BackgroundTricyclic (TCA) and monoamine oxidase inhibitor (MAOI) antidepressants are effective in the treatment of panic disorder. Two selective serotonin reuptake inhibitors (SSRIs) have also been licensed in the UK for this indication and studies with three other SSRIs have recently been completed. These provide further evidence for the role of serotonin in panic.MethodReview of clinical, animal and laboratory studies.ResultsSSRIs have been shown to be effective in the treatment of panic disorder. The reported rates of improvement of 60–70% of patients taking SSRIs are similar to those seen withTCAs and greater than placebo. Other serotonergic agents do not appear to be effective. Animal work and human studies including measures of 5-HT in plasma, cerebrospinal fluid and platelets, challenge paradigms and tryptophan depletion show that the relationship between 5-HT and anxiety is complex.ConclusionClinical trials have shown that of all the serotonergic agents only the SSRIs are effective in panic disorder. They are as beneficial as the TCAs and seem to be better tolerated which may be particularly significant in view of the chronic nature of the condition. Serotonin plays a role in panic disorder and serotonergic dysfunction, however the results and evidence do not fit one theory alone. It is also likely that different brain regions and 5-HTreceptors are involved in specific ways.