Can Ketorolac (NSAID) and Duloxetine (antidepressant) be combined?

From the Guidelines

I strongly advise against combining Ketorolac and Duloxetine without medical supervision due to potential interactions and increased risk of adverse effects. According to the 2022 CDC clinical practice guideline for prescribing opioids for pain 1, duloxetine can be used for osteoarthritis pain in multiple joints or incompletely controlled pain with topical NSAIDs, but systemic NSAIDs like ketorolac should be used with caution, particularly in older persons and in patients with cardiovascular comorbidities, chronic renal failure, or previous gastrointestinal bleeding.

Key Considerations

• The use of duloxetine for osteoarthritis pain is conditionally recommended, as stated in the 2019 American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee 1.
• Ketorolac, an NSAID, can increase the risk of gastrointestinal bleeding, cardiovascular events, and renal impairment, especially when used in combination with other medications that affect serotonin levels, such as duloxetine.
• Duloxetine, an SNRI antidepressant, can increase the risk of serotonin syndrome, a potentially life-threatening condition, when combined with other medications that affect serotonin levels.

Recommendations

• If considering combining ketorolac and duloxetine, consult with a healthcare provider to evaluate the specific medical history, current medications, and health status to determine if this combination is appropriate.
• The healthcare provider can provide proper dosing instructions and monitoring to minimize the risk of adverse effects.
• Never adjust the medication regimen without professional medical guidance, as this can lead to serious health consequences.

From the FDA Drug Label

Psychoactive Drugs Hallucinations have been reported when ketorolac tromethamine was used in patients taking psychoactive drugs (fluoxetine, thiothixene, alprazolam)

The combination of Ketorolac (NSAID) and Duloxetine (antidepressant) may be associated with an increased risk of adverse effects, such as hallucinations, although Duloxetine is not explicitly mentioned in the label. Caution should be used when combining these medications.

• Key consideration: Increased risk of adverse effects
• Recommendation: Monitor patients closely for signs of adverse effects, such as hallucinations, when combining Ketorolac and Duloxetine 2 2

From the Research

Combination of Ketorolac and Duloxetine

• The combination of Ketorolac, a nonsteroidal anti-inflammatory drug (NSAID), and Duloxetine, a serotonin and norepinephrine reuptake inhibitor, is not directly addressed in the provided studies.
• However, a study on the risk of bleeding with Duloxetine treatment in patients who use NSAIDs found that the combination of Duloxetine and NSAIDs was associated with a statistically significantly higher incidence of bleeding-related treatment-emergent adverse events compared with Duloxetine alone 3.
• Another study reviewed the pharmacology, pharmacokinetics, efficacy, safety, and drug interactions of Duloxetine, but did not specifically address the combination with Ketorolac 4.
• A review of Duloxetine's use in the treatment of major depressive disorder found that it is generally well tolerated, but may have a higher discontinuation rate due to adverse events when initiated at a dosage of 60 mg/day 5.
• A study on the chemistry, pharmacology, metabolism, safety, and adverse effects of serotonin and norepinephrine reuptake inhibitors, including Duloxetine, did not address the combination with Ketorolac 6.
• A study on the combination therapy with monoamine oxidase inhibitors and other antidepressants or stimulants for the management of treatment-resistant depression did not address the combination of Ketorolac and Duloxetine 7.

Bleeding Risk

• The combination of Duloxetine and NSAIDs, including Ketorolac, may increase the risk of bleeding-related adverse events 3.
• Patients taking Duloxetine and NSAIDs should be monitored for signs of bleeding, and the combination should be used with caution.

Dosage and Administration

• The recommended dosage of Duloxetine is 40-80 mg daily, depending on the indication, preferably split into two doses per day 4.
• The dosage of Ketorolac is not addressed in the provided studies, but it is typically administered at a dosage of 10-30 mg every 4-6 hours as needed for pain relief.