New Study Shows Some Antidepressants Can Make the Opioid Tramadol Less Effective

If you’re a chronic pain patient who’s ever been told you’re “just a drug-seeker” when say your pain meds aren’t working, a new study about the opioid tramadol might explain why the medication is less effective for some. An interaction between tramadol and specific types of popular antidepressants prevent tramadol from working correctly.

Tramadol and antidepressants fluoxetine (brand name Prozac), bupropion (brand name Wellbutrin) and paroxetine (Paxil) interact with CYP2D6 enzymes. CYP2D6 enzymes play a critical role in how your body processes or metabolizes many drugs, including antidepressants and opioids. The antidepressants inhibit or prevent CYP2D6 enzymes from working. Tramadol, on the other hand, works in part by activating the activity of CYP2D6 enzymes to provide pain relief. In combination, these types of antidepressants and tramadol can work against each other.

The recent study, which was published in the journal Pharmacotherapy in April, looked at the medical records of 152 inpatient patients between 2012 and 2017. Half the group reviewed were prescribed just the opioid pain medication tramadol and the other half both tramadol and one of the three antidepressants — fluoxetine, bupropion or paroxetine.

Researchers wanted to find out the impact of these drug interactions. Based on their findings, patients who took one of the three antidepressants known to block CYP2D6 enzymes required as much as three times more tramadol to reduce their breakthrough pain compared to patients who didn’t take an antidepressant. The study’s analysis showed the interaction was most significant with fluoxetine (brand name Prozac) and bupropion (brand name Wellbutrin), especially in female patients.

Researchers have long been aware of potential interactions between tramadol and some types of antidepressants. However, this was the first time researchers studied how the interaction played out among real patients. The researchers noted these medications, which are among the top 30 most commonly prescribed drugs, are still given to patients in combination. Tramadol is an opioid with a lower risk of addiction.

A significant number of people deal with mental health issues in addition to chronic illness and chronic pain. Chronic illness leads to a higher risk of depression and anxiety. Accordingly, your doctor may prescribe you an antidepressant in addition to pain medications to manage your mental health.

People with chronic illness and chronic pain, in particular, are often labeled by medical professionals as “drug-seeking,” especially when opioids are involved. However, if you’ve been prescribed fluoxetine or bupropion and tramadol for pain management and are not seeing reductions in your pain, it might not be effective at the standard dose.

Derek Frost, Pharm.D., lead researcher on the study, told ScienceDaily the “problem” of doctors prescribing these drugs in combination is easy to “fix.” Frost indicated doctors can prescribe antidepressants that don’t block CYP2D6 enzymes like sertraline (brand name Zoloft), citalopram (brand name Celexa) or escitalopram (brand name Lexapro). However, antidepressants all work differently for different people, so it’s not always as simple as “just” swapping out to a different antidepressant — or type of pain medication for that matter. It might not work for you.

A drug’s side effects, its interactions with other medications you’re taking and what is effective for your combination of symptoms and conditions will determine the right combination of medication. You should work with your doctor to find what medications may help you, and advocate for your needs if your antidepressant or pain management drugs aren’t working.

“For patients who have the combination of chronic pain and depression or anxiety, keep in mind that this interaction does exist,” Frost told ScienceDaily. “And for health care providers, if you have a patient approaching you saying this medication isn’t working for me, is there an interaction at play?”