Comparison of the Effects of Tianeptine, Amitriptyline and Placebo on Daytime Sleepiness, Performance and Nocturnal Sleep in Healthy Young Adults

Tianeptine is a novel tricyclic antidepressant known to increase the pre-synaptic uptake of serotonin, while paradoxically having antidepressant and anxiolytic effects. This study examined the effect of tianeptine on daytime sleepiness, performance and nocturnal sleep in healthy, young, adult volunteers. Twelve young healthy male volunteers visited the study center weekly for 3weeks. On each visit, the subjects received one of three treatments: tianeptine (12.5 mg t.i.d.), amitriptyline (25 mg b.i.d. and placebo at midday) or placebo (t.i.d.), The study used a double-blind, random Latin square sequence, cross-over design. All medications and the placebo were prepared in identical gelatin capsules. All subjects completed a battery of performance tests including digit cancellation, arithmetic addition, digit span, digit symbol substitution and word list memory, one hour after the second dose. All testing was conducted in the afternoon. Subjective assessments of daytime sleepiness and unwanted effects of the drugs were made using a modified Epworth Sleepiness Scale and a modified Uscandinavian Kociety of Usypharmacology side-effects rating scale (UKU Scale) at 0.5 hr before the last dose, which was administered in the late afternoon. Sleep on the night of the day of treatment was evaluated by a post-sleep questionnaire upon rising the following morning. Tianeptine showed no evidence of impairment on any performance test as compared to the placebo, and did not affect the daytime alertness/ drowsiness level or nocturnal sleep. Amitriptyline, however, produced considerable impairment of performance, associated with severe daytime sleepiness. Also, amitriptyline significantly affected nocturnal sleep. Amitriptyline was associated with quicker induction, more restful maintenance and longer period of sleep relative to the placebo. Adverse effects were significantly more frequent and severe after amitriptyline than after tianeptine or placebo treatments. These results confirmed the previous observations that tianeptine is not accompanied by significant daytime sedation, nocturnal sleep change or performance impairment. They also suggest that tianeptine may be a useful treatment option for the depressive patient, in particular for the ambulatory out-patient or the elderly.