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Background: Serotonin (5-HT) neuronal systems have been implicated in the modulation of obsessive-compulsive disorder (OCD) symptoms. 5-HT3 receptor antagonists have been found to act as anxiolytics in selected animal models of anxiety; in particular, those involving an element of risk assessment. Since the compulsions of OCD are frequently triggered by an abnormal perception of risk, a pilot study was initiated to determine whether the 5-HT3 receptor antagonist ondansetron might have efficacy in the treatment of OCD., Method: Eight medication-free subjects with a DSM-IV diagnosis of OCD and a Yale-Brown Obsessive Compulsive Scale (YBOCS) score > or = 16 entered an 8-week open-label trial of ondansetron at a fixed dose of 1 mg 3 times daily in a study conducted between February and October 1998., Results: Six subjects completed the trial. Three subjects (37%) achieved a clinically significant response (> or = 35% reduction in YBOCS score). For these subjects, the average reduction in YBOCS-rated symptoms was 55%. In aggregate, the 8 patients exhibited a 28% reduction in YBOCS-rated symptoms over the course of the trial. The medication was well tolerated., Conclusion: These results suggest that low-dose ondansetron may have promise as a monotherapy for some patients suffering from OCD.

Serotonin (5-HT) has been implicated in the pathophysiology of depressive syndromes and in the mechanism of antidepressant drug action. Rapid dietary depletion of tryptophan (TRP) provides a paradigm for studying the role of 5-HT in depressed patients. Drug-free depressed patients do not show mood changes during TRP depletion but about one third have a clinically apparent, transient improvement in mood on return to normal TRP intake. Depressed patients in clinical remission after 6 to 8 weeks of antidepressant therapy experience a transient depressive relapse during acute TRP depletion. The significance of these findings will be discussed. Tryptophan depletion in other psychiatric syndromes will also be reviewed.