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Introduction with a case
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Once upon a time at Genius General Hospital, a 25-year old man was admitted to the ICU for agitation. After exclusion of an acute medical or neurologic process, it became clear that he was suffering from schizophrenia with medication nonadherence. Unfortunately, his electronic medical record indicated that he had a history of anaphylaxis from haloperidol (no further details available). Psychiatry recommended avoiding all neuroleptic medications, using lorazepam instead to treat his agitation. Lorazepam was only transiently effective, and he continued to have frequent episodes of violent agitation. This process continued for days, with security frequently called to the ICU and some nurses injured. He was deemed too unstable to transfer to any other location in the hospital. Eventually, following literature review and discussion with the ICU pharmacist, the ICU team administered a dose of haloperidol. He tolerated this well with improvement in his agitation. Haloperidol was removed from his allergy list, and he was promptly stabilized and transferred out of the ICU.
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Extrapyramidal side effects may be misdiagnosed as allergic reactions
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Many cases of “allergy” to haloperidol are extrapyramidal reactions, probably dystonias moreso than akathasia. Haloperidol may cause a variety of acute dystonic reactions which may be dramatic (i.e., oculogyric crisis, tongue protrusion, trismus, torticollis). Severe cases may cause tongue laceration, tooth damage, or even rhabdomyolysis. Laryngeal dystonia may cause severe respiratory distress, stridor, dysphagia, and dysphonia, causing it to be misdiagnosed as anaphylaxis (Christodoulou 2005, Ilchef 1997).
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Opisthotonus is one type of dystonic reaction (source: jeffem.blogspot.com)
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Acute dystonia is a common side effect of haloperidol, primarily in younger patients. Studies report frequencies ranging up to 92%, with a weighted average of 21% (Jeanjean 1997). The prevalence of dystonia increases with ongoing exposure, reaching a plateau after about five days of therapy. Therefore, if a patient previously experienced a dystonic reaction during ongoing haloperidol therapy this is not particularly unusual, nor does it imply that a dystonic reaction will necessarily occur following brief re-exposure.
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There are almost no reports of anaphylaxis, angioedema, or cutaneous allergy to haloperidol
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Pubmed contains no report of haloperidol causing anaphylaxis, and other authors have also failed to find any publication of one (Kahlon 2012). None. Allergic skin reactions to haloperidol are similarly absent in the literature. Searching Pubmed for haloperidol plus the terms allergic, allergy, or cutaneous yields only one report of sensitivity to haloperidol in the form of leukocytoclastic vasculitis (Lee 1999).
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There are two reports of angioedema following haloperidol administration, only one of which is described in detail (Kahlon 2012, Muzyk 2012). Kahlon described a 29-year-old man who received intramuscular haloperidol with subsequent tongue swelling that responded to oral diphenhydramine. The following day he presented to the ED with recurrent tongue swelling which responded to diphenhydramine and epinephrine. Although these authors propose that this patient had biphasic angioedema, it may be more likely that he was suffering from acute dystonia. The patient's tongue and uvula were described as edematous, but there was no note of edema involving the lips or eyes. A dystonic protruding tongue could easily mimic an edematous tongue. The patient improved “within minutes” of receiving diphenhydramine and subcutaneous epinephrine, which may suggest a dystonic reaction which promptly responded to diphenhydramine. Finally, recent evidence suggests that severe biphasic reactions are extremely rare (more on this in the SGEM podcast with Dr. Swaminathan).
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Psychiatric hospitals in Germany, Austria, and Switzerland collaborated to produce a large-scale surveillance database designed to monitor psychopharmacology called the AMSP program (Arneimittelsicherheit in der Psychiatrie). Bender 2004 published data from the AMSP program from 1993-2000 describing all severe adverse drug reactions following the administration of neuroleptics to 86,439 patients. These authors classified anaphylaxis and angioedema as dermatologic adverse drug reactions. There was a notable absence of any allergic reaction to haloperidol (red arrow, figure below). Haloperidol was the most commonly used neuroleptic (administered to 16,293 patients), suggesting that the study was well-powered to detect rare events. Common causes of severe adverse reaction to haloperidol consisted of 33 patients with extrapyramidal symptoms, 10 with seizure, 9 with urinary retention, 8 with neuroleptic malignant syndrome, 6 with liver abnormality, and 5 with somnolence. Lange-Asschenfeldt 2009 published data from the AMSP program from 1993-2005 describing 214 patients with cutaneous adverse reactions to psychotropic medications, none of which were due to haloperidol.
