title: Is there a relationship between baseline and treatment-associated changes in [3H]-IMI platelet binding and clinical response in major depression?
abstract: A peripheral model for the central 5-HT neuron is the characterization of platelet imipramine binding. We studied an outpatient major depressive cohort who fulfilled Research Diagnostic Criteria for agitation. After a 1-week placebo lead-in, subjects were blindly randomized to either imipramine (IMI) or fluoxetine (FLU) during an 8-week, double-blind study period. Thirty-three subjects (15 IMI, 18 FLU) provided both baseline and endpoint samples for the platelet [3H]-IMI assay. Depression efficacy was comparable across the two treatments, whereas FLU was significantly more effective in reducing secondary anxiolysis (p = .023). Discontinuations due to an adverse event were significantly more frequent with IMI than FLU (p < .01). Baseline affinity (KD) was mildly predictive of change in the HAMD (r = -.22; p = .07). Whereas baseline to endpoint density (Bmax) changes (delta) were similar for IMI (183 +/- 329 fmol/mg) and FLU (196 +/- 402 fmol/mg), a statistically significant treatment difference in delta KD emerged (IMI -0.005 +/- 0.010 pmol/ml versus FLU 0.008 +/- 0.013 at p = 004). Moreover, the changes in KD and HAMD17 trended to a positive correlation among only the FLU-treated subjects (4 = 0.406, p = .095). The clinical effects of 5-HT-based selective antidepressant may be reflected by dynamic changes in the platelet 5-HT uptake apparatus. These data suggest that the baseline confirmational status of the [3H]-IMI:5-HT transporter may reflect a "capacity" for a treatment response.
authors.affiliation: Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Tollefson
authors.forename: J H
authors.initials: JH
authors.lastname: Heiligenstein
authors.forename: S L
authors.initials: SL
authors.lastname: Tollefson
authors.forename: M A
authors.initials: MA
authors.lastname: Birkett
authors.forename: D L
authors.initials: DL
authors.lastname: Knight
authors.forename: C B
authors.initials: CB
authors.lastname: Nemeroff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism*; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D006801:Humans; D007099:Imipramine / Q000378:metabolism / Q000627:therapeutic use*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011869:Radioligand Assay; D013997:Time Factors
chemical_list: D005473:Fluoxetine; D007099:Imipramine