Interactions between fluoxetine and opiate analgesia for postoperative dental pain.

In a double-blind placebo-controlled study we investigated the analgesic efficacy of combinations of the serotonergic tricyclic antidepressant fluoxetine with either the mu-opiate morphine or the kappa-opiate pentazocine. Administration of oral fluoxetine (10 mg p.o. daily for 7 days pre-operatively) had no effect on the immediate postoperative pain level. However, pre-operative administration of fluoxetine was found, compared to placebo, to antagonize analgesia seen after administration of morphine (6 mg, i.v.) in the immediate postoperative period. Attenuation of morphine analgesia consisted essentially of a shortening of the duration of action of the dose of morphine administered. Similar administration of fluoxetine had no effect on the analgesia produced by the kappa-opiate pentazocine (45 mg, i.v.). This effect probably results from alteration in the known serotonergic circuits in endogenous pain-modulating systems.