Can trazodone change urine color? (1+ mechanisms)

This article will explore whether trazodone can change urine color. It will discuss the reasons behind these rare, yet possible, urine color changes.

Additionally, the article will examine the factors that can influence the likelihood of experiencing a change in urine color while taking trazodone. Finally, it will provide suggestions on what to do if you notice any changes in urine color while on trazodone.

Can trazodone change urine color?

Yes, trazodone can change urine color in some individuals. However, this is very rare, and the cases reporting these symptoms are very minimal. 

It is important to know that trazodone does not directly impact urine color. Instead, it can potentially cause jaundice, which may lead to dark urine as a symptom.

Furthermore, like other antidepressants, trazodone increases the risk of bleeding. Thus, people with lots of risk factors for bleeding may experience bloody urine as a sign of trazodone-induced increased bleeding.

It is important to know that trazodone-induced liver injury does not always result in jaundice or dark urine, and trazodone-related bleeding won’t necessarily cause bloody urine. Furthermore, not everyone who takes trazodone will experience this, as this is very rare and people’s reactions to medications differ.

If you notice any unusual symptoms while taking trazodone, like easy bruising, increased bleeding, dark urine, bloody urine, or jaundice, it is essential to report them to your doctor as soon as possible.

How can trazodone cause dark urine?

Dark urine is a highly uncommon side effect of taking trazodone. However, if it does occur, it is crucial to understand the reasons behind it. To illustrate, trazodone may cause dark urine due to trazodone-induced hepatic injury and jaundice or trazodone-induced hematuria.

Trazodone-induced jaundice 

The mechanism by which trazodone may potentially harm the liver is not yet fully understood. However, it may be because it is extensively metabolized by the liver [1].

Trazodone is predominantly metabolized by the cytochrome P450 enzymes (CYP3A4), and the liver injury could be mediated by toxic byproducts during this metabolism [1].

Furthermore, individuals with enzyme deficiencies or those taking medications that are also extensively metabolized by the same enzymes may face a higher risk of liver injury when using trazodone. If trazodone does harm the liver, it can result in elevated bilirubin levels in the bloodstream.

Since bilirubin is excreted in urine, it can contribute to the noticeable dark coloration. Therefore, trazodone-induced liver injury may be associated with the manifestation of dark urine. Duloxetine may also cause dark urine as a result of liver injury.

Trazodone-induced hematuria

Serotonin plays a crucial role in preventing bleeding by being stored in platelets and released upon their activation. In the event of bleeding, the damaged blood vessel constricts temporarily to minimize blood loss. This triggers the release of serotonin from platelets [2].

Serotonin helps maintain vessel constriction and also activates nearby platelets and immune cells through serotonin receptors. Trazodone, on the other hand, is a serotonin antagonist and reuptake inhibitor (SARI), and it works by inhibiting serotonin type 2 receptors and the serotonin transporter [2,3].

By inhibiting the serotonin transporter, which is responsible for reabsorbing serotonin into nerve terminals and clearing it from the synaptic cleft, trazodone can potentially reduce serotonin storage in platelets [2,3].

This, in turn, may decrease platelet aggregation and raise the risk of bleeding. Individuals with existing high-risk bleeding factors or those taking blood thinners alongside trazodone are more likely to experience bloody urine while using trazodone.

Similarly, other serotonergic antidepressants, like citalopram and sertraline, can increase the risk of bleeding. Furthermore, trazodone can also be associated with other urinary side effects.

What does research suggest?

In a case report, a patient developed jaundice about 18 months after starting trazodone treatment, despite having no prior liver issues or risk factors. The patient also did not consume alcohol [1].

Alongside jaundice symptoms, the patient exhibited significantly elevated bilirubin levels (11.0 mg/dL) and increased serum aminotransferase levels. Discontinuing trazodone resulted in significant improvement and hospital discharge [1].

However, upon restarting trazodone after 7 days, the patient experienced jaundice again within two days. Ultimately, complete discontinuation of trazodone led to the resolution of liver problems and jaundice after 2 weeks [1].

This indicates that trazodone can indeed induce jaundice and elevated bilirubin levels, with dark urine being a manifestation of jaundice.

Furthermore, in the controlled clinical trials conducted to investigate the side effects of trazodone hydrochloride tablets, under widely varying conditions, hematuria was among the side effects that were found to occur in less than 2% of the subjects [4].

What factors influence trazodone’s impact on urine color?

Several factors can influence the risk or incidence of changing urine color while taking trazodone.

Taking very high doses of the drug, jumping to a high dose without applying proper dose escalation, or taking it for a long duration may increase the risk of side effects such as liver injury, jaundice, or increased bleeding. These side effects can lead to a change in urine color.

Additionally, pre-existing liver diseases like jaundice, genetic polymorphisms of the enzymes responsible for metabolizing trazodone (CYP 3A4 enzymes), or a general deficiency of these enzymes can increase the risk of trazodone-induced liver injury, potentially resulting in increased bilirubin and dark urine. 

Disruption in the metabolism of trazodone can also increase its levels and potency, leading to a higher risk of side effects like increased bleeding and hematuria. 

Concurrent administration of drugs that inhibit these enzymes or have a hepatotoxic effect can further increase the risk of a changed urine color while taking trazodone. Chronic alcoholism can also significantly increase the risk of liver disease in those taking trazodone. 

Factors influencing trazodone-induced bloody urine

Certain diseases, such as nephrotic syndrome, lupus nephritis, polycystic kidney disease, post-streptococcal glomerulonephritis, or complicated urinary tract infection, can further increase the likelihood of noticing a change in urine color to bloody red when taking trazodone [5].

People with bleeding disorders, deficiencies in platelets, clotting factors, or those concurrently taking blood thinners or certain anticancer drugs while on trazodone are also at an increased risk of experiencing such side effects.

What to do if trazodone changes the color of urine?

If you notice dark urine while taking trazodone and suspect it may be caused by a trazodone-related liver injury, it is important to report this to your doctor as soon as possible. They will assess your liver function and health and adjust your treatment plan accordingly. 

They will likely recommend discontinuing trazodone gradually to avoid withdrawal symptoms. It is crucial to follow your doctor’s recommendations and stop the drug under their supervision.

However, certain strategies can help. For instance, you may need to optimize your diet and choose foods that support liver health. These foods include fruits, vegetables, whole grains, and lean proteins. It is also advisable to avoid processed foods and excessive fats, and limit alcohol intake as much as possible.

If you notice bloody urine, it is also important to inform your doctor immediately. They may conduct necessary tests to ensure your urinary tract is not severely compromised. They will also assess your medication and medical history to determine whether there is a risk of trazodone-induced bleeding. 

Based on their evaluation, they may either decrease your dose and monitor your response or suggest discontinuing the drug after appropriately tapering down the dose. You should follow the doctor’s recommendations; don’t change anything in your treatment plan without consulting with them first.

Based on my research, trazodone may change the color of urine in some individuals, although this is rare. The most common causes of this are trazodone-induced jaundice and hematuria. It is important to understand that not everyone who takes trazodone will experience these side effects.

If you notice any unusual symptoms, like dark urine or bloody urine, while taking trazodone, I recommend reporting them to your doctor as soon as possible.

They will assess various factors, including liver function, bleeding risks, and urinary tract health, to determine the most appropriate course of action. From my perspective, they will likely recommend discontinuing trazodone gradually while monitoring your response closely.

Additionally, based on my knowledge, other factors such as high doses of trazodone, pre-existing liver disease or bleeding disorders, and the use of specific medications that inhibit liver enzymes or increase bleeding can contribute to a higher risk of trazodone-induced changes in urine color.

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