Serotonin, panic disorder and agoraphobia: short-term and long-term efficacy of citalopram in panic disorders

Abstract

A serotonin-anxiety connection has been widely recognized. In panic disorder (PD), however, most researchers have emphasized noradrenergic mechanisms. Serotonin related findings in PD, e.g. the documented antipanic potential of selective serotonin reuptake inhibitors (SSRIs), are reviewed, lending support for a serotonergic deficit contributing to the pathophysiology of PD. Since citalopram is the most selective SSRI described, it was chosen as a tool for testing whether the serotonin reuptake inhibition per se is responsible for this antipanic effect. Twenty patients with PD with or without agoraphobia (DSM-III-R criteria) were treated openly with citalopram and assessed with CAS, MADRS, SCL-90 the Agoraphobia Scale, other self-ratings, and a panic diary. Thirteen of the 17 patients completing 8 weeks of treatment were judged as responders. The response seemed similar to or better than that seen with other antidepressants. The response covered broad aspects of morbidity, e.g. anticipatory anxiety, agoraphobia and somatization. In the first week, a transient increase of panic-related symptoms was observed. Sixteen of the patients were enrolled in a 15 months' study of long-term maintenance treatment; 11 patients completed this phase. The gains were maintained during this follow-up, and further improvement was observed. Side-effects were similar to those of other SSRIs and mostly mild. For instance, weight-gain was not associated with citalopram treatment. The results support the hypothesis that serotonin reuptake inhibition is essential for the antipanic effect of antidepressants as well as for the initial paradoxical increase of anxiety often seen with these drugs. Thus, an initial deterioration, possibly due to transient decrease of serotonin transmission, turns to improvement when serotonergic potentiation has occurred.