What antidepressant has an antihistamine (antihistaminic) effect?

From the Guidelines

Doxepin is the most effective antidepressant with antihistamine effects, particularly at low doses of 3-6mg, due to its potent H1 and H2 antihistamine activity 1. When considering antidepressants with antihistamine properties, it's essential to weigh the benefits and potential side effects.

• Tricyclic antidepressants (TCAs) like amitriptyline and trimipramine have strong antihistamine effects, but may cause sedation, dry mouth, and weight gain 1.
• Newer antidepressants like mirtazapine (Remeron) have potent antihistamine activity, contributing to sedating effects and potential benefits for sleep and anxiety at doses of 15-45mg daily.
• Trazodone also has moderate antihistamine properties, but its efficacy and safety profile may vary compared to Doxepin. The antihistamine effect of these medications is often strongest at lower doses, which can be beneficial for patients with comorbid insomnia, anxiety, or allergic conditions, but may be undesirable for some patients due to sedating effects, especially during daytime hours 1. Key considerations include:
• Potential cognitive decline associated with sedating H1 antihistamines, particularly in the elderly population 1.
• The need for careful dosing and monitoring to minimize side effects and optimize therapeutic benefits.
• The importance of selecting the most appropriate antidepressant with antihistamine effects based on individual patient needs and medical history.

From the FDA Drug Label

Mirtazapine also acts as an antagonist of histamine (H1) receptors, peripheral α1-adrenergic receptors, and muscarinic receptors. Actions at these receptors may explain some of the other clinical effects of mirtazapine (e.g., its prominent somnolent effects and orthostatic hypotension may be explained by its inhibition of histamine (H1) receptors and peripheral α1-adrenergic receptors, respectively). Mirtazapine is an antidepressant with antihistamine effect, as it acts as an antagonist of histamine (H1) receptors 2.

• The antihistamine effect of mirtazapine may contribute to its somnolent effects.
• Mirtazapine's mechanism of action is not fully understood, but its efficacy in treating major depressive disorder may be mediated through its activity as an antagonist at central presynaptic α2-adrenergic inhibitory auto-receptors and heteroreceptors.

From the Research

Antidepressants with Antihistamine Effect

• Amitriptyline is a tricyclic antidepressant that also has antihistamine properties, which can cause sedation and dry mouth as side effects 3, 4, 5, 6.
• The antihistamine effect of amitriptyline can be beneficial for patients with depression who also experience insomnia or anxiety, as it can help with sleep and relaxation 4, 5, 6.
• However, the antihistamine effect can also increase the risk of side effects such as drowsiness, dizziness, and weight gain 4, 5, 6.
• Other antidepressants, such as paroxetine, do not have significant antihistamine effects and may be preferred for patients who are sensitive to these side effects 7.
• The choice of antidepressant should be based on the individual patient's needs and medical history, and should be made in consultation with a healthcare professional 3, 4, 5, 6, 7.

Comparison of Antidepressants

• Amitriptyline has been compared to other antidepressants, including paroxetine, in terms of efficacy and tolerability 4, 5, 6, 7.
• The results of these studies suggest that amitriptyline is at least as effective as other tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) in treating depression 4, 5, 6.
• However, amitriptyline may have a higher risk of side effects, such as anticholinergic effects and sedation, compared to some other antidepressants 4, 5, 6.
• Paroxetine, on the other hand, has been shown to be effective in treating depression, but may have a lower risk of side effects compared to amitriptyline 7.