Opioids and antidepressants: Which combinations to avoid

Abstract

Some opioids such as tramadol, pethidine, dextromethorphan and tapentadol increase serotonergic activity. Fentanyl and methadone also do this but to a lesser extent. These opioids may increase the risk of serotonin toxicity when combined with antidepressants. Some selective serotonin reuptake inhibitors block the metabolism of opioids. This may reduce the concentrations and analgesic effect of some opioids such as codeine and tramadol, and increase the concentrations and risk of adverse effects of other opioids such as methadone. Fluoxetine and irreversible monoamine oxidase inhibitors – tranylcypromine and phenelzine – have prolonged actions and may interact for weeks after they have been discontinued.