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 the role of 5-HT1A receptors in the mechanism of action of antipanic agents. This paper reports on the results of these two studies with flesinoxan. In study I, using a single-blind crossover design, five patients 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 were 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/day flesinoxan. In pilot study I patients' condition worsened during the 4-week flesinoxan treatment period. Anxiety was frequently reported as an adverse event. Symptoms returned to the pre-treatment level during 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 panic disorder, but the present data are not encouraging in this respect. The worsening of symptoms seen with the highest dose of flesinoxan is intriguing and might give a clue to the understanding of the mechanism underlying similar effects seen with antidepressants in panic disorder patients.