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

Abstract

1 Litoxetine is a selective serotonin reuptake inhibitor with antidepressant activity in animal models and in depressed patients. 2 This double-blind, cross-over, placebo-controlled study was carried out in 12 healthy young male volunteers. The aim was to assess the EEG profile of litoxetine in parallel with its pharmacokinetics after a single dose or multiple administrations for 4 days (6 doses) of two dosages (10 mg and 25 mg). Spectral analysis of four EEG leads (F4-T4, F3-T3, T4-02 and T3-01) was done up to 12 h post-dose. 3 In single or multiple doses, litoxetine induced EEG changes characterised by a doserelated increase in fast beta energies, mainly beta 2, without any changes in slow waves (delta and theta). A slight reduction in alpha activity occurred only after repeated doses. 4 EEG changes occurred after a single oral administration and lasted at least 12 h with litoxetine blood concentrations ranging from 4 to 10 ng ml-'. With repeated administrations, the pharmacodynamic steady-state was achieved as the increase in beta 2 energies was the same before and 12 h post-dose. These effects occurred with litoxetine blood concentrations ranging from 3 to 7 ng ml-1 with the 10 mg dosage and from 8 to 18 ng ml-1 with the 25 mg dosage. The EEG profile did not change after 4 days of repeated administration, indicating that tolerance did not develop. 5 Cmax and AUC showed proportionality between the administered dosages of 10 and 25 mg. Mean tmax ranged from 3 to 4 h and mean elimination half-life from 7 to 9 h independently of the dosage. Pharmacokinetic steady-state was achieved on day 4. Litoxetine did not accumulate with a twice daily regimen. 6 In conclusion, the EEG profile of litoxetine resembles those previously described with non-sedative antidepressants. Such EEG changes generally occur at therapeutic dosages.

The psychomotor and cognitive effects of litoxetine in young and middle aged volunteers.

“…Although statistical comparisons of the pharmacokinetic parameters between groups were not relevant due to the small number of young subjects, the values appear to be similar (see Table 4). These values correspond with data reported elsewhere [20]. There was also no age related effect in the tolerability profile of litoxetine.…”

“…From these results, it can be seen that the psychological effects of litoxetine were relatively small and that in all of the tests drug effects were weak. This may be due to the relatively small group size, however other evidence suggests that litoxetine possesses a similar profile to nonsedating antidepressants [20].…”

One‐week escitalopram intake alters the excitation–inhibition balance in the healthy female brain

“…Power of alpha oscillations could provide insight into EIB alterations due to its functional role in cortical inhibition (Klimesch, Sauseng, & Hanslmayr, 2007). For example, decreases in relative alpha power, thought to reflect enhanced cortical excitability (Klimesch et al, 2007), have been observed in healthy male participants (n = 12) following 1 week of litoxetine administration, an SSRI under development (Patat et al, 1994), as well as in depressed patients following 1 week of escitalopram administration (Leuchter et al, 2017). Another exploratory study in healthy male participants (Knott, Howson, Perugini, Ravindran, & Young, 1999; n = 14/group) found that decreased serotonin synthesis via tryptophan depletion was associated with a trend toward increased relative alpha power.…”

One-week escitalopram intake shifts excitation-inhibition balance in the healthy female brain

“…Power of alpha oscillations could provide insight into EIB alterations due to its functional role in cortical inhibition (19). For example, decreases in relative alpha power, thought to reflect enhanced cortical excitability (19,20), have been observed in healthy male participants (n = 12) following one week of litoxetine administration, an SSRI under development (21), as well as in depressed patients following one week of escitalopram administration (22). Another exploratory study in healthy male participants (23) (n = 14/group) found that decreased serotonin synthesis via tryptophan depletion was associated with a trend towards increased relative alpha power.…”