What is the interaction between Duloxetine (Cymbalta) and Trazodone?

From the Guidelines

Cymbalta (duloxetine) and trazodone can be safely taken together when prescribed by a healthcare provider, as they work in different ways to treat depression and other conditions. Cymbalta is a serotonin-norepinephrine reuptake inhibitor (SNRI) primarily used for depression, anxiety, and certain types of chronic pain, while trazodone is primarily used as a sleep aid and for depression. According to a study published in the Annals of Internal Medicine 1, second-generation antidepressants, including duloxetine, did not differ in efficacy in treating accompanying anxiety, insomnia, and pain. However, trazodone has been shown to improve sleep scores compared to fluoxetine 1. When combined, Cymbalta is typically taken in the morning at doses ranging from 30-60mg daily, while trazodone is usually taken at night at doses of 50-150mg to help with sleep.

Key Considerations

• The combination of Cymbalta and trazodone may be particularly helpful for patients with depression who also experience insomnia, as Cymbalta can sometimes cause sleep disturbances.
• Both medications affect serotonin levels, so there is a small risk of serotonin syndrome, characterized by confusion, rapid heart rate, dilated pupils, and muscle rigidity.
• Patients should report any unusual symptoms to their doctor immediately and should never adjust dosages without medical supervision.
• It's also important to be aware that both medications may cause dizziness, especially when standing up quickly, so caution is advised when starting this combination.

Monitoring and Precautions

• Regular monitoring of serotonin levels and symptoms of serotonin syndrome is crucial when taking this combination.
• Patients should be aware of the potential for increased dizziness and take necessary precautions to avoid falls.
• Dosage adjustments should only be made under the guidance of a healthcare provider to minimize the risk of adverse effects.

From the FDA Drug Label

1. Drug Interactions
2. 1 Drugs Having Clinically Important Interactions with Trazodone Hydrochloride Tablets Table 3: Clinically Important Drug Interactions with Trazodone Hydrochloride Tablets Other Serotonergic Drugs ClinicalImpact:The concomitant use of serotonergic drugs including Trazodone hydrochloride tablets and other serotonergic drugs increases the risk of serotonin syndrome Intervention:Monitorpatientsfor signsandsymptoms of serotoninsyndrome,particularly duringTrazodone hydrochloride tabletsinitiation. Ifserotoninsyndromeoccurs,considerdiscontinuation of Trazodone hydrochloride tablets and/or concomitantserotonergicdrugs[seeWARNINGS AND PRECAUTIONS(5. 2)]. Examples:triptans,antidepressants(tricyclicandserotoninuptakeinhibitors),fentanyl,lithium,tramadol,tryptophan,buspirone,andSt. John's Wort

The use of Cymbalta (a serotonin-norepinephrine reuptake inhibitor) and Trazodone together may increase the risk of serotonin syndrome. Patients should be monitored for signs and symptoms of serotonin syndrome, particularly during initiation of therapy. If serotonin syndrome occurs, consideration should be given to discontinuing one or both of the medications 2. Key considerations include:

• Monitoring for serotonin syndrome
• Potential need for discontinuation of one or both medications
• Increased risk of adverse reactions with concomitant use of serotonergic drugs

From the Research

Cymbalta (Duloxetine) and Trazodone

• Cymbalta, also known as duloxetine, is a serotonin-norepinephrine reuptake inhibitor used to treat major depressive disorder (MDD), generalized anxiety disorder (GAD), neuropathic pain (NP), fibromyalgia (FMS), and stress incontinence urinary (SUI) 3.
• Trazodone is an antidepressant with a unique mechanism of action, often used to treat MDD, insomnia, and anxiety, with a favorable profile and low risk of side effects 4.

Comparison of Cymbalta and Trazodone

• A systematic review compared the effectiveness of second-generation antidepressants, including duloxetine and trazodone, for accompanying anxiety, insomnia, and pain in depressed patients, but found limited evidence to guide the selection of an antidepressant based on accompanying symptoms 5.
• Another study compared the impacts of trazodone extended release vs selective serotonin reuptake inhibitors (SSRIs) on the health status and quality of life of patients with MDD, and found that trazodone provided greater improvements in terms of self-care, usual activities, pain/discomfort, and anxiety/depression measures 6.

Safety and Efficacy

• Duloxetine has been shown to be effective and safe for the treatment of various clinical conditions, including MDD, GAD, NP, FMS, and SUI, with a dual mechanism of action that benefits the treatment of comorbid clinical conditions 3.
• Trazodone has been found to be efficacious for the treatment of a broad array of depressive symptoms, including insomnia, anxiety, and psychomotor agitation, with a relatively low risk of side effects such as weight gain, sexual, or anticholinergic effects 4.

QT Prolongation Risk

• A comparison of the risk of QT prolongation among SSRIs found that fluoxetine, fluvoxamine, and sertraline had a low risk of QT prolongation, while paroxetine appeared to have the lowest risk 7. However, it is essential to note that Cymbalta is not an SSRI, and its risk of QT prolongation is not directly comparable to that of SSRIs.