Tryptophan depletion and serotonin loss in selective serotonin reuptake inhibitor–treated depression: An [18F] MPPF positron emission tomography study

Background Recurrence of depressive symptoms after tryptophan depletion (TD) in selective serotonin reuptake inhibitor (SSRI)-treated depression is an important, unexplained phenomenon. With [18F] MPPF positron emission tomography (PET), serotonin (5-hydroxytryptamine, 5-HT) 1A receptor binding potential (5-HT1ABP) was measured after TD in various brain regions in citalopram-treated depression. This 5-HT1ABP measurement is sensitive to changes in extracellular 5-HT in animal models. Methods Eight remitted patients with major depressive disorder received [18F] MPPF PET scans twice: once after TD and once after sham depletion. Behavioral measures were evaluated with the Hamilton Depression Rating Scale and visual analog scales. Results No effect on regional 5-HT1ABP was observed after TD, despite an 86% decrease in total plasma tryptophan and transient depressive relapse in six of eight patients. Conclusions Large-magnitude changes in extracellular 5-HT are not crucial for the mood effects observed in SSRI-treated subjects after TD. Therefore, greater consideration must be given to other mechanisms that involve vulnerability to small perturbations in extracellular 5-HT, such as impairment of signal transduction.