We review here the ra
pid try
pto
phan de
pletion (RTD) methodology and its controversial association with de
pressive rela
pse. RTD has been used over the
past decade to de
plete serotonin (5-hydroxy-try
ptamine, or 5-HT) in humans and to
probe the role of the central serotonin system in a variety of
psychiatric conditions. Its current
po
pularity was stimulated by re
ports that RTD reversed the antide
pressant effects of selective serotonin reu
ptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) in remitted
patients with a history of de
pression but not in
patients treated with antide
pressants which
promote catecholaminergic rather than serotonergic neurotransmission (such as tricyclic antide
pressants or bu
pro
prion). However, RTD has inconsistent effects in terms of full clinical rela
pse in de
pressed
patients. Pooling the data from all
published re
ports,
patients who are either unmedicated and/or fully remitted are much less likely to ex
perience rela
pse (7 of 61, or
![](/images/gly<font)
phs/BQ1.GIF>9 % ) than
patients who are recently medicated and
partially remitted (63 of 133, or
![](/images/gly<font)
phs/BQ1.GIF>47 % ; although, the numbers here may reflect
patient overla
p between re
ports). Recently remitted
patients who have been treated with non-
pharmacological thera
pies such as total slee
p de
privation, electroconvulsive thera
py, or bright light thera
py also do not commonly show full clinical rela
pse with RTD. We briefly review RTD effects in other
psychiatric disorders, many of which are treated with SSRIs. There is accumulating evidence to suggest that RTD affects central serotonergic neurotransmission. Nevertheless, many questions remain about the ability of RTD to reverse the beneficial effects of SSRIs or MAOIs, or to induce sym
ptoms in unmedicated sym
ptomatic or asym
ptomatic
patients.