Are Electroencephalographic and Psychomotor Measures Sensitive in Detecting Residual Sequelae of Benzodiazepine Hypnotics?
Purpose: The recent development of short-acting benzodiazepines without active metabolites calls for a differentiation between the hangover effects of long-acting (LBD) and short-acting (SBD) benzodiazepines, when used as nighttime sedatives. The question now arises as to which electrophysiological and psychometric tests can record these effects with the highest degree of sensitivity.
Subjects and methods: 35 healthy volunteers participated in 3 randomized double-blind placebo-controlled studies. In the first 2 studies the short-acting benzodiazepine (LORMetaze-pam 2 mg), the medium-acting BD (FLUNitrazepam 2 mg) and the long-acting BDs (FLURaze-pam 30 mg and DIAZepam 10 mg) were administered in single oral doses at bedtime. Hangover was measured in the morning hours prior to administration, and 12, 36, and either 60 h (first study) or 156 h (second study) p.a. The measurements included the pharmaco-EEG, particularly the relative power in the beta band; visual analogue scales for assessing the subjective quality of sleep, EWL-adjective check list; pegboard test and radioreceptor assay. In the third study, a single oral dose of LORM 2 mg was given and the acute sedative effects were measured by the Adaptive Pursuit Tracking Test, Pauli memory test, pegboard and Pursuit Rotor.
Results: The sleep-inducing properties of all BDs could be detected quite clearly on the first night p.a. Distinct hangover effects of LBD were apparent in the pegboard test and residual effects in different beta frequency bands after the first and, to a lesser degree, second nights. Such effects were barely detectable after the SBD. The time course of the RRA plasma levels of LORM and FLUN corresponded well to that of behaviour. The correspondence for DIAZ was less clear.
The pharmaco-EEG proved to be the most sensitive measure of benzodiazepine effects, followed by continuous performance measures, such as the pursuit tracking test and driving simulator. Relatively low discriminability was observed with the discontinuous psychomotor tests, such as pegboard. These results have been interpreted within a concept of “activation theory” and it has been concluded that benzodiazepines more likely affect higher central nervous activities, such as the level of vigilance and attention, than simple activities, such as visuomotor performance.
Key WordsAdaptive Pursuit Tracking Test Driving simulator EWL-adjective check list Hangover effects Flunitrazepam Lormetazepam Pauli memory test Pegboard test Pharmaco-EEG Pursuit Rotor Pursuit tracking test Radioreceptor assay Visual analogue scales
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- Dorow RG, Hammer K, Ott H, Sauerbrey N (1982 b) Correlation of benzodiazepine plasma levels with hangover effects as evaluated by radioreceptor assay, EEG and psychomotor performance. Paper presented at the Sixth European Congress of Sleep Research, ZurichGoogle Scholar
- Duffy E (1972) Activation. In: Greenfield NS, Sternbach RA (eds) Handbook of psycho-physiology. Holt, Rinehart and Winston, New York Chicago San Francisco AtlantaGoogle Scholar
- Herrmann WM (ed) (1982) Electroencephalography in drug research. G Fischer, Stuttgart New YorkGoogle Scholar
- Janke W, Debus G (1977) Eigenschaftswörterliste — Ein Verfahren zur Erfassung verschiedener Aspekte der Befindlichkeit (Version EWL-K). In: CIPS Collegium Internationale Psychiatrae Scalarum (eds) Internationale Skalen für Psychiatrie. Beltz Verlag, WeinheimGoogle Scholar
- Kugler J, Doenicke A, Suttmann H, Laub M, Speth M, Woeller L (1980) Ein Vergleich der hypnotischen Effekte von Flunitrazepam und Lormetazepam. In: Doenicke A, Ott H (eds) Lormetazepam — Noctamid®. Springer, Berlin Heidelberg New York, pp 7.1–7.13Google Scholar
- Kulikowski JJ, McGlone FF, Kranda K, Ott H (1984) Are the amplitudes of visual evoked potentials sensitive indices of hangover effects after repeated doses of benzodiazepines? In: Hindmarch I, Ott H, Roth T (eds) Sleep, benzodiazepines and performance: Experimental methodologies and research prospects. See this volume, pp 154–164Google Scholar
- Ott H, Oswald I, Fichte K, Sastre M (1981) Visuelle Analogskalen zur Erfassung von Schlafqualität. VIS-A und VIS-M. In: CIPS Collegium Internationale Psychiatriae Scalarum (eds) Internationale Skalen für Psychiatrie. Beltz Verlag, WeinheimGoogle Scholar
- Ott H, McDonald RJ, Fichte K, Herrmann WM (1982) Interpretation of correlations between EEG power spectra and psychological performance variables within the concepts of subvigilance, attention, and psychomotoric impulsion. In: Herrmann WM (ed) EEG in drug research. G Fischer, Stuttgart New YorkGoogle Scholar
- Pauli R, Arnold W (1951) Der Pauli-Test. Eine sachgemäße Durchführung und Auswertung. MünchenGoogle Scholar
- Randall LO (1961) Pharmacology of chlordiazepoxide (Librium). Dis Nerv System XXII, Sec 2, Suppl, 7–15Google Scholar
- Willumeit HP, Ott H, Neubert W (1984) Simulated car driving as a useful technique for the determination of residual effects and alcohol interaction after short- and long-acting benzodiazepines. In: Hindmarch I, Ott H, Roth T (eds) Sleep, benzodiazepines and performance: Experimental methodologies and research prospects. See this volume, pp 182–192Google Scholar