Can tramadol be taken with trazodone (antidepressant)?

From the Guidelines

It is strongly advised against taking tramadol with trazodone without medical supervision due to the risk of serotonin syndrome, a potentially life-threatening condition. This recommendation is based on the mechanism of action of both medications, as tramadol is a weak mu-opioid receptor agonist with some norepinephrine and serotonin reuptake inhibition 1, and trazodone is a serotonergic medication. The combination of these medications can lead to dangerously high serotonin levels, increasing the risk of serotonin syndrome, characterized by symptoms such as agitation, hallucinations, rapid heart rate, fever, excessive sweating, shivering, muscle stiffness, twitching, loss of coordination, nausea, vomiting, and diarrhea.

The National Comprehensive Cancer Network (NCCN) guidelines recommend using tramadol with caution or avoiding it in patients taking other serotonergic or monoamine oxidase inhibitors (MAOI)-like medications, such as trazodone, due to the risk of serotonin syndrome 1. Additionally, the combination of tramadol and trazodone may enhance central nervous system depression, potentially causing increased drowsiness, impaired thinking, and reduced motor coordination.

If you are currently taking one of these medications and your healthcare provider has prescribed the other, make sure they are aware of all medications you are taking. Never adjust dosages or combine these medications without explicit medical guidance. If you experience any unusual symptoms while taking these medications, seek immediate medical attention. Key considerations for healthcare providers include:

• Monitoring patients for signs of serotonin syndrome
• Adjusting dosages or switching medications if necessary
• Educating patients on the risks and symptoms of serotonin syndrome
• Encouraging patients to report any unusual symptoms promptly.

From the FDA Drug Label

Tramadol hydrochloride should be used with caution and in reduced dosages when administered to patients receiving CNS depressants such as alcohol, opioids, anesthetic agents, narcotics, phenothiazines, tranquilizers or sedative hypnotics. Tramadol may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression. Because of its added depressant effects, tramadol should be prescribed with caution for those patients whose medical condition requires the concomitant administration of sedatives, tranquilizers, muscle relaxants, antidepressants, or other CNS depressant drugs. Use tramadol hydrochloride with great caution in patients taking monoamine oxidase inhibitors. Concomitant use of tramadol hydrochloride with MAO inhibitors or SSRI’s increases the risk of adverse events, including seizure and serotonin syndrome Serotonin-norepinephrine reuptake inhibitors (SNRIs) and SSRIs, including Trazodone Hydrochloride Tablets, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort)

Tramadol and Trazodone Interaction:

• Tramadol and trazodone should be used with caution due to the potential for additive CNS depressant effects and increased risk of serotonin syndrome.
• Patients taking both medications should be closely monitored for signs of CNS depression, serotonin syndrome, and other adverse effects.
• The dosage of tramadol should be reduced when administered to patients receiving trazodone.
• Patients should be informed of the increased risk of adverse events, including seizure and serotonin syndrome, when taking tramadol and trazodone concomitantly 2, 3, 3.

From the Research

Tramadol and Trazodone Interaction

• The use of tramadol with trazodone may be associated with a risk of serotonin syndrome, a potentially life-threatening condition 4.
• A study found that the combination of tramadol and antidepressants, including trazodone, may increase the risk of serotonin syndrome, but this does not constitute a contraindication to their use 4.
• The risk of serotonin syndrome can be increased by factors such as increased age, higher dosages, and use of concomitant potent cytochrome P450 2D6 inhibitors 4.
• Another study found that concomitant use of tramadol with antidepressants, including trazodone, may increase the risk of respiratory depression 5.
• However, a study found that post-procedure tramadol may be associated with a significant reduction in opioid-induced respiratory depression 6.
• It is essential to monitor and counsel patients when starting a new serotonergic agent or when doses are increased, especially when combining tramadol with trazodone 4, 7.

Safety Precautions

• Patients should be closely monitored for signs of serotonin syndrome and respiratory depression when taking tramadol with trazodone 4, 5.
• The use of tramadol with trazodone should be approached with caution, especially in patients with increased age, higher dosages, and use of concomitant potent cytochrome P450 2D6 inhibitors 4.
• Patients should be educated on the risks and symptoms of serotonin syndrome and respiratory depression, and instructed to seek medical attention immediately if they experience any concerning symptoms 7.