The spectrum of efficacy of the serotonin selective reuptake inhibitor
(SSRI) antidepressant drugs continues to expand. In fact, no psychiat
ric syndrome seems to worsen with these agents, and few studies fail t
o demonstrate clinical improvement in some patients, regardless of any
nosologic nicety, such as precise DSM diagnosis. This suggests that t
he biological rubric of psychopathology is dimensional rather than cat
egorical. New research using in vivo microdialysis shows differences i
n neurochemistry among SSRIs, wherein fluoxetine blocks reuptake of do
pamine and norepinephrine, as well as serotonin, in medial prefrontal
cortex, and fluvoxamine has a relatively more selective neurochemical
profile. In the animal model of learned helplessness, which is a biobe
havioral model for stress-induced anxiety causing depression, the SSRI
s including fluvoxamine prevent helplessness. From these and other dat
a, a neurotransmitter balance theory of biopsychopathology is formulat
ed. In this hypothetical construct, dopamine, norepinephrine, and GABA
modulate thought, anxiety, and mood, respectively. Serotonin is a sta
bilizing agent, which assists in returning the mind to its homeostatic
setpoint.