Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response.
BACKGROUND
Treatment of major depression with antidepressants is generally associated with a delay in onset of clinical response. Functional brain correlates of this phenomenon have not been previously characterized.


METHODS
Time course of changes in brain glucose metabolism were measured using positron emission tomography in hospitalized unipolar depressed patients treated with fluoxetine. Time-specific and response-specific effects were examined at 1 and 6 weeks of treatment.


RESULTS
Changes were seen over time, and characterized by three distinct patterns: 1) common changes at 1 and 6 weeks, 2) reversal of the 1-week pattern at 6 weeks, and 3) unique changes seen only after chronic treatment. Fluoxetine responders and nonresponders, similar at 1 week, were differentiated by their 6-week pattern. Clinical improvement was uniquely associated with limbic and striatal decreases (subgenual cingulate, hippocampus, insula, and pallidum) and brain stem and dorsal cortical increases (prefrontal, parietal, anterior, and posterior cingulate). Failed response was associated with a persistent 1-week pattern and absence of either subgenual cingulate or prefrontal changes.


CONCLUSIONS
Chronic treatment and clinical response to fluoxetine was associated with a reciprocal pattern of subcortical and limbic decreases and cortical increases. Reversal in the week-1 pattern at 6 weeks suggests a process of adaptation in specific brain regions over time in response to sustained serotonin reuptake inhibition. The inverse patterns in responders and nonresponders also suggests that failure to induce these adaptive changes may underlie treatment nonresponse.
Mayberg
H S
HS
Research Imaging Center, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Brannan
S K
SK
Tekell
J L
JL
Silva
J A
JA
Mahurin
R K
RK
McGinnis
S
S
Jerabek
P A
PA
D001921:Brain / Q000378:metabolism; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005473:Fluoxetine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008032:Limbic System / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D013997:Time Factors; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome
D005473:Fluoxetine; D005947:Glucose; D017367:Selective Serotonin Reuptake Inhibitors