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It is difficult to prove a negative. It cannot be excluded that an episode of anaphylaxis or angioedema ever happened, nor that one will occur in the future. However, given the billions of doses of haloperidol which have been dispensed since its introduction in the 1950s, the absence of reports of anaphylaxis, angioedema, or cutaneous allergy is notable.
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Medical records documenting antipsychotic allergy are often incorrect
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Nurenberg 2009 evaluated 79 patients at a state psychiatric hospital with a documented allergy to antipsychotics using chart review and patient interview. Only 9% of these patients had a history consistent with allergy (defined as “any suggestion” that the drug was associated with a rash and/or acute respiratory event). The vast majority had no history of allergic symptoms, with some patients intentionally fabricating allergies in order to avoid receiving medications that they disliked. This study has substantial limitations: there was no gold standard for true antipsychotic allergy, and the ability to apply these findings to a broader patient populations is unclear. Nonetheless this is consistent with other evidence that self-reporting of allergic reactions is often inaccurate (for example, >80% of patients self-reporting penicillin allergy are not actually allergic on skin testing; Salkind 2001).
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Other serious reactions to haloperidol should be considered
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For a patient with haloperidol “allergy,” other considerations may include whether this was an episode of neuroleptic malignant syndrome or torsade-de-pointes due to QT prolongation. Further history if available may help exclude these possibilities. In general it would be extremely unusual and erroneous for these events to be recorded as a haloperidol allergy, as they imply that the patient should avoid entire groups of medications rather than simply haloperidol.
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Approach to a patient with agitated psychosis and haloperidol “allergy”
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It’s not uncommon to encounter a patient with haloperidol allergy. Often the nature of this allergy is unclear, and it may be impossible to obtain additional information from an agitated patient. This poses a problem, because butyrophenones (primarily haloperidol and droperidol) are very useful for the management of agitated psychosis.
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Most of these “allergies” probably represent minor adverse effects (i.e., lethargy, dysphoria) or dystonic reactions. A history of acute dystonia is not a contraindication to the use of any antipsychotic (Owens 2014). Atypical antipsychotics may be preferable to haloperidol in this situation. Nonetheless, haloperidol can be used with the addition of an anticholinergic agent (i.e., benztropine) to prevent dystonia (Winslow 1986). For a dangerously agitated patient, haloperidol could be used to stabilize the patient with prompt transition to an atypical antipsychotic for maintence therapy.
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Ultimately, approaching a patient with agitated psychosis and haloperidol “allergy” is a matter of clinical judgment. An undefined haloperidol allergy is not an absolute contraindication to its use. If there is concern about inducing a dystonic reaction, the addition of an anticholinergic will reduce this risk (i.e., diphenhydramine, which may also improve sedation). Alternatively the patient could be administered haloperidol and treated for dystonia if this occurs, noting that intravenous anticholinergics are promptly effective.
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Akathisia (distressing restlessness) may be more problematic than dystonia, because it is less responsive to medication. Furthermore, there is a danger of misdiagnosing akathisia as agitation, leading to additional haloperidol administration with exacerbation of the akathisia leading to a vicious cycle. Nonetheless this is not a life-threatening problem if recognized and treated. Among patients with Parkinson’s disease and related neurodegenerative disorders (i.e., Lewy-body dementia), there is an increased frequency and severity of extrapyramidal symptoms, and it is probably best to avoid typical antipsychotics.
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For patients with schizophrenia, haloperidol may be a useful medication for future episodes of agitation. Therefore, the benefits of administering a dose of haloperidol include both acute management as well as removing this from the patient's allergy list to facilitate future management. Failure to promptly control agitation endangers both the patient and staff.
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If you are fortunate enough to have access to both haloperidol and droperidol, then a reasonable approach could be to use droperidol instead. However, it should be noted that most reactions to haloperidol are class effects.
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Take-home points
- There are almost no reported cases of anaphylaxis, angioedema, or cutaneous allergy due to haloperidol. Severe allergic reactions to haloperidol are either nonexistent or extraordinarily rare.
- A patient who develops dyspnea and stridor following haloperidol is probably experiencing laryngeal dystonia. This may be managed similarly to other dystonic reactions with an anticholinergic agent (i.e., benztropine or diphenhydramine).
- Patients with Parkinson’s disease and related neurodegenerative disorders are at increased risk of extrapyramidal side-effects, and haloperidol should be avoided if possible.
- An undefined allergy to haloperidol is not an absolute contraindication to its use. In certain situations the benefits may outweigh the risks, and haloperidol may be used with close monitoring.
Josh is the creator of PulmCrit.org. He is an associate professor of Pulmonary and Critical Care Medicine at the University of Vermont.
