Cymbalta, known generically as duloxetine, is a serotonin-norepinephrine reuptake inhibitor (SNRI) used to treat major depressive disorder, generalized anxiety disorder, and chronic pain conditions. While effective for many, its interaction with other medications and substances can lead to serious and sometimes life-threatening side effects. Patients must be fully aware of these interactions and discuss all medications with their doctor or pharmacist to ensure safe treatment.
Serious and Potentially Fatal Interactions
The most severe drug interactions with Cymbalta involve an overabundance of serotonin in the body, leading to a condition known as serotonin syndrome.
Monoamine Oxidase Inhibitors (MAOIs)
Combining Cymbalta with MAOIs is strictly contraindicated due to the high risk of serotonin syndrome. MAOIs prevent the breakdown of serotonin and other neurotransmitters. Adding an SNRI like Cymbalta can lead to a dangerous buildup of serotonin. This interaction can cause symptoms including agitation, hallucinations, a rapid heart rate, and muscle rigidity.
Examples of MAOIs and MAOI-acting drugs to avoid:
- Phenelzine (Nardil)
- Isocarboxazid (Marplan)
- Tranylcypromine (Parnate)
- Selegiline (Emsam, Zelapar)
- Linezolid (Zyvox), an antibiotic
- Methylene blue, an injectable dye
Patients must wait a specific washout period between stopping an MAOI and starting Cymbalta, and vice versa. Typically, this means waiting at least 14 days after discontinuing an MAOI before starting Cymbalta, and at least 5 days after discontinuing Cymbalta before starting an MAOI.
Serotonergic Drugs
Mixing Cymbalta with other medications that increase serotonin levels can also elevate the risk of serotonin syndrome, though the risk may be lower than with MAOIs. Close monitoring is required for these combinations.
- Other Antidepressants: Taking Cymbalta with other SNRIs (e.g., venlafaxine), Selective Serotonin Reuptake Inhibitors (SSRIs like Zoloft or Prozac), or Tricyclic Antidepressants (TCAs like amitriptyline) increases the risk of serotonin syndrome.
- Opioid Pain Medications: The opioid analgesic tramadol and other opioids like fentanyl have serotonergic effects. Combining these with Cymbalta can lead to serotonin syndrome or increase the risk of seizures.
- Migraine Triptans: Migraine medications known as triptans (e.g., sumatriptan) can interact with SNRIs like Cymbalta and have been linked to serotonin syndrome.
- Herbal Supplements: St. John’s Wort is a commonly used herbal supplement for depression that significantly raises serotonin levels. It should never be taken with Cymbalta.
Interactions Increasing Bleeding Risk
Cymbalta can inhibit the function of platelets, which are crucial for blood clotting. This effect can increase the risk of bleeding, especially when combined with other drugs that have similar effects.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
NSAIDs are common pain relievers that increase the risk of gastrointestinal bleeding. Combining NSAIDs with Cymbalta further compounds this risk.
Examples of NSAIDs to be cautious with:
- Ibuprofen (Advil, Motrin)
- Naproxen (Aleve)
- Aspirin
Blood Thinners
Anticoagulants and antiplatelet drugs are specifically designed to reduce blood clotting. Combining these with Cymbalta requires careful monitoring by a doctor.
- Warfarin (Jantoven): Requires increased monitoring of INR (International Normalized Ratio) to adjust dosing.
- Other Blood Thinners: This includes direct oral anticoagulants like apixaban (Eliquis) and rivaroxaban (Xarelto).
Substance and Lifestyle Interactions
Besides other medications, certain substances and lifestyle habits can interact negatively with Cymbalta, increasing the risk of adverse effects.
Alcohol
Drinking alcohol, particularly in large quantities, while on Cymbalta is strongly discouraged. Both alcohol and duloxetine can independently cause liver damage, and combining them increases this risk. This can lead to serious liver problems, including fatal hepatic failure in rare cases.
CYP Inhibitors
Certain medications interfere with the enzymes that break down Cymbalta in the liver, such as cytochrome P450 1A2 (CYP1A2) and CYP2D6. Blocking these enzymes can cause duloxetine levels to rise, increasing the likelihood of side effects.
Examples of CYP inhibitors affecting Cymbalta:
- Fluvoxamine (Luvox)
- Ciprofloxacin (Cipro)
- Cimetidine (Tagamet HB)
- Quinidine
Comparison of Major Cymbalta Interaction Risks
| Interaction Risk | Mechanism | Symptoms to Watch For | Key Interacting Substances |
|---|---|---|---|
| Serotonin Syndrome | Excessive serotonin buildup in the brain. | Agitation, rapid heart rate, confusion, muscle twitching, sweating. | MAOIs, SSRIs, SNRIs, TCAs, Tramadol, Triptans, St. John's Wort. |
| Increased Bleeding | Cymbalta affects platelet function, inhibiting clotting. | Easy bruising, nosebleeds, bleeding gums, red or black stools, vomiting blood. | NSAIDs (ibuprofen, aspirin), Blood Thinners (warfarin, apixaban). |
| Liver Damage | Both Cymbalta and alcohol strain the liver's function. | Jaundice (yellowing skin/eyes), dark urine, abdominal pain, fatigue. | Excessive Alcohol Use, Pre-existing Liver Disease. |
Conclusion
The range of medications and substances that can interact with Cymbalta is extensive, from potent MAOIs to common over-the-counter NSAIDs and herbal supplements. The most significant dangers include serotonin syndrome, which is a contraindication with MAOIs, and an increased risk of serious bleeding when combined with NSAIDs or blood thinners. Always provide your healthcare provider with a complete and accurate list of all drugs, supplements, and vitamins you are taking to prevent harmful interactions. Being proactive is the best way to ensure the safe and effective use of Cymbalta.
For more information on understanding your mental health medications, consider visiting the National Alliance on Mental Illness (NAMI) website.
