What is the best antihistamine to take with amitriptyline (Amitriptyline)?

From the Guidelines

I strongly recommend using a second-generation antihistamine like fexofenadine (Allegra) when taking amitriptyline, as it has less sedative effect and fewer anticholinergic properties compared to other options. This is crucial because amitriptyline already has anticholinergic effects, and combining it with first-generation antihistamines could potentially increase side effects such as dry mouth, blurred vision, constipation, urinary retention, and confusion, ultimately affecting morbidity, mortality, and quality of life 1.

When considering the combination of antihistamines with amitriptyline, it's essential to prioritize medications with minimal sedative properties to avoid compounding the sedative effects of amitriptyline, which could lead to excessive drowsiness and impact daily functioning and safety. The choice among second-generation antihistamines, such as loratadine (Claritin), cetirizine (Zyrtec), or fexofenadine (Allegra), should be based on the patient's medical history, other medications, and the condition being treated, with a focus on minimizing potential interactions and side effects 1.

Key considerations include:

• The sedative properties of antihistamines: Fexofenadine, loratadine, and desloratadine do not cause sedation at recommended doses, making them preferable when combined with amitriptyline.
• Anticholinergic effects: First-generation antihistamines have significant anticholinergic properties, which could exacerbate the anticholinergic effects of amitriptyline, leading to increased morbidity.
• Personalized medical guidance: Consulting with a healthcare provider is crucial to determine the best antihistamine for each patient based on their specific needs and health status, ensuring the best possible outcome in terms of morbidity, mortality, and quality of life.

From the Research

Antihistamine Options

When considering the best antihistamine to take with amitriptyline, it's essential to look at the properties of various antihistamines.

• Second-generation antihistamines like cetirizine, desloratadine, fexofenadine, levocetirizine, and loratadine have reduced CNS effects compared to older generations, making them safer for use with other medications 2.
• Among these, levocetirizine appears to have a greater in vivo H1 receptor occupancy, which may confer an advantageous efficacy/safety profile 2.
• Fexofenadine has been shown to have a low occupancy of H1 antihistamine receptors in the brain, reducing the likelihood of sedation 2.

Comparison of Antihistamines

Studies comparing the efficacy of different antihistamines have shown:

• Levocetirizine, cetirizine, and fexofenadine were more effective in reducing histamine-induced skin reactions than loratadine and desloratadine 3.
• Fexofenadine had the earliest onset of action, while levocetirizine showed maximum inhibition of wheal response after three and six hours 4.
• Desloratadine showed greater inhibition of wheal size at the end of 24 hours, but this was not statistically significant 4.

Anticholinergic Activities

The anticholinergic activities of antihistamines can be a concern when taking them with other medications:

• Cetirizine and fexofenadine were found to be inactive in terms of anticholinergic activity in both in vitro and in vivo models 5.
• Desloratadine, loratadine, and diphenhydramine showed anticholinergic activity, but to a lesser extent than cyproheptadine and promethazine 5.