Serotonin function in panic disorder: a double blind placebo controlled study with fluvoxamine and ritanserin

Abstract

In order to evaluate serotonin (5-HT) function in panic disorder, a double blind placebo controlled study was conducted with ritanserin, a specific 5-HT2 receptor antagonist, and fluvoxamine, a selective 5-HT reuptake inhibitor, in 60 patients with panic disorder. Patients were treated for 8 weeks with 150 mg fluvoxamine, 20 mg ritanserin or placebo; these dose levels were reached after 1 week. In addition, as an index of 5-HT function in panic disorder, plasma concentration of beta-endorphin, cortisol and 5-hydroxyindolacetic-acid (5-HIAA) were measured. Furthermore, 5-HT uptake in blood platelets was assessed. Noradrenergic function was assessed by measuring plasma MHPG concentration. In addition, plasma melatonin concentration was measured. Treatment with fluvoxamine resulted in a profound reduction in the number of panic attacks, followed by a decrease in avoidance behavior. Treatment with ritanserin appeared to be ineffective. During treatment no significant changes were observed in plasma concentrations of beta-endorphin, cortisol, 5-HIAA and MHPG. With respect to 5-HT kinetics in blood platelets, a substantial increase in Km was observed after treatment with fluvoxamine, whereas Vmax decreased. After treatment with fluvoxamine, plasma concentration of melatonin was significantly increased, which suggests that melatonin synthesis is in part under serotonergic control. The findings of the present study do not support the hypothesis that 5-HT2 receptors are supersensitive in patients suffering from panic disorder, but allow no conclusions about the involvement of other 5-HT receptor subtypes.

Mouse defensive behaviors: pharmacological and behavioral assays for anxiety and panic

“…For example, the panic-provoking drug mCPP displayed marked antiaversive action in this test [57]. Similar effects were obtained following acute injection of the SSRIs¯uox-etine [60] and¯uvoxamine [62] which were both found to potentiate panic reactions in PD patients at the initiation of treatment [34,88]. Moreover, compounds that failed to alleviate panic symptoms in human (i.e.…”

Serotonin Function in Panic Disorder: Important, But Why?

“…Apart from 5-HT-ergic pathways, the panicogenic effect of ipsapirone may be mediated by a noradrenergic activation via the locus coeruleus (Sanghera et al, 1990). Patients with PD did not respond to treatment with 5-HT2A receptor antagonists, such as ritanserin, which actually exacerbated some symptoms, although these drugs may be beneficial in the treatment of GAD (Bressa et al, 1987;den Boer and Westenberg, 1990b). Altogether, these clinical data are in favor of the 5-HT-deficit hypothesis in PD.…”

“…Altogether, these clinical data are in favor of the 5-HT-deficit hypothesis in PD. Moreover, the fact that 5-HT antagonists have no clinically relevant antipanic effects argues against the 5-HT overactivity theory of PD (den Boer and Westenberg, 1990b;Marek et al, 1992).…”

Acute and Chronic Role of 5-HT3 Neuronal System on Behavioral and Neuroendocrine Changes Induced by Intravenous Cholecystokinin Tetrapeptide Administration in Humans

“…In contrast, comparative efficacy studies on buspirone, a 5-HT 1A partial agonist, fail to show statistical differences between buspirone and placebo (Pohl et al 1989). Likewise, antagonists of the 5-HT 2 receptor, ritanserine and trazodone, are ineffective (Charney et al 1986;den Boer and Westenberg 1990).…”