Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients.

Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) are used to treat depression. Whereas cardiovascular effects have occasionally been reported during controlled studies with SSRIs, TCA treatment poses a well-known problem in this respect. To investigate the putative correlation between antidepressant dose or serum levels and adverse effects, the authors devised a naturalistic study to evaluate the tricyclic antidepressants' and SSRIs' effect on the cardiovascular system. The authors also compared antidepressant serum levels to adverse effects. Inpatients treated with TCAs or SSRIs were included; an electrocardiogram (ECG) and a Schellong test were carried out on the day patients entered the hospital and during steady-state treatment with antidepressant drugs when blood was drawn for therapeutic drug monitoring. The patient population consisted of 114 acutely depressed patients; 81 patients were treated with TCAs and 33 with SSRIs. The TCAs comprised amitriptyline (n = 43), clomipramine (n = 11), doxepin (n = 19) and imipramine (n = 8); the SSRIs comprised fluvoxamine (n = 14) and paroxetine (n = 19). In TCA-treated patients, the authors observed the same type of abnormalities in conduction and orthostatic hypotension as had been observed earlier. The authors also observed cases of first-degree atrioventricular block, prolonged QTc interval, and orthostatic hypotension in SSRI-treated patients. Thus SSRIs also appear to affect the cardiovascular system, which might pose a problem for patients with preexisting conduction disease. The authors observed a strong correlation between the decrease in systolic pressure and antidepressant serum concentration (except for clomipramine and paroxetine), suggesting that antidepressant serum level is a better correlate than dose.

[A self-rating scale for adverse drug effects and its application in a study of antidepressants]. / Selbstbeurteilungsfragebogen für Arzneimittelnebenwirkungen und Anwendung im Rahmen einer Studie mit Antidepressiva.

Patient's complaints about adverse drug effects in the course of antidepressant drug therapy are related to a considerable extent to their subjective experience. Therefore general assessment of adverse drug effects that relies exclusively on the investigator's rating scales appears unsatisfactory. Additional assessment with self-rating scales should record the experience which arises from patient's perception. However, there are presently no satisfactory instruments available. Therefore, we developed the Bonner Erhebungsinstrument to assess subjective adverse drug effects. We administered this rating scale on 310 occasions to 130 patients. In order to evaluate the influence of indirect and direct questions, we devised an additional instrument the Erhebungsinstrument direkt. As it turned out, patients answering direct questions stated nearly twice as many side-effects than patients answering the indirect questionnaire. A comparison of our two rating scales with the observer-rating scale UKU showed, that investigators noted 79% of the symptoms that patients mentioned, but rated only 30% as probably due to a drug effect. A statistical evaluation of the data showed an interdependence between the number of adverse drug effects in the Bonner Erhebungsinstrument and fluvoxamine's daily dose; furthermore, the number of adverse drug effects of clomipramine correlated with its serum level; dose and serum concentrations of doxepin correlated significantly with the adverse side effects. Selective serotonin reuptake inhibitors are generally considered to have fewer side effects than tricyclic antidepressants; in our investigation this turned out to be true for the symptom "dry mouth" but not for other symptoms. Thus the novel Bonner Erhebungsinstrument discriminates well between different adverse drug effects; it provides important information to assess unwanted side effects and to understand and improve patients' compliance.