Reactivity of serotonin in whole blood: Relationship with drug response inobsessive-compulsive disorder

Background: Obsessive-compulsive disorder responds almost only to potent se rotonin reuptake inhibitors. previous studies have suggested a relation bet ween serotonergic function and clinical outcome in serotonin reuptake inhib itor treatment of obsessive - compulsive disorder. Methods: In a randomized, double-blind trial, comparing clomipramine, parox etine, and a placebo in obsessive-compulsive disorder, serotonin levels in whole blood (WB-5-HT) were measured at baseline, after 1 week, and after 4 weeks of treatment and related to clinical outcome in 36 patients. Results: In patients treated with serotonin reuptake inhibitors there was a pronounced decrease of WB-5-HT, variable after 1 week and uniformly maxima l after 4 weeks. The decrease of WB-5-HT after 1 week of serotonin reuptake inhibitor treatment correlated negatively with clinical outcome after 12 w eeks (r = -.61, p = .0006); hence, patients with slower WB-5-HT reactivity eventually responded better to treatment. Baseline WB-5-HT, but not WB-5-Ht reactivity, was related to season. Depression, autistic traits, and previo us serotonin reuptake inhibitor treatment predicted nonresponse. Conclusions: A fast decrease of WB-5-HT was associated with poor clinical o utcome. This may be related to faster serotonin efflux from platelets, whic h has previously been linked to autism. Further studies are necessary to id entify the underlying mechanism and discern whether serotonin reuptake inhi bitor-induced WB-5-Ht decrease is clinically useful.