From the Guidelines
The recommended non-serotonergic antihistamines include fexofenadine, loratadine, and desloratadine, as they do not cause sedation at recommended doses and have minimal impact on serotonin receptors. These second-generation antihistamines are preferred because they effectively block histamine H1 receptors to relieve allergy symptoms without causing significant drowsiness or interacting with serotonergic medications 1. Typical adult dosing is fexofenadine 180mg daily, loratadine 10mg daily, or desloratadine 5mg daily.
- Key benefits of these medications include:
- Relief of allergic rhinitis, urticaria, and other histamine-mediated conditions
- Minimal sedative properties at recommended doses
- Fewer central nervous system effects compared to first-generation antihistamines
- Safer options for patients taking SSRIs, SNRIs, or MAOIs, or those with conditions where serotonin levels are a concern
- It is essential to note that cetirizine and intranasal azelastine may cause sedation at recommended doses, and loratadine and desloratadine may cause sedation at doses exceeding the recommended dose 1. Therefore, fexofenadine, loratadine, and desloratadine are the preferred non-serotonergic antihistamines due to their favorable safety profile and efficacy.
From the FDA Drug Label
Fexofenadine hydrochloride, the major active metabolite of terfenadine, is an antihistamine with selective peripheral H1-receptor antagonist activity. Radiolabeled tissue distribution studies in rats indicated that fexofenadine does not cross the blood-brain barrier.
Non-serotonergic antihistamines are recommended to avoid serotonin-related side effects.
- Fexofenadine is a non-serotonergic antihistamine, as it does not cross the blood-brain barrier and therefore is less likely to affect serotonin levels in the brain 2. The recommended non-serotonergic antihistamine is fexofenadine, due to its selective peripheral H1-receptor antagonist activity and lack of central nervous system effects.
From the Research
Non-Serotonergic Antihistamines
- Non-serotonergic antihistamines are preferred due to their lower risk of sedation and central nervous system side effects compared to first-generation antihistamines 3, 4.
- Examples of non-serotonergic antihistamines include:
- Loratadine: a long-acting antihistamine with high selectivity for peripheral histamine H1-receptors, lacking central nervous system depressant effects 3.
- Fexofenadine: a nonsedating antihistamine, even at high doses, with excellent safety records 4, 5, 6.
- Cetirizine: although it can cause some sedation, it is generally considered a non-serotonergic antihistamine with a lower risk of sedation compared to first-generation antihistamines 4, 7, 6.
- Desloratadine and levocetirizine: active metabolites of loratadine and cetirizine, respectively, which offer comparable or superior clinical benefits with lower risk of sedation 5, 7.
Mechanism of Action
- These antihistamines work by blocking peripheral H1 receptors without penetrating the blood-brain barrier, reducing the risk of central nervous system side effects 3, 4, 5.
- They are effective in reducing histamine-induced skin reactions, wheal, and flare, as well as improving symptoms of allergic rhinitis and chronic urticaria 3, 7, 6.
Safety and Efficacy
- Non-serotonergic antihistamines have excellent safety records, with low risk of sedation, cardiovascular toxicity, and other side effects 4, 5, 6.
- They are effective in reducing symptoms of allergic diseases, with some studies showing comparable or superior efficacy to first-generation antihistamines 3, 7, 6.