Medication for Aggression: What Works and Where?


Using medications to induce calm is generally considered less desirable than other methods of de-escalation but is often necessary to prevent injury.

Aggressive behavior in some patients can be a tremendous challenge for clinicians who work in mental health. If nonpharmacological interventions fail, medication may be necessary.

Research suggests that uncurbed aggressive behavior can rewire brain chemistry over time and lead to an increase in aggressive behavior. Halting aggressive behavior before it harms the patient or another person is critical, especially with acute onset. Using medications to induce calm is generally considered less desirable than other methods of de-escalation but is often necessary to prevent injury.

A meta-analysis published in European Psychiatry indicates that studies on pharmacologic interventions rarely compare all available medications. This article reviews and suggests fast-acting medications to calm patients from an agitated state to reduce patient harm.

The authors examined 53 randomized controlled trials including drug interventions in acute agitation. The authors looked for outcomes of calmness within 2 hours of administration measured by a level of change on scales assessing aggressive behavior and the number/severity of adverse events to determine the safety of the medications used.

The meta-analysis suggests that haloperidol (a first-generation antipsychotic) plus promethazine (an antihistamine) is the strongest contender in decreasing agitation and returning a patient to calmness within 2 hours. Olanzapine (an atypical antipsychotic) also shows a significant effect on inducing calm.

Midazolam (a benzodiazepine) and droperidol (antidopaminergic) have both been shown to be effective and cause a reduction in aggression quickly. However, the result may not be sustained, and repeated administration may increase side effects including oversedation and respiratory depression. For this reason, the authors suggest using these drugs in the emergency room setting only (because support measures would be available in the event of drug-related emergency).

Most studies included in the analysis gave the medications through by intramuscular injection. Many healthcare providers in clinical practice prefer oral administration as it lends to better patient-staff collaboration.

Guidelines published over the years advocate the use of second-generation antipsychotics, but despite this recommendation doctors prefer the older antipsychotics and benzodiazepines. The researchers attribute this preference to clinical experience.

The authors conclude that recommendations are limited to the adult population, as few studies are available in juveniles and adolescents. Our knowledge base would benefit from a more in-depth look into pharmacological treatment of the young-adult population.


Bak M, Weltens I, Bervoets C, et al. The pharmacological management of agitated and aggressive behaviour: A systematic review and meta-analysis. Eur Psychiatry. 2019;57:78-100.

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