From the FDA Drug Label
Co-administration of duloxetine delayed-release capsules with drugs that are extensively metabolized by CYP2D6 and that have a narrow therapeutic index, including certain antidepressants (tricyclic antidepressants [TCAs], such as nortriptyline, amitriptyline, and imipramine), phenothiazines and Type 1C antiarrhythmics (e.g., propafenone, flecainide), should be approached with caution. Plasma TCA concentrations may need to be monitored and the dose of the TCA may need to be reduced if a TCA is co-administered with duloxetine delayed-release capsules
The combination of Cymbalta (duloxetine) and Amitriptyline should be approached with caution.
- Key considerations:
- Plasma TCA concentrations may need to be monitored.
- The dose of the TCA may need to be reduced if a TCA is co-administered with duloxetine delayed-release capsules. 1
From the Research
Combining Cymbalta (duloxetine) and amitriptyline is not recommended without close medical supervision due to potential serious interactions, including the risk of serotonin syndrome, a potentially life-threatening condition. These medications should not be taken together unless specifically prescribed by a healthcare provider who is monitoring your condition carefully. Both drugs affect serotonin levels in the brain and taking them together increases the risk of serotonin syndrome, characterized by agitation, hallucinations, rapid heart rate, fever, excessive sweating, shivering, muscle stiffness, twitching, loss of coordination, nausea, vomiting, and diarrhea 2.
Key Considerations
- The risk of serotonin syndrome is a major concern when combining these medications, as it can be life-threatening.
- Both medications can cause drowsiness, dizziness, and impair thinking, which may be intensified when combined.
- If you're currently taking one of these medications and your doctor is considering adding the other, they will likely start with lower doses and gradually increase while monitoring for side effects.
- Never adjust your medication regimen without consulting your healthcare provider, and if you experience symptoms like confusion, severe headache, rapid heartbeat, or high fever while taking these medications, seek immediate medical attention as these could indicate serotonin syndrome.
Evidence-Based Recommendation
The most recent and highest quality study on the topic of duloxetine, a systematic review published in 2020, confirms the efficacy, safety, and tolerability of duloxetine in short- and long-term treatments for various conditions, including major depressive disorder, generalized anxiety disorder, neuropathic pain, fibromyalgia, and stress urinary incontinence 2. However, this study does not specifically address the combination of duloxetine and amitriptyline.
Clinical Implications
In clinical practice, the combination of these medications should be approached with caution, and patients should be closely monitored for potential adverse effects. The potential benefits of combining these medications must be carefully weighed against the potential risks, and alternative treatment options should be considered. If the combination is deemed necessary, it is essential to start with lower doses and gradually increase while monitoring for side effects.