From the Guidelines
Doxepin has a higher affinity for histamine receptors at low doses, but it is not typically used at low doses to treat urticaria due to its sedating and anticholinergic side-effects 1.
Key Points
- Doxepin exhibits significant antihistaminic effects at low doses, with a notable affinity for histamine H1 receptors 1.
- Despite its antihistaminic properties, doxepin is not commonly used at low doses to treat urticaria, primarily due to its sedating and anticholinergic side-effects, which can be detrimental to patients requiring relief from urticaria without impairment 1.
- The treatment of urticaria typically involves the use of nonsedating H1 antihistamines, such as cetirizine, desloratadine, and fexofenadine, which are preferred due to their efficacy and safety profile 1.
- In some cases, sedating antihistamines like doxepin may be used at night to help patients sleep better, but their use is generally limited due to concerns about reduced concentration and performance 1.
- The management of chronic spontaneous urticaria involves a stepped approach, with recommendations to use higher than standard doses of antihistamines if needed, and to consider stepping down treatment when disease control is achieved 1.
Treatment Considerations
- The choice of antihistamine and dosage should be individualized based on patient response and tolerance, with consideration of potential side-effects and interactions 1.
- Patients with urticaria should be offered the choice of at least two nonsedating H1 antihistamines, and adjustments to the timing and dosage of medication can be helpful to ensure optimal symptom relief 1.
From the Research
Doxepin's Affinity for Histamine Receptors
- Doxepin has a high affinity for histamine H1 receptors, with a dissociation constant (KD) of 3.1 +/- 0.3 X 10(-10) M 2
- The Z-isomer of doxepin is bound to the histamine H1 receptor with an approximately 5.2-fold higher affinity than the E-isomer 3
- Doxepin's affinity for H1 receptors is 8-fold more potent than mepyramine, a classic antihistamine 4
Low-Dose Doxepin and Antihistaminic Properties
- Low-dose doxepin (3-6 mg) selectively antagonizes H1 receptors, promoting the initiation and maintenance of sleep 5, 6
- Doxepin's antihistaminic properties contribute to its clinical efficacy in the treatment of chronic urticaria 4
- Despite its antihistaminic properties, doxepin is not typically used at low doses to treat urticaria, possibly due to its primary use as an antidepressant and the availability of other antihistamines with fewer side effects
Clinical Efficacy and Tolerability
- Low-dose doxepin has been shown to be effective in improving sleep quality and duration in patients with chronic primary insomnia 5, 6
- Doxepin is generally well tolerated, with sedation/sleepiness and headache being the most common adverse events 5, 6
- The use of doxepin at low doses has not been associated with significant adverse side effects or rebound insomnia 5, 6