Can tramadol and other opioids be used in combination with selective serotonin reuptake inhibitors?
Tramadol, like selective serotonin reuptake inhibitors (SSRIs), inhibits reuptake of serotonin. Therefore, tramadol carries a risk for serotonin syndrome. Unlike tramadol, which inhibits reuptake of both norepinephrine and serotonin, tapentadol has limited interaction with serotonin transporter proteins and minimal effect upon serotonin reuptake. A compound without serotonergic activity would carry no risk of contributing to serotonin syndrome. Therefore, the risk of serotonin syndrome is drastically reduced and nearly non-existent with the use of tapentadol. Of note, methadone does inhibit reuptake of serotonin too, and therefore does in fact carry at least some elevated risk of serotonin syndrome when combined with SSRIs. Tramadol and methadone nevertheless can be used in combination with SSRIs or SNRIs; however, caution should be used with additive serotonergic agents. The lowest possible dosages should be used, and the patient and caregivers should be counseled on potential signs of serotonin syndrome: neuromuscular hyperactivity, autonomic hyperactivity, altered mental status, and seizures.