Haloperidol in the Emergency Department Setting

Dr. Scott Zeller suggests it is time to move away from emergency intramuscular haloperidol.

Haloperidol is not FDA approved for treatment of acute agitation and should be relegated to a secondary role in emergency rooms, according to Scott Zeller, MD.
Haloperidol is not FDA approved for treatment of acute agitation and should be relegated to a secondary role in emergency rooms, according to Scott Zeller, MD.

Since the 1980's, intramuscular (IM) haloperidol has been a mainstay of emergency rooms (ERs) and psychiatric facilities. Frequently given as part of a cocktail with lorazepam (often known as the “B-52” or “HAC”), it has been a default treatment, along with physical restraints, for patients with acute agitation in these settings.

But for more than a decade, newer, yet equally potent agents with better side effect profiles have been available, to the point that modern best-practices guidelines encourage these approaches over the traditional haloperidol.1 Of these, oral, inhaled and sublingual medications may be the most patient-friendly, whereas for cases when injections are still necessary, atypical antipsychotics offer efficacy with less oversedation and fewer untoward outcomes.2

Yet despite these alternative recommendations, many sites are still persisting in the use of IM haloperidol.3

If your site is among these holdouts, here are 8 good reasons to advocate moving forward to more contemporary medication strategies:

1. Oversedation

Too often, agitation has been treated with a “knock them out until the next shift” approach, especially when using the injected haloperidol and lorazepam cocktail, which can frequently result in a patient becoming obtunded for 8-12 hours, or even longer.4 There are a number of unwanted patient care issues as a result of this – an unconscious patient cannot answer questions, eat or drink, or otherwise provide self-care. And any medical issues or comorbidity will be masked, with very serious potential consequences.

Oversedation is also suboptimal from a systems perspective. ERs and other emergency sites need beds to turn over, to treat the many other individuals in the waiting room. Thus any bed with an unarousable patient is preventing other patients from accessing care, leading to long wait times and reduced throughput. In addition, psychiatric assessments and potential dispositions cannot proceed until a patient is fully awake, further delaying care interventions.

Because of these concerns, multiple best-practices guidelines for the treatment of agitation, most recently reiterated by the 2016 International Expert Consensus on Agitation, state that the main goal of pharmacological treatment should be to rapidly calm the agitated patient without over-sedation.5,6

2. Dystonic reactions

One of the most frightening side effects of intramuscular haloperidol can be dystonic reactions, including laryngospasm (where patients feel they are choking), oculogyric crisis (eyes appear to roll back into the head), and torticollis (contraction of the neck muscles causing the head to twist to one side). Development of such symptoms are a true emergency on psychiatric units, and are not uncommon; some reports indicate that as many as 10% of patients injected with a high-potency neuroleptic can develop dystonic reactions, especially in patients new to such agents.7 Patients who have experienced such reactions can be understandably apprehensive about agreeing to any psychiatric medications afterwards, leading to difficulty with treatment and therapeutic alliance.

Many Emergency Medicine physicians may not have seen a lot of dystonic reactions in patients injected with haloperidol, and so may be less concerned with the risk. But there's a reason for this lack of exposure – dystonic reactions typically do not occur until 12-24 hours after the haloperidol injection.7 Thus it is usually inpatient psychiatrists who are the ones intervening in dystonic reactions, long after the patients have left the medical ER.

3. Patient preference

Likely all acute care providers are familiar with patients reporting that they are ‘allergic to Haldol.' But no doubt the vast majority of these patients don't have a true allergy to this medication, but rather they've had the medication before, were unhappy with the results, and just don't want to receive it ever again.

In addition to the dystonic reactions and other unpleasant sequelae such as extrapyramidal symptoms and akathisia, a major side effect of haloperidol can be serious dysphoria. Patients often report feeling very low or ‘foggy' after getting a haloperidol injection.

It's hard to imagine a medication, so disliked by patients, to be continued to be favored by providers in other medical conditions besides urgent psychiatric care. Long-term treatment of chronic conditions such as schizophrenia and bipolar disorder require that patients trust and collaborate with psychiatrists; giving medications that patients don't like and don't want can seriously interfere with this bond.

