Antidepressant drugs produce striking effects on sleep architecture wh
ich are best understood in terms of their interactions with. the monoa
mine pathways controlling sleep and wakefulness. Sleep changes almost
invariably include a reduction in the amount of rapid eye movement (RE
M) sleep in both healthy volunteers and depressed patients. Four studi
es were conducted in normal male volunteers to determine the effects o
f nefazodone, a new antidepressant with a dual mode of action - 5-HT2
receptor antagonism and moderate inhibition of serotonin re-uptake - o
n sleep architecture. Use of normal volunteers allowed interpretation
of the effects in the absence of any interaction between the antidepre
ssant drug and the abnormal sleep patterns characteristic of depressio
n. From these studies it appears that, unlike most antidepressant trea
tments, nefazodone maintains or increases the amount of REM sleep. In
addition, nefazodone improves sleep continuity without causing sedatio
n. It is of interest that, in combination with lithium, nefazodone inc
reases slow-wave sleep. The sleep profile of nefazodone appears to be
distinct from that of TCAs and SSRIs.