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, Charles Nemeroff

Research output: Contribution to journalArticle

9 Citations (Scopus)

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
Pages (from-to)47-53
Number of pages7
JournalNeuropsychopharmacology
Volume14
Issue number1
DOIs
StatePublished - Feb 6 1996
Externally publishedYes

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Imipramine
Fluoxetine
Blood Platelets
Serotonin
Therapeutics
Double-Blind Method
Antidepressive Agents
Outpatients
Placebos
Neurons
Research

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

Is there a relationship between baseline and treatment-associated changes in [3H]-IMI platelet binding and clinical response in major depression? / Tollefson, G. D.; Heiligenstein, J. H.; Tollefson, S. L.; Birkett, M. A.; Knight, D. L.; Nemeroff, Charles.

In: Neuropsychopharmacology, Vol. 14, No. 1, 06.02.1996, p. 47-53.

Research output: Contribution to journalArticle

Tollefson, G. D. ; Heiligenstein, J. H. ; Tollefson, S. L. ; Birkett, M. A. ; Knight, D. L. ; Nemeroff, Charles. / Is there a relationship between baseline and treatment-associated changes in [3H]-IMI platelet binding and clinical response in major depression?. In: Neuropsychopharmacology. 1996 ; Vol. 14, No. 1. pp. 47-53.
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