Is there a relationship between baseline and treatment-associated changes in [3H]-IMI platelet binding and clinical response in major depression?

G. D. Tollefson, J. H. Heiligenstein, S. L. Tollefson, M. A. Birkett, D. L. Knight, C. B. Nemeroff

Research output: Contribution to journalArticle

9 Scopus citations

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 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 (K(D)) was mildly predictive of change in the HAMD (r = -.22; p = .07). Whereas baseline to endpoint density (B(max)) changes (Δ) were similar for IMI (183 ± 329 fmol/mg) and FLU (196 ± 402 fmol/mg), a statistically significant treatment difference in ΔK(D) emerged (IMI -0.005 ± 0.010 pmol/ml versus FLU 0.008 ± 0.013 at p = .004). Moreover, the changes in K(D) 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.

Original languageEnglish (US)
Pages (from-to)47-53
Number of pages7
JournalNeuropsychopharmacology
Volume14
Issue number1
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

Keywords

  • H-IMI binding
  • Depression
  • Fluoxetine
  • Platelet
  • Response prediction
  • Tricyclic

ASJC Scopus subject areas

  • Pharmacology

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