Cerebral blood volume and clinical changes on the third day of placebo substitution for SSRI treatment.
BACKGROUND
Interruptions in SSRI treatment have been associated with adverse effects that can resemble depressive illness. We hypothesized that brain regions implicated in depression, with extensive serotonergic innervation, would exhibit changes in activity associated with emergence of symptoms following drug discontinuation.


METHODS
Subjects meeting DSM-IV criteria for remitted major depression on 20 mg/day of either fluoxetine or paroxetine were recruited into this 6-week study. During weeks 2 and 6, subjects underwent a 3-day period in which either active drug or placebo was substituted for their medication under double-blind conditions. Cerebral blood volume (CBV) maps were obtained via dynamic susceptibility magnetic resonance imaging at the end of each double-blind period.


RESULTS
In the paroxetine group, change in CBV in left medial superior frontal region and left caudate nucleus correlated significantly with change in Discontinuation Emergent Symptom Scale and Hamilton Depression Rating Scale (HDRS; R2 = 0.66, p =.0007; R2 = 0.51, p =.006; and R2 = 0.43, p =.015; R2 = 0.32, p =.043, respectively).


CONCLUSIONS
These data demonstrate that changes in regional CBV of left prefrontal cortex and left caudate nucleus correlate with the emergence of discontinuation symptoms and increased HDRS after interruption of paroxetine treatment.
Henry
Michael E
ME
Brain Imaging Center, McLean Hospital and Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts 02478, USA.
Kaufman
Marc J
MJ
Hennen
John
J
Michelson
David
D
Schmidt
Mark E
ME
Stoddard
Eve
E
Vukovic
Alexander J
AJ
Barreira
Paul J
PJ
Cohen
Bruce M
BM
Renshaw
Perry F
PF
D000328:Adult; D002421:Caudate Nucleus / Q000033:anatomy & histology / Q000098:blood supply; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D017374:Paroxetine / Q000627:therapeutic use*; D017397:Prefrontal Cortex / Q000033:anatomy & histology / Q000098:blood supply*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011795:Surveys and Questionnaires
D005473:Fluoxetine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors