CLINICAL-RESPONSE AND PLASMA-CONCENTRATIONS OF AMITRIPTYLINE AND ITS METABOLITE-NORTRIPTYLINE IN DEPRESSIVE PATIENTS

Although many attempts have been made, to date no convincing evidence exists of a relationship between plasma concentrations of amitriptylin e (AT), its active metabolite nortriptyline (NT) and clinical response . Fifteen patients with primary depression (according to DSM-IV) were divided in two groups according to given doses: (I) 6 patients receive d 3 x 50 mg of AT daily; and (II) 9 patients received 3 x 25 mg of AT daily, for 6 weeks. The clinical status was determined with Hamilton D epression Rating Scale. Both investigated doses were therapeutically e ffective. AT and NT plasma concentrations were assayed by high perform ance liquid chromatography. Following administration of 3 x 50 mg of A T daily, the correlation of concentrations of AT, NT, total AT+NT and clinical response were r(AT) = -0.702 (P < 0.1), r(NT) = -0.761 (P < 0 .1), r(AT+NT) = -0.741 (P < 0.1). The linear and very high correlation were also present with concentrations of AT, NT, total AT+NT and clin ical response in depressive patients on 3 x 25 mg AT daily: r(AT) = -0 .785 (P < 0.02), r(NT) = -0.811 (P < 0.01), r(AT+NT) = -0.848 (P < 0.0 1). Our results support a high correlation between AT/NT plasma concen trations and clinical response indicating that therapeutic monitoring of AT and its metabolite, NT, can provide eventual clinical response.