Initial platelet serotonin (5-HT) transport kinetics predict nortriptyline treatment outcome.
According to the hypothesis of initial conditions, drug response may be determined by different initial states of neurotransmitter protein recognition systems. Platelet serotonin (5-HT) transport kinetics were studied as initial-conditions predictors of antidepressant response in 24 depressed patients before and after 3 weeks of treatment with nortriptyline (75 mg). The initial affinity of the 5-HT transporter (5-HTT) correctly predicted 71% of the outcome. The pretreatment affinity constant ( Km) correlated (r = 0.61; p < 0.002) with that measured after 3 weeks of treatment (Kapp). Responding patients had a significantly higher initial Km before treatment and a significantly higher Kapp after treatment. Nonresponders had an initial Km significantly lower than that of 24 controls. Nortriptyline plasma levels were not statistically different between response groups. These results are consistent with two previously published observations, which indicate that the initial affinity of the 5-HTT predicted response to fluvoxamine or fluoxetine in the same way. Insofar as all three drugs increase the apparent affinity of the 5-HTT, it appears that a better response is related to those cases where the initial affinity is already higher before treatment.
Rausch
Jeffrey L
JL
Department of Psychiatry, Veterans Affairs Medical Center, and The Medical College of Georgia, Augusta, Georgia 30912-3800, USA. jeffreyr@mail.mcg.edu
Moeller
Frederick G
FG
Johnson
Maria E
ME
D000328:Adult; D000368:Aged; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D001692:Biological Transport; D015415:Biomarkers / Q000032:analysis; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood*; D016022:Case-Control Studies; D003866:Depressive Disorder / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D009661:Nortriptyline / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D012701:Serotonin / Q000097:blood*; D050486:Serotonin Plasma Membrane Transport Proteins; D016896:Treatment Outcome
D000929:Antidepressive Agents, Tricyclic; D015415:Biomarkers; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D009661:Nortriptyline