Objective and subjective assessments of the effects of flupentixol and benzodiazepines on human psychomotor performance

Abstract

The aim of this double-blind crossover trial was to compare the objective and subjective effects of flupentixol and lorazepam on human performance, and to reveal possible interactions between flupentixol and diazepam. Twelve healthy students received at 1-week intervals oral single doses of flupentixol 1 mg, flupentixol 2 mg, lorazepam 2.5 mg, placebo, and diazepam 15 mg alone and with flupentixol 1 mg. After the baseline measurements, the drugs were given in capsule form, and the tests were repeated 1.5, 3 and 4.5 h later. Diazepam was given at 1.5 h, to time its peak effect to coincide with that of lorazepam. Drug effects were measured objectively (two tracking tests, digit substitution, letter cancellation, flicker fusion, Maddox wing, tapping, memory) and subjectively (visual analogue scales, questionnaire). Blood samples were taken after each test time. Flupentixol 1 mg did not differ from placebo objectively or subjectively. Flupentixol 2 mg proved nearly inert objectively and on visual analogue scales. Lorazepam impaired objectively measured test performance, the clearest effects occurring at 3 and 4.5 h. It also impaired subjectively assessed performance. Diazepam impaired objective performance less than lorazepam, its effects peaking at 1.5 h after intake. Diazepam caused subjective drowsiness, clumsiness, mental slowness etc. as much as or more than lorazepam. The combination of 1 mg flupentixol and diazepam modified performance as much as diazepam alone. After the administration of 1 mg flupentixol, plasma concentrations were undetectable and levels after 2 mg were hardly detectable. Concentrations of lorazepam exceeded those of diazepam in direct bioassay, but they were much lower when bioassayed after solvent extraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Suriclone enhances the actions of chlorpromazine on human psychomotor performance but not on memory or plasma prolactin in healthy subjects

“…As a whole, the two combinations studied impaired performance to about the same extent as had previously been found after 2 to 2.5 g lorazepam [19,25] or 15 mg diazepam + 100 mg remoxipride [27]. In the latter study, the remoxipride-induced increase in plasma prolactin was not modified by diazepam or by 0.8 g-kg-1 alcohol.…”

“…This type of delayed effect is interesting [24] and could result from slow penetration of suriclone into the brain and occupation of its receptors. Since the RIA method used for the suriclone assay also responds to suriclone metabolites, we subsequently "bioassayed" (Mattila, unpublished data) the plasma samples for suriclone and zopiclone, in diazepam equivalents, with a direct radioreceptor assay [25]. It appeared that suriclone concentrations were low or even undetectable, and the levels were similar at 2 and 4 h. Saletu et al [26] found that suriclone 0.4 mg improved sleep quality whereas 0.2 mg did not.…”

Study of effects of clobazam and lorazepam on memory and cognitive functions in healthy subjects

“…The study of psychomotor performance and cognitive function confirmed the very marked sedative effect of lorazepam which is manifested by an increased reaction time and a decrease in tapping and number of correct responses to a mental arithmetic test (Seppala et al, 1976(Seppala et al, , 1982Dundee et al, 1979;File and Bond, 1979;Aranko et al, 1985;Curran et al, 1987;Grunberger et al, 1988;Mattila et al, 1988;Saletu et al, 1988). The greater sedative effect of lorazepam has, moreover, been confirmed, comparatively with clobazam, in a quantitative EEG study (Saletu et al, 1985).…”

The use of microcomputer‐based psychomotor tests for the evaluation of benzodiazepine effects on human performance: a review with emphasis on temazepam.

“…The ability to share attention between two tasks is a requirement in many routine tasks, especially automobile driving, and so it is important to evaluate the effects of psychoactive drugs on this ability. The psychomotor impairing effects of benzodiazepines have also been noted on simple arithmetic tests, digit recall and matching-to-sample performance (Forrest & Galletly, 1988;Roache & Griffiths, 1987;Roache et al, 1990 (Forrest & Galletly, 1988;Gorenstein et al, 1990;Mattila et al, 1988a) but not by midazolam and lormetazepam on the morning following evening administration (Rettig et al, 1990 Where the exact formulation used in a study was described that information is included. Hindmarch (1975) (12) Nicholson (1979) An adaptive tracking task was used in this study to evaluate the effects of overnight administration of 10, 20 and 30 mg temazepam and morning administration of 10 and 20 mg temazepam.…”

“…These results indicate that the impairment measured in those studies was not simply a function of the subject's inability to perform the test because of loss of muscle control or some pure motor effect. Eventually doses were reached at which tapping rate was also impaired (Eves & Lader, 1989;Leigh et al, 1991;Mattila, 1988;Mattila et al, 1986Mattila et al, , 1988aPatat et al, 1988;Preston et al, 1988).…”