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

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 14; no. 1; pp. 47 - 53
• Main Authors: Tollefson, Gary D., Heiligenstein, John H., Tollefson, Sherrie L., Birkett, Martin A., Knight, David L., Nemeroff, Charles B.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.01.1996; Nature Publishing
• Subjects: 3H-IMI binding; Adolescent; Adult; Aged; Biological and medical sciences; Blood Platelets - metabolism; Depression; Depressive Disorder - blood; Depressive Disorder - drug therapy; Double-Blind Method; Female; Fluoxetine; Fluoxetine - therapeutic use; Humans; Imipramine - metabolism; Imipramine - therapeutic use; Kinetics; Male; Medical sciences; Middle Aged; Neuropharmacology; Pharmacology. Drug treatments; Platelet; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Radioligand Assay; Response prediction; Time Factors; Tricyclic; Depression; Platelet; Tricyclic; 3H-IMI binding; Fluoxetine; Response prediction; Human; Mood disorder; Serotonin; Psychotropic; Treatment efficiency; Prediction; Biological marker; Binding site; Tricyclic compound; Reuptake inhibitor; Chemotherapy; Biological fixation; Double blind study; Antidepressant agent
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1016/S0893-133X(96)80058-3

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 (Δ) were similar for IMI (183 ± 329 fmol/mg) and FLU (196 ± 402 fmol/mg), a statistically significant treatment difference in ΔKD 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.