Does trazodone have anticholinergic effects? (3+ studies)

In this article, we will talk about the anticholinergic effects of trazodone. We will also discuss the mechanism behind the anticholinergic effects of trazodone, mention some anticholinergic side effects of trazodone, and share how to manage those effects. 

Does trazodone have anticholinergic effects?

Yes, trazodone has anticholinergic effects although they are minimal. Trazodone is an antidepressant and is less likely to cause anticholinergic side effects as compared to other antidepressants.

Trazodone is a serotonin antagonist and reuptake inhibitor (SARI). It effectively treats major depressive disorder (MDD) and holds FDA approval for this specific use. It also has sedative properties so is used as a hypnotic off-label. 

Studies have shown that antidepressants are associated with anticholinergic side effects due to their ability to block muscarinic receptors. However, the risk of anticholinergic effects with trazodone is minimal. 

Some trials have demonstrated that trazodone did not cause anticholinergic effects. Thus, not every individual will experience these effects while taking trazodone. The chances of anticholinergic side effects with trazodone are very low. 

How does trazodone cause anticholinergic side effects?

Trazodone affects several neurotransmitters in the body. It inhibits serotonin reuptake and increases serotonin levels in the body. It has antagonist effects on some serotonin, histamine (H1), and alpha-1 adrenergic receptors (1). 

Due to the antagonist effects, trazodone also causes sedation. Its sedative effects are also because it reduces the neurotransmitters that promote arousal including serotonin, acetylcholine, dopamine, and histamine (1). 

A drug is said to have anticholinergic properties when it blocks the actions of acetylcholine (ACh), a neurotransmitter at muscarinic receptors. Trazodone may bind to some of the muscarinic receptors to produce anticholinergic effects. 

What does research suggest?

Several studies have investigated the anticholinergic effects of trazodone. In one study, researchers compared trazodone’s affinity for muscarinic receptors in the brain of rats to that of a tricyclic antidepressant (TCA) (2).

The study findings indicated that trazodone exhibited no interaction with muscarinic receptors and showed no activity at the ACh binding side (2). 

In another study, the anticholinergic effects of trazodone were studied on healthy individuals and compared to a TCA named imipramine. Results demonstrated that unlike imipramine trazodone had no anticholinergic activity (3). 

Several studies have compared the anticholinergic activity of trazodone with TCAs because TCAs are associated with a high risk of anticholinergic side effects. Results suggest that trazodone has little to no anticholinergic activity unlike TCAs (4,5). 

Thus the research shows that although anticholinergic effects are officially documented side effects of trazodone, their incidence and risk are very low. 

What are the anticholinergic effects of trazodone?

The anticholinergic effects of trazodone are not frequently reported. Some of the reported anticholinergic side effects include (6): 

• dry mouth
• blurred vision
• constipation
• urinary retention
• dry eyes
• angle closure glaucoma 
• pupil dilation 

These side effects occur due to the decrease in ACh levels caused by trazodone. ACh affects multiple organ systems in the body. In the digestive system, it increases gut motility and secretion of digestive juices (7). 

In the urinary system, ACh facilitates bladder emptying by acting on different muscles. ACh also controls the contraction of the pupil and secretion from different exocrine glands like salivary glands (7). 

Thus, by inhibiting ACh, these actions are interrupted and the above-mentioned side effects are produced. However, the anticholinergic activity of trazodone is minimal. 

What factors contribute to the anticholinergic effects of trazodone? 

Although the risk of anticholinergic effects is low with trazodone, some factors may increase the risk while taking trazodone. They include: 

Dosage: 

Trazodone’s therapeutic effects depend on the dose being taken. At low doses of 25-100 mg, it does not have antidepressant activity. At higher doses, it occupies different receptors to produce its effects. 

Thus, individuals taking higher doses of trazodone are likely to experience anticholinergic effects as the risk increases with increasing doses. 

Other medications: 

Different medications have anticholinergic effects and some medications may be prescribed with trazodone. The concomitant use of medications with trazodone should be done under medical oversight. Anticholinergic drugs include (8): 

• benztropine
• trihexyphenidyl
• tricyclic antidepressants 
• oxybutynin 
• tolterodine 
• antihistamines
• scopolamine
• atropine
• glycopyrrolate
• antipsychotics

Health conditions:

Some health conditions may make the individual more susceptible to the anticholinergic side effects of trazodone. Individuals with untreated narrow angles are more susceptible to trazodone-induced angle closure glaucoma (6). 

Similarly, individuals with pre-existing constipation or bladder emptying issues may experience worsening of their issues while taking trazodone. 

Individual variations: 

Individual response to medication varies and some individuals may experience more side effects than others while taking trazodone. Factors like genetic makeup, age, metabolism, and overall health impact the individual’s response to trazodone.

What to do if trazodone causes anticholinergic effects? 

Trazodone is associated with a minimal risk of anticholinergic side effects. If the effects occur, they are of low intensity and well-tolerated by the patients.

If you experience intense anticholinergic effects while taking trazodone, you must contact your healthcare provider. Your healthcare provider may consider reducing the dose of trazodone to relieve the symptoms.

If you are taking other medications associated with anticholinergic effects while taking trazodone, your healthcare provider may reduce the dose of those medicines. 

You may use the following tips to manage the anticholinergic effects of trazodone:

• drink plenty of water to manage a dry mouth. Drinking cold water or sucking ice chips may also keep the mouth moistened. 
• for dry eyes, your healthcare provider may recommend artificial tears or eye drops that lubricate your eyes. 
• to manage constipation, consume a fiber-rich diet, and maintain adequate hydration. OTC laxatives can also be used for constipation.
• scheduled washroom visits can help with urinary retention. 

What are some other side effects of trazodone? 

Anticholinergic side effects are infrequent when using trazodone. Some common side effects of trazodone include (1):

• fatigue
• orthostatic hypotension
• QT prolongation 
• lightheadedness 
• suicidal thoughts
• changes in sex drive
• acid reflux
• nightmares 

In my perspective, trazodone may result in anticholinergic effects however the chances are minimal. Trazodone is less likely to cause anticholinergic side effects as compared to other antidepressants. 

Different studies have shown that trazodone has little to no anticholinergic effects. Some factors may increase the risk of anticholinergic effects of trazodone like dosage, individual characteristics, other medications, and health conditions. 

Anticholinergic side effects of trazodone are generally well-tolerated. You must contact your healthcare provider if you experience intense anticholinergic effects while taking trazodone. 

References