Reactivity of serotonin in whole blood: relationship with drug response in obsessive-compulsive disorder

Background: Obsessive-compulsive disorder responds almost only to potent serotonin reuptake inhibitors. Previous studies have suggested a relation between serotonergic function and clinical outcome in serotonin reuptake inhibitor treatment of obsessive–compulsive disorder. Methods: In a randomized, double-blind trial, comparing clomipramine, paroxetine, 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 maximal after 4 weeks. The decrease of WB–5-HT after 1 week of serotonin reuptake inhibitor treatment correlated negatively with clinical outcome after 12 weeks (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 previous serotonin reuptake inhibitor treatment predicted nonresponse. Conclusions: A fast decrease of WB–5-HT was associated with poor clinical outcome. This may be related to faster serotonin efflux from platelets, which has previously been linked to autism. Further studies are necessary to identify the underlying mechanism and discern whether serotonin reuptake inhibitor–induced WB–5-HT decrease is clinically useful.