Duloxetine Drug Interactions: Wellbutrin, Xanax, Etc.

Last Updated: June 16, 2020

Authored by Sharon Levy, MD, MPH

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

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 Cymbalta and cannabis for medical purposes should work closely with their doctors to determine the right dosage and minimize the risks.
Sometimes, drug abusers wonder whether duloxetine can get them high and supplement it with marijuana upon discovering no psychoactive properties. In this case, it is incredibly difficult to monitor the dose of both substances and the person’s condition.

Cymbalta And Caffeine

Duloxetine interactions are not limited to other medications. It is not recommended to use Cymbalta along with excessive consumption of caffeine. Although it is most frequently applied to treat depression, duloxetine uses also include battling anxiety disorders 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 and caffeine interaction

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 Cymbalta to whether their prescription medications are safe to use with duloxetine. While there are drugs which are safe to use with duloxetine, there are some which pose health hazards, including worsening withdrawal from Cymbalta. Cymbalta drug interactions can have high, moderate, and low levels of risk.

Major Interactions

Wellbutrin. Coadministration of Wellbutrin and Cymbalta together significantly increases the risk of seizures, particularly in elderly patients and those with a history of seizures, 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 duloxetine without talking to their health care provider.
Tramadol. Some patients wonder what pain reliever they can take with Cymbalta, 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.
Adderall. The concurrent use of duloxetine and Adderall can result in increased anxiety, restlessness, and racing thoughts. The combination may also trigger the development of serotonin syndrome and become potentially life-threatening. Besides, Adderall can worsen the symptoms of depression.
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. Amphetamines such as Vyvanse should not be taken with SNRIs. The combination of 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, resulting in the effects similar to those a patient would experience during an overdose on Cymbalta.
Lexapro. Being 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 Cymbalta, 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. Similarly 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. This 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 drug addiction facility to be guided the further course of actions.
duloxetine drug interactions

Moderate Interactions

  • Xanax. Xanax and Cymbalta might result in prolonged respiratory and CNS depression.
  • Gabapentin. Gabapentin and Cymbalta might cause respiratory depression and dizziness.
  • Ibuprofen. Ibuprofen and duloxetine can increase the risk of bleeding. In the case of unusual bleeding, dizziness, or weakness, immediate medical attention is required.
  • Lyrica. Lyrica and Cymbalta can cause dizziness, impairment in judgment, and motor coordination.
  • Abilify. Abilify and Cymbalta might cause seizures, low blood pressure, and abnormal muscle movements.
  • Lamictal. Lamictal and duloxetine can reduce mental alertness and cause respiratory depression.
  • Oxycodone. Oxycodone and Cymbalta result in a high risk of serotonin syndrome.
  • Benadryl. Duloxetine increases the plasma concentrations of Benadryl.
  • Hydrocodone. Hydrocodone and Cymbalta can cause serotonin syndrome, tremors, and nausea.
  • Klonopin. Klonopin and duloxetine together can cause dizziness, confusion, and CNS depression.
  • Seroquel. Seroquel and Cymbalta increase drowsiness and make it difficult to concentrate.
  • Percocet. Percocet and duloxetine can cause serotonin syndrome, fever, and shaking.
  • Ativan. Ativan and Cymbalta are generally safe to take together; however, severe respiratory depression may occur when the drugs are used with alcohol.
  • Naproxen. Cymbalta and Naproxen can result in 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 Cymbalta and Advil is not recommended to patients with liver or kidney disease due to an increased risk of bleeding.
  • Topamax. Topamax and Cymbalta 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. Cymbalta with Aspirin might increase the risk of bleeding. However, those looking for pain medication that can be taken with Cymbalta may ask their doctor about Aspirin, since its benefits can sometimes outweigh the risks.
  • Suboxone. Combination of both drugs can increase the risks of serotonin syndrome. It can also lead to coma and death.

Minor Interactions

Medicines that have a minor interaction with duloxetine include:

  • Nexium
  • Omeprazole
  • Amoxicillin
  • Calcium carbonate
  • Donepezil
  • Rabeprazole
  • Zantac
  • Lidocaine
  • Riopan
  • Citrolith
  • Tritec
  • Detrol
  • Alka-Seltzer Heartburn Relief
  • Protonix
  • Axid
  • Pepcid
  • Namzaric
  • Polycitra
  • Renacidin
  • Nephrox

Know Cymbalta Drug Interactions

Duloxetine drug interactions can have severe consequences and present a significant issue for many patients. The medication has hazardous interactions with Tramadol and Ibuprofen. Individuals suffering from chronic pain and wondering what pain meds they can take with Cymbalta may ask their doctors about Aspirin and Naproxen. In general, duloxetine should not be taken with Wellbutrin and other drugs that increase the risk of seizures. Some over-the-counter medicines such as Nexium and Axid may also interact with duloxetine. It is, therefore, crucial to always receive a medical consultation prior to taking any medications along with Cymbalta and get professional treatment if needed.

Page Sources

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4668773/
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309786/

Published on: May 30th, 2019

Updated on: June 16th, 2020

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.


Leave a comment

  • Barbara Wheat
    I have been on Duloxetine & Lexapro for a few years now. And I feel stuck. I get nothing accomplished all day. I don’t want to go anywhere or do anything. I don’t know what to do. I need help.
    • Lauren
      Maybe drop the lexapro and add abilify?? Ask your doctor!! You need to switch it up and reset yourself. I was on Effexor for 10 years and added abilify and it really helped. Just 2mg. Unfortunately I had an impulsive moment and quit them all. Now I’m on Cymbalta and it seems to be working really well!! I was the same way on Effexor only. I was sooo depressed and I didn’t want to do ANYTHING.