe that brilliantly patients who would be described as having schizophrenia today. Some people have argued that alot of Kraepelin's patients had more classic brain rot such as post-encephelitic syndromes which would be associated with dyskinesias. Interestingly the autoimmune limbic encephalitides often present with dyskinesias.

Finally, even if dyskinetic/choreoathetoid movements were found in chronic psychiatric patients (more accurate than describing them as "schizophrenic"), this was far, far less common than in the post-drug era. Bleuler said he never saw these movements in patients with schizophrenia. Also, this would not explain the observation that manic-depressive patients were more liable to develop TD compared with patients with schizophrenia.

 

[MacDonaldTriad]

If that is true, then I’m definitely wrong. I have noticed that the reported incidence of TD vary widely across studies and more specifically across examiners. I think what one researcher calls TD can be very subtle and questionable where as others are much more conservative with their AIMS scores. The use of traditionals is now so small; we may never have a chance to answer this question for sure. Probably a very good thing.

 

[splik]

If that is true, then I’m definitely wrong. I have noticed that the reported incidence of TD vary widely across studies and more specifically across examiners. I think what one researcher calls TD can be very subtle and questionable where as others are much more conservative with their AIMS scores. The use of traditionals is now so small; we may never have a chance to answer this question for sure. Probably a very good thing.

they could look at this in other countries where typicals are more commonly used. I'm not sure what it is now but when I was a medical student about 50% of treated pts w/ schizophrenia in the UK were on first general neuroleptics. That might be less now but it's still probably not as sharp a difference as in the US. There must be other countries where their use is still very high I would imagine.

 

[Ceke2002]

Anecdotally the only time I've experienced EPS with SGA's was at a Seroquel dosage of between 1000 and 1200 mgs. It was the reason I was first taken off Seroquel (aside from the incessant binge eating and rapid weight gain). Tried Seroquel again several years later, at more reasonable doses of around 150-300mgs, and no EPS, but I did develop peripheral oedema and some sort of heart arrhythmia thing, which is when I stopped taking the medication for the second time. Switched over to Olanzapine, can't remember the exact dose but not that high, and had no problems apart from fluid retention and weight gain that wasn't actually associated with an increase in caloric intake.

 

[Shikima]

I see it at all doses of Abilify and don't see it yet with Saphris or Latuda (haven't had too many yet on those).

I just had to take someone off of Latuda for TD at a low dosage inducing it.

General reminder to all; even if the drug companies declare their product is going to be 'cleaner' from the drug trials, they can't account for individual variation in neurochemistry.