Duloxetine Interactions with Drugs: Wellbutrin, Xanax, Etc.

Last Updated: June 16, 2021

Authored by Sharon Levy, MD, MPH

Reviewed by Michael Espelin APRN

Cymbalta medication is a powerful antidepressant that can interact with many medicines, foods, and substances. The effects of drug interactions can range from benign or even beneficial to potentially life-threatening. Therefore, patients need to have the correct information on what not to take with this drug and what drugs can be used during the treatment with minimal health risks.

Cymbalta and Wellbutrin

Coadministration of Cymbalta and Wellbutrin significantly increases the possibility of seizures, particularly in elderly patients and those with a history of a seizure disorder, CNS infections, brain tumors, head traumas, and addiction to opiates or stimulants. Both drugs have epileptogenic effects and may amplify each other. Patients should never take Wellbutrin with this drug without talking to their health care provider.

However, information from studies shows that Cymbalta and Wellbutrin may have benefits in the management of treatment-resistant depression. There was an improved response seen in those who used Cymbalta and Wellbutrin in combination for this disorder as opposed to those on duloxetine alone.

Adderall and Cymbalta

The concurrent use of Adderall and Cymbalta can result in increased anxiety, restlessness, and racing thoughts. This is because duloxetine can increase the effects of Adderall. The combination of Adderall and Cymbalta may also trigger serotonin syndrome development, a rare disorder. It can manifest with seizures, hallucinations, extreme blood pressure changes, fever, muscle spasms, and more. It can become potentially life-threatening. Besides, Adderall can worsen the symptoms of depression.

Xanax and Cymbalta

Xanax is the brand name for alprazolam, a benzodiazepine. Both of these drugs possess depressant effects on the CNS and respiratory system, so when Xanax and Cymbalta are used together, these effects are increased.

Bottles of different prescription pills.

It can be dangerous as it will cause sedation, poor judgment, and impaired motor function. It will have a similar impact when used with any benzodiazepine. It is crucial to ensure your doctor has information on all medications that you are on.

Trazodone and Cymbalta

When trazodone and Cymbalta are used together, the primary concern is the risk of serotonin syndrome developing. As earlier stated, this disorder can cause a coma and even death in severe cases. The symptoms that arise from this syndrome can be very distressing, such as vomiting, diarrhea, blurred vision, muscle spasms and pain, tremors, and more. This condition is rare, but it is important to inform your medical doctor of all medications you may be taking.

Cymbalta and Abilify

One of the important duloxetine interactions to keep note of is that between Cymbalta and Abilify. When used together, it can increase the effects of Abilify in the body by increasing its blood levels. It will be seen with symptoms such as irregular muscle movements, reduced blood pressure, seizures, and drowsiness. The reason for this effect of Cymbalta and Abilify on health is because duloxetine inhibits the enzymes responsible for breaking down aripiprazole.

Cymbalta And Marijuana

The simultaneous use of duloxetine and weed can produce moderate to severe side effects. Both Cymbalta medication and cannabis display CNS- and respiratory-depressant properties, which can turn hazardous when the substances are combined. For this reason, patients who use it and cannabis for medical purposes should work closely with their doctors in providing the correct information on the current drugs they use to determine the proper dosage and minimize the risks.

Sometimes, drug abusers supplement it with marijuana upon discovering no psychoactive properties. It is challenging to monitor the dose of both substances and the person’s condition in this case.

Medical cannabis and Cymbalta in bottles.

This way, mixing this drug and recreational marijuana might result in prolonged central nervous system effects and difficulty breathing. Another popular combination is duloxetine and alcohol that can be particularly dangerous when mixed with cannabis.

Cymbalta And Caffeine

Duloxetine interactions are not limited to other medications. It is not recommended to use it along with excessive consumption of caffeine. Although it is most frequently applied to treat depression, duloxetine uses also include battling anxiety disorder and panic attacks. Caffeine acts as a stimulant, increasing the levels of psychological disturbance and opposing the therapeutic effects of the medication. The interaction might also result in hypertension, increased heart rate, and serotonin syndrome.

Cymbalta Interactions With Other Drugs

Since treatment with the antidepressant can last for months, many patients develop questions ranging from what to take for headache while on this medication to whether their prescription medications are safe to use with it. While there are safe drugs to use with duloxetine, there are some that pose health hazards, including worsening withdrawal from Cymbalta.

Major drug interactions indicate highly clinically significant effects of combining duloxetine with other medicines. They can lead to severe symptoms, long-lasting damage to health, and even death.

