Modification of fentanyl analgesia by antidepressants

Clinical practice often requires simultaneous administration of antidepressants with opioids (oncology, rheumatology). Coadministration may either attenuate or potentiate opioid analgesia. The purpose of this paper was to verify how the analgesic action of fentanyl (0.05 mg/kg) is affected by single administration as well as 4- or 21-day premedication with antidepressants characterized by various mechanisms of action. The effects of amitriptyline 3 mg/kg, moclobemide 5 mg/kg, fluoxetine 5 mg/kg and reboxetine 0.08 mg/kg were investigated. Experiments were conducted on normotensive Wistar Kyoto rats. The pain threshold was measured using an analgesimeter. It was concluded that the single administration of an antidepressant increases the analgesic action of fentanyl. Four-day premedication with fluoxetine and reboxetine significantly attenuated the antinociceptive action of fentanyl, whereas 21-day premedication with all antidepressants investigated (fluoxetine, amitriptyline, moclobemide, reboxetine) markedly decreased it. The potential clinical importance of this observation is discussed.