Agitation or aggression is a common symptom in patients with psychosis and is often harmful to others. Previously, droperidol had the potential to treat agitation. However, its use was left due to reports of complications on the cardiovascular system. Now, there is recent research that looks again at the potential for droperidol as sedation.


How to manage and what drugs are used for agitation?

In most patients, the management of agitation uses verbal de-escalation and oral medications. Meanwhile, cases that fail to be treated using verbal de-escalation and oral medication often require physical restraints or parenteral medication. Pharmacotherapy modalities to treat agitation or aggression in patients with psychosis are injecting antipsychotics and benzodiazepines as rapid tranquilization.



What is Droperidol?

Droperidol is a typical antipsychotic of the butyrophenone group. Droperidol is effective in treating agitation or aggression in patients with psychosis. Indications Droperidol is for sedation in agitated psychotic patients. Droperidol has a fast onset of action, a long duration, and fewer side effects. However, this drug has received a black box warning from the FDA because it is thought to have torsades de pointes as the side effect due to prolonged QT interval and various cardiovascular side effects. However, this drug is widely recommended for treating agitation or aggression in patients with psychosis because of its effectiveness.


Droperidol to Overcome Agitation

Research by Khokhar et al. showed that droperidol could relieve agitation or aggression within 30 minutes. Also, the use of droperidol reduced the need for the use of other additional drugs.
Over a wide range of doses, droperidol has different effects:
  • 0.25 - 1.5 mg (low dose): antiemetic effect
  • 5 - 20 mg: Sedation effect
  • 10 - 200 mg / hour: anesthetic effect
Droperidol is rapidly absorbed after intramuscular administration at a dose of 5-10 mg. The onset of droperidol effects occurs within 3-10 minutes after injection, although the peak of action does not appear after 30 minutes. The duration of sedation and sedation is 2-4 hours.

Foo et al. even reported that the duration of droperidol sedation was up to 6 hours. However, the disturbance of alertness can last up to 12 hours.


Side Effects of Droperidol 

In dealing with agitation in psychosis, droperidol can be used monotherapy or combined with benzodiazepines. However, combined use with benzodiazepines can increase the risk of respiratory depression.

The currently recommended method of administration of droperidol is by intramuscular injection. Administering droperidol by intravenous injection increases the risk of side effects of QT prolongation, extrapyramidal syndrome, and hypotension.

Commonly reported side effects of droperidol are hypotension, tachycardia, restlessness, hyperactivity, dysphoria, and extrapyramidal syndrome. So it is advisable to monitor blood pressure during droperidol administration.

One of the side effects of worrying about using droperidol is arrhythmia. However, Khokhar and Rathbone's review reported no strong evidence to prove that droperidol causes greater arrhythmias and airway suppression than placebo.


Comparison of Droperidol with Other Drugs

Some studies have shown some advantages of droperidol. Droperidol is better than haloperidol at inducing a sedative effect in 30 minutes and requires less additional drug in 60 minutes. However, there is no difference in efficacy between droperidol and haloperidol. The effectiveness of droperidol and haloperidol is equivalent to controlling agitation. They also reported that droperidol does not cause more cardiovascular side effects than haloperidol. When given by intramuscular, droperidol has a faster onset, elimination, and fewer side effects than haloperidol.

Compared with the atypical antipsychotic drug olanzapine, droperidol and olanzapine's sedative effect was not significantly different. In fact, droperidol outperformed the need for additional drugs after 60 minutes when compared to olanzapine. Droperidol requires less additional drug within 60 minutes than olanzapine. Also, there is no evidence to suggest that droperidol causes more cardiorespiratory side effects than olanzapine.

Other drugs that can be used to treat agitated patients with psychosis are the benzodiazepines, such as diazepam and midazolam. The sedative effect onset of droperidol is slower than midazolam. The side effects of droperidol and midazolam did not differ significantly. But, those receiving midazolam were at risk of requiring airway support maneuvers.



Conclusion
Agitation or aggression in psychosis patients is an emergency condition that requires rapid treatment. The first line of management is by verbal de-escalation or oral medication. If these methods fail, then physically restrain, or rapid tranquilization is required. Drugs often used for rapid tranquilization are typical antipsychotics, atypical antipsychotics, and benzodiazepines.

The recommended method of administration for rapid tranquilization is the use of intramuscular injection. However, the administration intravenously increases the risk of developing side effects. The combination of antipsychotics with benzodiazepines increases the risk of developing respiratory depression.

Droperidol is a typical butyrophenone antipsychotic that is a recommended drug for rapid tranquilization. Droperidol has a faster onset and elimination time, minimal need for additional sedation, and fewer side effects than haloperidol.

Droperidol received a black box warning from the FDA because of concerns about this drug's cardiovascular side effects. However, Khokhar and Rathbone's review showed that droperidol's cardiovascular side effects were no different from other antipsychotics.


References
1. Baldaçara L, Diaz AP, Leite V, Pereira LA, dos Santos RM, Gomes Júnior V de P, et al. Brazilian guidelines for the management of psychomotor agitation. Part 2. Pharmacological approach. Braz. J. Psychiatry 2019; 41: 324–35. [https://pubmed.ncbi.nlm.nih.gov/30843960/]
2. Calver L, Drinkwater V, Gupta R, Page CB, Isbister GK. Droperidol v. haloperidol for sedation of aggressive behavior in acute mental health: Randomised controlled trial. Br J Psychiatry 2015; 206: 223–8. [https://pubmed.ncbi.nlm.nih.gov/25395689/]
3. Foo L-K, Duffull SB, Calver L, Schneider J, Isbister GK. Population pharmacokinetics of intramuscular droperidol in acutely agitated patients: Pharmacokinetics of intramuscular droperidol. Br J Clin Pharmacol 2016; 82: 1550–6. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099560/]
4. Khokhar MA, Rathbone J. Droperidol for psychosis-induced aggression or agitation. Cochrane Database of Systematic Reviews. 2016 (12): CD002830 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463952/]
5. Sadock BJ, Sadock VA, Ruiz P, Kaplan HI, editors. Kaplan & Sadock’s comprehensive textbook of psychiatry. 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2009.
6. Sadock BJ, Sadock VA, Ruiz P. Kaplan & Sadock’s synopsis of psychiatry: behavioral sciences/clinical psychiatry. Eleventh edition. Philadelphia: Wolters Kluwer; 2015.