Taking Oxycodone at the same time as certain Selective Serotonin Reuptake Inhibitors (SSRIs), a commonly prescribed class of antidepressants, can increase the risk of opioid overdose, according to a study my colleagues and I published. Doctors prescribe the opioid oxycodone to treat moderate to severe pain after surgeries and injuries or certain conditions like cancer. Opioids are also a common drug of abuse.
In the U.S., over 70 percent of drug overdose deaths in 2019 involved an opioid. Because many patients with depression also experience chronic pain, opioids are often co-prescribed with antidepressants like SSRIs. Prior research has shown that certain SSRIs, namely fluoxetine (Prozac or Sarafem) and paroxetine (Paxil, Pexeva or Brisdelle), can strongly inhibit a liver enzyme crucial to the proper breakdown of drugs in the body, including oxycodone. The resulting increased concentration of oxycodone in the blood may lead to accidental overdose.
To see whether different types of SSRIs might affect a patient's risk of overdosing on oxycodone, my colleagues and I examined data from three large US health insurance claims databases. We included over 2 million adults who began taking oxycodone while using SSRIs between 2000 and 2020. The average age of the group was around 50, and a little over 72 percent were women. A little over 30 percent were taking the SSRIs paroxetine and fluoxetine. We found that patients taking paroxetine or fluoxetine had a 23 percent higher risk of overdosing on oxycodone than those using other SSRIs.