What is the interaction between Trazodone (triazolopyridine) and Cymbalta (duloxetine)?

From the Guidelines

Trazodone and Cymbalta can be prescribed together under medical supervision, but it is crucial to monitor for potential serotonin syndrome due to their combined effect on serotonin levels 1. When considering the combination of trazodone and Cymbalta (duloxetine), it's essential to understand their mechanisms of action and potential interactions. Cymbalta is a serotonin-norepinephrine reuptake inhibitor (SNRI), while trazodone is an antidepressant that can be used at lower doses for insomnia.

Key Considerations

• The combination may be beneficial for patients with depression and sleep disturbances, as trazodone can help with sleep issues at doses of 50-100mg at bedtime, and Cymbalta can manage depression, anxiety, or certain pain conditions at doses of 30-60mg daily, taken in the morning.
• However, the risk of serotonin syndrome, a potentially serious condition characterized by agitation, confusion, rapid heart rate, and high blood pressure, must be carefully monitored, especially when combining serotonergic/adrenergic drugs like Cymbalta with other medications that may interact with them, as noted in studies on drug-drug interactions 1.
• Side effects may include increased drowsiness, dizziness, dry mouth, and constipation, emphasizing the need for careful monitoring and potentially adjusting doses under medical supervision.
• Patients should start with lower doses when beginning this combination and report any unusual symptoms to their healthcare provider immediately, highlighting the importance of close medical supervision when combining these medications.

From the Research

Trazodone and Cymbalta Interaction

• There is no direct evidence in the provided studies regarding the interaction between trazodone and Cymbalta (duloxetine) 2, 3, 4, 5, 6.
• However, a case report describes a patient on trazodone and duloxetine who developed serotonin syndrome after receiving fentanyl following a percutaneous liver biopsy 5.
• Another study discusses the risk of serotonin syndrome when combining serotonergic medications, including trazodone and duloxetine, but does not specifically address their interaction 4.
• Trazodone is known to have a favorable profile for the treatment of depression, with a low risk of anticholinergic side effects, weight gain, and sexual side effects 6.
• Duloxetine, on the other hand, is a serotonin-norepinephrine reuptake inhibitor (SNRI) that can increase the risk of serotonin syndrome when combined with other serotonergic medications 4, 5.

Serotonin Syndrome Risk

• The risk of serotonin syndrome is a concern when combining serotonergic medications, including trazodone and duloxetine 2, 4, 5.
• A case report describes a patient who developed serotonin syndrome after rapid titration of risperidone, trazodone, and sertraline 2.
• Another study discusses the mechanisms of drug-drug interactions that can increase the risk of serotonin syndrome, including pharmacodynamic, pharmacokinetic, and pharmacogenetic factors 4.

Clinical Guidance

• Trazodone is an established medication for the treatment of major depressive disorder, with a relatively low risk of side effects 6.
• The appropriate antidepressant doses of trazodone are usually 150-300 mg/day, and it is often used to augment the antidepressant effect of another medication 6.
• Clinicians should be aware of the increased risk of serotonin syndrome when combining serotonergic medications, including trazodone and duloxetine, and monitor patients closely for signs and symptoms of this condition 4, 5.