Antipsychotic-Induced Dystonia: Diagnosis and Management
Michael D. Jibson, MD, PhD
Professor of Psychiatry
Director of Residency Education
University of Michigan
Last updated: April 5, 2018
Acute dystonic reactions are associated with antipsychotic use, especially with high-potency first-generation antipsychotics. About 90% of these reactions occur either in the first four days of treatment or after an increase in dose.
Risk factors include large muscle mass, younger age and being male. Acute dystonic reactions are class effects, not individual antipsychotic effects. It is not appropriate to tell patients that they are allergic to a particular medication because they had an acute dystonic reaction.
The drugs used to address the acute dystonic reaction are the anticholinergics (benztropine or trihexyphenidyl) or the antihistamine diphenhydramine. This presentation discusses dosing for each medication.
Acute dystonic reactions are one of the things that we think of in emergency psychiatry. The definition of acute dystonic reaction is that it is a sudden, sustained, involuntary muscle spasm anywhere in the body in response to an antipsychotic medication.
It can occur in any muscle group but the most common places are small muscles in the head and neck area.
And some of these are so common that they have their own names. Like muscle cramps in the eyes is oculogyric crisis in which gaze is deviated in a particular direction and usually way out at the extreme of how far they can move by the nature of the muscle cramping.
Cramp in the neck muscles called torticollis is usually represented by the chin being twisted clear over to where it is touching a shoulder. It is quite scary and painful. All of these are.
The most dangerous of them, however, is spasm of the throat. People feel like they are going to choke. Laryngospasm is in fact the possibility. And so there is a medical danger here. It’s quite rare but it does occur.
Jaw cramping, trismus, has been described and also can occur. These aren’t the only places where things happen. One can get cramping in any of the extremities. Back muscles are fairly common, occasionally abdominal muscles. And one shouldn’t assume that it is going to be in one place versus another.
As we look at the risk factors, class of medication is at the top of the list. About 20% to 40% risk of this occurring with the first generation antipsychotics. That’s an incredibly high risk compared with the others.
The lower potency first generation antipsychotics, chlorpromazine, for example, or thioridazine, are less likely to cause this but all of them still more likely than the second generation drugs.
Even with the highest risk of the second generation drugs, risperidone and paliperidone, acute dystonic reactions are relatively rare.
The others, but I have just listed some, there are some additional second-generation drugs that would fit on this list at this point, the acute dystonic reactions are quite rare but should not be ruled out if you see someone having cramping. They have not been reported with quetiapine or clozapine. And so one would not expect these things to be seen with these drugs.
Other risk factors to consider are time and dose. The large majority, about 90%, of these reactions occur either in the first four days of treatment or after first four days after an increase in dose.
You can see people who have been maintained for a long time on a lower dose of medicine who if the dose is increased by a large amount suddenly go into a period of high risk. And so you can see this during those times. Generally, it is a time when there is a rapid escalation of dose as well as being early in treatment.
The most interesting thing that we see in the timing of the reaction is that the reactions are most likely to occur during a trough serum level, not during the high level, the peak level that would follow a dose. This is why when we’d be rounding on our inpatient unit we do this first thing in the morning before the morning medications were given out. Some of the less experienced staff would sometimes think this was malingering on the part of our patients claiming they have one of these reactions to avoid getting more of the antipsychotic. We cannot rule that out but in fact, most of the time, it was simply that they were at the trough level of the medication.
Patient risk factors. Larger muscle mass. It’s not clear if they actually have more cramping or if the cramping is simply harder to control with the large muscle mass. This is a centrally mediated phenomenon. It is not occurring at the level of the muscles but this was a risk factor that we observed.
Younger patients and male patients are more likely to have the acute dystonic reaction than women or older patients. The usual rule with the older female patients, this is where you want to start low and go slow. And you get some young buffed up men that are otherwise healthy and you think you’ll just blast them with whatever medication you want and it is going to be okay. Just the opposite is true in the case of acute dystonic reactions. The older female patients tolerate the medications better than the younger otherwise healthy patients.
