From the Guidelines
I strongly advise against combining low doses of Benadryl (diphenhydramine) and amitriptyline without proper medical supervision, as this combination can lead to severe sedation, anticholinergic effects, and potentially life-threatening heart rhythm changes, particularly in older adults. Both medications can cause sedation and anticholinergic effects, such as dry mouth, blurred vision, constipation, and urinary retention, which can be intensified when taken together 1. The combination may also lead to excessive drowsiness, confusion, memory problems, and potentially dangerous heart rhythm changes, especially in older adults 1.
When considering the use of these medications together, it is essential to have proper medical supervision with appropriate dosing. The doctor may recommend lower doses of each medication if they must be used concurrently. Never adjust medication doses on your own, as this can lead to severe adverse effects. These medications interact because they affect similar neurotransmitter systems in the body, influencing histamine and acetylcholine pathways, which is why their side effects can compound when combined 1.
It is crucial to inform all healthcare providers about all medications being taken to prevent potentially harmful drug interactions. Additionally, caution should be exercised when combining two or more non-MAOI serotonergic drugs, including antidepressants, opioids, and other pain medications, as this can increase the risk of serotonin syndrome 1. Always prioritize medical supervision and monitoring when using these medications together to minimize the risk of adverse effects and ensure the best possible outcome.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Low Dose Benadryl and Amitriptyline
- The combination of low dose Benadryl (diphenhydramine) and amitriptyline is not directly addressed in the provided studies.
- However, the studies discuss the effects and side effects of diphenhydramine and amitriptyline separately.
- Diphenhydramine is a first-generation antihistamine that can cause sedation and impair cognitive function 2, 3.
- Amitriptyline is an antidepressant that has been used for migraine prevention and has a sedating effect, which can be beneficial for patients with comorbid insomnia 4.
- Newer antihistamines, such as cetirizine, have been shown to be effective in preventing hypersensitivity infusion reactions with less sedation compared to diphenhydramine 5.
- The use of antidepressants, including amitriptyline, for migraine prevention is supported by evidence, but the side effect burden can be substantial 4.
Side Effects and Interactions
- Diphenhydramine can cause sedation, impaired cognitive function, and increased risk of toxicity in overdose 2, 3.
- Amitriptyline can cause sedation, dry mouth, and other side effects, and its use can lead to withdrawal effects 4.
- The combination of diphenhydramine and amitriptyline may increase the risk of sedation and other side effects, but this is not directly addressed in the provided studies.
- Newer antihistamines, such as cetirizine, may be a safer alternative to diphenhydramine, with less sedation and fewer side effects 2, 5.