From the Guidelines
Combining amitriptyline with duloxetine (Cymbalta) for fibromyalgia treatment is generally not recommended due to the increased risk of serotonin syndrome. Both medications increase serotonin levels in the brain, and using them together can lead to potentially dangerous serotonin excess 1. If the patient is not responding adequately to Cymbalta alone, it would be better to either increase the Cymbalta dose (if not already at maximum), switch completely to amitriptyline, or consider adding a medication from a different class such as pregabalin (Lyrica) or gabapentin.
Some key points to consider when managing fibromyalgia include:
- The use of non-pharmacological therapies as the initial management approach, including aerobic and strengthening exercise, cognitive behavioral therapies, and multicomponent therapies 1.
- The consideration of pharmacological therapies, such as amitriptyline, duloxetine, and pregabalin, which have been shown to improve pain, function, and quality of life in patients with fibromyalgia 1.
- The importance of monitoring patients closely for signs of serotonin syndrome and other side effects when using combination therapy, and educating them about these warning signs.
If a healthcare provider does decide to try this combination in exceptional circumstances, it should be done with extreme caution, starting with a very low dose of amitriptyline (10mg at bedtime), monitoring closely for signs of serotonin syndrome (agitation, confusion, rapid heart rate, dilated pupils, muscle rigidity, and elevated temperature), and educating the patient about these warning signs. The combination also increases the risk of other side effects like drowsiness, dry mouth, constipation, and urinary retention.
In terms of the evidence, the most recent and highest quality study is from 2022, which recommends the use of tricyclic and SNRI antidepressants, NSAIDs, and specific anticonvulsants for the treatment of fibromyalgia 1. However, it also notes that tricyclic antidepressants should be used judiciously in older adults due to the risk of confusion and falls. Overall, the decision to combine amitriptyline with duloxetine should be made on a case-by-case basis, taking into account the individual patient's needs and medical history.
From the Research
Trial of Amitriptyline with a Patient on Cymbalta for Fibromyalgia
- The use of amitriptyline and duloxetine (Cymbalta) for fibromyalgia has been studied in various research papers 2, 3, 4, 5, 6.
- A study published in 2013 found that patients with fibromyalgia who started amitriptyline or duloxetine had similar clinical characteristics and medication use patterns, but the treatment was only continued for a short time 2.
- Another study published in 2023 found that duloxetine, milnacipran, pregabalin, and amitriptyline are potentially effective medications for fibromyalgia, but nonsteroidal anti-inflammatory drugs and opioids have not demonstrated benefits for fibromyalgia and have significant limitations 3.
- A randomized controlled trial published in 2016 found that combining pregabalin with duloxetine for fibromyalgia improves multiple clinical outcomes compared to monotherapy, but the study did not specifically examine the combination of amitriptyline and duloxetine 4.
- A network meta-analysis published in 2022 found that amitriptyline 25mg was superior to other alternatives for reducing pain intensity by 50% in adult patients with fibromyalgia, while pregabalin 450mg was superior for reducing pain intensity by 30% 5.
- A comparative efficacy study published in 2010 found that duloxetine, milnacipran, and pregabalin are effective for reducing symptoms of fibromyalgia, but have different effects on key symptoms and side effects 6.
- There is no direct evidence to suggest that trialing amitriptyline with a patient on Cymbalta (duloxetine) for fibromyalgia is contraindicated, but the decision to do so should be based on individual patient needs and medical history, and should be made in consultation with a healthcare professional 2, 3, 4, 5, 6.