What medication can be given to an agitated patient with intellectual impairment, who has previously received diazepam (Diazepam is a benzodiazepine)?

From the Guidelines

For an agitated patient with intellectual impairment who has already received diazepam but continues to disturb other patients, I would recommend low-dose haloperidol 0.5-1 mg orally at night and every 2 hours when required, as suggested by the most recent guideline evidence 1. This approach is based on the latest guidance from the BMJ in 2020, which provides recommendations for managing symptoms, including delirium, in the community. The use of haloperidol is preferred due to its efficacy in reducing agitation with a relatively favorable side effect profile compared to other antipsychotics. Before administering haloperidol, it is crucial to attempt non-pharmacological interventions such as reorientation, providing a quiet environment, or having a familiar person present, as these methods can sometimes de-escalate the situation without the need for additional medication. If the patient remains agitated, consideration can be given to adding a benzodiazepine like lorazepam or midazolam, but this should be done with caution due to the potential for increased respiratory depression, especially since the patient has already received diazepam. Regular monitoring of vital signs, particularly blood pressure and respiratory rate, is essential when initiating or adjusting any medication for agitation. It's also important to be aware of the potential risks associated with antipsychotic use in patients with dementia, including an increased risk of mortality, and to weigh these risks against the benefits of treatment in each individual case. Starting with the lowest effective dose and frequently reassessing the patient's condition can help minimize side effects while maintaining therapeutic efficacy. Key considerations include:

• Monitoring for extrapyramidal symptoms, which can be a side effect of haloperidol
• Being cautious with dose increments, especially in elderly patients
• Considering alternative medications if haloperidol is not effective or is contraindicated
• Ensuring that the patient's care plan is regularly reviewed and updated to reflect any changes in their condition or response to treatment.

From the FDA Drug Label

The benzodiazepines, including lorazepam, produce increased CNS-depressant effects when administered with other CNS depressants such as alcohol, barbiturates, antipsychotics, sedative/hypnotics, anxiolytics, antidepressants, narcotic analgesics, sedative antihistamines, anticonvulsants, and anesthetics Abuse, Misuse, and Addiction Inform patients that the use of lorazepam even at recommended doses, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose and death, especially when used in combination with other medications (e.g., opioid analgesics), alcohol, and/or illicit substances.

Lorazepam may be considered for the agitated patient, but with caution due to the potential for:

• Increased CNS-depressant effects when combined with other medications
• Abuse, misuse, and addiction
• The patient has already had diazepam, which is also a benzodiazepine, and the risk of cumulative effects should be considered 2
• Intellectual impairment may be a concern, as benzodiazepines can cause cognitive impairment, and the patient's condition should be closely monitored 3 Key considerations:
• Monitor the patient closely for signs of respiratory depression, sedation, and other adverse reactions
• Use the lowest effective dose for the shortest duration necessary
• Consider alternative treatments or consult with a specialist if the patient's condition does not improve or worsens 2

From the Research

Agitation Management

• The patient has already been given diazepam, but alternative options can be considered for agitation management, especially in cases of intellectual impairment.
• Haloperidol can be used off-label for agitation and/or delirium in older individuals, with a recommended initial intramuscular or intravenous dose of 0.5 to 1 mg 4.
• Low-dose haloperidol (≤0.5 mg) has been shown to be similar in effect to higher doses, with fewer adverse effects 4, 5.
• Atypical antipsychotics such as risperidone, olanzapine, or quetiapine may also be effective in managing delirium, with a lower incidence of extrapyramidal adverse effects 5.

Combination Therapy

• The combination of lorazepam and haloperidol has been shown to be effective in reducing agitation, with significant mean decreases from baseline at every hourly evaluation 6.
• However, patients receiving haloperidol alone tended to have more extrapyramidal system symptoms, while the combination treatment had superior results 6.

Alternative Options

• Valproic acid has been shown to be as effective as haloperidol in decreasing agitation levels, with a better safety profile and fewer extrapyramidal symptoms 7, 8.
• Sodium valproate has also been found to be as efficacious as haloperidol in the management of acute mania, with a faster response and fewer adverse effects 8.