EFFECTS OF THE 5-HT1A RECEPTOR AGONIST FLESINOXAN IN PANIC DISORDER

The effects of flesinoxan, a potent and selective 5-HT1A agonist, were studied in two pilot studies in panic disorder patients to explore th e role of 5-HT1A receptors in the mechanism of action of antipanic age nts. This paper reports on the results of these two studies with flesi noxan. In study I, using a single-blind crossover design, five patient s were treated for 1 week with placebo, 4 weeks with flesinoxan (up to 2.4 mg per day), and 2 weeks with placebo. In study II, 15 patients w ere enrolled in a double-blind, three-armed study with placebo and two dosages of flesinoxan. After a single-blind placebo run-in phase of 1 week, patients were treated for 8 weeks with placebo, 0.6 or 1.2 mg/d ay flesinoxan. In pilot study I patients' condition worsened during th e 4-week flesinoxan treatment period. Anxiety was frequently reported as an adverse event. Symptoms returned to the pre-treatment level duri ng the 2-week placebo washout period. In pilot study II, no treatment effects in either group were observed. Anxiety as an adverse event was less prominent than in the first pilot study. A lowering of mood was seen in some patients. The sample sizes of these two pilot studies are too small to draw firm conclusions on the efficacy of flesinoxan in p anic disorder, but the present data are not encouraging in this respec t. The worsening of symptoms seen with the highest dose of flesinoxan is intriguing and might give a clue to the understanding of the mechan ism underlying similar effects seen with antidepressants in panic diso rder patients.