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

Abstract

This was a double-blind, placebo-controlled crossover study in 15 healthy female volunteers. It consisted of five sessions, separated by 1 week wash-out between sessions. The purpose of the trial was to study the potential amnesic and sedative activity of clobazam and lorazepam, and the potential antagonism between these effects under the joint influence of a high noise level and intense intermittent light stimulation (ILS), aimed at increasing the level of alertness. The study drugs were administered as a single daily oral dose. The amnesic and sedative effects were evaluated by objective measurements (digit span, Buschke selective reminding test, critical flicker fusion, reaction time, tapping, mental arithmetic test) and subjective measurements (visual analogue scale and adverse effect questionnaire) before each administration, then 1 h, 2 h, 2 5 h, 3 h, 4 h and 7 h post-dosing. An analysis of variance according to a balanced Latin square design was performed. Clobazam, at a dosage of 10 mg, was devoided of sedative and amnesic effects; at a dosage of 30 mg it induced only moderate memory disturbances. In contrast, lorazepam, administered at doses of 1 and 3 mg, produced marked and dose-dependent disturbances of memory, alertness and cognitive functions. The use of visual and sound stimuli, designed to increase the level of alertness, did not counteract the sedative effects induced by lorazepam.

Lack of interaction between a new antihistamine, mizolastine, and lorazepam on psychomotor performance and memory in healthy volunteers.

“…The deficit in psychomotor skills peaked 2 to 4 h after dosing and was persistent, being present at the last determination, 8 h post-dosing, for some of the tests used. Similar impairment had already been demonstrated up to 12 h post-dose [12,13,[15][16][17]28]. Lorazepam also impaired short-term memory, as demonstrated by the decrease in the number of words correctly remembered after the first immediate free recall or throughout the 10 learning trials and by the increase in the reaction time recorded in the Steinberg memory scanning test.…”

“…Mizolastine, a new benzimidazole derivative, is a more in healthy volunteers has antihistaminic activity selective, peripherally-acting, histamine Hi-receptor (histamine challenge), being most effective at [10][11][12][13][14][15][16][17][18][19][20] antagonist. It is more potent in several animal models mg [3][4][5].…”

“…Therefore, this study was designed to detect a possible pharmacodynamic interaction between the therapeutic dose of mizolastine, 10 mg, at steady state, and a single dose of lorazepam 2 mg, the sedative and amnesic properties of which are well documented [12][13][14][15][16][17].…”

Pharmacodynamic interactions of a solid formulation of sodium oxybate and ethanol in healthy volunteers

“…Benzodiazepine use has been associated with a wide range of cognitive side effects [46,77,78]. Few studies have compared SO and benzodiazepines on cognitive tasks [76][77][78][79], and due to differences in study populations and in cognitive tasks, the data of this study cannot be compared with Carter's data [76,79]. Nevertheless, the present results showed that sedation induced by SMO.IR remained mainly subjective and was less frequently observed in performance tasks.…”

Cognitive functions in myoclonic epilepsy with ragged red fibres – a case report

“…Levetiracetam (Koo et al, 2013) shows also very favourable cognitive profile. In contrast clobazam (Patat et al, 1991) is known to cause memory impairment in healthy volunteers (at the dose of 30 mg). In patients with epilepsy the data are conflicting because CLB use in drug resistant epilepsies entailed cognitive improvement due to significant seizures reduction; in some studies it is highlighted that the cognitive side-effect profile of CLB is similar to other benzodiazepines but with substantially decreased sedation and increased psychomotor performance (Wheless and Phelps, 2013).…”