Using antidepressants and tramadol may reduce tramadol’s pain-relieving effects, increasing the likelihood of using higher doses of opioids.

New findings from University Hospitals show certain antidepressants may interact with the opioid pain medication tramadol, making it less effective at relieving pain. Researchers believe the relationship between tramadol and antidepressants could explain why some people take higher doses of tramadol, which can increase the risk of addiction. These drug interactions may be related to the continuing opioid epidemic in America.

The study looked at the medication records of 152 patients from UH Cleveland Medical Center and UH Geauga Medical Center. The patients received scheduled tramadol for at least 24 hours. Participants were either admitted as inpatients or placed under observation.

Medication Interactions Between Tramadol and Antidepressants

Participants in the study were taking antidepressants, including Prozac, Paxil and Wellbutrin. Compared to patients not taking antidepressants, these participants required three times more pain medication each day to control their pain.

Researchers believe this effect occurs because tramadol needs the activation of the CYP2D6 enzyme to control pain. The enzyme can be blocked by medications that are inhibitors, including Prozac, Paxil and Wellbutrin.

This was the first study to document interactions between tramadol and antidepressants in a real setting with patients. Previous studies have found similar relationships between tramadol and antidepressants with healthy volunteers.

Derek Frost, a pharmacist at UH and the lead author of the study, says millions of Americans may experience the negative effects of using tramadol and antidepressants together. He says the drugs are commonly used, and depression, pain and anxiety all go “hand in hand.” Frost also says many patients with chronic pain are taking antidepressants, usually selective serotonin reuptake inhibitors (SSRIs). Many SSRIs are CYP2D6 inhibitors.

Frost says there is a way to combat the interaction between tramadol and antidepressants. He suggests that doctors consider the use of antidepressants that don’t affect tramadol, such as Zoloft or Lexapro. Another option is to consider non-opioid forms of pain control.

Risks of Leaving Patients with Undertreated Pain

Though pain medications may carry a risk of addiction, there are risks of leaving patients with undertreated pain as well. Pain is what the body uses to signal that something is wrong. Untreated or undertreated chronic pain can affect nearly all areas of a person’s life by causing:

  • Sleep dysfunction
  • Cognitive and brain function impairment
  • Mood and mental health problems, such as depression
  • Impairment of sexual function
  • Issues with cardiovascular health
  • Loss of mobility and physical function

Undertreated or untreated pain can cause problems in relationships, families, careers and life in general. Undertreated pain can also lead people to obtain medication illegally or take more than prescribed.

Doctors have a difficult task when looking at the links between tramadol and antidepressants. Their goal is usually to find an effective pain-management strategy that weighs the risks of pain medications with the risks of untreated pain.

Reducing Stigma and Improving Patient-Doctor Communication

The study could help reduce the stigma of addiction. For example, when patients are suspected of drug-seeking, they may actually be seeking a more effective pain-reliever. A patient being treated with antidepressants and tramadol may experience more pain than someone using tramadol alone.

In addition, the study can help create a better understanding of the relationship between chronic pain and depression. It reveals the interactions between pain medications and antidepressants. It also points to reasons why some people take larger doses of tramadol and are at a higher risk of addiction.

By using facts and research to reduce the stigma of addiction, people may feel more comfortable about seeking treatment. Doctors may use the research to help give patients more effective pain relief or alternate treatment.

If you or someone you love is dealing with a substance use disorder, The Recovery Village is here to help. Our facilities serve communities from Florida to Washington, specializing in a range of addiction recovery services. Contact us today to learn about treatment programs that can work well for you.

a man wearing a blue and white striped shirt.
Editor – Jonathan Strum
Jonathan Strum graduated from the University of Nebraska Omaha with a Bachelor's in Communication in 2017 and has been writing professionally ever since. Read more

Ives, James. “Interaction between antidepressants and […] lesser pain relief.” News Medical Life Sciences, June 26, 2019. Accessed August 5, 2019.

Medical Disclaimer

The Recovery Village aims to improve the quality of life for people struggling with substance use or mental health disorder with fact-based content about the nature of behavioral health conditions, treatment options and their related outcomes. We publish material that is researched, cited, edited and reviewed by licensed medical professionals. The information we provide is not intended to be a substitute for professional medical advice, diagnosis or treatment. It should not be used in place of the advice of your physician or other qualified healthcare providers.