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The influence of amitriptyline on the plasma level of various neuroleptics was studied in 25 chronic schizophrenic patients. The study lasted 20 weeks. Patients were kept first 4 weeks on their former neuroleptic medication, with amitriptyline added for 12 subsequent weeks, and withdrawn during the last 4 weeks when only the neuroleptic medication was continued unchanged. The plasma level of neuroleptics was assayed by gas-liquid chromatography, once weekly throughout the study. The amitriptyline plasma level was also evaluated once weekly during the 12 weeks of its administration. The mean neuroleptic plasma values for each 4-week period were pooled together in three groups: aliphatic, piperidine and piperazine phenothiazine derivatives. Amitriptyline provoked some increase of the plasma level of all phenothiazine derivatives. This augmentation was significant only transitorily, however. The putative mechanisms of this neuroleptic tricyclic antidepressant interaction are discussed.

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.

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