Decreased neurotransmission of serotonin (5-HT) was shown to be related to the development of depressive symptoms, whereas recent preliminary evidence suggests that acute mania may be related to a hyperserotonergic state. The reduction of central nervous 5-HT synthesis achieved by a new modification of the dietary rapid tryptophan depletion technique, with the relevant amino acids dosed according to body weight, is hypothesized by the authors to be a further option of treatment during acute mania, in particular in view of a decrease in adverse reactions, a reduced amount of amino acids needed for sufficient depletion, but also improved tolerability. However, ethical issues may limit such studies investigating this relationship in acutely manic patients, in particular in view of informed consent.