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.