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  • 1
    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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  • 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: 1432-1041
    Keywords: amitriptyline ; imipramine ; clomipramine ; antidepressant overdose ; clinical effects ; pharmacokinetics ; cardiotoxicity ; maprotiline ; doxepine ; nortriptyline ; opipramol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty-nine cases of self-poisoning with antidepressants (amitriptyline, imipramine, clomipramine, maprotiline, doxepine, nortriptyline, opipramol) were examined by frequent observation of CNS effects, heart rate, blood pressure and standard ECG, 24 h-ECG-monitoring, measurement of systolic time intervals, EEG recordings and frequent measurement of serum levels of antidepressants and primary metabolites. None of the patients died. Maximum total serum antidepressant level (parent compound + desmethyl metabolite) ranged from 20 to 2200 µg/l, with concentrations above 500 µg/l in 11 cases. The serum amitriptyline concentration remained high for 3–4 days in some of the severely intoxicated patients and the decay curves were compatible with partly saturated elimination. A degree of unconsciousness and the occurrence of excitation and hallucinations were generally seen in cases with total serum antidepressant levels above 500 µg/l. Grand mal seizures occurred more frequently at high antidepressant levels, but could not be predicted from the EEG recordings. Increased heart rate and prolonged QRS- and QTc-intervals were significantly correlated with the total serum antidpressant level. 24 h-ECG-monitoring revealed no serious arrhythmias or instances of heart block. Hypotension was only seen initially in few patients. Systolic time interval measurements showed changes suggesting impaired myocardial performance (elevated PEP/LVET ratio) at intermediate (60–500 µg/l) but not high (〉500 µg/l) total serum antidepressant levels. Measurement of serum concentration in antidepressant intoxication is important for identification of patients with high serum levels and the corresponding risk of developing toxic reactions, and to exclude patients with a low concentration who do not require intensive observation.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 26 (1984), S. 749-752 
    ISSN: 1432-1041
    Keywords: dextropropoxyphene ; pharmacokinetics ; half-life ; 3-compartment model ; steady state prediction ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Data from a previously published single dose study of d-propoxyphene 65 mg given i.v. to 8 healthy subjects have been subjected to non linear regression analysis by a curve-fitting program to test the applicability of a 2- and a 3-compartment open model. Analysis of residuals (difference between observed and computed concentrations) revealed similar systematic deviations in all 8 subjects when the 2-compartment model was used (5–10 h negative residuals, after 13 h positive residuals). In contrast, curve-fit by a 3-compartment model (with two parallel peripheral compartments) was good with no systematic deviations. The data show that a terminal monoexponential decline in d-propoxyphene concentrations cannot be expected until 15–30 h after single dose administration, and that the determination of the corresponding half-life is rather inaccurate. Accordingly, precise steady state level predictions may be difficult to obtain from conventional single dose studies with d-propoxyphene.
    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: 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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