Interaction between amitriptyline and phenothiazine in man: effect on plasma concentration of amitriptyline and its metabolite nortriptyline and the correlation with clinical response.
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Biomedical subjects
Publications and source records attributed to R Volmat.
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Plasma levels of amitriptyline and nortriptyline were measured twice weekly in 62 patients treated for three weeks with i.m. amitriptyline 120 mg/day. In half the patients the ratio of amitriptyline to nortriptyline was under 1 and in the other half it was greater than 1. 30 of these 62 patients were clinically monitored with the Hamilton Rating Scale and the side effects of the drug were recorded. There was no correlation between plasma level of the drug and its side effects, but there was a statistically significant curvilinear correlation between the plasma levels of amitriptyline plus nortriptyline and nortriptyline alone, and the clinical effect. The practical value of this type of investigation was demonstrated by showing that patients whose drug plasma level was not in the therapeutic range, were clinically improved after adjustment of the dose. The plasma level of amitriptyline plus nortriptyline must lie between 60 to 220 ng/ml, and that of nortriptyline between 60 to 140 ng/ml, to obtain the best clinical effect. Associated treatments, age, weight and sex of patients, and the type of depression did not appear significantly to affect the plasma level of the drug.
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The authors relate eight cases of amineptine dependency collected between 1980 and 1988 in 7 women and 1 man treated in the CHU of Besançon (France). The pharmacodependency appeared to be limited mainly to an abuse and a psychic dependence, i.e. a compulsive need to use the drug on a periodic (two cases) or continuing (six cases) basis in order to experience its psychomotor stimulant like effect. The used dosages ranged between 1,000 and 2,500 mg per day. The daily dose was divided into little doses, every hour for example. The induction modality was progressive during weeks or months and a stable dose period was then encountered. In one patient only, we observed a progressive increase of the dose without stabilisation of the dose. The withdrawal of amineptine was obtained without problem except in 2 cases where we observed clinical manifestations of anxiety, psychomotor agitation or bulimia during one day. Four years after the beginning, amineptine dependence was still present in 2 patients. In 4 patients we obtained an interruption of the amineptine pharmacodependency for one to three years. We did not see again the two remaining patients. In two cases, the main diagnosis, according to DSM III, was a major personality disorder (borderline). In the six other cases the diagnosis was a bipolar affective disorder (including four cases with only hypomanic episodes only). In these six patients the main characteristic of their affective illness was the association with other psychiatric disorders, especially personality disorders, such as borderline personality in one case and atypical personality with uncontrolled behavior as the main feature, in the 5 other patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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It is common clinical experience that depressed patients comply poorly with their treatment schedules. In a retrospective study, the authors studied the compliance with the tricyclic antidepressant treatment (TCA) in 1,023 in-patients and evaluated the frequency of the plasma levels under or above the therapeutic range, following a first prescription of TCA. To describe the adherence to the TCA regimen, the investigators have classified patients as either "compliant" or "bad compliant" on the basis of two different arbitrary dividing points: plasma levels of tertiary OR secondary amine lower than 20 ng/ml, or plasma levels of tertiary AND secondary amine lower than 20 ng/ml. The antidepressant plasma levels were measured, on steady state conditions, using a gas chromatographic method. The incidence of bad compliance ranged between about 2.5 and 10%, depending on the criteria used, the incidence of plasma levels under or above the therapeutic window ranged respectively between 26 and 54%-4 and 24%. The results from this study should encourage TCA plasma level measurements.