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  • 1
    ISSN: 1432-2072
    Keywords: Antidepressant drug ; Plasma drug level ; Orthostatic hypotension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Orthostatic hypotension, the clinically most important side effect in treatment with tricyclic antidepressants, was investigated in a double-blind study with clomipramine and the selective serotonin reuptake inhibitor citalopram given for 5 weeks. All patients were initially given placebo for 1 week. In the clomipramine group (n=17) a significant orthostatic drop in the systolic blood pressure was observed during treatment; this remained significant over the whole investigational period. A curvilinear correlation was demonstrated between the orthostatic drop in systolic blood pressure and the plasma levels of clomipramine and desmethylclomipramine. The most pronounced orthostatic reaction was thus seen in 1–2 weeks, at plasma levels of 25–75 μg/l (clomipramine). The correlation between the subjective symptoms and the measured orthostatic drop was poor, as was the correlation between the subjective symptoms and the plasma levels of the two active compounds. The change in orthostatic heart rate during clomipramine treatment was insignificant. In the citalopram group (n=15) no significant changes in orthostatic blood pressure or heart rate were demonstrated during treatment and these patients had no orthostatic complaints.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Elderly patients ; Mianserin therapy ; Plasma level monitoring ; Orthostatic blood pressure ; 24-h Electrocardiographic recording ; Systolic time intervals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cardiovascular effects of the tetracyclic antidepressant drug mianserin were examined in a prospective study including ten elderly depressed patients (age 60–77 years). During 1 week on placebo and 5 weeks on mianserin, 60 mg per day, orthostatic blood pressure testing, recording of standard electrocardiogram, 24-h electrocardiographic recording and systolic time intervals were carried out along with frequent monitoring of plasma levels of mianserin (13–57 μg/l) and the primary metabolite desmethylmianserin (7–27 μg/l). Mianserin caused a significant increase in orthostatic systolic blood pressure drop, and this correlated well with the plasma mianserin levels (r s=0.70). There were no significant changes in supine blood pressure or in orthostatic changes in heart rate. No cardiac conduction disturbances or arrhythmias were provoked, but mianserin caused changes in systolic time intervals indicating impairment of left ventricular contractility and performance. Like tricyclic antidepressants mianserin should thus be used with caution in patients with latent or overt cardiovascular disease.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Imipramine ; Nortriptyline ; Elderly ; Dose dependent kinetics ; Depression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a group of elderly depressed patients treated with imipramine (50–200 mg/day), six patients had the dose changed after 1–3 weeks of treatment. In all cases an increased dose resulted in a considerably disproportional rise in the plasma level of the active metabolite desipramine. In a group of elderly depressed patients treated with nortriptyline (40–100 mg/day) the dose/plasma level ratio could be examined in 6 patients, and there was no tendency towards a disproportional rise in plasma level, when the dose was raised. Dose changes, thus, may result in unpredictable changes in plasma levels during imipramine treatment and therapy control by plasma level monitoring may be difficult in these patients. Additional treatment with perphenazine (8–16 mg/day) to patients on imipramine (N=3) or nortriptyline (N=2) caused a marked rise in drug levels for imipramine in particular affecting the desipramine levels.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Serotonin (5-HT) uptake inhibition ; Anti-depressants ; Citalopram ; Plasma levels ; Long-term treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a phase II study the antidepressive effect of citalopram, a selective and potent serotonin reuptake inhibitor, was examined in 20 endogenously and three nonendogenously depressed hospitalized patients. Four endogenously depressed patients dropped out due to deterioration early in the treatment period. The remaining 19 patients completed a 4–6 week treatment schedule. Of 16 endogenously depressed patients 11 responded, one was a partial responder and four did not respond. Of three patients with non-endogenous depressions, two responded and one did not respond. No correlation between plasma citalopram concentration and therapeutic outcome was found. Fourteen patients were given maintenance treatment for 8–113 weeks. One patient developed depression when the dose was reduced from 60 to 40 mg and one patient became manic. After discontinuation of treatment seven patients had a depressive relapse and six of these who again were treated with citalopram responded completely. Side effect rating scores of symptoms usually associated with depression or treatment with tricyclic antidepressants declined during treatment. Three patients complained of increased need of sleep for a period after several weeks of treatment. Apart from an unspecific, transient rise in liver enzymes in two patients, detailed biochemical laboratory tests were all normal. There were no effects on blood pressure, pulse rate, orthostatic reaction, or electrocardiogram. One patient took an overdose of citalopram resulting in plasma levels about six times higher than the average therapeutic level, but there were no signs of severe toxicity. In particular no change in consciousness, electrocardiogram or blood pressure occurred. Pharmacokinetic variables such as dose schedule, steady state kinetics, and metabolism are discussed.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2072
    Keywords: Depression rating ; Improvement scores ; Hamilton Depression Scale ; Antidepressant treatment ; Effect monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A total of 97 patients, who participated in two studies on the relationship between the clinical effect and plasma levels of imipramine and clomipramine, were examined for improvement curves by use of weekly ratings on the Hamilton Depression Scale (HDS). Although we confirmed that our six-item HDS subscale, in contrast to the total 17-item HDS, was a one-dimensional measure of depression, the Rasch analysis showed that the weekly improvement in subscale scores only applied to the individual patient, i.e. an average improvement curve for a group of depressed patients is an abstraction to which the individual curves cannot be transferred. Our results indicate, however, that when the subscale scores are transformed into three clinical categories of depression: no, mild (minor), moderate/-severe (major) they could be described by a common improvement curve for all patients. This is illustrated by the percentage of patients who, week to week, changed from major to minor or no depression, or from minor to no depression. We found no specific improvement pattern for imipramine or clomipramine which could be used diagnostically. There is reason to assume that patients completing a controlled trial necessarily will follow a monotonic improvement curve, and the improvement pattern of all patients fulfilling the entry criteria should, therefore, always be reported. The present study thus indicates that calculation of average improvement curves is neither clinically nor statistically meaningful, and should be replaced by measures of changes in number of patients in different main severity categories, or by the final rating score. No difference in outcome between imipramine and clomipramine was shown neither on the subscale nor on the 17-item HDS.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2072
    Keywords: Elderly patients ; Antidepressive treatment ; Orthostatic blood pressure ; Systolic time intervals ; 24-hour ambulatory ECG
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cardiovascular effects in elderly depressed patients (age 62–78 years) treated with imipramine (N=11) or nortriptyline (N=10) were recorded by monitoring of heart rate, blood pressure, systolic time intervals, standard ECG and 24-h ECG. The two drugs exhibited distinctly different cardiovascular reactions. The use of imipramine was severely limited by orthostatic hypotension occurring at subtherapeutic plasma levels, which resulted in falls with fracture in two patients. In contrast, nortriptyline at therapeutic drug levels did not significantly influence orthostatic blood pressure regulation. Nortriptyline caused moderate changes in systolic time intervals, indicating impairment in myocardial contractility. This effect was not seen with imipramine, but a majority of the patients did not reach therapeutic plasma levels because of the blood pressure reactions. Neither imipramine nor nortriptyline induced changes in cardiac conduction time measurements or arrhythmias. In addition to the blood pressure reactions, the use of imipramine was complicated by dose dependent kinetics.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2072
    Keywords: Elderly patients ; Antidepressive treatment ; Orthostatic blood pressure ; Systolic time intervals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thirteen elderly depressed patients (age 60–82 years) were treated for 5 weeks with a fixed dose of amitriptyline 100 mg (sustained release preparation). In all patients the sum of concentrations of amitriptyline and nortriptyline exceeded 130 μg/l, which is the recommended plasma level. Cardiovascular side effects were recorded by monitoring heart rate, blood pressure, standard ECG and systolic time intervals. During treatment, a transient increase in the supine heart rate was observed without significant changes in the supine blood pressure. The orthostatic drop in blood pressure was markedly increased during treatment without a compensatory increase in heart rate, and these changes remained significant during the whole investigational period. PQ and QRS were significantly increased during treatment, and significant changes in the systolic time intervals were found indicating impairment of myocardial conduction and contractility. In three patients medication was discontinued due to cardiovascular side effects.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-2072
    Keywords: Antidepressant medication ; Cortisol ; Dexamethasone ; Oxazepam ; Distress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In 72 consecutive depressed hospitalized patients afternoon plasma cortisol was measured in three ways before treatment with antidepressants: 1) Spontaneous (n=72), 2) 2 h after oxazepam suppression (45 mg, n=28; 60 mg, n=37) and 3) 16 h after dexamethasone suppression (2 mg, n=71). In addition, spontaneous cortisol was measured after 3 weeks' treatment (n=55) and 5 weeks' treatment (n=36). Both spontaneous and suppressed cortisol levels seemed to have a predictive value in the endogenously depressed patients: complete responders had significantly lower pretreatment cortisol levels compared to poor responders. However, other covarying factors such as distress and age may as well account for the differences in treatment effect. During treatment a significant decrease of spontaneous cortisol was found from about 400 nM in poor responders and 325 nM in complete responders to about 300 nM in all groups. There was a positive correlation between pre- and post-treatment cortisol levels and between pretreatment levels and per cent fall in spontaneous cortisol levels.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2072
    Keywords: Serum levels ; Depot neuroleptic ; Zuclopenthixol decanoate ; Schizophrenia ; Clinical state
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Serum concentrations of zuclopenthixol were determined in a group of 20 patients treated with a depot preparation, zuclopenthixol decanoate in Viscoleo. Clinical assessments according to a Clinical Global Impression (CGI) scale, Comprehensive Psychological Rating Scale (CPRS), 16-item subscale for schizophrenia, and the UKU side effect scale were performed on 3 consecutive days of injection. The serum concentrations showed a limited individual variation and a high and significant correlation between dose and serum concentration. One patient had a particularly high serum concentration of zuclopenthixol. This patient also had an elevated concentration of the N-dealkyl metabolite, but a low concentration of the sulphoxide. For serum concentrations versus clinical state and side effects some significant correlations were found. All correlations were positive, which means that the higher the serum concentration the poorer the clinical state of the patient. We think that this probably reflects a common clinical pattern of increasing the dose, when the antipsychotic response is unsatisfactory. The study also showed that for moderately ill patients, who were given the optimum dose of drug, the subgroup of patients not experiencing side effects had significantly lower serum concentrations than the subgroup with side effects.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 11 (1967), S. 255-264 
    ISSN: 1432-2072
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Radioactive imipramine was administered by mouth to psychiatric patients and metabolites in urine was studied by total counting, extraction and thin layer chromatography. 2. Some 40 per cent of the radioactive dose administered appeared in the urine during the first 24 hour period; a total of some 70 per cent during the first 72 hour period. 3. Of the administered radioactivity 15 per cent was excreted in the form of non-conjugated metabolites, 35 per cent as conjugated metabolites, 23 per cent as non-extractable. 4. Thin layer chromatography showed 4 unknown metabolites containing considerable amounts of radioactivity.
    Type of Medium: Electronic Resource
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