PILOT-STUDY OF FLESINOXAN, A 5-HT1A AGONIST, IN MAJOR DEPRESSION - EFFECTS ON SLEEP REM LATENCY AND BODY-TEMPERATURE

Flesinoxan is a highly potent and selective 5-HT1A full agonist, activ e in several models of depression. In this pilot open study, flesinoxa n (4 mg/d) was administered orally for 4 weeks in 16 major depressive, mostly treatment-resistant inpatients exhibiting a score of at least 19 on the Hamilton depression sale. Weekly ratings included Hamilton d epression scale, Montgomery and Asberg depression scale (MADRS), and C linical Global Impressions (CGI). Results showed considerable improvem ent in depressive symptomatology, with mean MADRS scores (SD) dropping from 35.7 (10-0) to 13.0 (11.9) and CGI-illness severity from 5-69 (1 .14) to 2-73 (1.62) after 4 weeks of treatment. Moreover, 13 patients were classified as much or very much improved on the CGI-global improv ement. The tolerance of flesinoxan was excellent, with only four patie nts exhibiting side-effects. In contrast to acute studies with 5HT1A a gonists, flesinoxan induced no significant decrease in daily oral temp erature over the 4-week period. In eight melancholic patients, the mea n REM latency (SD) of respectively 35.6 (15.9) and 40.2 (17.9) min dur ing two baseline nights significantly increased to 51.9 (20.9) min dur ing a double-blind challenge night with flesinoxan 1 mg as compared to 42-0 (16.1) min with placebo, and to respectively 55.6 (29.9) and 55. 6 (30.2) min during the last two treatment nights. All these findings encourage further developments of flesinoxan as a promising antidepres sant.