Why is promethazine given with haloperidol (antipsychotic)?

From the Guidelines

Promethazine is given with haloperidol to enhance its antipsychotic effects, reduce side effects, and provide a sedative effect, as evidenced by a randomized controlled drug trial 1. This combination is particularly useful in managing acute agitation or psychosis. Promethazine, an antihistamine with sedative properties, helps counteract the extrapyramidal side effects (movement disorders) that haloperidol can cause, such as akathisia, dystonia, and parkinsonian symptoms.

The key benefits of this combination include:

• Enhanced antipsychotic effects
• Reduced extrapyramidal side effects
• Faster calming effects in agitated patients
• Sedative properties of promethazine complement haloperidol's antipsychotic action

A study by Alexander et al 1 found that a combination of haloperidol (10 mg) and promethazine (25-50 mg) produced more patients tranquil or asleep at 15,30,60, and 120 minutes compared to lorazepam (4 mg). However, it's essential to note that the study had limitations, including patients being entered at physician discretion and varying doses of promethazine used.

In clinical practice, a typical regimen might include haloperidol 5mg with promethazine 25-50mg, administered intramuscularly or orally, depending on the clinical situation. The combination works because promethazine blocks histamine receptors and has anticholinergic properties that help balance the dopamine blockade caused by haloperidol. For ongoing treatment, the doses may need adjustment based on patient response and side effect profile. It's crucial to monitor for excessive sedation, anticholinergic effects (dry mouth, constipation, urinary retention), and cardiovascular effects when using this combination 1.

From the Research

Rationale for Combining Promethazine with Haloperidol

• The combination of haloperidol and promethazine is used to treat acute agitation in psychiatric patients, as it combines the sedative properties of the antihistamine with the calming action of haloperidol 2.
• Promethazine is added to haloperidol to reduce the risk of extrapyramidal symptoms, which are a common side effect of haloperidol 2, 3.
• The combination of haloperidol and promethazine has been shown to be more effective than haloperidol alone in rapidly tranquillizing agitated patients, with a reduced risk of acute dystonia 3.
• Studies have compared the combination of haloperidol and promethazine to other treatments, such as olanzapine, ziprasidone, and midazolam, and found it to be a safe and effective option for managing psychosis-induced aggression 4, 5, 6.

Benefits of the Combination

• The combination of haloperidol and promethazine has been shown to be more effective than haloperidol alone in reducing agitation and aggression in psychiatric patients 3, 5.
• The addition of promethazine to haloperidol reduces the risk of extrapyramidal symptoms, making it a safer option for patients 2, 3.
• The combination has been found to be effective in reducing the need for restraints and sedation in agitated patients 5.

Comparison to Other Treatments

• The combination of haloperidol and promethazine has been compared to other treatments, such as olanzapine, ziprasidone, and midazolam, and found to be a safe and effective option for managing psychosis-induced aggression 4, 5, 6.
• Olanzapine and ziprasidone have been found to be viable options for rapid tranquillization, but may have a higher risk of resumption of aggression and subsequent need for re-injection 5.
• Midazolam has been found to be a swift and effective option for tranquillization, but may cause respiratory depression 5.