Can Lorazepam (Ativan) and Diphenhydramine (Benadryl) be mixed?

From the Guidelines

Mixing Lorazepam (Ativan) and Diphenhydramine (Benadryl) is not recommended without medical supervision due to potentially dangerous additive effects. Both medications are central nervous system depressants that can cause increased sedation, dizziness, confusion, and impaired coordination when taken together, as benzodiazepines like lorazepam have anxiolytic, amnestic, sedating, hypnotic, and anticonvulsant effects 1. This combination may also lead to respiratory depression in some individuals, particularly the elderly or those with underlying respiratory conditions, as benzodiazepines can cause respiratory depression and systemic hypotension, especially when administered in conjunction with other cardiopulmonary depressants 1.

Some key points to consider when evaluating the safety of combining these medications include:

• The potency and clearance of lorazepam, which is more potent than midazolam and has a slower clearance, especially in patients with renal failure 1
• The increased sensitivity of elderly patients to the sedative effects of benzodiazepines, which can lead to delayed emergence from sedation 1
• The potential for benzodiazepine-induced cardiopulmonary instability, particularly in critically ill patients with baseline respiratory insufficiency and/or cardiovascular instability 1
• The risk of tolerance to benzodiazepines developing with long-term administration, which can further complicate the management of patients taking these medications 1

If you're considering taking these medications together, it is essential to consult with your healthcare provider first, as they can evaluate your specific medical situation, consider potential drug interactions with any other medications you're taking, and provide personalized guidance 1. In some cases, a doctor might intentionally prescribe both medications together at appropriate doses for specific conditions, but self-combining these medications without medical oversight poses significant risks. If you're experiencing anxiety (which Ativan treats) and allergies or sleep issues (which Benadryl treats), discuss with your doctor as there may be safer alternative treatment options for your specific symptoms.

From the Research

Mixing Lorazepam and Diphenhydramine

• The combination of lorazepam (Ativan) and diphenhydramine (Benadryl) has been studied in various contexts, including their use as part of an antiemetic regimen in end-of-life care 2 and for the treatment of insomnia in patients with generalized anxiety disorder 3.
• In the study on nonorganic insomnia in generalized anxiety disorder, the combination of lorazepam and diphenhydramine (Somnium) showed synergistic effects in hypnotic properties and antagonistic effects in regard to toxicity, compared to lorazepam alone 3.
• Another study found that a combination antiemetic preparation (ABHR) containing lorazepam, diphenhydramine, haloperidol, and metoclopramide was effective in managing nausea and vomiting in end-of-life cancer patients 2.
• A study on the visual compatibility and particle counter evaluations of syringes of intramuscular psychotropic coadministered solutions found that the combination of lorazepam and diphenhydramine was physically compatible 4.
• However, it is essential to note that the safety and efficacy of mixing lorazepam and diphenhydramine can depend on various factors, including the specific context of use, dosage, and individual patient characteristics.

Key Findings

• The combination of lorazepam and diphenhydramine has been found to be effective in certain contexts, such as managing insomnia and nausea in patients with generalized anxiety disorder and end-of-life cancer patients, respectively 3, 2.
• The physical compatibility of lorazepam and diphenhydramine in syringes has been established, which can be beneficial for healthcare professionals administering multiple psychotropic medications to patients in acute agitation 4.
• However, the use of benzodiazepines, including lorazepam, in the treatment of delirium is controversial, and current guidelines do not recommend their use for this indication due to uncertainty about their effectiveness and potential harm 5.