The Mood-Lowering Effect of Tryptophan Depletion: Possible Explanation for Discrepant Findings

Tryptophan depletion (TD) is an experimental procedure for studying brain serotonin function. The mood-lowering effect of TD has been demonstrated in formerly depressed patients treated with selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase inhibitors¹ and in medication-free women with a history of recurrent depressive episodes.² Typically, a little more than half of the patients experience the effect. It is not exactly clear why some patients experience the effect while others do not. Several studies have recently found that the effect may be less consistent than previously thought. Moore et al³ observed no effect on mood in fully remitted patients medicated with SSRIs. In a study⁴ of patients who had responded to treatment with citalopram, only 5 of 12 patients relapsed, and the effect seemed to be clinically significant in only 1 patient. In a third study,⁵ only 33% of 21 patients experienced a relapse. Moore et al³ suggest that their unexpected finding may be related to sample differences. In comparison with earlier studies, their patients had been in treatment longer and were less depressed. Therefore, the effect of TD may be limited to recently recovered, medicated patients.³ However, clinically significant symptom increases have been observed in euthymic patients who had not been receiving medications for at least 6months.² Another factor that might be involved is a patient's history of suicidal ideation.⁶