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Now I understand better about it. But I’m very thankful that I don’t have this kind of allergy or any allergies for that matter. Maybe I am not able to discover it but so far, I don’t experience any allergies in my body. But just in case it may happen, at least I have a little background already because of this post of yours.
Omg! I found my answer! Thank you so much! I am a psych nurse. I have seen two episodes of tongue protruding suddenly after a few doses of Thorazine in one case and haldol in another case. In both cases no edema was present on patient’s face whatsoever. The lips were not swollen neither were the eyelids. The tongue did not look swollen at all. It looked stiff and centered, blocking the airway. Patients vital signs WNL except for the heart rate slightly over 100%,, sats 99% on room air. Patients responded to Benadryl IM within min. What drove me… Read more »
excellent, again , Josh. so now the trick is to convince the nurses when we have a potentially violent, dangerous and perhaps manipulative patient , who is screaming ‘i am deathly allergic to haldol!” and there are guards and maybe police, and the atmosphere is less than zen-ish. and i walk calmly in, and say “i just read a great article last night (eyes rolling) ; no one is allergic to haldol”. and the patient (who, while perhaps schizophrenic, is often sharper and smarter than i am, and is threatening to sue the city, the hospital , and especially me… Read more »
Yeah I am that unicersity honors classes student that’s a combat veteran ,I would say from my stand point, if anyone says they are allergic to a drug why force sedate them you are being paid to handle humans ,not just fall back on lower empathy long hours,stereotypesand persona dislikes You have any idea how horrible it is when no one cares you are not sczophenic and are having a allgery reaction to haldol. What about the Hippocratic oath, that part of the reason why I do not wanna got medical school ,just to work in some Crappy ER. Ruining… Read more »
They did that to my fiancee. He was fine, he just struggled with depression and now they forced anti-psychotics and a bunch of other medicines on him. They made him completely catatonic, paranoid. How long does ot take to get back to normal ??
His research is bs I have had 2 severe reactions to it.
This is disgusting. I happen to be one of the 1 in 36,000 people who gets neuroleptic malignant syndrome from haldol, and one of my most “treasured” PTSD memories was being held down while a nurse came at me with a needle, me saying I can’t have it because I’m allergic (or, call it a potentially letahal interaction if the TECHNICAL definition of “allergy” isn’t good enough”, only to have her WINK at me, say ok them, and inject me anyway. Have you ever seen the movie “Awakenings”? It’s horiffic. It’s happened multiple times over my life, and the effects… Read more »
Fry, or Tom Fiero, omg, the same exact thing happened to my fiancee. It’s horrible. He’s never had a delusion in his whole life, just depression and his mother took him into a psycheward and they put him on 7 different medications then said he’s schizophrenic ?! He was happy and normal and he came out catatonic, paranoid and extremely depressed. They put him on all kinds of medicines for problems he doesn’t have just to make money off him.
I am told I need cognitive therapy to even trust medications again, because of the hell I experienced from this horrable drug! The first time I was 12 yrs old and had to be taken by ambulance from school to the hospital for what they believed to be a siezure at first, to find out it was severe distonic reaction from haldol. Then was sent home and the same time the next day I had another severe distonic reaction and ended up in the emergancy room again all from 1 single pill! Then it happened again when I was 34… Read more »
So many things to add here, but keeping it short and to the point…This is not correct. Acute laryngeal dystonia can be fatal. There have also been cases of sudden death with Haldol. Aside from the misinformation you share, I’m guessing you have never experienced the pain of dystonia, as evidenced by your lack of empathy. I have always loved the ones in the profession who INSIST they know more about the patient’s allergies than the patient themself. Come on! Patients deserve better care than that.
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Once I got a shot of Haloperidol, because I acted a little agressively in the hospital. I was in with suicide attempt, but it wasnt like it sounds. Im not crazy, I never was. I just lost my only parent who I had. Long story short, I was frustrated, because the doctor told me that I should sign a piece of paper, in which I promise, I wont do it again. I said no. Then she said I should stay for more days. Then I got angry. How a piece of paper can mean anything? How can they force me… Read more »
So sad, but anyone who has looked after a loved one with mental illness or dementia will know how hard it is physically and mentally. One of the hardest things in the world is mourning someone who is still alive. My son was diagnosed with schizophrenia 5years ago, with a series of life-threatening symptoms of hallucinations, delusion, and depression, Even with rigorous therapies, antipsychotic medications, and some controversial alternative treatments the condition didn’t improve. Today, it makes 2years since my son recovered after taking Consummo treatment without any treatment, he is now living a complete, normal, healthy life and has… Read more »