Can trazodone be taken with tramadol?

From the Guidelines

Taking trazodone and tramadol together is not recommended without medical supervision due to the risk of serotonin syndrome, a potentially serious drug interaction. Both medications affect serotonin levels in the brain, and when combined, they can cause excessive serotonin accumulation leading to symptoms like confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and in severe cases, seizures or loss of consciousness 1. According to the NCCN clinical practice guidelines in oncology, tramadol and tapentadol should be used with caution or avoided in patients taking other serotonergic or monoamine oxidase inhibitors (MAOI)-like medications, such as trazodone, due to the risk of serotonin syndrome 1.

If your doctor has prescribed both medications, they have likely weighed the benefits against these risks for your specific situation. Never adjust the dosage or timing of either medication without consulting your healthcare provider. It is essential to monitor for signs of serotonin syndrome, such as agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, or diarrhea, and seek immediate medical attention if these symptoms occur 1.

Key considerations when taking trazodone and tramadol together include:

• Monitoring for signs of serotonin syndrome
• Adjusting dosages or timing only under medical supervision
• Being aware of the potential for increased adverse effects, such as vomiting, dizziness, and weakness
• Considering alternative pain management options to minimize the risk of serotonin syndrome 1.

Ultimately, the decision to take trazodone and tramadol together should be made under the guidance of a healthcare provider, who can assess the individual's specific situation and weigh the potential benefits against the risks.

From the FDA Drug Label

Serotonin Syndrome Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of Trazodone Hydrochloride Tablets with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St John’s Wort, and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid).

1. 2 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) and with drugs that impair metabolism of serotonin, i. e., MAOIs [see CONTRAINDICATIONS (4), DRUG INTERACTIONS (7.1)].

Trazodone can be taken with tramadol, but it increases the risk of serotonin syndrome, a potentially life-threatening condition. Patients should be monitored for symptoms of serotonin syndrome, and the healthcare provider should be informed if any symptoms occur 2, 2.

• Key points:
  • Increased risk of serotonin syndrome
  • Monitor for symptoms of serotonin syndrome
  • Inform healthcare provider if symptoms occur
  • Concomitant use is not contraindicated, but caution is advised.

From the Research

Trazodone and Tramadol Interaction

• The use of trazodone with tramadol may be associated with a risk of serotonin syndrome, a potentially life-threatening condition 3.
• However, a review of case reports suggests that the risk of serotonin syndrome is relatively low, and tramadol can be safely combined with antidepressants, including trazodone, with proper monitoring and counseling 3.
• The mechanisms of the drug-drug interaction involve pharmacodynamic, pharmacokinetic, and possible pharmacogenetic factors, and factors such as increased age, higher dosages, and use of concomitant potent cytochrome P450 2D6 inhibitors may increase the risk of serotonin syndrome 3.
• Another study found that tramadol's serotonin and norepinephrine reuptake inhibitory effects result in a unique adverse effect profile, including serotonin syndrome and seizures, but the prevalence of these events is modest in the general population 4.
• A study on the neurobehavioral consequences of long-term tramadol utilization found that tramadol produces seizures through inhibition of nitric oxide, serotonin reuptake, and inhibitory effects on GABA receptors, and extensive tramadol intake alters redox balance, leading to neurotoxicity and neurobehavioral deficits 5.
• In terms of specific interactions between trazodone and tramadol, one study found that the combination of tramadol with diazepam (a benzodiazepine) did not significantly differ in terms of median lethal dose, but the combination abolished seizures and enhanced sedation and respiratory depression 6.
• Another study found that tramadol overdose causes seizures and respiratory depression, but serotonin toxicity appears unlikely, and opioid-like effects and adrenergic effects were prominent 7.

Key Considerations

• Patients taking trazodone and tramadol should be monitored for signs of serotonin syndrome, such as agitation, confusion, rapid heart rate, and changes in blood pressure 3, 4.
• The risk of seizures and respiratory depression should also be considered, particularly in patients taking high doses of tramadol or combining tramadol with other central nervous system depressants 5, 6, 7.
• Healthcare providers should be aware of the potential for drug-drug interactions and take steps to minimize the risk of adverse events, such as adjusting doses or monitoring patients more closely 3, 4, 6.