Major Duloxetine Interactions Are: 

  • Tramadol: Some patients wonder what pain reliever they can take with this drug, and tramadol is one of the worst choices. The concurrent use of tramadol and duloxetine significantly increases the risk of serotonin syndrome and seizures. Serotonin syndrome might result in hallucinations, confusion, tachycardia, and death.
  • Phentermine: Duloxetine enhances the action of phentermine, sometimes causing such severe symptoms as hallucinations, seizures, and incoordination. Also, phentermine is an appetite suppressant and can inhibit the recovery of patients whose depression manifests in the loss of appetite.
  • Vyvanse: Patients should not take amphetamines such as Vyvanse with SNRIs. Combining the drugs can lead to tachycardia, hyperthermia, and drastic changes in the person’s mental state.
  • Zoloft: Duloxetine and Zoloft should not be used together. Sertraline influences the production of serotonin in the same way as duloxetine does. It results in effects similar to those a patient would experience during an overdose on Cymbalta.
  • Lexapro: A selective serotonin reuptake inhibitor, Lexapro and duloxetine should not be used together. Their interaction can induce serotonin syndrome, resulting in altered consciousness, nausea, seizures, and death. If an individual is looking for an antidepressant that works well with this medication, it is important to avoid SSRIs and SNRIs.
  • Amitriptyline: The use of amitriptyline, together with duloxetine, should be approached with extreme caution. It is an SSRI that amplifies the action of duloxetine and can cause serotonin syndrome.
  • Buspar: Similar to the medicines above, Buspar should not be used with duloxetine if it can be avoided. Moreover, sequential use of the drugs must be carefully monitored since prolonged duloxetine half-life can make the medicines interact even after the patient stops taking Cymbalta.
  • Imitrex: The concurrent use of Imitrex and Cymbalta can lead to shivering, mydriasis, ataxia, and vomiting. It is necessary to get medical help as soon as possible if these symptoms of serotonin syndrome are present.
  • Remeron: Combined with duloxetine, Remeron can cause serotonin syndrome. The symptoms of the condition may include irritability, anxiety, sweating, nausea, and confusion.
  • Lithium: Lithium is known to increase the effects of SSRIs, including duloxetine. It may lead to serotonin syndrome as well as to a more severe manifestation of Cymbalta side effects. If the abuse signs are noticed, a patient needs to contact a drug addiction facility to be guided in the further course of action.

Moderate duloxetine interactions signal that it is inadvisable to use Cymbalta with any of the listed medicines. The effects of duloxetine interactions with the following drugs can be potentially dangerous to health.

These Are: 

  • Xanax: Xanax and Cymbalta might result in prolonged respiratory and CNS depression.
  • Gabapentin: Gabapentin and Cymbalta might cause respiratory depression and dizziness.
  • Ibuprofen: It and ibuprofen can increase the likelihood of bleeding. In the case of unusual bleeding, dizziness, or weakness, immediate medical attention is required.
  • Lyrica: Adding Lyrica can cause dizziness, impairment in judgment, and motor coordination.
  • Lamictal: Lamictal and duloxetine can reduce mental alertness and cause respiratory depression.
  • Hydrocodone: Hydrocodone, when added, can cause serotonin syndrome, tremors, and nausea.
  • Oxycodone: Oxycodone and this medication result in a high risk of serotonin syndrome.
  • Klonopin: Klonopin with the medicine together can cause dizziness, confusion, and CNS depression.
  • Seroquel: Seroquel and this medication increase drowsiness and make it difficult to concentrate.
  • Percocet: Percocet and duloxetine can cause serotonin syndrome, fever, and shaking.
  • Ativan: Ativan and duloxetine are generally safe to take together; however, severe respiratory depression may occur when the drugs are used with alcohol.
  • Naproxen: Combining it with Naproxen can increase the risk of bleeding.
  • Valium: Valium and duloxetine can result in drowsiness and confusion.
  • Ambien: Duloxetine and Ambien can affect alertness and motor coordination.
  • Advil: The use of this drug with Advil is not recommended to patients with liver or kidney disease due to an increased risk of bleeding.
  • Topamax: Combined with Topamax, they can sometimes cause increased drowsiness and respiratory depression.
  • Kratom: Although Cymbalta is not a controlled substance, it can cause psychological dependence. Some individuals wonder how to stop taking Cymbalta and turn to Kratom as a withdrawal aid. The combination of the two can result in increased anxiety and insomnia.
  • Aspirin: Taking it with Aspirin might cause bleeding. However, those looking for pain medication to take with this medication may ask their doctor about Aspirin since its benefits can sometimes outweigh the risks.
  • Suboxone: The combination of both drugs can increase the risks of serotonin syndrome. It can also lead to coma and death.

Know Cymbalta Drug Interactions

Duloxetine interactions can range from being mild inconveniences to being potentially life-threatening and severe. It is important to make your medical doctor aware of any medication that you may be on. When taking this drug, it is essential to avoid starting any drugs without making your doctor aware.

Having the right information on these drug interactions and avoiding indiscriminate drug use will help avoid adverse health effects.

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Published on: May 30th, 2019

Updated on: June 16th, 2021

About Author

Sharon Levy, MD, MPH

After successful graduation from Boston University, MA, Sharon gained a Master’s degree in Public Health. Since then, Sharon devoted herself entirely to the medical niche. Sharon Levy is also a certified addiction recovery coach.

Medically Reviewed by

Michael Espelin APRN

8 years of nursing experience in wide variety of behavioral and addition settings that include adult inpatient and outpatient mental health services with substance use disorders, and geriatric long-term care and hospice care.  He has a particular interest in psychopharmacology, nutritional psychiatry, and alternative treatment options involving particular vitamins, dietary supplements, and administering auricular acupuncture.