There are some studies that have indicated that patients with Asian genetics may be more likely to experience an acute dystonic reaction. That hasn’t been systematically studied as it might be.
In making the diagnosis, you want to look for the overall setting in which the cramping is occurring.
So you’re going to expect that it is relatively early in treatment or after a change in treatment.
The onset is going to be rapid. Generally, these cramps occur very quickly rather than over long period of time. Certainly, they would be likely to occur within one day rather than over weeks.
They tend to be localized. This is critical. They tend to be localized to one or just a few muscles generally in the same area and that’s rather a generalized rigidity and that’s going to be one of the key diagnostic features.
Other things to look for: no alteration in consciousness, no alteration in vital signs.
Now, these last three items are to distinguish an acute dystonic reaction from neuroleptic malignant syndrome, a far more serious and dangerous disorder that requires discontinuation of the medication over a substantial period of time and monitoring in an intensive care unit. Acute dystonic reactions do not require that level of care.
Treatment is straightforward, injectable benztropine or trihexyphenidyl. Right now, benztropine is usually going to be a little bit more available in most hospital settings. But either one of these medications is perfectly appropriate as an anticholinergic. Benztropine 2 mg, trihexyphenidyl 5 mg can be given at intervals from 15 to 30 minutes. And in each case, up to four doses can be given safely. One expects to see a response within minutes of the injection. So at 15 minutes, it is reasonable to expect to have seen some response. At 30 minutes, you’re probably seeing about as much as you are going to see with that dose. And if things haven’t cleared up substantially, then another dose is appropriate. The average number of doses that’s given with these medications is two but you can give up to four and may still see a response at that point.
The second option for acute treatment is an antihistamine. And the one that’s most commonly used is diphenhydramine which is also anticholinergic. So you want to be a little bit cautious using this particular antihistamine together with the anticholinergics. But 50 mg doses IM again at intervals of 15 to 30 minutes and up to four doses can be used. Not listed here but some other secondary treatments that can be used to at least relax the muscles not necessarily addressing what is going on centrally but to relax the muscles would be a benzodiazepine or a muscle relaxant. But those would clearly be second-line agents. The anticholinergics or antihistamines are generally going to control things pretty well.
After this occurs, you’re probably going to want to implement maintenance treatment.
And so the same medications can be used at a somewhat lower dose range, 1 or 2 mg of benztropine every six hours up to a maximum of 8 mg a day, trihexyphenidyl same thing 2 to 5 mg every six hours up to 20 mg a day. So again, maximum six-hour dosing will be effective at heading this off. It does come with the side effects that go with anticholinergic medications. So we don’t always want to do this prophylactically. But if a patient has had an acute reaction, then it is a good idea to have this medication on board.
Other alternatives, diphenhydramine 25 to 50 mg every six hours or a dopaminergic agent such as amantadine at 100 mg every six to eight hours up to 300 mg a day would all be reasonable options.
Other treatment considerations, reduce the medication dose. You’re almost certainly going to want to do that.
Slow down the rate of titration.
Consider an alternative medication.
Be aware that acute dystonic reactions are class effects, not individual medicine effects. It is not appropriate to tell a patient that they are allergic to a particular medication because they had an acute dystonic reaction. In fact, they are prone to acute dystonic reactions and they are going to be prone to those reactions with any medication that is comparable on the list of risks. What we should say is that with this class of medicines, the reaction is at higher risk.
So consider an alternative class, a lower risk medication and consider gradually decreasing or rather be aware that the risk is gradually decreasing with time and that the patient may well tolerate a medication later that they had a reaction with early in treatment.
So take home points here. Acute dystonic reactions are associated with antipsychotics and especially with high potency first generation antipsychotics especially early in treatment.
The drugs to use to address the acute dystonic reaction are the anticholinergics, benztropine or trihexyphenidyl or the antihistamine, diphenhydramine. And the responses to these medicines tend to be brisk and very effective.
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