Does doxylamine interact with trazodone? (+3 interactions)

In this article, we will discuss whether doxylamine interacts with trazodone. We will also discuss the potential interactions between doxylamine and trazodone and some other related information. 

Does doxylamine interact with trazodone?

Yes, doxylamine interacts with trazodone. Both drugs have sedative effects and taking them together enhances the sedation. Concomitant use of doxylamine and trazodone also amplifies the shared side effects. 

Trazodone is a serotonin antagonist and reuptake inhibitor (SARI), an antidepressant. It is FDA-approved to treat major depressive disorder (MDD). Due to its sedative properties, it is also used in patients with insomnia. (1). 

Doxylamine is an antihistamine, that belongs to the first generation and blocks H1 histamine receptors. It is used to manage nausea and vomiting in pregnancy, allergic rhinitis, and insomnia. It is an over-the-counter medication (2). 

Taking trazodone and doxylamine together can be risky due to the enhanced sedative effects. Especially, if you are taking trazodone at high doses, you must be very careful while using antihistamines. 

What are the interactions between trazodone and doxylamine? 

Trazodone and doxylamine interact in the following ways:

Enhanced sedative effects: 

Trazodone is a well-known drug for insomnia and its use for sleep disturbances has exceeded its use for antidepressants. It produces sedative effects in low doses, starting from 25 mg. The maximum dose of trazodone for sleep is 100 mg (1). 

Doxylamine is also approved for insomnia and can be used in patients 12 years and older. The recommended dose of doxylamine for insomnia is 25 to 50 mg orally (2). Both drugs cause sedation by blocking histamine H1 receptors. 

Using trazodone and doxylamine together significantly enhances the sedative effects which can produce extreme drowsiness, dizziness, and confusion. Their concomitant use without proper medical guidance is extremely risky. 

Enhanced anticholinergic side effects: 

Trazodone and doxylamine are associated with anticholinergic side effects. Doxylamine blocks muscarinic receptors to produce these side effects (2). The risk of these side effects in trazodone is less as compared to other antidepressants (1).

Concomitant use of these medications enhances the incidence of anticholinergic side effects. Anticholinergic side effects associated with trazodone include (3):

  • dry mouth
  • constipation
  • blurred vision

Anticholinergic side effects of doxylamine include (2):

  • constipation
  • urinary retention
  • anhidrosis
  • pupil dilation
  • delirium 
  • hyperthermia
  • flushing of the skin

Increased side effects:

Both trazodone and doxylamine are associated with some side effects other than the anticholinergic effects. Some of the side effects are shared by both drugs so their concomitant use can amply the side effects.

Side effects associated with trazodone include (1,3):

  • headache
  • fatigue
  • orthostatic hypotension
  • QT prolongation
  • dizziness
  • drowsiness
  • priapism
  • visual hallucinations
  • acid reflux 
  • diarrhea
  • malaise

Side effects associated with doxylamine include (2):

  • drowsiness
  • impaired coordination
  • dysuria
  • diplopia
  • impaired vigilance 

Trazodone vs. doxylamine: which one to use for insomnia? 

The choice of drug for insomnia is based on different factors like symptoms, the goal of the treatment, the patient’s response to the previous treatments, comorbid conditions, drug-drug interactions, and the patient’s preference (4). 

Trazodone belongs to the sedating antidepressants that are considered for insomnia after the treatment with short-or-intermediate-acting benzodiazepine receptor agonists (BzRAs) or melatonin agonists has failed (4). 

Trazodone has shown efficacy in treating insomnia at low doses. It is commonly used in patients with comorbid depression. The evidence for using trazodone for insomnia in the absence of depression is limited (5). 

Doxylamine is available over the counter as a sleeping aid. Studies on the use of first-generation antihistamines for insomnia have shown that patients build tolerance rapidly and show no response after 3-4 days (4).

The effectiveness of doxylamine in inducing sleep is minimal, it may negatively affect sleep quality and is associated with residual drowsiness. It also results in anticholinergic side effects (4,5). 

Thus, the use of doxylamine for insomnia is not recommended. Trazodone is also not the first line of treatment for insomnia. Although doxylamine and trazodone both induce sleep, they are not considered primarily for insomnia.

The evidence shows that trazodone and doxylamine induce sleep but are primarily used for other conditions. If you have insomnia, your healthcare provider will prescribe you a drug based on your symptoms. 

How to treat allergic rhinitis while you are taking trazodone? 

Trazodone is mainly prescribed for depression. Doxylamine is used for allergic rhinitis and nausea and vomiting in pregnancy. As they are not primary treatments for insomnia which is their only common use, they are unlikely to be prescribed together. 

While you are being treated with trazodone for depression or other conditions it is known to treat you might develop allergic rhinitis. In this condition, antihistamines are among the first choice of treatment (6). 

Symptoms of allergic rhinitis include sneezing, a runny and itchy nose, and nasal congestion (6). Do not take doxylamine if you are taking trazodone and have developed these symptoms. 

Although doxylamine is an OTC drug, it should be used cautiously if you are taking a medication that also induces sleep. The best way to manage allergic rhinitis in this condition is to contact your healthcare provider. 

Your healthcare provider may consider second-generation antihistamines which are non-sedating or are less sedating than doxylamine. Second-generation antihistamines include (6):

  • fexofenadine
  • loratadine
  • desloratadine
  • cetirizine 

In my perspective, doxylamine and trazodone interact with each other. Trazodone is an antidepressant that also has antihistaminic properties. Doxylamine is a first-generation antihistamine.

Trazodone and doxylamine have sedating properties and are used in sleep disturbances. Taking them together enhances their sedating effects, increases the anticholinergic side effects, and also amplifies the shared side effects.

Trazodone and doxylamine are not the primary treatments for insomnia. If someone develops allergic rhinitis while being treated with trazodone, they must contact their healthcare provider. 

The healthcare provider may prescribe second-generation antihistamines which are less sedating. Using trazodone and doxylamine together is risky and results in increased drowsiness, dizziness, and impaired concentration. 

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