Date:  September 20, 2013
Title: Vitamin H – Haloperidol
Guest Skeptic: Dr. Anthony (Tony) Seupaul, Chair of EM, University of Arkansas

Case Scenario: 23 yr man with schizophrenia presents with police after being picked up for violent outburst at a coffee shop. He is clearly agitated and you need to chemically restrain him.

Question:  Is haloeridol the safest and most effective method of tranquilization for patients with psychosis induced aggression or agitation?

Serious Reactions (from Epocrates) and delivered by Dr. Michael del Castillo-Hegyi (Chief Resident AUMS):


  • Neurologic (extrapyramidal, tardive dyskinesia, akithisia, dystonia and seizure)
  • Hyperpyrexia or heat stroke
  • Neuroleptic Malignant Syndrome
  • Pneumonia
  • Hypotension or hypertension
  • Cardiac (see Keener Kontest)
  • Sudden Death
  • Hyponatremia
  • Hepatic impairment
  • Hematologic (leukopenia, neutropenia and agranulocytosis)
  • Ocular (cataracts and retinopathy)

Reference: Powney MJ et al. Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation). Cochrane Database of Systematic Reviews  2012, Issue 11. Art. No.: CD009377. DOI: 10.1002/14651858.CD009377.pub2.

  • Population: RCTs involving people with agitation or aggression thought to be due to psychosis
  • Intervention: Haloperidol
  • Comparison: Nothing, placebo or 18 other treatments
  • Outcome: Asleep, repeat injections, or side effects

Methods: This was a Cochrane systematic review and they tend to be very well done. The authors searched the Cochrane Schizophrenia Group Trials Register which included major databases, hand searches, and conference proceedings.  Those authors of RCTs included in this review were contacted for additional trial data.

One author extracted data using standardized forms and 10% of the data was extracted by a second author to ensure reliability.  Discrepancies were resolved by consensus or adjudication.  A similar process was used to assess risk of bias (REF). Methodological heterogeneity was assessed using the I2 statistic and the Chi2 P value.  Data were pooled, if appropriate, using a fixed effects model.  Pooled binary outcome results were expressed as a relative risk (RR with 95% confidence intervals) while pooled continuous data were expressed as a mean difference.

Results: There were 669 potential studies identified in the search. Thirty-two studies were included for analysis. The age of patients ranged from 18-73 years. Over 80% of patients had a diagnosis of schizophrenia while a minority had drug induced psychosis or an organic mental disorder.

Table 1.  Summary of time to falling asleep expressed as a relative risk with 95% confidence intervals. * Denotes statistical significance.

Screen Shot 2013-09-22 at 12.53.42 PM

Interestingly, addition of lorazapam did not offset haloperidol induced dystonia (N=67, RR=8.25, CI=0.46 to 147.45) or the need for anti-parkinson medications  (RR=2.74, CI=0.81 to 9.25).  One trial investigated the addition of promethazine but was stopped after an interim analysis found that patients in the haloperidol alone group experienced more dystonia (N=316, RR=19.48, CI=1.14 to 331.92) and adverse events (N=316, RR=11.28, CI=1.47 to 86.35).

Authors’ Conclusion: “If no other alternative exists, sole use of intramuscular haloperidol could be life-saving. Where additional drugs to offset the adverse effects are available, sole use of haloperidol for the extreme emergency, in situations of coercion, could be considered unethical. Addition of the sedating promethazine has support from better-grade evidence from within randomised trials. Use of an alternative antipsychotic drug is only partially supported by fragmented and poor-grade evidence. Evidence for use of newer generation antipsychotic alternatives is no stronger than that for older drugs. Adding a benzodiazepine to haloperidol does not have strong evidence of benefit and carries a risk of additional harm.”

BEEM Comments: The case scenario of needing rapid and safe chemical restraint of an agitated and/or aggressive patient is common in the ED. While physical restraints can be effective they are not without risk to the patient and health care providers. Avoiding over-sedation can be difficult in these situations. Many protocols using single agents or combinations of agents have been investigated. Most trials exploring combination therapy have unfortunately not been done in the ED and are methodologically flawed. The recommends from ACEP is the use of a benzodiazepine (midazolam or lorazepam) OR conventional anti-psychotics (droperidol or haloperidol) as monotherapy for the undifferentiated agitated patient. Based on this SR with limited RCT data, haloperidol is effective but should be used in combination with medications that minimize the occurrence of common side effects such as dystonia and akithisia. The authors of this review found that promethazine, benzodiazepines, and anticholinergics are useful but caution that they may add to the sedating effects of haloperidol. One interesting finding was that the use of newer atypical antipsychotics was not superior to the use of haloperidol. In fact, haloperidol may be superior as it is more broadly availability and less expensive. BEEM Bottom Line: Haloperidol works and should be used with medication(s) to avert side effects if possible.

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Case Resolution: You sedate this 23yo known schizophrenic with Haloperidol 5mg IM. He is settled and sleeping in 2hrs. Screening blood work is sent off and he waits for psychiatry service to assess.

KEENER KONTESTLast weeks winner was Paul Haskins from Edmonton, Canada. Paul gave the criteria for SIRS (Systemic Inflammatory Response Syndrome). Need two or more to meet definition of SIRS.

  • Temp less than 36°C(96.8°F) or greater than 38°C(100.4°F)
  • Tachycardic (HR> 90 bpm)
  • Tachypnea (RR>20bpm or an arterial partial pressure of carbon dioxide less than 4.3 kPa (32 mmHg)
  • Abnormal WBC (leukocytes <4000 cells/mm³ or >12,000 cells/mm³; or the presence of greater than 10% band)

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Listen to the podcast to hear this weeks question. Send your answers to TheSGEM@gmail.com with keener kontest in the subject line. Be the first one correctly answer the question and you will receive a cool skeptical prize.

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Thank you to Dr. Tony Seupaul

Remember to be skeptical of anything you learn, even if you heard it on The Skeptics’ Guide to Emergency Medicine.