Double‐blind comparisons of a selective serotonin reuptake inhibitor, zimelidine, and placebo on quantified EEG parameters and psychological variables

Abstract

A double-blind crossover comparison of three different single doses of a selective serotonin reuptake inhibitor, zimelidine, and a placebo on quantified EEG parameters and psychological variables was carried out in ten healthy male volunteers. Each subject randomly received 100 mg, 200 rng and 300 mg of zimelidine as well as placebo. C,-P,, P, +, G P , ,Prol and F r o , EEG samples were taken by means of collodium Ag/ AgCl stick on electrodes. 3 min average Fast Fourier Transformation power spectra based on 5 sec epochs were established. Additionally, performance tests and a subjective self-rating were carried out. The measurements, performed according to a strictly controlled schedule, were repeated 1,2,4 and 6 h post baseline (i.e. 8 a.m.). The data analysis was performed by means of two-way variance analysis for repeated measurements.Administration of three different single oral doses of zimelidine was found to significantly stabilize the average vigilance behaviour in terms of reduced slow wave EEG activity and of increased monorhythmic alpha activity. Simultaneously, concentration ability was improved and mild feelings of activation were reported. The results are discussed in the light of biochemical aspects and with regard to neurophysiological vigilance concepts.The pharmacoelectroencephalographic classificational approach is, up to now, based on a rather operational model of drug efficacy in normals and patients, respectively (e.g. Fink [ , 19691, Ztil [1968). The most important presumption is that psychotropic drug effects are due to neurobiochemical actions which are qualitatively identical in both healthy and mentally diseased persons. According to this working model, biochemical CNS changes during the course of psychiatric disturbances primarily reflect quantitative deviations, i.e. disturbances in the normal ratios or relationships of the brain's biochemical entities. This can best be understood in terms of an imbalance of the normal coordination or homoeostasis of the entire biochemical CNS system.From the pharmacoelectroencephalographic experience much evidence appears in support of this model. Classically, the major types of psychotropic drugs were tested (mostly in normals) to establish typical profiles of the electroencephalographic (EEG)

Sleep Laboratory Study on Single and Repeated Dose Effects of Paroxetine, Alprazolam and Their Combination in Healthy Young Volunteers

“…Deteriorated sleep could be expected in PSG as activating properties have been demonstrated in quantitative EEG studies in healthy volunteers by signifi cant decreases in ␦ and and increases in ␣ and ␤ activities [24,25] . Indeed, this is consistent with the pharmaco-EEG profi les of other SSRIs, such as sertraline [26] , zimelidine [26,27] , fl uvoxamine [28,29] and fl uoxetine [30] , all characterized as antidepressants with alerting qualities. Nevertheless, the major paroxetine-induced changes concerned REM sleep, the suppression of which has been consistently reported as a noticeable dose-related effect [22,23,31] .…”

EEG profile of litoxetine after single and repeated administration in healthy volunteers.

“…In the 50 to 300 mg dose range, it exhibited a typical desipramine profile with a marked increase in alpha activity and, even with the highest dose, an increase in beta energies [16,17]. These activating properties were confirmed by improvements in attention and concentration evidenced by psychometric tests [16].…”

Covert REM sleep effects on REM mentation: Further methodological considerations and supporting evidence

“…In line with the foregoing, reductions in REM, seen particularly with antidepressants, are generally accompanied by a reorganization of sleep; that is, marked increases in light SWS and corresponding decreases in deep SWS as well as frequent awakening (Cohen et al 1982;Kupfer et al 1989;Nicholson & Pascoe 1988;Saletu et al 1983;Schenk et al 1981;Shipley et al 1984;Staner et al 1995;Wyatt et al 1971b). For the SSRIs, this has been referred to as the "alerting" effect on sleep of these antidepressants (Kupfer et al 1989;Nicholson & Pascoe 1988;Saletu et al 1983;Schenk et al 1981;Shipley et al 1984;Staner et al 1995).…”