4. Similar efficacy with less coercion

Numerous studies have shown similar efficacy to haloperidol in a number of alternative approaches to agitation, including avoiding injections altogether by the use of oral, inhaled, or sublingual medications.2 These options can even circumvent the use of physical restraints and enhance patient cooperation in mild-to-moderate agitation states. Avoiding physical restraints can have many benefits, such as heightened safety for staff and patients, and improving the patient experience, and also by adding disposition options to sites that won't consider accepting patients who have been restrained.4

Even in more severely impaired patients for whom an injection is inescapable, the IM atypical antipsychotics have been shown to have comparable efficacy and onset of action to haloperidol.1

5. Meta-analyses discourage the use of haloperidol

In a 2013 Cochrane Review of 25 haloperidol studies, the authors made this recommendation: “Haloperidol is a potent antipsychotic drug but has a high propensity to cause adverse effects. …where a choice of drug is available, people with schizophrenia and clinicians may wish to prescribe an alternative antipsychotic with less likelihood of adverse effects such as parkinsonism, akathisia and acute dystonias.”8

6. Cost is not a factor

Most alternatives to haloperidol are now available as generic options. And the two most commonly used injectable atypical antipsychotics, ziprasidone and olanzapine, only cost about $10-$15 more than IM haloperidol (and actually less overall than the haloperidol-lorazepam-benztropine cocktail). Even in a straight-up comparison versus haloperidol alone, it's hard to argue that the extra ten dollars is cost-prohibitive in ERs, where frequently-placed intravenous line starter kits are priced at over $75. Further, the overall savings of improved throughput and patient outcomes vastly exceed the slight difference in cost.

7. QT prolongation is lengthier in haloperidol than IM atypical antipsychotics

Many physicians have reported reluctance to use intramuscular ziprasidone due to concerns about QT prolongation. But IM haloperidol actually leads to more QT prolongation than either IM ziprasidone or IM olanzapine.5 Simply put, if you weren't concerned with QT prolongation when injecting haloperidol, you shouldn't be avoiding IM atypicals for that reason.

8. Haloperidol is not FDA approved for treatment of acute agitation

In an era where physicians and pharmacists are paying strict attention to FDA approval status, it's interesting to note that IM haloperidol is solely approved for ‘treatment of schizophrenia.'9 Only the following agents are specifically approved for the treatment of acute agitation in schizophrenia and bipolar disorder: IM ziprasidone, IM olanzapine, IM aripiprazole, and inhaled loxapine.2

Indeed, one can imagine it would be very difficult to get IM haloperidol approved as a new drug to a hospital formulary committee in this day and age, given its off-label status for treatment of agitation, its high-risk side effect profile, and the availability of suitable alternative agents.

Overall, IM haloperidol will likely still have a role in acute care of agitation for some time to come, and we are not yet to a point where its use should be completely avoided or discontinued. However, there are compelling arguments that other options should now be first-line choices in acute agitation, and haloperidol should be relegated to a secondary role, for when these other agents are ineffective or contraindicated.

Scott Zeller, MD, is the Vice President of Psychiatry for CEP America, in Emeryville, CA, and past president of the American Association for Emergency Psychiatry. He is also a member of the Psychiatry Advisor editorial board. Dr. Zeller is co-editor of the new textbook "The Diagnosis and Management of Agitation", to be published by Cambridge University Press in February 2017.

References

1. Wilson MP et al. The Psychopharmacology of Agitation: Consensus Statement of the American Association for Emergency Psychiatry Project BETA Psychopharmacology Workgroup. West J Emerg Med. 2012;13(1):26-34.

2. Zeller SL, Citrome L. Managing Agitation Associated with Schizophrenia and Bipolar Disorder in the Emergency Setting. West J Emerg Med. 2016;17(2):165-172.

3. Wilson MP et al. Despite expert recommendations, second-generation antipsychotics are not often prescribed in the emergency department. J Emerg Med. 2014;46(6):808-813.

4. Holloman GH, Zeller SL. Overview of Project BETA: Best Practices in Evaluation and Treatment of Agitation. West J Emerg Med. 2012;13(1):1-2.

5. Allen MH, et al. The expert consensus guideline series. Treatment of behavioral emergencies 2005. J Psychiatr Pract. 2005;11:5-108.

6. Garriga M. Assessment and management of agitation in psychiatry: Expert consensus. World J Biol Psychiatry. 2016;17(2):86-128.

7. Jhee SS. Delayed onset of oculogyric crisis and torticollis with intramuscular haloperidol. Ann Pharmacother. 2003;37(10):1434-1437.

8. Adams CE et al. Haloperidol versus placebo for schizophrenia. Cochrane Database Syst Rev. 2013. 15;(11):CD003082.

9. Haloperidol for Injection Label. http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/018701s059lbl.pdf  Accessed October 7, 2016.

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