Serotonin and the prediction of response time to fluoxetine in patients with mild depression

Serotonin (5-HT) dysregulation has been associated with major depressive disorder (MDD); a blunted prolactin (PRL) response to D,L-fenfluramine (FEN) has been associated with MDD. Pharmacologic manipulation of the serotonin system with a selective serotonin reuptake inhibitor (SSRI) is effective in the treatment of depression. However, the relationship between pre-treatment 5-HT activity and response to SSRIs is not well understood. This study investigated the relationship between 5-HT dysregulation and response to fluoxetine (FLU). Twenty patients with MDD entered a double-blind placebo-controlled trial of fluoxetine preceded by D,L-fenfluramine stimulation. Patients were assigned randomly to either FLU, 20 mg QD, or placebo (PLA) for an 11-week trial. No relationship was found between the PRL response to FEN and response to FLU. Among the seven responding to FLU, there was a significant negative correlation between PRL response and the time until sustained response to FLU (r = -0.93, P < 0.001, n = 7). Although preliminary, this study suggests that low baseline serotonin activity may be associated with a slower response to FLU in depression.