Some antidepressant drugs, especially tricyclic ones - (TCA), have cardiovascular side effects. To compare the effects of antidepressant drugs, the electrocardiogram (ECG), vectorcardiogram (VCG), and body surface maps (BSM) were recorded in psychiatric patients without cardiovascular diseases treated by a) TCA amitriptyline or dosulepin (daily dose 50-200 mg, 22 patients), b) lithium (serum level 0.66±0.08 meq/1, 21 patients), c) selective serotonine reuptake inhibitor citalopram (daily doses 20-60 mg, 30 patients), and in 23 control patients. In the TCA-treated patients, the heart rate was increased, QT and RR intervals shortened (p<0.01, antimuscarinic effect). This was not observed in lithium- and citalopram-treated patients. All antidepressants decreased the absolute maximum values of depolarization isointegral maps, lithium and TCA reduced the initial and citalopram the later phase of depolarization. Citalopram slightly diminished the amplitude of the R wave. The results confirm the antimuscarinic effects of TCA in therapeutic doses and specify the intraventricular effects of antidepressants.
In children and adolescents (250 healthy subjects) serum dopamine-beta-hydroxylase (DBH) activity (23.95.2 to 57.117.5 μmol/min/ml) increases with the age between 3-10 years, later it decreases approximately by the age of 10-14 years. At the age of 21 to 60 years DBH level is stable. Our study described decreasing DBH activity in adolescents at the age of 10-14 years in the studied sample of healthy persons. Experimental animals (200 Wistar rats, 5-120 days old) show the same trend of enzymatic activity, similarly as in humans. DBH activity in rats is between 0.850.1 to 2.80.05 μmol/min/ml. This activity is highest in 5-day-old rats; it decreases till the age of 14 days and increases mainly in 14- to 35-day-old animals. Decrease of DBH activity in rats between 35 to 40 days is significant and corresponds to the reduction of DBH activity in adolescent humans (10-14 years). Adult rats (aged 90-120 days) show a stable DBH activity. DBH activity intermediately decreases in 10- to 14-year-old children. This decrease corresponds to the intermediate developmental changes of electrophysiological parameters (decreasing EEG activity in healthy adolescents occurs in 10-14 years old children). Puberty is coupled with intermediate decreasing of DBH activity in man and also in experimental animals in the period of prominent psychological and physiological changes.
The aim of the study was to detect the changes of QT dispersion (QTd) due to cardiotoxicity of tricyclic antidepressant dosulepin. Electrocardiographic and vectorcardiographic recordings were obtained using Cardiag 112.2 diagnostic system from 28 psychiatric outpatients treated with prophylactic doses of dosulepin and compared to those obtained from 37 healthy volunteers. From these recordings following parameters were evaluated: QTd, spatial QRS-STT angle and amplitude of T-wave. The acquired data were correlated with the dosulepin plasma levels using Spearman´s rank order correlation test. The average QTd (±S.D.) in the dosulepin group was significantly higher (70±21 ms) than that in the control group (34±12 ms) (P<0.001). Moreover, the correlation between QTd and the dosulepin plasma levels was highly significant (r = 0.7871, P<0.001). Similar results were obtained when QTc dispersion was used. On the contrary, the QRS-STT space angle did not correlate with the dosulepin plasma levels. Furthermore, the T-wave amplitude was not significantly correlated to the QT-interval. Thus we can conclude that the QT dispersion could be used as a simple marker of the dosulepin effect on the myocardium.
We tested the hypothesis considering the role of hypothalamic-pituitary-thyroid axis (HPT), L-triiodothyronine (L-T3) uptake into erythrocytes, and the role of membrane lipids in the development and treatment of affective disorders. Changes in kinetic parameters (Vmax, maximal velocity and KM, apparent Michaelis constant) of L-T3 uptake into red blood cells (RBCs) and changes in membrane fluidity in a group of 24 patients with major depression were measured before treatment and after 1 month of treatment with citalopram. Parameters Vmax and KM, as well as membrane microviscosity, were significantly increased in depressed patients both before and after treatment in comparison with healthy subjects. We concluded that the function of the membrane transporter for L-T3 in RBC is changed in depression. This change is probably connected with alteration of membrane fluidity and/or transporter–lipid interactions. We did not find any normalization of the measured parameters after 1 month of treatment. The results show the importance of composition and physical properties of the lipid bilayer for transmembrane transport of L-T3 and support the hypothesis that the HPT axis is in depression.